,Unnamed: 0,entry,protein2,uniprot_description,rank,protein1,protein_name,function,GPT_description,all_description
0,0,Q8N884-D95A,MQPWHGKAMQRASEAGATAPKASARNARGAPMDPTESPAAPEAALPKAGKFGPARKSGSRQKKSAPDTQERPPVRATGARAKKAPQRAQDTQPSAATSAPGAEGLEPPAAREPALSRAGSCRQRGARCSTKPRPPPGPWDVPSPGLPVSAPILVRRDAAPGASKLRAVLEKLKLSRDDISTAAGMVKGVVDHLLLRLKCDSAFRGVGLLNTGSYYEHVKISAPNEFDVMFKLEVPRIQLEEYSNTRAYYFVKFKRNPKENPLSQFLEGEILSASKMLSKFRKIIKEEINDIKDTDVIMKRKRGGSPAVTLLISEKISVDITLALESKSSWPASTQEGLRIQNWLSAKVRKQLRLKPFYLVPKHAKEGNGFQEETWRLSFSHIEKEILNNHGKSKTCCENKEEKCCRKDCLKLMKYLLEQLKERFKDKKHLDKFSSYHVKTAFFHVCTQNPQDSQWDRKDLGLCFDNCVTYFLQCLRTEKLENYFIPEFNLFSSNLIDKRSKEFLTKQIEYERNNEFPVFDEF,No effect on type I IFN and RSAD2 induction. No effect on cleavage by CASP1; when associated with A-33; A-67 and A-90. Highly decreases cleavage by CASP1 and enhances RSAD2 induction upon DNA virus infection; when associated with A-33; A-67; A-90 and A-140. Abolishes cleavage by CASP1 and enhances RSAD2 induction upon DNA virus infection; when associated with A-33; A-67; A-90; A-140 and A-157.,,MQPWHGKAMQRASEAGATAPKASARNARGAPMDPTESPAAPEAALPKAGKFGPARKSGSRQKKSAPDTQERPPVRATGARAKKAPQRAQDTQPSDATSAPGAEGLEPPAAREPALSRAGSCRQRGARCSTKPRPPPGPWDVPSPGLPVSAPILVRRDAAPGASKLRAVLEKLKLSRDDISTAAGMVKGVVDHLLLRLKCDSAFRGVGLLNTGSYYEHVKISAPNEFDVMFKLEVPRIQLEEYSNTRAYYFVKFKRNPKENPLSQFLEGEILSASKMLSKFRKIIKEEINDIKDTDVIMKRKRGGSPAVTLLISEKISVDITLALESKSSWPASTQEGLRIQNWLSAKVRKQLRLKPFYLVPKHAKEGNGFQEETWRLSFSHIEKEILNNHGKSKTCCENKEEKCCRKDCLKLMKYLLEQLKERFKDKKHLDKFSSYHVKTAFFHVCTQNPQDSQWDRKDLGLCFDNCVTYFLQCLRTEKLENYFIPEFNLFSSNLIDKRSKEFLTKQIEYERNNEFPVFDEF,Cyclic GMP-AMP synthase,"Nucleotidyltransferase that catalyzes the formation of cyclic GMP-AMP (2',3'-cGAMP) from ATP and GTP and plays a key role in innate immunity. Catalysis involves both the formation of a 2',5' phosphodiester linkage at the GpA step and the formation of a 3',5' phosphodiester linkage at the ApG step, producing c[G(2',5')pA(3',5')p]. Acts as a key DNA sensor: directly binds double-stranded DNA (dsDNA), inducing the formation of liquid-like droplets in which CGAS is activated, leading to synthesis of 2',3'-cGAMP, a second messenger that binds to and activates STING1, thereby triggering type-I interferon production. Preferentially recognizes and binds curved long dsDNAs of a minimal length of 40 bp. Acts as a key foreign DNA sensor, the presence of double-stranded DNA (dsDNA) in the cytoplasm being a danger signal that triggers the immune responses. Has antiviral activity by sensing the presence of dsDNA from DNA viruses in the cytoplasm. Also acts as an innate immune sensor of infection by retroviruses, such as HIV-2, by detecting the presence of reverse-transcribed DNA in the cytosol. In contrast, HIV-1 is poorly sensed by CGAS, due to its capsid that cloaks viral DNA from CGAS detection. Detection of retroviral reverse-transcribed DNA in the cytosol may be indirect and be mediated via interaction with PQBP1, which directly binds reverse-transcribed retroviral DNA. Also detects the presence of DNA from bacteria, such as M.tuberculosis. 2',3'-cGAMP can be transferred from producing cells to neighboring cells through gap junctions, leading to promote STING1 activation and convey immune response to connecting cells. 2',3'-cGAMP can also be transferred between cells by virtue of packaging within viral particles contributing to IFN-induction in newly infected cells in a cGAS-independent but STING1-dependent manner. Also senses the presence of neutrophil extracellular traps (NETs) that are translocated to the cytosol following phagocytosis, leading to synthesis of 2',3'-cGAMP. In addition to foreign DNA, can also be activated by endogenous nuclear or mitochondrial DNA. When self-DNA leaks into the cytosol during cellular stress (such as mitochondrial stress, SARS-CoV-2 infection causing severe COVID-19 disease, DNA damage, mitotic arrest or senescence), or is present in form of cytosolic micronuclei, CGAS is activated leading to a state of sterile inflammation. Acts as a regulator of cellular senescence by binding to cytosolic chromatin fragments that are present in senescent cells, leading to trigger type-I interferon production via STING1 and promote cellular senescence. Also involved in the inflammatory response to genome instability and double-stranded DNA breaks: acts by localizing to micronuclei arising from genome instability. Micronuclei, which are frequently found in cancer cells, consist of chromatin surrounded by their own nuclear membrane: following breakdown of the micronuclear envelope, a process associated with chromothripsis, CGAS binds self-DNA exposed to the cytosol, leading to 2',3'-cGAMP synthesis and subsequent activation of STING1 and type-I interferon production. Activated in response to prolonged mitotic arrest, promoting mitotic cell death. In a healthy cell, CGAS is however kept inactive even in cellular events that directly expose it to self-DNA, such as mitosis, when cGAS associates with chromatin directly after nuclear envelope breakdown or remains in the form of postmitotic persistent nuclear cGAS pools bound to chromatin. Nuclear CGAS is inactivated by chromatin via direct interaction with nucleosomes, which block CGAS from DNA binding and thus prevent CGAS-induced autoimmunity. Also acts as a suppressor of DNA repair in response to DNA damage: inhibits homologous recombination repair by interacting with PARP1, the CGAS-PARP1 interaction leading to impede the formation of the PARP1-TIMELESS complex. In addition to DNA, also sense translation stress: in response to translation stress, translocates to the cytosol and associates with collided ribosomes, promoting its activation and triggering type-I interferon production. In contrast to other mammals, human CGAS displays species-specific mechanisms of DNA recognition and produces less 2',3'-cGAMP, allowing a more fine-tuned response to pathogens.",,No effect on type I IFN and RSAD2 induction. No effect on cleavage by CASP1; when associated with A-33; A-67 and A-90. Highly decreases cleavage by CASP1 and enhances RSAD2 induction upon DNA virus infection; when associated with A-33; A-67; A-90 and A-140. Abolishes cleavage by CASP1 and enhances RSAD2 induction upon DNA virus infection; when associated with A-33; A-67; A-90; A-140 and A-157.
1,1,P06276-L153F,MHSKVTIICIRFLFWFLLLCMLIGKSHTEDDIIIATKNGKVRGMNLTVFGGTVTAFLGIPYAQPPLGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVWIPAPKPKNATVLIWIYGGGFQTGTSSFHVYDGKFLARVERVIVVSMNYRVGALGFLALPGNPEAPGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAASVSLHLLSPGSHSLFTRAILQSGSFNAPWAVTSLYEARNRTLNLAKLTGCSRENETEIIKCLRNKDPQEILLNEAFVVPYGTPLSVNFGPTVDGDFLTDMPDILLELGQFKKTQILVGVNKDEGTAFLVYGAPGFSKDNNSIITRKEFQEGLKIFFPGVSEFGKESILFHYTDWVDDQRPENYREALGDVVGDYNFICPALEFTKKFSEWGNNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLERRDNYTKAEEILSRSIVKRWANFAKYGNPNETQNNSTSWPVFKSTEQKYLTLNTESTRIMTKLRAQQCRFWTSFFPKVLEMTGNIDEAEWEWKAGFHRWNNYMMDWKNQFNDYTSKKESCVGL,In BCHED; seems to cause reduced expression of the protein.,,MHSKVTIICIRFLFWFLLLCMLIGKSHTEDDIIIATKNGKVRGMNLTVFGGTVTAFLGIPYAQPPLGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVWIPAPKPKNATVLIWIYGGGFQTGTSSLHVYDGKFLARVERVIVVSMNYRVGALGFLALPGNPEAPGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAASVSLHLLSPGSHSLFTRAILQSGSFNAPWAVTSLYEARNRTLNLAKLTGCSRENETEIIKCLRNKDPQEILLNEAFVVPYGTPLSVNFGPTVDGDFLTDMPDILLELGQFKKTQILVGVNKDEGTAFLVYGAPGFSKDNNSIITRKEFQEGLKIFFPGVSEFGKESILFHYTDWVDDQRPENYREALGDVVGDYNFICPALEFTKKFSEWGNNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLERRDNYTKAEEILSRSIVKRWANFAKYGNPNETQNNSTSWPVFKSTEQKYLTLNTESTRIMTKLRAQQCRFWTSFFPKVLEMTGNIDEAEWEWKAGFHRWNNYMMDWKNQFNDYTSKKESCVGL,Cholinesterase,Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.,The mutation in the BCHE gene leads to reduced expression of BChE protein.,In BCHED; seems to cause reduced expression of the protein. The mutation in the BCHE gene leads to reduced expression of BChE protein.
2,2,P63096-E245L,MGCTLSAEDKAAVERSKMIDRNLREDGEKAAREVKLLLLGAGESGKSTIVKQMKIIHEAGYSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMTAELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVKTTGIVETHFTFKDLHFKMFDVGGQRSERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEMNRMHLSMKLFDSICNNKWFTDTSIILFLNKKDLFEEKIKKSPLTICYPEYAGSNTYEEAAAYIQCQFEDLNKRKDTKEIYTHFTCATDTKNVQFVFDAVTDVIIKNNLKDCGLF,Enhances interaction (inactive GDP-bound) with RGS14.,,MGCTLSAEDKAAVERSKMIDRNLREDGEKAAREVKLLLLGAGESGKSTIVKQMKIIHEAGYSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMTAELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVKTTGIVETHFTFKDLHFKMFDVGGQRSERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEMNRMHESMKLFDSICNNKWFTDTSIILFLNKKDLFEEKIKKSPLTICYPEYAGSNTYEEAAAYIQCQFEDLNKRKDTKEIYTHFTCATDTKNVQFVFDAVTDVIIKNNLKDCGLF,Guanine nucleotide-binding protein G,"Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal. Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins. Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels (By similarity). The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. Required for normal cytokinesis during mitosis. Required for cortical dynein-dynactin complex recruitment during metaphase.",,Enhances interaction (inactive GDP-bound) with RGS14.
3,3,O35244-S32A,MPGGLLLGDEAPNFEANTTIGHIRFHDFLGDAWGILFSHPRDFTPVCTTELGRAAKLAPEFAKRNVKLIALSIDSVEDHFAWSKDINAYNGAAPTEKLPFPIIDDKDRDLAILLGMLDPAEKDEKGMPVTARVVFIFGPDKKLKLSILYPATTGRNFDEILRVVDSLQLTASNPVATPVDWKKGESVMVLPTLPEEEAKQLFPKGVFTKELPSGKKYLRYTPQP,Abolishes lipid binding.,,MPGGLLLGDEAPNFEANTTIGHIRFHDFLGDSWGILFSHPRDFTPVCTTELGRAAKLAPEFAKRNVKLIALSIDSVEDHFAWSKDINAYNGAAPTEKLPFPIIDDKDRDLAILLGMLDPAEKDEKGMPVTARVVFIFGPDKKLKLSILYPATTGRNFDEILRVVDSLQLTASNPVATPVDWKKGESVMVLPTLPEEEAKQLFPKGVFTKELPSGKKYLRYTPQP,Peroxiredoxin-6,"Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Can reduce H(2)O(2) and short chain organic, fatty acid, and phospholipid hydroperoxides. Also has phospholipase activity, can therefore either reduce the oxidized sn-2 fatty acyl group of phospholipids (peroxidase activity) or hydrolyze the sn-2 ester bond of phospholipids (phospholipase activity). These activities are dependent on binding to phospholipids at acidic pH and to oxidized phospholipds at cytosolic pH. Plays a role in cell protection against oxidative stress by detoxifying peroxides and in phospholipid homeostasis. Exhibits acyl-CoA-dependent lysophospholipid acyltransferase which mediates the conversion of lysophosphatidylcholine (1-acyl-sn-glycero-3-phosphocholine or LPC) into phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine or PC). Shows a clear preference for LPC as the lysophospholipid and for palmitoyl CoA as the fatty acyl substrate.","Increased Prdx6 alpha-helical content, key role in maintaining Prdx6 structure and for phospholipid substrate binding.","Abolishes lipid binding. Increased Prdx6 alpha-helical content, key role in maintaining Prdx6 structure and for phospholipid substrate binding."
4,4,P80365-R337C,MERWPWPSGGAWLLVAARALLQLLRSDLRLGRPLLAALALLAALDWLCQRLLPPPAALAVLAAAGWIALSRLARPQRLPVATRAVLITGCDSGFGKETAKKLDSMGFTVLATVLELNSPGAIELRTCCSPRLRLLQMDLTKPGDISRVLEFTKAHTTSTGLWGLVNNAGHNEVVADAELSPVATFRSCMEVNFFGALELTKGLLPLLRSSRGRIVTVGSPAGDMPYPCLGAYGTSKAAVALLMDTFSCELLPWGVKVSIIQPGCFKTESVRNVGQWEKRKQLLLANLPQELLQAYGKDYIEHLHGQFLHSLRLAMSDLTPVVDAITDALLAARPRRCYYPGQGLGLMYFIHYYLPEGLRRRFLQAFFISHCLPRALQPGQPGTTPPQDAAQDPNLSPGPSPAVAR,"In AME; decreased half-life from 21 to 4 hours compared to wild-type, probably due to degradation via the proteasomal pathway.",,MERWPWPSGGAWLLVAARALLQLLRSDLRLGRPLLAALALLAALDWLCQRLLPPPAALAVLAAAGWIALSRLARPQRLPVATRAVLITGCDSGFGKETAKKLDSMGFTVLATVLELNSPGAIELRTCCSPRLRLLQMDLTKPGDISRVLEFTKAHTTSTGLWGLVNNAGHNEVVADAELSPVATFRSCMEVNFFGALELTKGLLPLLRSSRGRIVTVGSPAGDMPYPCLGAYGTSKAAVALLMDTFSCELLPWGVKVSIIQPGCFKTESVRNVGQWEKRKQLLLANLPQELLQAYGKDYIEHLHGQFLHSLRLAMSDLTPVVDAITDALLAARPRRRYYPGQGLGLMYFIHYYLPEGLRRRFLQAFFISHCLPRALQPGQPGTTPPQDAAQDPNLSPGPSPAVAR,11-beta-hydroxysteroid dehydrogenase type 2,"Catalyzes the conversion of biologically active 11beta-hydroxyglucocorticoids (11beta-hydroxysteroid) such as cortisol, to inactive 11-ketoglucocorticoids (11-oxosteroid) such as cortisone, in the presence of NAD(+). Functions as a dehydrogenase (oxidase), thereby decreasing the concentration of active glucocorticoids, thus protecting the nonselective mineralocorticoid receptor from occupation by glucocorticoids. Plays an important role in maintaining glucocorticoids balance during preimplantation and protects the fetus from excessive maternal corticosterone exposure. Catalyzes the oxidation of 11beta-hydroxytestosterone (11beta,17beta-dihydroxyandrost-4-ene-3-one) to 11-ketotestosterone (17beta-hydroxyandrost-4-ene-3,11-dione), a major bioactive androgen. Catalyzes the conversion of 11beta-hydroxyandrostenedione (11beta-hydroxyandrost-4-ene-3,17-dione) to 11-ketoandrostenedione (androst-4-ene-3,11,17-trione), which can be further metabolized to 11-ketotestosterone. Converts 7-beta-25-dihydroxycholesterol to 7-oxo-25-hydroxycholesterol in vitro. 7-beta-25-dihydroxycholesterol (not 7-oxo-25-hydroxycholesterol) acts as ligand for the G-protein-coupled receptor (GPCR) Epstein-Barr virus-induced gene 2 (EBI2) and may thereby regulate immune cell migration. May protect ovulating oocytes and fertilizing spermatozoa from the adverse effects of cortisol.","This mutation has been discovered in a consanguineous Iranian family with three siblings suffering from Apparent Mineralocorticoid Excess (AME). The mutation in the HSD11B2 gene is associated with apparent mineralocorticoid excess (AME). This mutation results in a deficiency of 11 beta-hydroxysteroid dehydrogenase type 2 enzyme activity, leading to pre- and postnatal growth failure, juvenile hypertension, hypokalemic metabolic alkalosis, and hyporeninemic hypoaldosteronism. The 11 beta HSD2 enzyme is responsible for the conversion of cortisol to the inactive metabolite cortisone, and the mutation impairs this conversion, causing mineralocorticoid receptors to be exposed to excessive cortisol levels.","In AME; decreased half-life from 21 to 4 hours compared to wild-type, probably due to degradation via the proteasomal pathway. This mutation has been discovered in a consanguineous Iranian family with three siblings suffering from Apparent Mineralocorticoid Excess (AME). The mutation in the HSD11B2 gene is associated with apparent mineralocorticoid excess (AME). This mutation results in a deficiency of 11 beta-hydroxysteroid dehydrogenase type 2 enzyme activity, leading to pre- and postnatal growth failure, juvenile hypertension, hypokalemic metabolic alkalosis, and hyporeninemic hypoaldosteronism. The 11 beta HSD2 enzyme is responsible for the conversion of cortisol to the inactive metabolite cortisone, and the mutation impairs this conversion, causing mineralocorticoid receptors to be exposed to excessive cortisol levels."
5,5,P9WMI9-C4S,MLTSEMRESALARLGRALADPTRCRILVALLDGVCYPGQLAAHLGLTRSNVSNHLSCLRGCGLVVATYEGRQVRYALADSHLARALGELVQVVLAVDTDQPCVAERAASGEAVEMTGS,No effect.,,MLTCEMRESALARLGRALADPTRCRILVALLDGVCYPGQLAAHLGLTRSNVSNHLSCLRGCGLVVATYEGRQVRYALADSHLARALGELVQVVLAVDTDQPCVAERAASGEAVEMTGS,HTH-type transcriptional regulator CmtR,Metal-responsive transcriptional repressor for the cmt operon. Binding of cadmium or lead causes the repressor to dissociate from the DNA.,Substitution of C4 with S is obligatory for Cd(II) detection.,No effect. Substitution of C4 with S is obligatory for Cd(II) detection.
6,6,Q16539-T175A,MSQERPTFYRQELNKTIWEVPERYQNLSPVGSGAYGSVCAAFDTKTGLRVAVKKLSRPFQSIIHAKRTYRELRLLKHMKHENVIGLLDVFTPARSLEEFNDVYLVTHLMGADLNNIVKCQKLTDDHVQFLIYQILRGLKYIHSADIIHRDLKPSNLAVNEDCELKILDFGLARHADDEMTGYVATRWYRAPEIMLNWMHYNQTVDIWSVGCIMAELLTGRTLFPGTDHIDQLKLILRLVGTPGAELLKKISSESARNYIQSLTQMPKMNFANVFIGANPLAVDLLEKMLVLDSDKRITAAQALAHAYFAQYHDPDDEPVADPYDQSFESRDLLIDEWKSLTYDEVISFVPPPLDQEEMES,No effect on either the kinase activity or tyrosine phosphorylation.,,MSQERPTFYRQELNKTIWEVPERYQNLSPVGSGAYGSVCAAFDTKTGLRVAVKKLSRPFQSIIHAKRTYRELRLLKHMKHENVIGLLDVFTPARSLEEFNDVYLVTHLMGADLNNIVKCQKLTDDHVQFLIYQILRGLKYIHSADIIHRDLKPSNLAVNEDCELKILDFGLARHTDDEMTGYVATRWYRAPEIMLNWMHYNQTVDIWSVGCIMAELLTGRTLFPGTDHIDQLKLILRLVGTPGAELLKKISSESARNYIQSLTQMPKMNFANVFIGANPLAVDLLEKMLVLDSDKRITAAQALAHAYFAQYHDPDDEPVADPYDQSFESRDLLIDEWKSLTYDEVISFVPPPLDQEEMES,Mitogen-activated protein kinase 14,"Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1. RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2. MAPK14 interacts also with casein kinase II, leading to its activation through autophosphorylation and further phosphorylation of TP53/p53. In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. In a similar way, MAPK14 phosphorylates the ubiquitin ligase SIAH2, regulating its activity towards EGLN3. MAPK14 may also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9. Another function of MAPK14 is to regulate the endocytosis of membrane receptors by different mechanisms that impinge on the small GTPase RAB5A. In addition, clathrin-mediated EGFR internalization induced by inflammatory cytokines and UV irradiation depends on MAPK14-mediated phosphorylation of EGFR itself as well as of RAB5A effectors. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Another p38 MAPK substrate is FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A. The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates CDC25B and CDC25C which is required for binding to 14-3-3 proteins and leads to initiation of a G2 delay after ultraviolet radiation. Phosphorylates TIAR following DNA damage, releasing TIAR from GADD45A mRNA and preventing mRNA degradation. The p38 MAPKs may also have kinase-independent roles, which are thought to be due to the binding to targets in the absence of phosphorylation. Protein O-Glc-N-acylation catalyzed by the OGT is regulated by MAPK14, and, although OGT does not seem to be phosphorylated by MAPK14, their interaction increases upon MAPK14 activation induced by glucose deprivation. This interaction may regulate OGT activity by recruiting it to specific targets such as neurofilament H, stimulating its O-Glc-N-acylation. Required in mid-fetal development for the growth of embryo-derived blood vessels in the labyrinth layer of the placenta. Also plays an essential role in developmental and stress-induced erythropoiesis, through regulation of EPO gene expression. Isoform MXI2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2. Isoform EXIP may play a role in the early onset of apoptosis. Phosphorylates S100A9 at 'Thr-113'. Phosphorylates NLRP1 downstream of MAP3K20/ZAK in response to UV-B irradiation and ribosome collisions, promoting activation of the NLRP1 inflammasome and pyroptosis.(Microbial infection) Activated by phosphorylation by M.tuberculosis EsxA in T-cells leading to inhibition of IFN-gamma production; phosphorylation is apparent within 15 minutes and is inhibited by kinase-specific inhibitors SB203580 and siRNA.",,No effect on either the kinase activity or tyrosine phosphorylation.
7,7,P28845-K6S,MAFMKSYLLPILGLFMAYYYYSANEEFRPEMLQGKKVIVTGASKGIGREMAYHLAKMGAHVVVTARSKETLQKVVSHCLELGAASAHYIAGTMEDMTFAEQFVAQAGKLMGGLDMLILNHITNTSLNLFHDDIHHVRKSMEVNFLSYVVLTVAALPMLKQSNGSIVVVSSLAGKVAYPMVAAYSASKFALDGFFSSIRKEYSVSRVNVSITLCVLGLIDTETAMKAVSGIVHMQAAPKEECALEIIKGGALRQEEVYYDSSLWTTLLIRNPCRKILEFLYSTSYNMDRFINK,No effect on topology or activity.,,MAFMKKYLLPILGLFMAYYYYSANEEFRPEMLQGKKVIVTGASKGIGREMAYHLAKMGAHVVVTARSKETLQKVVSHCLELGAASAHYIAGTMEDMTFAEQFVAQAGKLMGGLDMLILNHITNTSLNLFHDDIHHVRKSMEVNFLSYVVLTVAALPMLKQSNGSIVVVSSLAGKVAYPMVAAYSASKFALDGFFSSIRKEYSVSRVNVSITLCVLGLIDTETAMKAVSGIVHMQAAPKEECALEIIKGGALRQEEVYYDSSLWTTLLIRNPCRKILEFLYSTSYNMDRFINK,11-beta-hydroxysteroid dehydrogenase 1,"Controls the reversible conversion of biologically active glucocorticoids such as cortisone to cortisol, and 11-dehydrocorticosterone to corticosterone in the presence of NADP(H). Participates in the corticosteroid receptor-mediated anti-inflammatory response, as well as metabolic and homeostatic processes. Plays a role in the secretion of aqueous humor in the eye, maintaining a normotensive, intraocular environment. Bidirectional in vitro, predominantly functions as a reductase in vivo, thereby increasing the concentration of active glucocorticoids. It has broad substrate specificity, besides glucocorticoids, it accepts other steroid and sterol substrates. Interconverts 7-oxo- and 7-hydroxy-neurosteroids such as 7-oxopregnenolone and 7beta-hydroxypregnenolone, 7-oxodehydroepiandrosterone (3beta-hydroxy-5-androstene-7,17-dione) and 7beta-hydroxydehydroepiandrosterone (3beta,7beta-dihydroxyandrost-5-en-17-one), among others. Catalyzes the stereo-specific conversion of the major dietary oxysterol, 7-ketocholesterol (7-oxocholesterol), into the more polar 7-beta-hydroxycholesterol metabolite. 7-oxocholesterol is one of the most important oxysterols, it participates in several events such as induction of apoptosis, accumulation in atherosclerotic lesions, lipid peroxidation, and induction of foam cell formation. Mediates the 7-oxo reduction of 7-oxolithocholate mainly to chenodeoxycholate, and to a lesser extent to ursodeoxycholate, both in its free form and when conjugated to glycine or taurine, providing a link between glucocorticoid activation and bile acid metabolism. Catalyzes the synthesis of 7-beta-25-dihydroxycholesterol from 7-oxo-25-hydroxycholesterol in vitro, which acts as ligand for the G-protein-coupled receptor (GPCR) Epstein-Barr virus-induced gene 2 (EBI2) and may thereby regulate immune cell migration.",Mutation of K(6) to S did not affect the subcellular localization or catalytic activity of 11beta-HSD1.,No effect on topology or activity. Mutation of K(6) to S did not affect the subcellular localization or catalytic activity of 11beta-HSD1.
8,8,P56513-K63G,MAPLHHILVLCVGFLTTATAEAPQEHDPFTYDYQSLRIGGLIIAGILFILGILIVLSRRCRCGFNQQQRTGEPDEEEGTFRSSIRRLSTRRR,Loss of glutathionylation and loss of ability to reduce glutathionylation of ATP1B1.,,MAPLHHILVLCVGFLTTATAEAPQEHDPFTYDYQSLRIGGLIIAGILFILGILIVLSRRCRCKFNQQQRTGEPDEEEGTFRSSIRRLSTRRR,Phospholemman,"Associates with and regulates the activity of the sodium/potassium-transporting ATPase (NKA) which transports Na(+) out of the cell and K(+) into the cell. Inhibits NKA activity in its unphosphorylated state and stimulates activity when phosphorylated. Reduces glutathionylation of the NKA beta-1 subunit ATP1B1, thus reversing glutathionylation-mediated inhibition of ATP1B1. Contributes to female sexual development by maintaining the excitability of neurons which secrete gonadotropin-releasing hormone.",The mutation in the FXYD protein family affects the reactivity of the Na(+)-K(+) pump and modulates its activity.,Loss of glutathionylation and loss of ability to reduce glutathionylation of ATP1B1. The mutation in the FXYD protein family affects the reactivity of the Na(+)-K(+) pump and modulates its activity.
9,9,Q9I6V6-L264K,MGLFNAHAVAQQRADRIATLLQSFADGQLDTAVGEAPAPGYERLYDSLRALQRQLREQRAELQQVESLEAGLAEMSRQHEAGWIDQTIPAERLEGRAARIAKGVNELVAAHIAVKMKVVSVVTAYGQGNFEPLMDRLPGKKAQITEAIDGVRERLRGAAEATSAQLATAAYNARIKSALDNVSANVMIADNDLNIIYMNRTVSEMLGRAEADIRKQLPNFDAGRLMGANIDVFHKNPAHQRHLLANLTGVHKAELNLGGRRFSKDVVPVFNDANERLGSAVQWTDRTEEHRAEQEVSQLVQAAAAGDFSKRVEEAGKEGFFLRLAKDLNSLVDTADRGLRDVSRMLGALAQGDLTQRIEADYQGTFGQLKDFSNDTAQSLSRMLGQIREAADTINTAASEIASGNAELSARTEQQASSLEETASSMEELTSTVKLNAENARQANSLAANASEVATQGGTVVQKVVSTMSSINESARKIADIIGVIDGIAFQTNILALNAAVEAARAGEQGRGFAVVAGEVRTLAQRSAAAAKEIKTLISDSVDKVENGNTLVAQAGQTMSDIVVAIRRVTDIMSEIAAASAEQSTGIEEVNSAVSQMDDMTQQNAALVEEAAAAAEAMQEQAGLLNQSVAVFRLDTPPSVVQLASARPSAPRPSAPAPLARSGMARASKARKEDGWEEF,Signal-off mutant that does not respond to the addition or removal of O(2). Does not bind either O(2) or CO.,,MGLFNAHAVAQQRADRIATLLQSFADGQLDTAVGEAPAPGYERLYDSLRALQRQLREQRAELQQVESLEAGLAEMSRQHEAGWIDQTIPAERLEGRAARIAKGVNELVAAHIAVKMKVVSVVTAYGQGNFEPLMDRLPGKKAQITEAIDGVRERLRGAAEATSAQLATAAYNARIKSALDNVSANVMIADNDLNIIYMNRTVSEMLGRAEADIRKQLPNFDAGRLMGANIDVFHKNPAHQRHLLANLTGVHKAELNLGGRRFSLDVVPVFNDANERLGSAVQWTDRTEEHRAEQEVSQLVQAAAAGDFSKRVEEAGKEGFFLRLAKDLNSLVDTADRGLRDVSRMLGALAQGDLTQRIEADYQGTFGQLKDFSNDTAQSLSRMLGQIREAADTINTAASEIASGNAELSARTEQQASSLEETASSMEELTSTVKLNAENARQANSLAANASEVATQGGTVVQKVVSTMSSINESARKIADIIGVIDGIAFQTNILALNAAVEAARAGEQGRGFAVVAGEVRTLAQRSAAAAKEIKTLISDSVDKVENGNTLVAQAGQTMSDIVVAIRRVTDIMSEIAAASAEQSTGIEEVNSAVSQMDDMTQQNAALVEEAAAAAEAMQEQAGLLNQSVAVFRLDTPPSVVQLASARPSAPRPSAPAPLARSGMARASKARKEDGWEEF,Methyl-accepting chemotaxis protein McpB,"Chemoreceptor that plays a critical role in the virulence and pathogenesis of P.aeruginosa in a variety of hosts. Probably acts through oxygen sensing. Uses a heme-based sensor. Could be involved in chemotaxis. When expressed in E.coli, is able to sense and mediate repellent responses to oxygen, carbon monoxide and nitric oxide.",formed a hexacoordinate heme.,Signal-off mutant that does not respond to the addition or removal of O(2). Does not bind either O(2) or CO. formed a hexacoordinate heme.
10,10,O13828-R18A,MSFTNATFSQVLDDLSAAFILNLPAEEQSSVERLCFQIEQAHWFYEDFIRAQNDQLPSLGLRVFSAKLFAHCPLLWKWSKVHEEAFDDFLRYKTRIPVRGAIMLDMSMQQCVLVKGWKASSGWGFPKGKIDKDESDVDCAIREVYEETGFDCSSRINPNEFIDMTIRGQNVRLYIIPGISLDTRFESRTRKEISKIEWHNLMDLPTFKKNKPQTMKNKFYMVIPFLAPLKKWIKKRNIANNTTKEKNISVDVDADASSQLLSLLKSSTAPSDLATPQPSTFPQPPVESHSSFDIKQKILHLLNEGNEPKSPIQLPPVSNLPLNPPIQSSNSRLSHDNNSFDPFAYLGLDPKNPSASFPRVVSQNNMLTNKPVLNNHFQQSMYSNLLKDQNSVQHLFAASDMPSPMELPSPSTVYHQVFYPPTSTSVSSYGLGKTPQPAYGSSSPYVNGHQTQQISSLPPFQSQTQFLARNSDNSGQSYNSEGDSNSKRLLSMLSQQDTTPSSSTLSKEANVQLANLFLTPNSLETKKFSDNSQGEEISDNLHGESCNNPNANSVHSAQLLQALLHPSATETKEETPKKTSDSLSLLTLLKSGLPTPANDLQNKSQNNERKASSQVKELEVKNYSKSTDLLKKTLRIPRNDEPLEAANQFDLLKVSPQQKSEVPPKRNELSQSKLKNRKKKENSETNKNHVDMSPGFVKILKRSPLADQKKEDTQESDFKGSDDHFLSYLQSVVSSNSNGLH,Abolishes interaction with dcp1.,,MSFTNATFSQVLDDLSARFILNLPAEEQSSVERLCFQIEQAHWFYEDFIRAQNDQLPSLGLRVFSAKLFAHCPLLWKWSKVHEEAFDDFLRYKTRIPVRGAIMLDMSMQQCVLVKGWKASSGWGFPKGKIDKDESDVDCAIREVYEETGFDCSSRINPNEFIDMTIRGQNVRLYIIPGISLDTRFESRTRKEISKIEWHNLMDLPTFKKNKPQTMKNKFYMVIPFLAPLKKWIKKRNIANNTTKEKNISVDVDADASSQLLSLLKSSTAPSDLATPQPSTFPQPPVESHSSFDIKQKILHLLNEGNEPKSPIQLPPVSNLPLNPPIQSSNSRLSHDNNSFDPFAYLGLDPKNPSASFPRVVSQNNMLTNKPVLNNHFQQSMYSNLLKDQNSVQHLFAASDMPSPMELPSPSTVYHQVFYPPTSTSVSSYGLGKTPQPAYGSSSPYVNGHQTQQISSLPPFQSQTQFLARNSDNSGQSYNSEGDSNSKRLLSMLSQQDTTPSSSTLSKEANVQLANLFLTPNSLETKKFSDNSQGEEISDNLHGESCNNPNANSVHSAQLLQALLHPSATETKEETPKKTSDSLSLLTLLKSGLPTPANDLQNKSQNNERKASSQVKELEVKNYSKSTDLLKKTLRIPRNDEPLEAANQFDLLKVSPQQKSEVPPKRNELSQSKLKNRKKKENSETNKNHVDMSPGFVKILKRSPLADQKKEDTQESDFKGSDDHFLSYLQSVVSSNSNGLH,mRNA decapping complex subunit 2,"Catalytic component of the decapping complex necessary for the degradation of mRNAs, both in normal mRNA turnover and in nonsense-mediated mRNA decay. Removes the 7-methyl guanine cap structure from mRNA molecules, yielding a 5'-phosphorylated mRNA fragment and 7m-GDP. Decapping is the major pathway of mRNA degradation in yeast. It occurs through deadenylation, decapping and subsequent 5' to 3' exonucleolytic decay of the transcript body.",The N-terminal domain of Dcp2p affects the efficiency of Dcp2p function.,Abolishes interaction with dcp1. The N-terminal domain of Dcp2p affects the efficiency of Dcp2p function.
11,11,Q92830-T735A,MAEPSQAPTPAPAAQPRPLQSPAPAPTPTPAPSPASAPIPTPTPAPAPAPAAAPAGSTGTGGPGVGSGGAGSGGDPARPGLSQQQRASQRKAQVRGLPRAKKLEKLGVFSACKANETCKCNGWKNPKPPTAPRMDLQQPAANLSELCRSCEHPLADHVSHLENVSEDEINRLLGMVVDVENLFMSVHKEEDTDTKQVYFYLFKLLRKCILQMTRPVVEGSLGSPPFEKPNIEQGVLNFVQYKFSHLAPRERQTMFELSKMFLLCLNYWKLETPAQFRQRSQAEDVATYKVNYTRWLCYCHVPQSCDSLPRYETTHVFGRSLLRSIFTVTRRQLLEKFRVEKDKLVPEKRTLILTHFPKFLSMLEEEIYGANSPIWESGFTMPPSEGTQLVPRPASVSAAVVPSTPIFSPSMGGGSNSSLSLDSAGAEPMPGEKRTLPENLTLEDAKRLRVMGDIPMELVNEVMLTITDPAAMLGPETSLLSANAARDETARLEERRGIIEFHVIGNSLTPKANRRVLLWLVGLQNVFSHQLPRMPKEYIARLVFDPKHKTLALIKDGRVIGGICFRMFPTQGFTEIVFCAVTSNEQVKGYGTHLMNHLKEYHIKHNILYFLTYADEYAIGYFKKQGFSKDIKVPKSRYLGYIKDYEGATLMECELNPRIPYTELSHIIKKQKEIIKKLIERKQAQIRKVYPGLSCFKEGVRQIPVESVPGIRETGWKPLGKEKGKELKDPDQLYATLKNLLAQIKSHPSAWPFMEPVKKSEAPDYYEVIRFPIDLKTMTERLRSRYYVTRKLFVADLQRVIANCREYNPPDSEYCRCASALEKFFYFKLKEGGLIDK,Slightly reduced ability to acetylate and inhibit PPARGC1A. Strongly reduced ability to acetylate and inhibit PPARGC1A; when associated with Q-549 and A-735.,,MAEPSQAPTPAPAAQPRPLQSPAPAPTPTPAPSPASAPIPTPTPAPAPAPAAAPAGSTGTGGPGVGSGGAGSGGDPARPGLSQQQRASQRKAQVRGLPRAKKLEKLGVFSACKANETCKCNGWKNPKPPTAPRMDLQQPAANLSELCRSCEHPLADHVSHLENVSEDEINRLLGMVVDVENLFMSVHKEEDTDTKQVYFYLFKLLRKCILQMTRPVVEGSLGSPPFEKPNIEQGVLNFVQYKFSHLAPRERQTMFELSKMFLLCLNYWKLETPAQFRQRSQAEDVATYKVNYTRWLCYCHVPQSCDSLPRYETTHVFGRSLLRSIFTVTRRQLLEKFRVEKDKLVPEKRTLILTHFPKFLSMLEEEIYGANSPIWESGFTMPPSEGTQLVPRPASVSAAVVPSTPIFSPSMGGGSNSSLSLDSAGAEPMPGEKRTLPENLTLEDAKRLRVMGDIPMELVNEVMLTITDPAAMLGPETSLLSANAARDETARLEERRGIIEFHVIGNSLTPKANRRVLLWLVGLQNVFSHQLPRMPKEYIARLVFDPKHKTLALIKDGRVIGGICFRMFPTQGFTEIVFCAVTSNEQVKGYGTHLMNHLKEYHIKHNILYFLTYADEYAIGYFKKQGFSKDIKVPKSRYLGYIKDYEGATLMECELNPRIPYTELSHIIKKQKEIIKKLIERKQAQIRKVYPGLSCFKEGVRQIPVESVPGIRETGWKPLGKEKGKELKDPDQLYTTLKNLLAQIKSHPSAWPFMEPVKKSEAPDYYEVIRFPIDLKTMTERLRSRYYVTRKLFVADLQRVIANCREYNPPDSEYCRCASALEKFFYFKLKEGGLIDK,Histone acetyltransferase KAT2A,"Protein lysine acyltransferase that can act as a acetyltransferase, glutaryltransferase, succinyltransferase or malonyltransferase, depending on the context. Acts as a histone lysine succinyltransferase: catalyzes succinylation of histone H3 on 'Lys-79' (H3K79succ), with a maximum frequency around the transcription start sites of genes. Succinylation of histones gives a specific tag for epigenetic transcription activation. Association with the 2-oxoglutarate dehydrogenase complex, which provides succinyl-CoA, is required for histone succinylation. In different complexes, functions either as an acetyltransferase (HAT) or as a succinyltransferase: in the SAGA and ATAC complexes, acts as a histone acetyltransferase. Has significant histone acetyltransferase activity with core histones, but not with nucleosome core particles. Acetylation of histones gives a specific tag for epigenetic transcription activation. Recruited by the XPC complex at promoters, where it specifically mediates acetylation of histone variant H2A.Z.1/H2A.Z, thereby promoting expression of target genes. Involved in long-term memory consolidation and synaptic plasticity: acts by promoting expression of a hippocampal gene expression network linked to neuroactive receptor signaling. Acts as a positive regulator of T-cell activation: upon TCR stimulation, recruited to the IL2 promoter following interaction with NFATC2 and catalyzes acetylation of histone H3 at 'Lys-9' (H3K9ac), leading to promote IL2 expression. Required for growth and differentiation of craniofacial cartilage and bone by regulating acetylation of histone H3 at 'Lys-9' (H3K9ac). Regulates embryonic stem cell (ESC) pluripotency and differentiation. Also acetylates non-histone proteins, such as CEBPB, PPARGC1A, PLK4 and TBX5. Involved in heart and limb development by mediating acetylation of TBX5, acetylation regulating nucleocytoplasmic shuttling of TBX5. Acts as a negative regulator of centrosome amplification by mediating acetylation of PLK4. Acts as a negative regulator of gluconeogenesis by mediating acetylation and subsequent inactivation of PPARGC1A. Also acts as a histone glutaryltransferase: catalyzes glutarylation of histone H4 on 'Lys-91' (H4K91glu), a mark that destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes.(Microbial infection) In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes.",,Slightly reduced ability to acetylate and inhibit PPARGC1A. Strongly reduced ability to acetylate and inhibit PPARGC1A; when associated with Q-549 and A-735.
12,12,Q3L8N0-R328A,MDGFSRRRMLMTGGALGAVGALGAATRALARPLWTWSPSASVAGTGVGVDPEYVWDEEADPVLAAVIDRGEVPAVNALLKQWTRNDQALPGGLPGDLREFMEHARRMPSWADKAALDRGAQFSKTKGIYVGALYGLGSGLMSTAIPRESRAVYYSKGGADMKDRIAKTARLGYDIGDLDAYLPHGSMIVTAVKTRMVHAAVRHLLPQSPAWSQTSGGQKIPISQADIMVTWHSLATFVMRKMKQWGVRVNTADAEAYLHVWQVSAHMLGVSDEYIPATWDAANAQSKQVLDPILAHTPEGEALTEVLLGIVAELDAGLTRPLIGAFSAYTLGGEVGDMIGLAKQPVLERLIATAWPLLVAFREGLIPLPAVPAVLWTLEEALRKFVLLFLSEGRRIAIDIPDVNRPS,No effect on catalytic activity and on heme binding.,,MDGFSRRRMLMTGGALGAVGALGAATRALARPLWTWSPSASVAGTGVGVDPEYVWDEEADPVLAAVIDRGEVPAVNALLKQWTRNDQALPGGLPGDLREFMEHARRMPSWADKAALDRGAQFSKTKGIYVGALYGLGSGLMSTAIPRESRAVYYSKGGADMKDRIAKTARLGYDIGDLDAYLPHGSMIVTAVKTRMVHAAVRHLLPQSPAWSQTSGGQKIPISQADIMVTWHSLATFVMRKMKQWGVRVNTADAEAYLHVWQVSAHMLGVSDEYIPATWDAANAQSKQVLDPILAHTPEGEALTEVLLGIVAELDAGLTRPLIGAFSRYTLGGEVGDMIGLAKQPVLERLIATAWPLLVAFREGLIPLPAVPAVLWTLEEALRKFVLLFLSEGRRIAIDIPDVNRPS,Rubber oxygenase,"Involved in the initial step of rubber degradation. Catalyzes the oxidative C-C cleavage of poly(cis-1,4-isoprene) in synthetic as well as in natural rubber by the addition of oxygen (O2) to the double bonds, leading to a mixture of oligonucleotide-isoprenoids with terminal keto and aldehyde groups (endo-type cleavage). The cleavage products are of different lengths, ranging from C20 (four isoprene units) to higher oligo-isoprenoids. Is not able to cleave low-molecular-weight substrate analogs with isoprenoid structure such as squalene (1,4-trans-isoprenoid), carotenoids, or alpha-tocopherol.",The mutation in LcpK30 affected protein stability.,No effect on catalytic activity and on heme binding. The mutation in LcpK30 affected protein stability.
13,13,Q9UBM7-I145L,MAAKSQPNIPKAKSLDGVTNDRTASQGQWGRAWEVDWFSLASVIFLLLFAPFIVYYFIMACDQYSCALTGPVVDIVTGHARLSDIWAKTPPITRKAAQLYTLWVTFQVLLYTSLPDFCHKFLPGYVGGIQEGAVTPAGVVNKYQLNGLQAWLLTHLLWFANAHLLSWFSPTIIFDNWIPLLWCANILGYAVSTFAMVKGYFFPTSARDCKFTGNFFYNYMMGIEFNPRIGKWFDFKLFFNGRPGIVAWTLINLSFAAKQRELHSHVTNAMVLVNVLQAIYVIDFFWNETWYLKTIDICHDHFGWYLGWGDCVWLPYLYTLQGLYLVYHPVQLSTPHAVGVLLLGLVGYYIFRVANHQKDLFRRTDGRCLIWGRKPKVIECSYTSADGQRHHSKLLVSGFWGVARHFNYVGDLMGSLAYCLACGGGHLLPYFYIIYMAILLTHRCLRDEHRCASKYGRDWERYTAAVPYRLLPGIF,In SLOS.,,MAAKSQPNIPKAKSLDGVTNDRTASQGQWGRAWEVDWFSLASVIFLLLFAPFIVYYFIMACDQYSCALTGPVVDIVTGHARLSDIWAKTPPITRKAAQLYTLWVTFQVLLYTSLPDFCHKFLPGYVGGIQEGAVTPAGVVNKYQINGLQAWLLTHLLWFANAHLLSWFSPTIIFDNWIPLLWCANILGYAVSTFAMVKGYFFPTSARDCKFTGNFFYNYMMGIEFNPRIGKWFDFKLFFNGRPGIVAWTLINLSFAAKQRELHSHVTNAMVLVNVLQAIYVIDFFWNETWYLKTIDICHDHFGWYLGWGDCVWLPYLYTLQGLYLVYHPVQLSTPHAVGVLLLGLVGYYIFRVANHQKDLFRRTDGRCLIWGRKPKVIECSYTSADGQRHHSKLLVSGFWGVARHFNYVGDLMGSLAYCLACGGGHLLPYFYIIYMAILLTHRCLRDEHRCASKYGRDWERYTAAVPYRLLPGIF,7-dehydrocholesterol reductase,"7-dehydrocholesterol reductase of the cholesterol biosynthetic pathway reducing the C7-C8 double bond of cholesta-5,7-dien-3beta-ol (7-dehydrocholesterol/7-DHC) and cholesta-5,7,24-trien-3beta-ol, two intermediates in that pathway.",The mutation in the DHCR7 gene results in a functional alteration of the 7-dehydrocholesterol reductase protein.,In SLOS. The mutation in the DHCR7 gene results in a functional alteration of the 7-dehydrocholesterol reductase protein.
14,14,Q15126-K19M,MAPLGGAPRLVLLFSGKRMSGKDFVTEALQSRLGADVCAVLRLSGPLKEQYAQEHGLNFQRLLDTSTYKEAFRKDMIRWGEEKRQADPGFFCRKIVEGISQPIWLVSDTRRVSDIQWFREAYGAVTQTVRVVALEQSRQQRGWVFTPGVDDAESECGLDNFGDFDWVIENHGVEQRLEEQLENLIEFIRSRL,Approximately 9-fold decrease in Vmax for MgATP and R-MVP. Approximately 10-fold increase in KM for MgATP and R-MVP.,,MAPLGGAPRLVLLFSGKRKSGKDFVTEALQSRLGADVCAVLRLSGPLKEQYAQEHGLNFQRLLDTSTYKEAFRKDMIRWGEEKRQADPGFFCRKIVEGISQPIWLVSDTRRVSDIQWFREAYGAVTQTVRVVALEQSRQQRGWVFTPGVDDAESECGLDNFGDFDWVIENHGVEQRLEEQLENLIEFIRSRL,Phosphomevalonate kinase,"Catalyzes the reversible ATP-dependent phosphorylation of mevalonate 5-phosphate to produce mevalonate diphosphate and ADP, a key step in the mevalonic acid mediated biosynthesis of isopentenyl diphosphate and other polyisoprenoid metabolites.","Substrate K(m) values for have been measured for forward and reverse reactions; in comparison with wild-type PMK values, only modest (<12-fold) changes are observed.","Approximately 9-fold decrease in Vmax for MgATP and R-MVP. Approximately 10-fold increase in KM for MgATP and R-MVP. Substrate K(m) values for have been measured for forward and reverse reactions; in comparison with wild-type PMK values, only modest (<12-fold) changes are observed."
15,15,O22476-Y956F,MKTFSSFFLSVTTLFFFSFFSLSFQASPSQSLYREIHQLISFKDVLPDKNLLPDWSSNKNPCTFDGVTCRDDKVTSIDLSSKPLNVGFSAVSSSLLSLTGLESLFLSNSHINGSVSGFKCSASLTSLDLSRNSLSGPVTTLTSLGSCSGLKFLNVSSNTLDFPGKVSGGLKLNSLEVLDLSANSISGANVVGWVLSDGCGELKHLAISGNKISGDVDVSRCVNLEFLDVSSNNFSTGIPFLGDCSALQHLDISGNKLSGDFSRAISTCTELKLLNISSNQFVGPIPPLPLKSLQYLSLAENKFTGEIPDFLSGACDTLTGLDLSGNHFYGAVPPFFGSCSLLESLALSSNNFSGELPMDTLLKMRGLKVLDLSFNEFSGELPESLTNLSASLLTLDLSSNNFSGPILPNLCQNPKNTLQELYLQNNGFTGKIPPTLSNCSELVSLHLSFNYLSGTIPSSLGSLSKLRDLKLWLNMLEGEIPQELMYVKTLETLILDFNDLTGEIPSGLSNCTNLNWISLSNNRLTGEIPKWIGRLENLAILKLSNNSFSGNIPAELGDCRSLIWLDLNTNLFNGTIPAAMFKQSGKIAANFIAGKRYVYIKNDGMKKECHGAGNLLEFQGIRSEQLNRLSTRNPCNITSRVYGGHTSPTFDNNGSMMFLDMSYNMLSGYIPKEIGSMPYLFILNLGHNDISGSIPDEVGDLRGLNILDLSSNKLDGRIPQAMSALTMLTEIDLSNNNLSGPIPEMGQFETFPPAKFLNNPGLCGYPLPRCDPSNADGYAHHQRSHGRRPASLAGSVAMGLLFSFVCIFGLILVGREMRKRRRKKEAELEMYAEGHGNSGDRTANNTNWKLTGVKEALSINLAAFEKPLRKLTFADLLQATNGFHNDSLIGSGGFGDVYKAILKDGSAVAIKKLIHVSGQGDREFMAEMETIGKIKHRNLVPLLGYCKVGDERLLVFEFMKYGSLEDVLHDPKKAGVKLNWSTRRKIAIGSARGLAFLHHNCSPHIIHRDMKSSNVLLDENLEAR,Loss of kinase activity.,,MKTFSSFFLSVTTLFFFSFFSLSFQASPSQSLYREIHQLISFKDVLPDKNLLPDWSSNKNPCTFDGVTCRDDKVTSIDLSSKPLNVGFSAVSSSLLSLTGLESLFLSNSHINGSVSGFKCSASLTSLDLSRNSLSGPVTTLTSLGSCSGLKFLNVSSNTLDFPGKVSGGLKLNSLEVLDLSANSISGANVVGWVLSDGCGELKHLAISGNKISGDVDVSRCVNLEFLDVSSNNFSTGIPFLGDCSALQHLDISGNKLSGDFSRAISTCTELKLLNISSNQFVGPIPPLPLKSLQYLSLAENKFTGEIPDFLSGACDTLTGLDLSGNHFYGAVPPFFGSCSLLESLALSSNNFSGELPMDTLLKMRGLKVLDLSFNEFSGELPESLTNLSASLLTLDLSSNNFSGPILPNLCQNPKNTLQELYLQNNGFTGKIPPTLSNCSELVSLHLSFNYLSGTIPSSLGSLSKLRDLKLWLNMLEGEIPQELMYVKTLETLILDFNDLTGEIPSGLSNCTNLNWISLSNNRLTGEIPKWIGRLENLAILKLSNNSFSGNIPAELGDCRSLIWLDLNTNLFNGTIPAAMFKQSGKIAANFIAGKRYVYIKNDGMKKECHGAGNLLEFQGIRSEQLNRLSTRNPCNITSRVYGGHTSPTFDNNGSMMFLDMSYNMLSGYIPKEIGSMPYLFILNLGHNDISGSIPDEVGDLRGLNILDLSSNKLDGRIPQAMSALTMLTEIDLSNNNLSGPIPEMGQFETFPPAKFLNNPGLCGYPLPRCDPSNADGYAHHQRSHGRRPASLAGSVAMGLLFSFVCIFGLILVGREMRKRRRKKEAELEMYAEGHGNSGDRTANNTNWKLTGVKEALSINLAAFEKPLRKLTFADLLQATNGFHNDSLIGSGGFGDVYKAILKDGSAVAIKKLIHVSGQGDREFMAEMETIGKIKHRNLVPLLGYCKVGDERLLVYEFMKYGSLEDVLHDPKKAGVKLNWSTRRKIAIGSARGLAFLHHNCSPHIIHRDMKSSNVLLDENLEAR,Protein BRASSINOSTEROID INSENSITIVE 1,"Receptor with a dual specificity kinase activity acting on both serine/threonine- and tyrosine-containing substrates. Regulates, in response to brassinosteroid binding, a signaling cascade involved in plant development, including expression of light- and stress-regulated genes, promotion of cell elongation, normal leaf and chloroplast senescence, and flowering. Binds brassinolide (BL), and less effectively castasterone (CS), but not 2,3,22,23-O-tetramethylbrassinolide or ecdysone. May be involved in a feedback regulation of brassinosteroid biosynthesis. Phosphorylates BRI1-associated receptor kinase 1 (BAK1), Transthyretin-Like protein (TTL) and SERK1 on 'Ser-299' and 'Thr-462' in vitro. May have a guanylyl cyclase activity. Phosphorylates BSK1, BSK2 and BSK3 in vitro. Phosphorylates BSK1, BSK3, BSK5, BSK6, BSK8 and BSK11 in vitro.",Y-956 in kinase subdomain V is essential for activity. mutant is catalytically inactive.,Loss of kinase activity. Y-956 in kinase subdomain V is essential for activity. mutant is catalytically inactive.
16,16,Q15303-P854Q,MKPATGLWVWVSLLVAAGTVQPSDSQSVCAGTENKLSSLSDLEQQYRALRKYYENCEVVMGNLEITSIEHNRDLSFLRSVREVTGYVLVALNQFRYLPLENLRIIRGTKLYEDRYALAIFLNYRKDGNFGLQELGLKNLTEILNGGVYVDQNKFLCYADTIHWQDIVRNPWPSNLTLVSTNGSSGCGRCHKSCTGRCWGPTENHCQTLTRTVCAEQCDGRCYGPYVSDCCHRECAGGCSGPKDTDCFACMNFNDSGACVTQCPQTFVYNPTTFQLEHNFNAKYTYGAFCVKKCPHNFVVDSSSCVRACPSSKMEVEENGIKMCKPCTDICPKACDGIGTGSLMSAQTVDSSNIDKFINCTKINGNLIFLVTGIHGDPYNAIEAIDPEKLNVFRTVREITGFLNIQSWPPNMTDFSVFSNLVTIGGRVLYSGLSLLILKQQGITSLQFQSLKEISAGNIYITDNSNLCYYHTINWTTLFSTINQRIVIRDNRKAENCTAEGMVCNHLCSSDGCWGPGPDQCLSCRRFSRGRICIESCNLYDGEFREFENGSICVECDPQCEKMEDGLLTCHGPGPDNCTKCSHFKDGPNCVEKCPDGLQGANSFIFKYADPDRECHPCHPNCTQGCNGPTSHDCIYYPWTGHSTLPQHARTPLIAAGVIGGLFILVIVGLTFAVYVRRKSIKKKRALRRFLETELVEPLTPSGTAPNQAQLRILKETELKRVKVLGSGAFGTVYKGIWVPEGETVKIPVAIKILNETTGPKANVEFMDEALIMASMDHPHLVRLLGVCLSPTIQLVTQLMPHGCLLEYVHEHKDNIGSQLLLNWCVQIAKGMMYLEERRLVHRDLAARNVLVKSQNHVKITDFGLARLLEGDEKEYNADGGKMPIKWMALECIHYRKFTHQSDVWSYGVTIWELMTFGGKPYDGIPTREIPDLLEKGERLPQPPICTIDVYMVMVKCWMIDADSRPKFKELAAEFSRMARDPQRYLVIQGDDRMKLPSPNDSKFFQNLLDEEDLEDMMDAEEYLV,No effect on kinase activity.,,MKPATGLWVWVSLLVAAGTVQPSDSQSVCAGTENKLSSLSDLEQQYRALRKYYENCEVVMGNLEITSIEHNRDLSFLRSVREVTGYVLVALNQFRYLPLENLRIIRGTKLYEDRYALAIFLNYRKDGNFGLQELGLKNLTEILNGGVYVDQNKFLCYADTIHWQDIVRNPWPSNLTLVSTNGSSGCGRCHKSCTGRCWGPTENHCQTLTRTVCAEQCDGRCYGPYVSDCCHRECAGGCSGPKDTDCFACMNFNDSGACVTQCPQTFVYNPTTFQLEHNFNAKYTYGAFCVKKCPHNFVVDSSSCVRACPSSKMEVEENGIKMCKPCTDICPKACDGIGTGSLMSAQTVDSSNIDKFINCTKINGNLIFLVTGIHGDPYNAIEAIDPEKLNVFRTVREITGFLNIQSWPPNMTDFSVFSNLVTIGGRVLYSGLSLLILKQQGITSLQFQSLKEISAGNIYITDNSNLCYYHTINWTTLFSTINQRIVIRDNRKAENCTAEGMVCNHLCSSDGCWGPGPDQCLSCRRFSRGRICIESCNLYDGEFREFENGSICVECDPQCEKMEDGLLTCHGPGPDNCTKCSHFKDGPNCVEKCPDGLQGANSFIFKYADPDRECHPCHPNCTQGCNGPTSHDCIYYPWTGHSTLPQHARTPLIAAGVIGGLFILVIVGLTFAVYVRRKSIKKKRALRRFLETELVEPLTPSGTAPNQAQLRILKETELKRVKVLGSGAFGTVYKGIWVPEGETVKIPVAIKILNETTGPKANVEFMDEALIMASMDHPHLVRLLGVCLSPTIQLVTQLMPHGCLLEYVHEHKDNIGSQLLLNWCVQIAKGMMYLEERRLVHRDLAARNVLVKSPNHVKITDFGLARLLEGDEKEYNADGGKMPIKWMALECIHYRKFTHQSDVWSYGVTIWELMTFGGKPYDGIPTREIPDLLEKGERLPQPPICTIDVYMVMVKCWMIDADSRPKFKELAAEFSRMARDPQRYLVIQGDDRMKLPSPNDSKFFQNLLDEEDLEDMMDAEEYLV,Receptor tyrosine-protein kinase erbB-4,"Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell proliferation, differentiation, migration and apoptosis. Required for normal cardiac muscle differentiation during embryonic development, and for postnatal cardiomyocyte proliferation. Required for normal development of the embryonic central nervous system, especially for normal neural crest cell migration and normal axon guidance. Required for mammary gland differentiation, induction of milk proteins and lactation. Acts as cell-surface receptor for the neuregulins NRG1, NRG2, NRG3 and NRG4 and the EGF family members BTC, EREG and HBEGF. Ligand binding triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Ligand specificity and signaling is modulated by alternative splicing, proteolytic processing, and by the formation of heterodimers with other ERBB family members, thereby creating multiple combinations of intracellular phosphotyrosines that trigger ligand- and context-specific cellular responses. Mediates phosphorylation of SHC1 and activation of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Isoform JM-A CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1, leading to the activation of phosphatidylinositol 3-kinase and AKT1 and protect cells against apoptosis. Isoform JM-A CYT-1 and isoform JM-B CYT-1 mediate reorganization of the actin cytoskeleton and promote cell migration in response to NRG1. Isoform JM-A CYT-2 and isoform JM-B CYT-2 lack the phosphotyrosine that mediates interaction with PIK3R1, and hence do not phosphorylate PIK3R1, do not protect cells against apoptosis, and do not promote reorganization of the actin cytoskeleton and cell migration. Proteolytic processing of isoform JM-A CYT-1 and isoform JM-A CYT-2 gives rise to the corresponding soluble intracellular domains (4ICD) that translocate to the nucleus, promote nuclear import of STAT5A, activation of STAT5A, mammary epithelium differentiation, cell proliferation and activation of gene expression. The ERBB4 soluble intracellular domains (4ICD) colocalize with STAT5A at the CSN2 promoter to regulate transcription of milk proteins during lactation. The ERBB4 soluble intracellular domains can also translocate to mitochondria and promote apoptosis.",,No effect on kinase activity.
17,17,P77667-C50S,MDMHSGTFNPQDFAWQGLTLTPAAAIHIRELVAKQPGMVGVRLGVKQTGSAGFGYVLDSVSEPDKDDLLFEHDGAKLFVPLQAMPFIDGTEVDFVREGLNQIFKFHNPKAQNECGCGESFGV,Decrease of sulfur binding activity.,,MDMHSGTFNPQDFAWQGLTLTPAAAIHIRELVAKQPGMVGVRLGVKQTGCAGFGYVLDSVSEPDKDDLLFEHDGAKLFVPLQAMPFIDGTEVDFVREGLNQIFKFHNPKAQNECGCGESFGV,Protein SufA,"Member of gene cluster sufABCDSE that mediates iron-sulfur cluster assembly under oxidative stress and iron limitation conditions. Binds [2Fe2S] cluster by mobilizing sulfur atoms provided by the SufS-SufE cysteine desulfurase system and then transfers the assembled Fe-S cluster to target proteins including ferredoxin and aconitase. Seems to act as a Fe-S cluster carrier rather than a scaffold, this role being performed by SufB and SufC.","Investigation of site-directed mutants and peptide mapping experiments performed on digested sulfurated SufA demonstrate that binding exclusively occurs at the three conserved cysteines (cys50, cys114, cys116). In contrast, it binds iron only weakly (K(a)=5 x 10(5)M(-1)) and not specifically to the conserved cysteines as shown by Mössbauer spectroscopy.","Decrease of sulfur binding activity. Investigation of site-directed mutants and peptide mapping experiments performed on digested sulfurated SufA demonstrate that binding exclusively occurs at the three conserved cysteines (cys50, cys114, cys116). In contrast, it binds iron only weakly (K(a)=5 x 10(5)M(-1)) and not specifically to the conserved cysteines as shown by Mössbauer spectroscopy."
18,18,Q9NX04-S134A,MTQDRPLLAVQEALKKCFPVVEEQQGLWQSALRDCQPLLSSLSNLAEQLQAAQNLRFEDVPALRAFPDLKERLRRKQLVAGDIVLDKLGERLAILLKVRDMVSSHVERVFQIYEQHADTVGIDAVLQPSAVSPAVADMLEWLQDIERHYRKSYLKRKYLLSSIQWGDLANIQALPKAWDRISKDEHQDLVQDILLNVSFFLEE,Abolishes phosphorylation by CK2 kinase; when associated with A-104 and A-182.,,MTQDRPLLAVQEALKKCFPVVEEQQGLWQSALRDCQPLLSSLSNLAEQLQAAQNLRFEDVPALRAFPDLKERLRRKQLVAGDIVLDKLGERLAILLKVRDMVSSHVERVFQIYEQHADTVGIDAVLQPSAVSPSVADMLEWLQDIERHYRKSYLKRKYLLSSIQWGDLANIQALPKAWDRISKDEHQDLVQDILLNVSFFLEE,AFG2-interacting ribosome maturation factor,"Involved in the cytoplasmic maturation steps of pre-60S ribosomal particles by promoting the release of shuttling protein RSL24D1/RLP24 from the pre-ribosomal particles. Acts together with SPATA5, SPATA5L1 and CINP.",,Abolishes phosphorylation by CK2 kinase; when associated with A-104 and A-182.
19,19,P28700-S22A,MDTKHFLPLDFSTQVNSSSLNAPTGRGSMAVPSLHPSLGPGIGSPLGSPGQLHSPISTLSSPINGMGPPFSVISSPMGPHSMSVPTTPTLGFGTGSPQLNSPMNPVSSTEDIKPPLGLNGVLKVPAHPSGNMASFTKHICAICGDRSSGKHYGVYSCEGCKGFFKRTVRKDLTYTCRDNKDCLIDKRQRNRCQYCRYQKCLAMGMKREAVQEERQRGKDRNENEVESTSSANEDMPVEKILEAELAVEPKTETYVEANMGLNPSSPNDPVTNICQAADKQLFTLVEWAKRIPHFSELPLDDQVILLRAGWNELLIASFSHRSIAVKDGILLATGLHVHRNSAHSAGVGAIFDRVLTELVSKMRDMQMDKTELGCLRAIVLFNPDSKGLSNPAEVEALREKVYASLEAYCKHKYPEQPGRFAKLLLRLPALRSIGLKCLEHLFFFKLIGDTPIDTFLMEMLEAPHQAT,Loss of constituitive phosphorylation. No effect on RXRA transcriptional activity.,,MDTKHFLPLDFSTQVNSSSLNSPTGRGSMAVPSLHPSLGPGIGSPLGSPGQLHSPISTLSSPINGMGPPFSVISSPMGPHSMSVPTTPTLGFGTGSPQLNSPMNPVSSTEDIKPPLGLNGVLKVPAHPSGNMASFTKHICAICGDRSSGKHYGVYSCEGCKGFFKRTVRKDLTYTCRDNKDCLIDKRQRNRCQYCRYQKCLAMGMKREAVQEERQRGKDRNENEVESTSSANEDMPVEKILEAELAVEPKTETYVEANMGLNPSSPNDPVTNICQAADKQLFTLVEWAKRIPHFSELPLDDQVILLRAGWNELLIASFSHRSIAVKDGILLATGLHVHRNSAHSAGVGAIFDRVLTELVSKMRDMQMDKTELGCLRAIVLFNPDSKGLSNPAEVEALREKVYASLEAYCKHKYPEQPGRFAKLLLRLPALRSIGLKCLEHLFFFKLIGDTPIDTFLMEMLEAPHQAT,Retinoic acid receptor RXR-alpha,"Receptor for retinoic acid that acts as a transcription factor. Forms homo- or heterodimers with retinoic acid receptors (RARs) and binds to target response elements in response to their ligands, all-trans or 9-cis retinoic acid, to regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 to regulate transcription. The high affinity ligand for retinoid X receptors (RXRs) is 9-cis retinoic acid. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and coactivators are recruited leading to transcriptional activation. Serves as a common heterodimeric partner for a number of nuclear receptors, such as RARA, RARB and PPARA. The RXRA/RARB heterodimer can act as a transcriptional repressor or transcriptional activator, depending on the RARE DNA element context. The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes. Together with RARA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells. Acts as an enhancer of RARA binding to RARE DNA element. May facilitate the nuclear import of heterodimerization partners such as VDR and NR4A1. Promotes myelin debris phagocytosis and remyelination by macrophages. Plays a role in the attenuation of the innate immune system in response to viral infections, possibly by negatively regulating the transcription of antiviral genes such as type I IFN genes. Involved in the regulation of calcium signaling by repressing ITPR2 gene expression, thereby controlling cellular senescence.",Hyperphosphorylation at S22 is specific to the RXRalpha1 isoform. S(22) is dispensable for RA-induced endodermal differentiation but is crucial for the expression of several RA-responsive genes. S(22) is also indispensable for the antiproliferative effect of RA and necessary for the RA-induced down-regulation of p21(CIP) and p27(KIP) CKIs proteins that are known to be involved in the control of cell cycle progression.,Loss of constituitive phosphorylation. No effect on RXRA transcriptional activity. Hyperphosphorylation at S22 is specific to the RXRalpha1 isoform. S(22) is dispensable for RA-induced endodermal differentiation but is crucial for the expression of several RA-responsive genes. S(22) is also indispensable for the antiproliferative effect of RA and necessary for the RA-induced down-regulation of p21(CIP) and p27(KIP) CKIs proteins that are known to be involved in the control of cell cycle progression.
20,20,P84022-K43A,MSSILPFTPPIVKRLLGWKKGEQNGQEEKWCEKAVKSLVKKLAKTGQLDELEKAITTQNVNTKCITIPRSLDGRLQVSHRKGLPHVIYCRLWRWPDLHSHHELRAMELCEFAFNMKKDEVCVNPYHYQRVETPVLPPVLVPRHTEIPAEFPPLDDYSHSIPENTNFPAGIEPQSNIPETPPPGYLSEDGETSDHQMNHSMDAGSPNLSPNPMSPAHNNLDLQPVTYCEPAFWCSISYYELNQRVGETFHASQPSMTVDGFTDPSNSERFCLGLLSNVNRNAAVELTRRHIGRGVRLYYIGGEVFAECLSDSAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLAQSVNQGFEAVYQLTRMCTIRMSFVKGWGAEYRRQTVTSTPCWIELHLNGPLQWLDKVLTQMGSPSIRCSSVS,Little effect on interaction with DNA or JUN. Abolishes interaction with DNA and JUN; when associated with A-40; A-41 and A-44.,,MSSILPFTPPIVKRLLGWKKGEQNGQEEKWCEKAVKSLVKKLKKTGQLDELEKAITTQNVNTKCITIPRSLDGRLQVSHRKGLPHVIYCRLWRWPDLHSHHELRAMELCEFAFNMKKDEVCVNPYHYQRVETPVLPPVLVPRHTEIPAEFPPLDDYSHSIPENTNFPAGIEPQSNIPETPPPGYLSEDGETSDHQMNHSMDAGSPNLSPNPMSPAHNNLDLQPVTYCEPAFWCSISYYELNQRVGETFHASQPSMTVDGFTDPSNSERFCLGLLSNVNRNAAVELTRRHIGRGVRLYYIGGEVFAECLSDSAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLAQSVNQGFEAVYQLTRMCTIRMSFVKGWGAEYRRQTVTSTPCWIELHLNGPLQWLDKVLTQMGSPSIRCSSVS,Mothers against decapentaplegic homolog 3,"Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD3/SMAD4 complex, activates transcription. Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP-1/SMAD site to regulate TGF-beta-mediated transcription. Has an inhibitory effect on wound healing probably by modulating both growth and migration of primary keratinocytes and by altering the TGF-mediated chemotaxis of monocytes. This effect on wound healing appears to be hormone-sensitive. Regulator of chondrogenesis and osteogenesis and inhibits early healing of bone fractures. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.",,Little effect on interaction with DNA or JUN. Abolishes interaction with DNA and JUN; when associated with A-40; A-41 and A-44.
21,21,P03685-K3A,MAAMMQREITKTTVNVAKMVMVDGEVQVEQLPSETFVGNLTMEQAQWRMKRKYKGEPVQVVSVEPNTEVYELPVEKFLEVATVRVEKDEDQEEQTEAPEEQVAE,Decreased DNA-binding affinity. No effect on dimerization.,,MAKMMQREITKTTVNVAKMVMVDGEVQVEQLPSETFVGNLTMEQAQWRMKRKYKGEPVQVVSVEPNTEVYELPVEKFLEVATVRVEKDEDQEEQTEAPEEQVAE,Histone-like protein p6,"Histone-like nucleoprotein that binds to the viral dsDNA and responsible for wrapping and compacting the viral DNA about 4-fold. Forms a nucleoprotein complex in which the DNA adopts a right-handed toroidal conformation winding around a protein core. Binds ito most, if not all, the viral genome, although with different affinity, the highest one corresponding to the genome ends. The formation of the nucleoprotein complex at the genome ends, activates the initiation of viral DNA replication. The binding of p6 would recruit the complex formed by the TP and the DNA polymerase to the origin. Protein p6 also represses early transcription from promoter C2, and, together with protein p4, represses transcription from promoters A2b and A2c and activates late transcription from promoter A3. Protein p6 is therefore involved in the early to late transcription switch. The formation of the nucleoprotein complex at the right end of the phage genome where the early promoter C2 is located affects local topology, which may contribute to the promoter repression.",,Decreased DNA-binding affinity. No effect on dimerization.
22,22,Q9NZ71-K48R,MPKIVLNGVTVDFPFQPYKCQQEYMTKVLECLQQKVNGILESPTGTGRTLCLLCTTLAWREHLRDGISARKIAERAQGELFPDRALSSWGNAAAAAGDPIACYTDIPKIIYASRTHSQLTQVINELRNTSYRPKVCVLGSREQLCIHPEVKKQESNHLQIHLCRKKVASRSCHFYNNVEEKSLEQELASPILDIEDLVKSGSKHRVCPYYLSRNLKQQADIIFMPYNYLLDAKSRRAHNIDLKGTVVIFDEAHNVEKMCEESASFDLTPHDLASGLDVIDQVLEEQTKAAQQGEPHPEFSADSPSPGLNMELEDIAKLKMILLRLEGAIDAVELPGDDSGVTKPGSYIFELFAEAQITFQTKGCILDSLDQIIQHLAGRAGVFTNTAGLQKLADIIQIVFSVDPSEGSPGSPAGLGALQSYKVHIHPDAGHRRTAQRSDAWSTTAARKRGKVLSYWCFSPGHSMHELVRQGVRSLILTSGTLAPVSSFALEMQIPFPVCLENPHIIDKHQIWVGVVPRGPDGAQLSSAFDRRFSEECLSSLGKALGNIARVVPYGLLIFFPSYPVMEKSLEFWRARDLARKMEALKPLFVEPRSKGSFSETISAYYARVAAPGSTGATFLAVCRGKASEGLDFSDTNGRGVIVTGLPYPPRMDPRVVLKMQFLDEMKGQGGAGGQFLSGQEWYRQQASRAVNQAIGRVIRHRQDYGAVFLCDHRFAFADARAQLPSWVRPHVRVYDNFGHVIRDVAQFFRVAERTMPAPAPRATAPSVRGEDAVSEAKSPGPFFSTRKAKSLDLHVPSLKQRSSGSPAAGDPESSLCVEYEQEPVPARQRPRGLLAALEHSEQRAGSPGEEQAHSCSTLSLLSEKRPAEEPRGGRKKIRLVSHPEEPVAGAQTDRAKLFMVAVKQELSQANFATFTQALQDYKGSDDFAALAACLGPLFAEDPKKHNLLQGFYQFVRPHHKQQFEEVCIQLTGRGCGYRPEHSIPRRQRAQPVLDPTGRTAPDPKLTVSTAAAQQLDPQEHLNQ,Abolishes ATPase activity.,,MPKIVLNGVTVDFPFQPYKCQQEYMTKVLECLQQKVNGILESPTGTGKTLCLLCTTLAWREHLRDGISARKIAERAQGELFPDRALSSWGNAAAAAGDPIACYTDIPKIIYASRTHSQLTQVINELRNTSYRPKVCVLGSREQLCIHPEVKKQESNHLQIHLCRKKVASRSCHFYNNVEEKSLEQELASPILDIEDLVKSGSKHRVCPYYLSRNLKQQADIIFMPYNYLLDAKSRRAHNIDLKGTVVIFDEAHNVEKMCEESASFDLTPHDLASGLDVIDQVLEEQTKAAQQGEPHPEFSADSPSPGLNMELEDIAKLKMILLRLEGAIDAVELPGDDSGVTKPGSYIFELFAEAQITFQTKGCILDSLDQIIQHLAGRAGVFTNTAGLQKLADIIQIVFSVDPSEGSPGSPAGLGALQSYKVHIHPDAGHRRTAQRSDAWSTTAARKRGKVLSYWCFSPGHSMHELVRQGVRSLILTSGTLAPVSSFALEMQIPFPVCLENPHIIDKHQIWVGVVPRGPDGAQLSSAFDRRFSEECLSSLGKALGNIARVVPYGLLIFFPSYPVMEKSLEFWRARDLARKMEALKPLFVEPRSKGSFSETISAYYARVAAPGSTGATFLAVCRGKASEGLDFSDTNGRGVIVTGLPYPPRMDPRVVLKMQFLDEMKGQGGAGGQFLSGQEWYRQQASRAVNQAIGRVIRHRQDYGAVFLCDHRFAFADARAQLPSWVRPHVRVYDNFGHVIRDVAQFFRVAERTMPAPAPRATAPSVRGEDAVSEAKSPGPFFSTRKAKSLDLHVPSLKQRSSGSPAAGDPESSLCVEYEQEPVPARQRPRGLLAALEHSEQRAGSPGEEQAHSCSTLSLLSEKRPAEEPRGGRKKIRLVSHPEEPVAGAQTDRAKLFMVAVKQELSQANFATFTQALQDYKGSDDFAALAACLGPLFAEDPKKHNLLQGFYQFVRPHHKQQFEEVCIQLTGRGCGYRPEHSIPRRQRAQPVLDPTGRTAPDPKLTVSTAAAQQLDPQEHLNQ,Regulator of telomere elongation helicase 1,"ATP-dependent DNA helicase implicated in telomere-length regulation, DNA repair and the maintenance of genomic stability. Acts as an anti-recombinase to counteract toxic recombination and limit crossover during meiosis. Regulates meiotic recombination and crossover homeostasis by physically dissociating strand invasion events and thereby promotes noncrossover repair by meiotic synthesis dependent strand annealing (SDSA) as well as disassembly of D loop recombination intermediates. Also disassembles T loops and prevents telomere fragility by counteracting telomeric G4-DNA structures, which together ensure the dynamics and stability of the telomere.",Loss of HR control after deregulation of RTEL1 may be a critical event that drives genome instability and cancer.,Abolishes ATPase activity. Loss of HR control after deregulation of RTEL1 may be a critical event that drives genome instability and cancer.
23,23,Q07009-K230E,MAGIAMKLAKDREAAEGLGSHERAIKYLNQDYETLRNECLEAGALFQDPSFPALPSSLGFKELGPYSSKTRGIEWKRPTEICADPQFIIGGATRTDICQGALGDCWLLAAIASLTLNEEILARVVPLDQSFQENYAGIFHFQFWQYGEWVEVVVDDRLPTKDGELLFVHSAEGSEFWSALLEKAYAKINGCYEALSGGATTEGFEDFTGGIAEWYELRKPPPNLFKIIQEALEKGSLLGCSIDITSAADSEAVTYQKLVKGHAYSVTGAEEVESSGSLQKLIRIRNPWGQVEWTGKWNDNCPSWNTVDPEVRANLTERQEDGEFWMSFSDFLRHYSRLEICNLTPDTLTCDSYKKWKLTKMDGNWRRGSTAGGCRNYPNTFWMNPQYLIKLEEEDEDDEDGERGCTFLVGLIQKHRRRQRKMGEDMHTIGFGIYEVPEELTGQTNIHLSKNFFLTTRARERSDTFINLREVLNRFKLPPGEYVLVPSTFEPHKNGDFCIRVFSEKKADYQTVDDEIEANIEEIEANEEDIGDGFRRLFAQLAGEDAEISAFELQTILRRVLAKREDIKSDGFSIETCKIMVDMLDEDGSGKLGLKEFYILWTKIQKYQKIYREIDVDRSGTMNSYEMRKALEEAGFKLPCQLHQVIVARFADDELIIDFDNFVRCLVRLEILFKIFKQLDPENTGTIQLDLISWLSFSVL,84% decrease in activity.,,MAGIAMKLAKDREAAEGLGSHERAIKYLNQDYETLRNECLEAGALFQDPSFPALPSSLGFKELGPYSSKTRGIEWKRPTEICADPQFIIGGATRTDICQGALGDCWLLAAIASLTLNEEILARVVPLDQSFQENYAGIFHFQFWQYGEWVEVVVDDRLPTKDGELLFVHSAEGSEFWSALLEKAYAKINGCYEALSGGATTEGFEDFTGGIAEWYELRKPPPNLFKIIQKALEKGSLLGCSIDITSAADSEAVTYQKLVKGHAYSVTGAEEVESSGSLQKLIRIRNPWGQVEWTGKWNDNCPSWNTVDPEVRANLTERQEDGEFWMSFSDFLRHYSRLEICNLTPDTLTCDSYKKWKLTKMDGNWRRGSTAGGCRNYPNTFWMNPQYLIKLEEEDEDDEDGERGCTFLVGLIQKHRRRQRKMGEDMHTIGFGIYEVPEELTGQTNIHLSKNFFLTTRARERSDTFINLREVLNRFKLPPGEYVLVPSTFEPHKNGDFCIRVFSEKKADYQTVDDEIEANIEEIEANEEDIGDGFRRLFAQLAGEDAEISAFELQTILRRVLAKREDIKSDGFSIETCKIMVDMLDEDGSGKLGLKEFYILWTKIQKYQKIYREIDVDRSGTMNSYEMRKALEEAGFKLPCQLHQVIVARFADDELIIDFDNFVRCLVRLEILFKIFKQLDPENTGTIQLDLISWLSFSVL,Calpain-2 catalytic subunit,"Calcium-regulated non-lysosomal thiol-protease which catalyze limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. Proteolytically cleaves MYOC at 'Arg-226'. Proteolytically cleaves CPEB3 following neuronal stimulation which abolishes CPEB3 translational repressor activity, leading to translation of CPEB3 target mRNAs.",,84% decrease in activity.
24,24,Q15583-P292S,MVLAQSRVSAGVGSPHCSGSGGGGSDSFPWPASHPGNPQCSFSTAFLASPRLSRGTLAYLPPAPWSSLATPSALLGSSCAPPPPPARCPQPRALSPELGTKAGPRRPHRWELPRSPSQGAQGPAPRRRLLETMKGIVAASGSETEDEDSMDIPLDLSSSAGSGKRRRRGNLPKESVQILRDWLYEHRYNAYPSEQEKALLSQQTHLSTLQVCNWFINARRRLLPDMLRKDGKDPNQFTISRRGAKISETSSVESVMGIKNFMPALEETPFHSCTAGPNPTLGRPLSPKPSSSGSVLARPSVICHTTVTALKDVPFSLCQSVGVGQNTDIQQIAAKNFTDTSLMYPEDTCKSGPSTNTQSGLFNTPPPTPPDLNQDFSGFQLLVDVALKRAAEMELQAKLTA,,,MVLAQSRVSAGVGSPHCSGSGGGGSDSFPWPASHPGNPQCSFSTAFLASPRLSRGTLAYLPPAPWSSLATPSALLGSSCAPPPPPARCPQPRALSPELGTKAGPRRPHRWELPRSPSQGAQGPAPRRRLLETMKGIVAASGSETEDEDSMDIPLDLSSSAGSGKRRRRGNLPKESVQILRDWLYEHRYNAYPSEQEKALLSQQTHLSTLQVCNWFINARRRLLPDMLRKDGKDPNQFTISRRGAKISETSSVESVMGIKNFMPALEETPFHSCTAGPNPTLGRPLSPKPSSPGSVLARPSVICHTTVTALKDVPFSLCQSVGVGQNTDIQQIAAKNFTDTSLMYPEDTCKSGPSTNTQSGLFNTPPPTPPDLNQDFSGFQLLVDVALKRAAEMELQAKLTA,Homeobox protein TGIF1,"Binds to a retinoid X receptor (RXR) responsive element from the cellular retinol-binding protein II promoter (CRBPII-RXRE). Inhibits the 9-cis-retinoic acid-dependent RXR alpha transcription activation of the retinoic acid responsive element. Active transcriptional corepressor of SMAD2. Links the nodal signaling pathway to the bifurcation of the forebrain and the establishment of ventral midline structures. May participate in the transmission of nuclear signals during development and in the adult, as illustrated by the down-modulation of the RXR alpha activities.","The splice variant Meis2e, which has a truncated homeodomain, cannot bind to the D(1A) ACT sequence or activate transcription. However, Meis2e is an effective dominant negative regulator by blocking Meis2d-induced transcription activation. Thus, truncated homeoproteins with no DNA binding domains can have important regulatory functions.","The splice variant Meis2e, which has a truncated homeodomain, cannot bind to the D(1A) ACT sequence or activate transcription. However, Meis2e is an effective dominant negative regulator by blocking Meis2d-induced transcription activation. Thus, truncated homeoproteins with no DNA binding domains can have important regulatory functions."
25,25,P77398-N102A,MKTVVFAYHDMGCLGIEALLAAGYEISAIFTHTDNPGEKAFYGSVARLAAERGIPVYAPDNVNHPLWVERIAQLSPDVIFSFYYRHLIYDEILQLAPAGAFALHGSLLPKYRGRAPLNWVLVNGETETGVTLHRMVKRADAGAIVAQLRIAIAPDDIAITLHHKLCHAARQLLEQTLPAIKHGNILEIAQRENEATCFGRRTPDDSFLEWHKPASVLHNMVRAVADPWPGAFSYVGNQKFTVWSSRVHPHASKAQPGSVISVAPLLIACGDGALEIVTGQAGDGITMQGSQLAQTLGLVQGSRLNSQPACTARRRTRVLILGVNGFIGNHLTERLLREDHYEVYGLDIGSDAISRFLNHPHFHFVEGDISIHSEWIEYHVKKCDVVLPLVAIATPIEYTRNPLRVFELDFEENLRIIRYCVKYRKRIIFPSTSEVYGMCSDKYFDEDHSNLIVGPVNKPRWIYSVSKQLLDRVIWAYGEKEGLQFTLFRPFNWMGPRLDNLNAARIGSSRAITQLILNLVEGSPIKLIDGGKQKRCFTDIRDGIEALYRIIENAGNRCDGEIINIGNPENEASIEELGEMLLASFEKHPLRHHFPPFAGFRVVESSSYYGKGYQDVEHRKPSIRNAHRCLDWEPKIDMQETIDETLDFFLRTVDLTDKPS,No formyltransferase activity.,,MKTVVFAYHDMGCLGIEALLAAGYEISAIFTHTDNPGEKAFYGSVARLAAERGIPVYAPDNVNHPLWVERIAQLSPDVIFSFYYRHLIYDEILQLAPAGAFNLHGSLLPKYRGRAPLNWVLVNGETETGVTLHRMVKRADAGAIVAQLRIAIAPDDIAITLHHKLCHAARQLLEQTLPAIKHGNILEIAQRENEATCFGRRTPDDSFLEWHKPASVLHNMVRAVADPWPGAFSYVGNQKFTVWSSRVHPHASKAQPGSVISVAPLLIACGDGALEIVTGQAGDGITMQGSQLAQTLGLVQGSRLNSQPACTARRRTRVLILGVNGFIGNHLTERLLREDHYEVYGLDIGSDAISRFLNHPHFHFVEGDISIHSEWIEYHVKKCDVVLPLVAIATPIEYTRNPLRVFELDFEENLRIIRYCVKYRKRIIFPSTSEVYGMCSDKYFDEDHSNLIVGPVNKPRWIYSVSKQLLDRVIWAYGEKEGLQFTLFRPFNWMGPRLDNLNAARIGSSRAITQLILNLVEGSPIKLIDGGKQKRCFTDIRDGIEALYRIIENAGNRCDGEIINIGNPENEASIEELGEMLLASFEKHPLRHHFPPFAGFRVVESSSYYGKGYQDVEHRKPSIRNAHRCLDWEPKIDMQETIDETLDFFLRTVDLTDKPS,Bifunctional polymyxin resistance protein ArnA,Bifunctional enzyme that catalyzes the oxidative decarboxylation of UDP-glucuronic acid (UDP-GlcUA) to UDP-4-keto-arabinose (UDP-Ara4O) and the addition of a formyl group to UDP-4-amino-4-deoxy-L-arabinose (UDP-L-Ara4N) to form UDP-L-4-formamido-arabinose (UDP-L-Ara4FN). The modified arabinose is attached to lipid A and is required for resistance to polymyxin and cationic antimicrobial peptides.,Point mutation abolishes activity.,No formyltransferase activity. Point mutation abolishes activity.
26,26,P83561-K58A,MKAPATTLILVMSLISVLWATPDLEEGDLLAELGDLIATDDEYPMKPEERGCKLTFWACKNKKECCGWNACALGICMPR,No change in activity.,,MKAPATTLILVMSLISVLWATPDLEEGDLLAELGDLIATDDEYPMKPEERGCKLTFWKCKNKKECCGWNACALGICMPR,Beta-hexatoxin-Mg1a,"Insect and vertebrate active toxin. Binds to site 4 of mammalian voltage-gated sodium channels and shifts the activation voltage of the mammalian Nav1.2a/SCN2A channel to more hyperpolarized voltages, whereas the insect channel, DmNav1 (para), is not affected. Competes for binding at site 3 of the insect sodium channel. Causes temporary paralysis when injected into lepidopteran larvae at 8.6 nmol/g. A low intracranial injection dose into mice causes lacrimation, closure of the eyes and sweating. A high injection dose causes extensive lacrimation and death.",Unknown,No change in activity. Unknown
27,27,O00763-R277A,MVLLLCLSCLIFSCLTFSWLKIWGKMTDSKPITKSKSEANLIPSQEPFPASDNSGETPQRNGEGHTLPKTPSQAEPASHKGPKDAGRRRNSLPPSHQKPPRNPLSSSDAAPSPELQANGTGTQGLEATDTNGLSSSARPQGQQAGSPSKEDKKQANIKRQLMTNFILGSFDDYSSDEDSVAGSSRESTRKGSRASLGALSLEAYLTTGEAETRVPTMRPSMSGLHLVKRGREHKKLDLHRDFTVASPAEFVTRFGGDRVIEKVLIANNGIAAVKCMASIRRWAYEMFRNERAIRFVVMVTPEDLKANAEYIKMADHYVPVPGGPNNNNYANVELIVDIAKRIPVQAVWAGWGHASENPKLPELLCKNGVAFLGPPSEAMWALGDKIASTVVAQTLQVPTLPWSGSGLTVEWTEDDLQQGKRISVPEDVYDKGCVKDVDEGLEAAERIGFPLMIKASEGGGGKGIRKAESAEDFPILFRQVQSEIPGSPIFLMKLAQHARHLEVQILADQYGNAVSLFGRDCSIQRRHQKIVEEAPATIAPLAIFEFMEQCAIRLAKTVGYVSAGTVEYLYSQDGSFHFLELNPRLQVEHPCTEMIADVNLPAAQLQIAMGVPLHRLKDIRLLYGESPWGVTPISFETPSNPPLARGHVIAARITSENPDEGFKPSSGTVQELNFRSSKNVWGYFSVAATGGLHEFADSQFGHCFSWGENREEAISNMVVALKELSIRGDFRTTVEYLINLLETESFQNNDIDTGWLDYLIAEKVQAEKPDIMLGVVCGALNVADAMFRTCMTDFLHSLERGQVLPADSLLNLVDVELIYGGVKYILKVARQSLTMFVLIMNGCHIEIDAHRLNDGGLLLSYNGNSYTTYMKEEVDSYRITIGNKTCVFEKENDPTVLRSPSAGKLTQYTVEDGGHVEAGSSYAEMEVMKMIMTLNVQERGRVKYIKRPGAVLEAGCVVARLELDDPSKVHPAEPFTGELPAQQTLPILGEKLHQVFHSVLENLTNVMSGFCLPEPVFSIKLKEW,Loss of regulation of oligomerization by phosphorylation at S-222.,,MVLLLCLSCLIFSCLTFSWLKIWGKMTDSKPITKSKSEANLIPSQEPFPASDNSGETPQRNGEGHTLPKTPSQAEPASHKGPKDAGRRRNSLPPSHQKPPRNPLSSSDAAPSPELQANGTGTQGLEATDTNGLSSSARPQGQQAGSPSKEDKKQANIKRQLMTNFILGSFDDYSSDEDSVAGSSRESTRKGSRASLGALSLEAYLTTGEAETRVPTMRPSMSGLHLVKRGREHKKLDLHRDFTVASPAEFVTRFGGDRVIEKVLIANNGIAAVKCMRSIRRWAYEMFRNERAIRFVVMVTPEDLKANAEYIKMADHYVPVPGGPNNNNYANVELIVDIAKRIPVQAVWAGWGHASENPKLPELLCKNGVAFLGPPSEAMWALGDKIASTVVAQTLQVPTLPWSGSGLTVEWTEDDLQQGKRISVPEDVYDKGCVKDVDEGLEAAERIGFPLMIKASEGGGGKGIRKAESAEDFPILFRQVQSEIPGSPIFLMKLAQHARHLEVQILADQYGNAVSLFGRDCSIQRRHQKIVEEAPATIAPLAIFEFMEQCAIRLAKTVGYVSAGTVEYLYSQDGSFHFLELNPRLQVEHPCTEMIADVNLPAAQLQIAMGVPLHRLKDIRLLYGESPWGVTPISFETPSNPPLARGHVIAARITSENPDEGFKPSSGTVQELNFRSSKNVWGYFSVAATGGLHEFADSQFGHCFSWGENREEAISNMVVALKELSIRGDFRTTVEYLINLLETESFQNNDIDTGWLDYLIAEKVQAEKPDIMLGVVCGALNVADAMFRTCMTDFLHSLERGQVLPADSLLNLVDVELIYGGVKYILKVARQSLTMFVLIMNGCHIEIDAHRLNDGGLLLSYNGNSYTTYMKEEVDSYRITIGNKTCVFEKENDPTVLRSPSAGKLTQYTVEDGGHVEAGSSYAEMEVMKMIMTLNVQERGRVKYIKRPGAVLEAGCVVARLELDDPSKVHPAEPFTGELPAQQTLPILGEKLHQVFHSVLENLTNVMSGFCLPEPVFSIKLKEW,Acetyl-CoA carboxylase 2,"Mitochondrial enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA and plays a central role in fatty acid metabolism. Catalyzes a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA. Through the production of malonyl-CoA that allosterically inhibits carnitine palmitoyltransferase 1 at the mitochondria, negatively regulates fatty acid oxidation. Together with its cytosolic isozyme ACACA, which is involved in de novo fatty acid biosynthesis, promotes lipid storage.",,Loss of regulation of oligomerization by phosphorylation at S-222.
28,28,Q08050-S730A,MKTSPRRPLILKRRRLPLPVQNAPSETSEEEPKRSPAQQESNQAEASKEVAESNSCKFPAGIKIINHPTMPNTQVVAIPNNANIHSIITALTAKGKESGSSGPNKFILISCGGAPTQPPGLRPQTQTSYDAKRTEVTLETLGPKPAARDVNLPRPPGALCEQKRETCADGEAAGCTINNSLSNIQWLRKMSSDGLGSRSIKQEMEEKENCHLEQRQVKVEEPSRPSASWQNSVSERPPYSYMAMIQFAINSTERKRMTLKDIYTWIEDHFPYFKHIAKPGWKNSIRHNLSLHDMFVRETSANGKVSFWTIHPSANRYLTLDQVFKPLDPGSPQLPEHLESQQKRPNPELRRNMTIKTELPLGARRKMKPLLPRVSSYLVPIQFPVNQSLVLQPSVKVPLPLAASLMSSELARHSKRVRIAPKVLLAEEGIAPLSSAGPGKEEKLLFGEGFSPLLPVQTIKEEEIQPGEEMPHLARPIKVESPPLEEWPSPAPSFKEESSHSWEDSSQSPTPRPKKSYSGLRSPTRCVSEMLVIQHRERRERSRSRRKQHLLPPCVDEPELLFSEGPSTSRWAAELPFPADSSDPASQLSYSQEVGGPFKTPIKETLPISSTPSKSVLPRTPESWRLTPPAKVGGLDFSPVQTSQGASDPLPDPLGLMDLSTTPLQSAPPLESPQRLLSSEPLDLISVPFGNSSPSDIDVPKPGSPEPQVSGLAANRSLTEGLVLDTMNDALSKILLDISFPGLDEDPLGPDNINWSQFIPELQ,Prevents phosphorylation by PLK1 and impairs transcription activity; when associated with A-739.,,MKTSPRRPLILKRRRLPLPVQNAPSETSEEEPKRSPAQQESNQAEASKEVAESNSCKFPAGIKIINHPTMPNTQVVAIPNNANIHSIITALTAKGKESGSSGPNKFILISCGGAPTQPPGLRPQTQTSYDAKRTEVTLETLGPKPAARDVNLPRPPGALCEQKRETCADGEAAGCTINNSLSNIQWLRKMSSDGLGSRSIKQEMEEKENCHLEQRQVKVEEPSRPSASWQNSVSERPPYSYMAMIQFAINSTERKRMTLKDIYTWIEDHFPYFKHIAKPGWKNSIRHNLSLHDMFVRETSANGKVSFWTIHPSANRYLTLDQVFKPLDPGSPQLPEHLESQQKRPNPELRRNMTIKTELPLGARRKMKPLLPRVSSYLVPIQFPVNQSLVLQPSVKVPLPLAASLMSSELARHSKRVRIAPKVLLAEEGIAPLSSAGPGKEEKLLFGEGFSPLLPVQTIKEEEIQPGEEMPHLARPIKVESPPLEEWPSPAPSFKEESSHSWEDSSQSPTPRPKKSYSGLRSPTRCVSEMLVIQHRERRERSRSRRKQHLLPPCVDEPELLFSEGPSTSRWAAELPFPADSSDPASQLSYSQEVGGPFKTPIKETLPISSTPSKSVLPRTPESWRLTPPAKVGGLDFSPVQTSQGASDPLPDPLGLMDLSTTPLQSAPPLESPQRLLSSEPLDLISVPFGNSSPSDIDVPKPGSPEPQVSGLAANRSLTEGLVLDTMNDSLSKILLDISFPGLDEDPLGPDNINWSQFIPELQ,Forkhead box protein M1,"Transcription factor regulating the expression of cell cycle genes essential for DNA replication and mitosis. Plays a role in the control of cell proliferation. Also plays a role in DNA break repair, participating in the DNA damage checkpoint response. Promotes transcription of PHB2.",,Prevents phosphorylation by PLK1 and impairs transcription activity; when associated with A-739.
29,29,Q92838-A349T,MGYPEVERRELLPAAAPRERGSQGCGCGGAPARAGEGNSCLLFLGFFGLSLALHLLTLCCYLELRSELRRERGAESRLGGSGTPGTSGTLSSLGGLDPDSPITSHLGQPSPKQQPLEPGEAALHSDSQDGHQMALLNFFFPDEKPYSEEESRRVRRNKRSKSNEGADGPVKNKKKGKKAGPPGPNGPPGPPGPPGPQGPPGIPGIPGIPGTTVMGPPGPPGPPGPQGPPGLQGPSGAADKAGTRENQPAVVHLQGQGSAIQVKNDLSGGVLNDWSRITMNPKVFKLHPRSGELEVLVDGTYFIYSQVEVYYINFTDFASYEVVVDEKPFLQCTRSIETGKTNYNTCYTTGVCLLKARQKIAVKMVHADISINMSKHTTFFGAIRLGEAPAS,In XHED.,,MGYPEVERRELLPAAAPRERGSQGCGCGGAPARAGEGNSCLLFLGFFGLSLALHLLTLCCYLELRSELRRERGAESRLGGSGTPGTSGTLSSLGGLDPDSPITSHLGQPSPKQQPLEPGEAALHSDSQDGHQMALLNFFFPDEKPYSEEESRRVRRNKRSKSNEGADGPVKNKKKGKKAGPPGPNGPPGPPGPPGPQGPPGIPGIPGIPGTTVMGPPGPPGPPGPQGPPGLQGPSGAADKAGTRENQPAVVHLQGQGSAIQVKNDLSGGVLNDWSRITMNPKVFKLHPRSGELEVLVDGTYFIYSQVEVYYINFTDFASYEVVVDEKPFLQCTRSIETGKTNYNTCYTAGVCLLKARQKIAVKMVHADISINMSKHTTFFGAIRLGEAPAS,Ectodysplasin-A,"Cytokine which is involved in epithelial-mesenchymal signaling during morphogenesis of ectodermal organs. Functions as a ligand activating the DEATH-domain containing receptors EDAR and EDA2R. May also play a role in cell adhesion.Binds only to the receptor EDAR, while isoform 3 binds exclusively to the receptor EDA2R.Binds only to the receptor EDA2R.","The mutation was revealed in the third patient. This mutation caused a substitution in the extracellular domain of ectodysplasin A, which is a member of the TNF ligand superfamily involved in the communication between cells responsible for the development of skin appendages.","In XHED. The mutation was revealed in the third patient. This mutation caused a substitution in the extracellular domain of ectodysplasin A, which is a member of the TNF ligand superfamily involved in the communication between cells responsible for the development of skin appendages."
30,30,Q641K1-H912S,MSKLKVVGEKSLTNSSRVVGLLAQLEKINTDSTESDTARYVTSKILHLAQSQEKTRREMTTKGSTGMEVLLSTLENTKDLQTVLNILSILIELVSSGGGRRASFLVAKGGSQILLQLLMNASKDSPPHEEVMVQTHSILAKIGPKDKKFGVKARVNGALTVTLNLVKQHFQNYRLVLPCLQLLRVYSTNSVNSVSLGKNGVVELMFKIIGPFSKKNSGLMKVALDTLAALLKSKTNARRAVDRGYVQVLLTIYVDWHRHDNRHRNMLIRKGILQSLKSVTNIKLGRKAFIDANGMKILYNTSQECLAVRTLDPLVNTSSLIMRKCFPKNRLPLPTIKSSFHFQLPIIPVTGPVAQLYSLPPEVDDVVDESDDNDDIDLEVENELENEDDLDQSFKNDDIETDINKLRPQQVPGRTIEELKMYEHLFPELVDDFQDYELISKEPKPFVFEGKARGPIVVPTAGEEVPGNSGSVKKGVVMKERASPKGEEAKEDPKGHDRTLPQQLGGQSRVAPSAHSFNNDLVKALDRITLQNVPSQVASGLNAGMRKDFGLPLTVLSCTKACPHVAKCGSTLFEGRTVHLGKLCCTGVETEDDEDTESHSSTEQAPSVEASDGPTLHDPDLYIEIVKNTKSVPEYSEVAYPDYFGHIPPPFKEPILERPYGVQRTKIAQDIERLIHQNDIIDRVVYDLDNPTYTTPEEGDTLKFNSKFESGNLRKVIQIRKSEYDLILNSDINSNHYHQWFYFEVSGMRPGVAYRFNIINCEKSNSQFNYGMQPLMYSVQEALNARPWWIRMGTDICYYKNHFSRSSVAAGGQKGKSYYTITFTVNFPHKDDVCYFAYHYPYTYSTLQMHLQKLESAHNPQQIYFRKDVLCETLSGNICPLVTITAMPESNYYEHICQFRTRPYIFLSARVSPGETNASWVMKGTLEYLMSNSPTAQSLRESYIFKIVPMLNPDGVINGNHRCSLSGEDLNRQWQSPNPELHPTIYHAKGLLQYLAAVKRLPLVYCDYHGHSRKKNVFMYGCSI,Abolishes deglutamylase activity; when associated with Q-915.,,MSKLKVVGEKSLTNSSRVVGLLAQLEKINTDSTESDTARYVTSKILHLAQSQEKTRREMTTKGSTGMEVLLSTLENTKDLQTVLNILSILIELVSSGGGRRASFLVAKGGSQILLQLLMNASKDSPPHEEVMVQTHSILAKIGPKDKKFGVKARVNGALTVTLNLVKQHFQNYRLVLPCLQLLRVYSTNSVNSVSLGKNGVVELMFKIIGPFSKKNSGLMKVALDTLAALLKSKTNARRAVDRGYVQVLLTIYVDWHRHDNRHRNMLIRKGILQSLKSVTNIKLGRKAFIDANGMKILYNTSQECLAVRTLDPLVNTSSLIMRKCFPKNRLPLPTIKSSFHFQLPIIPVTGPVAQLYSLPPEVDDVVDESDDNDDIDLEVENELENEDDLDQSFKNDDIETDINKLRPQQVPGRTIEELKMYEHLFPELVDDFQDYELISKEPKPFVFEGKARGPIVVPTAGEEVPGNSGSVKKGVVMKERASPKGEEAKEDPKGHDRTLPQQLGGQSRVAPSAHSFNNDLVKALDRITLQNVPSQVASGLNAGMRKDFGLPLTVLSCTKACPHVAKCGSTLFEGRTVHLGKLCCTGVETEDDEDTESHSSTEQAPSVEASDGPTLHDPDLYIEIVKNTKSVPEYSEVAYPDYFGHIPPPFKEPILERPYGVQRTKIAQDIERLIHQNDIIDRVVYDLDNPTYTTPEEGDTLKFNSKFESGNLRKVIQIRKSEYDLILNSDINSNHYHQWFYFEVSGMRPGVAYRFNIINCEKSNSQFNYGMQPLMYSVQEALNARPWWIRMGTDICYYKNHFSRSSVAAGGQKGKSYYTITFTVNFPHKDDVCYFAYHYPYTYSTLQMHLQKLESAHNPQQIYFRKDVLCETLSGNICPLVTITAMPESNYYEHICQFRTRPYIFLSARVHPGETNASWVMKGTLEYLMSNSPTAQSLRESYIFKIVPMLNPDGVINGNHRCSLSGEDLNRQWQSPNPELHPTIYHAKGLLQYLAAVKRLPLVYCDYHGHSRKKNVFMYGCSI,Cytosolic carboxypeptidase 1,"Metallocarboxypeptidase that mediates protein deglutamylation of tubulin and non-tubulin target proteins. Catalyzes the removal of polyglutamate side chains present on the gamma-carboxyl group of glutamate residues within the C-terminal tail of alpha- and beta-tubulin. Specifically cleaves tubulin long-side-chains, while it is not able to remove the branching point glutamate. Also catalyzes the removal of polyglutamate residues from the carboxy-terminus of alpha-tubulin as well as non-tubulin proteins such as MYLK. Involved in KLF4 deglutamylation which promotes KLF4 proteasome-mediated degradation, thereby negatively regulating cell pluripotency maintenance and embryogenesis.",Mutation of the site in the Nna1 gene affects its ability to support neuron survival. Loss of function of Nna1 causes Purkinje cell degeneration (pcd) in mice. The pcd mice display altered proteolytic processing of Nna1 interacting proteins and mitochondrial abnormalities. The mutation in CCP1 catalyzes the shortening of polyglutamate chains.,Abolishes deglutamylase activity; when associated with Q-915. Mutation of the site in the Nna1 gene affects its ability to support neuron survival. Loss of function of Nna1 causes Purkinje cell degeneration (pcd) in mice. The pcd mice display altered proteolytic processing of Nna1 interacting proteins and mitochondrial abnormalities. The mutation in CCP1 catalyzes the shortening of polyglutamate chains.
31,31,Q9CFU9-S295P,MQPYNQSVNEVLEETKSQFEGLSPKEVKNRQAKDGFNELKEKKKTSTWELFIDTLKDPMVIILLLVAFVQLFLGEFVESLVIFIVLMINSVVAVVQTKRAESSLDALRQMSAPSAKVLRNGEKTSIPARELVVGDIVSLEAGDFIPADGRLIDVQNLRVEEGMLTGESEPVEKFSDVIEGEVALGDRKNMVFSSSLVVYGRADFLVTAIAEQTEIGKIAQMLETAEAKQTPLQQKLEKFGKQLGWVILALCALIFAVQILRLFTTNQTADMQKAVLDSFMFAVAVAVAAIPEALPSVVTIVLSVGTNKMAKQHAIMRNLPAVETLGSTSVICTDKTGTLTQNKMTVVDSFLPTQGSKELTDLTQADQKLLLNAMVLCNDSSFSQEGQLLGDPTEVALIAYSDKIGYPYQDLREKSPRLAEFPFDSERKLMSTINDFEGQKTIFVKGGPDVLFNRCNQVFLDGKVQEFTPELKEKFQAQNEAFSQKALRVLAYAYKPVSDNKTELTLTDENDLILIGLSAMIDPPREAVYDSIAEAKKAGIKTIMITGDHKTTAQAIAKDIGLMNEGDMALTGQELDALTEDELRENLEKISVYARVSPENKIRIVRAWQNEHQVTAMTGDGVNDAPALKQANIGIAMGSGTDVAKDASSMILTDDNFVSIVSAVSIGRVVYDNIKKSISYLFSGNLGAIIAIVFALVVGWVNPFTALQLLFINLVNDSVPAIALGMEKAEPDVMEKAPRQLNEGIFANGLMRVILIRGSLIGIAAIISQYVGQKTSPEMGVAMAFTTLILARTLQTFAARSNSQNILKLGFTTNKYVLMAVTFCLALYSLTTLPFLREIFSIPAAFGWSQWIVAAGLAVIAVICMEILKSIKGVFEKH,Increases sensitivity to CPA. CPA-sensitive; when associated with Q-54 and L-59.,,MQPYNQSVNEVLEETKSQFEGLSPKEVKNRQAKDGFNELKEKKKTSTWELFIDTLKDPMVIILLLVAFVQLFLGEFVESLVIFIVLMINSVVAVVQTKRAESSLDALRQMSAPSAKVLRNGEKTSIPARELVVGDIVSLEAGDFIPADGRLIDVQNLRVEEGMLTGESEPVEKFSDVIEGEVALGDRKNMVFSSSLVVYGRADFLVTAIAEQTEIGKIAQMLETAEAKQTPLQQKLEKFGKQLGWVILALCALIFAVQILRLFTTNQTADMQKAVLDSFMFAVAVAVAAIPEALSSVVTIVLSVGTNKMAKQHAIMRNLPAVETLGSTSVICTDKTGTLTQNKMTVVDSFLPTQGSKELTDLTQADQKLLLNAMVLCNDSSFSQEGQLLGDPTEVALIAYSDKIGYPYQDLREKSPRLAEFPFDSERKLMSTINDFEGQKTIFVKGGPDVLFNRCNQVFLDGKVQEFTPELKEKFQAQNEAFSQKALRVLAYAYKPVSDNKTELTLTDENDLILIGLSAMIDPPREAVYDSIAEAKKAGIKTIMITGDHKTTAQAIAKDIGLMNEGDMALTGQELDALTEDELRENLEKISVYARVSPENKIRIVRAWQNEHQVTAMTGDGVNDAPALKQANIGIAMGSGTDVAKDASSMILTDDNFVSIVSAVSIGRVVYDNIKKSISYLFSGNLGAIIAIVFALVVGWVNPFTALQLLFINLVNDSVPAIALGMEKAEPDVMEKAPRQLNEGIFANGLMRVILIRGSLIGIAAIISQYVGQKTSPEMGVAMAFTTLILARTLQTFAARSNSQNILKLGFTTNKYVLMAVTFCLALYSLTTLPFLREIFSIPAAFGWSQWIVAAGLAVIAVICMEILKSIKGVFEKH,Calcium-transporting ATPase 1,Catalyzes the hydrolysis of ATP coupled with the transport of calcium.,,Increases sensitivity to CPA. CPA-sensitive; when associated with Q-54 and L-59.
32,32,Q96EY5-Y204F,MDPVPGTDSAPLAGLAWSSASAPPPRGFSAISCTVEGAPASFGKSFAQKSGYFLCLSSLGSLENPQENVVADIQIVVDKSPLPLGFSPVCDPMDSKASVSKKKRMCVKLLPLGATDTAVFDVRLSGKTKTVPGYLRIGDMGGFAIWCKKAKAPRPVPKPRGLSRDMQGLSLDAASQPSKGGLLERTASRLGSRASTLRRNDSIFEASSLYGISAMDGVPFTLHPRFEGKSCSPLAFSAFGDLTIKSLADIEEEYNYGFVVEKTAAARLPPSVS,Abolishes interaction with CD2AP and CIN85/SH3KBP1.,,MDPVPGTDSAPLAGLAWSSASAPPPRGFSAISCTVEGAPASFGKSFAQKSGYFLCLSSLGSLENPQENVVADIQIVVDKSPLPLGFSPVCDPMDSKASVSKKKRMCVKLLPLGATDTAVFDVRLSGKTKTVPGYLRIGDMGGFAIWCKKAKAPRPVPKPRGLSRDMQGLSLDAASQPSKGGLLERTASRLGSRASTLRRNDSIYEASSLYGISAMDGVPFTLHPRFEGKSCSPLAFSAFGDLTIKSLADIEEEYNYGFVVEKTAAARLPPSVS,Multivesicular body subunit 12A,"Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies. May be involved in the ligand-mediated internalization and down-regulation of EGF receptor.",The CFBP protein was found to be phosphorylated at tyrosine 204 upon EGF stimulation. The tyrosine phosphorylation of CFBP regulates the affinity of its interaction with the CIN85/CD2AP family. Overexpression of CFBP induced morphological changes with actin reorganization. CFBP also accelerated the EGF receptor's down-regulation by facilitating the recruitment of Cbl to the CD2AP/CIN85 complex.,Abolishes interaction with CD2AP and CIN85/SH3KBP1. The CFBP protein was found to be phosphorylated at tyrosine 204 upon EGF stimulation. The tyrosine phosphorylation of CFBP regulates the affinity of its interaction with the CIN85/CD2AP family. Overexpression of CFBP induced morphological changes with actin reorganization. CFBP also accelerated the EGF receptor's down-regulation by facilitating the recruitment of Cbl to the CD2AP/CIN85 complex.
33,33,Q84L30-I46A,MKIFVKTLSGSNFEIEVKPADKVSDVKTAIETVKGAEYPAAKQMLAHQGKVLKDETTLEENNVVENSFIVIMLSKTKASPSGASTASAPAPSATQPQTVATPQVSAPTASVPVPTSGTATAAAPATAASVQTDVYGQAASNLVAGTTLESTVQQILDMGGGSWDRDTVVRALRAAFNNPERAVEYLYSGIPAQAEIPPVAQAPATGEQAANPLAQPQQAAAPAAATGGPNANPLNLFPQGMPAADAGAGAGNLDFLRNSQQFQALRAMVQANPQILQPMLQELGKQNPQLVRLIQEHQADFLRLINEPVEGEENVMEQLEAAMPQAVTVTPEEREAIERLEGMGFDRAMVLEVFFACNKNEELAANYLLDHMHEFEDQ,Abolishes interaction with RPN10.,,MKIFVKTLSGSNFEIEVKPADKVSDVKTAIETVKGAEYPAAKQMLIHQGKVLKDETTLEENNVVENSFIVIMLSKTKASPSGASTASAPAPSATQPQTVATPQVSAPTASVPVPTSGTATAAAPATAASVQTDVYGQAASNLVAGTTLESTVQQILDMGGGSWDRDTVVRALRAAFNNPERAVEYLYSGIPAQAEIPPVAQAPATGEQAANPLAQPQQAAAPAAATGGPNANPLNLFPQGMPAADAGAGAGNLDFLRNSQQFQALRAMVQANPQILQPMLQELGKQNPQLVRLIQEHQADFLRLINEPVEGEENVMEQLEAAMPQAVTVTPEEREAIERLEGMGFDRAMVLEVFFACNKNEELAANYLLDHMHEFEDQ,Ubiquitin receptor RAD23d,"May be involved in nucleotide excision repair. Binds and presumably selects ubiquitin-conjugates for destruction. Prefers multiubiquitin chains rather than single ubiquitins, with a binding affinity for 'Lys-48'-linked ubiquitin chains. Acts as a ubiquitin receptor that associates with the 26S proteasomal docking subunit RPN10 for the indirect recognition of ubiquitinated substrates of ubiquitin/26S proteasome-mediated proteolysis (UPP).",,Abolishes interaction with RPN10.
34,34,Q92784-C360R,MATVIHNPLKALGDQFYKEAIEHCRSYNSRLCAERSVRLPFLDSQTGVAQNNCYIWMEKRHRGPGLAPGQLYTYPARCWRKKRRLHPPEDPKLRLLEIKPEVELPLKKDGFTSESTTLEALLRGEGVEKKVDAREEESIQEIQRVLENDENVEEGNEEEDLEEDIPKRKNRTRGRARGSAGGRRRHDAASQEDHDKPYVCDICGKRYKNRPGLSYHYAHTHLASEEGDEAQDQETRSPPNHRNENHRPQKGPDGTVIPNNYCDFCLGGSNMNKKSGRPEELVSCADCGRSGHPTCLQFTLNMTEAVKTYKWQCIECKSCILCGTSENDDQLLFCDDCDRGYHMYCLNPPVAEPPEGSWSRHLCWELLKEKASAFGCQA,Abolishes binding to acetylated histones H3 and H4; when associated with R-363.,,MATVIHNPLKALGDQFYKEAIEHCRSYNSRLCAERSVRLPFLDSQTGVAQNNCYIWMEKRHRGPGLAPGQLYTYPARCWRKKRRLHPPEDPKLRLLEIKPEVELPLKKDGFTSESTTLEALLRGEGVEKKVDAREEESIQEIQRVLENDENVEEGNEEEDLEEDIPKRKNRTRGRARGSAGGRRRHDAASQEDHDKPYVCDICGKRYKNRPGLSYHYAHTHLASEEGDEAQDQETRSPPNHRNENHRPQKGPDGTVIPNNYCDFCLGGSNMNKKSGRPEELVSCADCGRSGHPTCLQFTLNMTEAVKTYKWQCIECKSCILCGTSENDDQLLFCDDCDRGYHMYCLNPPVAEPPEGSWSCHLCWELLKEKASAFGCQA,Zinc finger protein DPF3,"Belongs to the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a post-mitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to post-mitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth. Muscle-specific component of the BAF complex, a multiprotein complex involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Specifically binds acetylated lysines on histone 3 and 4 (H3K14ac, H3K9ac, H4K5ac, H4K8ac, H4K12ac, H4K16ac). In the complex, it acts as a tissue-specific anchor between histone acetylations and methylations and chromatin remodeling. It thereby probably plays an essential role in heart and skeletal muscle development.Acts as a regulator of myogenesis in cooperation with HDGFL2. Mediates the interaction of HDGFL2 with the BAF complex. HDGFL2-DPF3a activate myogenic genes by increasing chromatin accessibility through recruitment of SMARCA4/BRG1/BAF190A (ATPase subunit of the BAF complex) to myogenic gene promoters.",,Abolishes binding to acetylated histones H3 and H4; when associated with R-363.
35,35,P11217-W798R,MSRPLSDQEKRKQISVRGLAGVENVTELKKNFNRHLHFTLVKDRNVATPRDYYFALAHTVRDHLVGRWIRTQQHYYEKDPKRIYYLSLEFYMGRTLQNTMVNLALENACDEATYQLGLDMEELEEIEEDAGLGNGGLGRLAACFLDSMATLGLAAYGYGIRYEFGIFNQKISGGWQMEEADDWLRYGNPWEKARPEFTLPVHFYGHVEHTSQGAKWVDTQVVLAMPYDTPVPGYRNNVVNTMRLWSAKAPNDFNLKDFNVGGYIQAVLDRNLAENISRVLYPNDNFFEGKELRLKQEYFVVAATLQDIIRRFKSSKFGCRDPVRTNFDAFPDKVAIQLNDTHPSLAIPELMRILVDLERMDWDKAWDVTVRTCAYTNHTVLPEALERWPVHLLETLLPRHLQIIYEINQRFLNRVAAAFPGDVDRLRRMSLVEEGAVKRINMAHLCIAGSHAVNGVARIHSEILKKTIFKDFYELEPHKFQNKTNGITPRRWLVLCNPGLAEVIAERIGEDFISDLDQLRKLLSFVDDEAFIRDVAKVKQENKLKFAAYLEREYKVHINPNSLFDIQVKRIHEYKRQLLNCLHVITLYNRIKREPNKFFVPRTVMIGGKAAPGYHMAKMIIRLVTAIGDVVNHDPAVGDRLRVIFLENYRVSLAEKVIPAADLSEQISTAGTEASGTGNMKFMLNGALTIGTMDGANVEMAEEAGEENFFIFGMRVEDVDKLDQRGYNAQEYYDRIPELRQVIEQLSSGFFSPKQPDLFKDIVNMLMHHDRFKVFADYEDYIKCQEKVSALYKNPRERTRMVIRNIATSGKFSSDRTIAQYAREIWGVEPSRQRLPAPDEAI,In GSD5.,,MSRPLSDQEKRKQISVRGLAGVENVTELKKNFNRHLHFTLVKDRNVATPRDYYFALAHTVRDHLVGRWIRTQQHYYEKDPKRIYYLSLEFYMGRTLQNTMVNLALENACDEATYQLGLDMEELEEIEEDAGLGNGGLGRLAACFLDSMATLGLAAYGYGIRYEFGIFNQKISGGWQMEEADDWLRYGNPWEKARPEFTLPVHFYGHVEHTSQGAKWVDTQVVLAMPYDTPVPGYRNNVVNTMRLWSAKAPNDFNLKDFNVGGYIQAVLDRNLAENISRVLYPNDNFFEGKELRLKQEYFVVAATLQDIIRRFKSSKFGCRDPVRTNFDAFPDKVAIQLNDTHPSLAIPELMRILVDLERMDWDKAWDVTVRTCAYTNHTVLPEALERWPVHLLETLLPRHLQIIYEINQRFLNRVAAAFPGDVDRLRRMSLVEEGAVKRINMAHLCIAGSHAVNGVARIHSEILKKTIFKDFYELEPHKFQNKTNGITPRRWLVLCNPGLAEVIAERIGEDFISDLDQLRKLLSFVDDEAFIRDVAKVKQENKLKFAAYLEREYKVHINPNSLFDIQVKRIHEYKRQLLNCLHVITLYNRIKREPNKFFVPRTVMIGGKAAPGYHMAKMIIRLVTAIGDVVNHDPAVGDRLRVIFLENYRVSLAEKVIPAADLSEQISTAGTEASGTGNMKFMLNGALTIGTMDGANVEMAEEAGEENFFIFGMRVEDVDKLDQRGYNAQEYYDRIPELRQVIEQLSSGFFSPKQPDLFKDIVNMLMHHDRFKVFADYEDYIKCQEKVSALYKNPREWTRMVIRNIATSGKFSSDRTIAQYAREIWGVEPSRQRLPAPDEAI,"Glycogen phosphorylase, muscle form","Allosteric enzyme that catalyzes the rate-limiting step in glycogen catabolism, the phosphorolytic cleavage of glycogen to produce glucose-1-phosphate, and plays a central role in maintaining cellular and organismal glucose homeostasis.",The lack of enzyme activity in the proband's muscle is consistent with a crucial role of the amino acid 797 in the normal function of the PYGM protein. The mutation was not mentioned in the document.,In GSD5. The lack of enzyme activity in the proband's muscle is consistent with a crucial role of the amino acid 797 in the normal function of the PYGM protein. The mutation was not mentioned in the document.
36,36,Q01831-F756A,MARKRAAGGEPRGRELRSQKSKAKSKARREEEEEDAFEDEKPPKKSLLSKVSQGKRKRGCSHPGGSADGPAKKKVAKVTVKSENLKVIKDEALSDGDDLRDFPSDLKKAHHLKRGATMNEDSNEEEEESENDWEEVEELSEPVLGDVRESTAFSRSLLPVKPVEIEIETPEQAKTRERSEKIKLEFETYLRRAMKRFNKGVHEDTHKVHLLCLLANGFYRNNICSQPDLHAIGLSIIPARFTRVLPRDVDTYYLSNLVKWFIGTFTVNAELSASEQDNLQTTLERRFAIYSARDDEELVHIFLLILRALQLLTRLVLSLQPIPLKSATAKGKKPSKERLTADPGGSSETSSQVLENHTKPKTSKGTKQEETFAKGTCRPSAKGKRNKGGRKKRSKPSSSEEDEGPGDKQEKATQRRPHGRERRVASRVSYKEESGSDEAGSGSDFELSSGEASDPSDEDSEPGPPKQRKAPAPQRTKAGSKSASRTHRGSHRKDPSLPAASSSSSSSKRGKKMCSDGEKAEKRSIAGIDQWLEVFCEQEEKWVCVDCVHGVVGQPLTCYKYATKPMTYVVGIDSDGWVRDVTQRYDPVWMTVTRKCRVDAEWWAETLRPYQSPFMDREKKEDLEFQAKHMDQPLPTAIGLYKNHPLYALKRHLLKYEAIYPETAAILGYCRGEAVYSRDCVHTLHSRDTWLKKARVVRLGEVPYKMVKGFSNRARKARLAEPQLREENDLGLFGYWQTEEYQPPVAVDGKVPRNEAGNVYLFLPSMMPIGCVQLNLPNLHRVARKLDIDCVQAITGFDFHGGYSHPVTDGYIVCEEFKDVLLTAWENEQAVIERKEKEKKEKRALGNWKLLAKGLLIRERLKRRYGPKSEAAAPHTDAGGGLSSDEEEGTSSQAEAARILAASWPQNREDEEKQKLKGGPKKTKREKKAAASHLFPFEQL,Reduces DNA repair activity; abolishes single-stranded DNA binding; reduces binding to homoduplex DNA; reduces localization at DNA damaged foci.,,MARKRAAGGEPRGRELRSQKSKAKSKARREEEEEDAFEDEKPPKKSLLSKVSQGKRKRGCSHPGGSADGPAKKKVAKVTVKSENLKVIKDEALSDGDDLRDFPSDLKKAHHLKRGATMNEDSNEEEEESENDWEEVEELSEPVLGDVRESTAFSRSLLPVKPVEIEIETPEQAKTRERSEKIKLEFETYLRRAMKRFNKGVHEDTHKVHLLCLLANGFYRNNICSQPDLHAIGLSIIPARFTRVLPRDVDTYYLSNLVKWFIGTFTVNAELSASEQDNLQTTLERRFAIYSARDDEELVHIFLLILRALQLLTRLVLSLQPIPLKSATAKGKKPSKERLTADPGGSSETSSQVLENHTKPKTSKGTKQEETFAKGTCRPSAKGKRNKGGRKKRSKPSSSEEDEGPGDKQEKATQRRPHGRERRVASRVSYKEESGSDEAGSGSDFELSSGEASDPSDEDSEPGPPKQRKAPAPQRTKAGSKSASRTHRGSHRKDPSLPAASSSSSSSKRGKKMCSDGEKAEKRSIAGIDQWLEVFCEQEEKWVCVDCVHGVVGQPLTCYKYATKPMTYVVGIDSDGWVRDVTQRYDPVWMTVTRKCRVDAEWWAETLRPYQSPFMDREKKEDLEFQAKHMDQPLPTAIGLYKNHPLYALKRHLLKYEAIYPETAAILGYCRGEAVYSRDCVHTLHSRDTWLKKARVVRLGEVPYKMVKGFSNRARKARLAEPQLREENDLGLFGYWQTEEYQPPVAVDGKVPRNEFGNVYLFLPSMMPIGCVQLNLPNLHRVARKLDIDCVQAITGFDFHGGYSHPVTDGYIVCEEFKDVLLTAWENEQAVIERKEKEKKEKRALGNWKLLAKGLLIRERLKRRYGPKSEAAAPHTDAGGGLSSDEEEGTSSQAEAARILAASWPQNREDEEKQKLKGGPKKTKREKKAAASHLFPFEQL,DNA repair protein complementing XP-C cells,"Involved in global genome nucleotide excision repair (GG-NER) by acting as damage sensing and DNA-binding factor component of the XPC complex. Has only a low DNA repair activity by itself which is stimulated by RAD23B and RAD23A. Has a preference to bind DNA containing a short single-stranded segment but not to damaged oligonucleotides. This feature is proposed to be related to a dynamic sensor function: XPC can rapidly screen duplex DNA for non-hydrogen-bonded bases by forming a transient nucleoprotein intermediate complex which matures into a stable recognition complex through an intrinsic single-stranded DNA-binding activity. The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single-stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair. In vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts. XPC:RAD23B contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. XPC:RAD23B induces a bend in DNA upon binding. XPC:RAD23B stimulates the activity of DNA glycosylases TDG and SMUG1.In absence of DNA repair, the XPC complex also acts as a transcription coactivator: XPC interacts with the DNA-binding transcription factor E2F1 at a subset of promoters to recruit KAT2A and histone acetyltransferase complexes (HAT). KAT2A recruitment specifically promotes acetylation of histone variant H2A.Z.1/H2A.Z, but not H2A.Z.2/H2A.V, thereby promoting expression of target genes.","The alanine substitution of F756 in human XPC protein was tested for DNA-binding activity, accumulation in tracks and foci of DNA lesions, nuclear protein mobility, and the induction of downstream GGR reactions.","Reduces DNA repair activity; abolishes single-stranded DNA binding; reduces binding to homoduplex DNA; reduces localization at DNA damaged foci. The alanine substitution of F756 in human XPC protein was tested for DNA-binding activity, accumulation in tracks and foci of DNA lesions, nuclear protein mobility, and the induction of downstream GGR reactions."
37,37,Q2W8Q2-H263A,MIEVGETMGELPTNKIVFCERSWKTPVSILAFLIFVTFAWGIYLLDHYDEDDNFHGADDLSVGQFLVRNIAMPHVQRLYHTVPPAVVGVGGGGVNAGPVASGAIVGTNGYVITTLHSVSKLPEISVQVATTGGIRRFPAQVVKTIPGHDLALLKMQTTEKFLHFRMADVQTVVPGQQVFAFGRNMAGAPLVRQGLVQSADAPLAVGATQITHLLRSDAVYSWEQTGGPLVNAQGDLVGINIAATGPTGKVEGFTVPAQVIVSALQDVVRFKKGSATAPGQPQTQTVAAGSTNWWSKARAVVGGPTAIPGMGMNVVQGNVVKGNVAPSIPSGMPFIDTDHVGGAKIGGYSVADIVGLVMLALAAGVTGGMMTMGGGVLQVAGMMVFFGYGMYLIRPVVFLTNVVVYGAASLRNDKAQLVQWDKVKPLIPWGIAGVILGYFIGNAIGDSVVGILLGLFALIMAGKAVMEILQPNAGEETAESISATEAEDEMDELMALADGTSRPKASGLALPEGHARSAVLGLPMGLFSGILGISGGVIEVPLQRYVGRISLQNAIANSSVLVFWASVAGSVVAFLHGSSTGLIHWEAPVTLALVMIPGAYVGGIIGARLMRVLPVRVLKGVYAATMAAIALKMLTSV,"Loss of magnetic response, no crystal formation when amb1002 to amb1007 are also deleted. Slightly improved Ni(2+) binding; when associated with A-148.",,MIEVGETMGELPTNKIVFCERSWKTPVSILAFLIFVTFAWGIYLLDHYDEDDNFHGADDLSVGQFLVRNIAMPHVQRLYHTVPPAVVGVGGGGVNAGPVASGAIVGTNGYVITTLHSVSKLPEISVQVATTGGIRRFPAQVVKTIPGHDLALLKMQTTEKFLHFRMADVQTVVPGQQVFAFGRNMAGAPLVRQGLVQSADAPLAVGATQITHLLRSDAVYSWEQTGGPLVNAQGDLVGINIAATGPTGKVEGFTVPAQVIVSHLQDVVRFKKGSATAPGQPQTQTVAAGSTNWWSKARAVVGGPTAIPGMGMNVVQGNVVKGNVAPSIPSGMPFIDTDHVGGAKIGGYSVADIVGLVMLALAAGVTGGMMTMGGGVLQVAGMMVFFGYGMYLIRPVVFLTNVVVYGAASLRNDKAQLVQWDKVKPLIPWGIAGVILGYFIGNAIGDSVVGILLGLFALIMAGKAVMEILQPNAGEETAESISATEAEDEMDELMALADGTSRPKASGLALPEGHARSAVLGLPMGLFSGILGISGGVIEVPLQRYVGRISLQNAIANSSVLVFWASVAGSVVAFLHGSSTGLIHWEAPVTLALVMIPGAYVGGIIGARLMRVLPVRVLKGVYAATMAAIALKMLTSV,Probable membrane transporter protein MamO,"Plays 2 roles; promotes magnetite nucleation/formation and activates the MamE protease (Probable). Despite its near conservation of a protease-like sequence, this is probably not a protease  (Probable). Required in conjunction with MamP for proteolysis of at least MamE, itself and MamP. May transport a solute that controls MamE's protease activity. May place individual iron atoms into the magnetite lattice (Probable).",,"Loss of magnetic response, no crystal formation when amb1002 to amb1007 are also deleted. Slightly improved Ni(2+) binding; when associated with A-148."
38,38,P25745-C199A,MSETAKKVIVGMSGGVDSSVSAWLLQQQGYQVEGLFMKNWEEDDGEEYCTAAADLADAQAVCDKLGIELHTVNFAAEYWDNVFELFLAEYKAGRTPNPDILCNKEIKFKAFLEFAAEDLGADYIATGHYVRRADVDGKSRLLRGLDSNKDQSYFLYTLSHEQIAQSLFPVGELEKPQVRKIAEDLGLVTAKKKDSTGIAFIGERKFREFLGRYLPAQPGKIITVDGDEIGEHQGLMYHTLGQRKGLGIGGTKEGTEEPWYVVDKDVENNILVVAQGHEHPRLMSVGLIAQQLHWVDREPFTGTMRCTVKTRYRQTDIPCTVKALDDDRIEVIFDEPVAAVTPGQSAVFYNGEVCLGGGIIEQRLPLPV,Abolishes the incorporation of sulfur from the sulfur-relay system; loss of activity.,,MSETAKKVIVGMSGGVDSSVSAWLLQQQGYQVEGLFMKNWEEDDGEEYCTAAADLADAQAVCDKLGIELHTVNFAAEYWDNVFELFLAEYKAGRTPNPDILCNKEIKFKAFLEFAAEDLGADYIATGHYVRRADVDGKSRLLRGLDSNKDQSYFLYTLSHEQIAQSLFPVGELEKPQVRKIAEDLGLVTAKKKDSTGICFIGERKFREFLGRYLPAQPGKIITVDGDEIGEHQGLMYHTLGQRKGLGIGGTKEGTEEPWYVVDKDVENNILVVAQGHEHPRLMSVGLIAQQLHWVDREPFTGTMRCTVKTRYRQTDIPCTVKALDDDRIEVIFDEPVAAVTPGQSAVFYNGEVCLGGGIIEQRLPLPV,tRNA-specific 2-thiouridylase MnmA,"Catalyzes the 2-thiolation of uridine at the wobble position (U34) of tRNA(Lys), tRNA(Glu) and tRNA(Gln), leading to the formation of s(2)U34, the first step of tRNA-mnm(5)s(2)U34 synthesis. Sulfur is provided by IscS, via a sulfur-relay system. Binds ATP and its substrate tRNAs.",,Abolishes the incorporation of sulfur from the sulfur-relay system; loss of activity.
39,39,P24188-T201A,MPVLHNRISNDALKAKMLAESEPRTTISFYKYFHIADPKATRDALYQLFTALNVFGRVYLAHEGINAQISVPASNVETFRAQLYAFDPALEGLRLNIALDDDGKSFWVLRMKVRDRIVADGIDDPHFDASNVGEYLQAAEVNAMLDDPDALFIDMRNHYEYEVGHFENALEIPADTFREQLPKAVEMMQAHKDKKIVMYCAGGIRCEKASAWMKHNGFNKVWHIEGGIIEYARKAREQGLPVRFIGKNFVFDERMGERISDEIIAHCHQCGAPCDSHTNCKNDGCHLLFIQCPVCAEKYKGCCSEICCEESALPPEEQRRRRAGRENGNKIFNKSRGRLNTTLCIPDPTE,Reduced 5-carboxymethoxyuridine formation.,,MPVLHNRISNDALKAKMLAESEPRTTISFYKYFHIADPKATRDALYQLFTALNVFGRVYLAHEGINAQISVPASNVETFRAQLYAFDPALEGLRLNIALDDDGKSFWVLRMKVRDRIVADGIDDPHFDASNVGEYLQAAEVNAMLDDPDALFIDMRNHYEYEVGHFENALEIPADTFREQLPKAVEMMQAHKDKKIVMYCTGGIRCEKASAWMKHNGFNKVWHIEGGIIEYARKAREQGLPVRFIGKNFVFDERMGERISDEIIAHCHQCGAPCDSHTNCKNDGCHLLFIQCPVCAEKYKGCCSEICCEESALPPEEQRRRRAGRENGNKIFNKSRGRLNTTLCIPDPTE,tRNA uridine,"Catalyzes oxygen-dependent 5-hydroxyuridine (ho5U) modification at position 34 in tRNAs, the first step in 5-carboxymethoxyuridine (cmo5U) biosynthesis. May be part of an alternate pathway, which is able to bypass cmo5U biogenesis in a subset of tRNAs under aerobic conditions.",,Reduced 5-carboxymethoxyuridine formation.
40,40,D0CY60-H163A,MTLENVLEAARHLHQTLPALSEFGNWPTDLTATGLQPRAIPATPLVQALDQPGSPRTTGLVQAIRSAAHLAHWKRTYTEAEVGADFRNRYGYFELFGPTGHFHSTQLRGYVAYWGAGLDYDWHSHQAEELYLTLAGGAVFKVDGERAFVGAEGTRLHASWQSAAMSTGDQPILTFVLWRGEGLNALPRMDAA,Strongly decreased enzyme activity toward DMSP in vitro.,,MTLENVLEAARHLHQTLPALSEFGNWPTDLTATGLQPRAIPATPLVQALDQPGSPRTTGLVQAIRSAAHLAHWKRTYTEAEVGADFRNRYGYFELFGPTGHFHSTQLRGYVAYWGAGLDYDWHSHQAEELYLTLAGGAVFKVDGERAFVGAEGTRLHASWQSHAMSTGDQPILTFVLWRGEGLNALPRMDAA,Dimethylsulfonioproprionate lyase DddQ,"Able to cleave dimethylsulfonioproprionate (DMSP) in vitro, releasing dimethyl sulfide (DMS). DMS is the principal form by which sulfur is transported from oceans to the atmosphere. The real activity of the protein is however subject to debate and it is unclear whether it constitutes a real dimethylsulfonioproprionate lyase in vivo: the very low activity with DMSP as substrate suggests that DMSP is not its native substrate.","The mutation in the DddQ protein was found to be essential for catalysis in the cleavage of DMSP. This mutation resulted in a loss of activity, indicating that H163 plays a critical role in the conversion of DMSP into DMS.","Strongly decreased enzyme activity toward DMSP in vitro. The mutation in the DddQ protein was found to be essential for catalysis in the cleavage of DMSP. This mutation resulted in a loss of activity, indicating that H163 plays a critical role in the conversion of DMSP into DMS."
41,41,Q8N653-R619H,MAGPGSTGGQIGAAALAGGARSKVAPSVDFDHSCSDSVEYLTLNFGPFETVHRWRRLPPCDEFVGARRSKHTVVAYKDAIYVFGGDNGKTMLNDLLRFDVKDCSWCRAFTTGTPPAPRYHHSAVVYGSSMFVFGGYTGDIYSNSNLKNKNDLFEYKFATGQWTEWKIEGRLPVARSAHGATVYSDKLWIFAGYDGNARLNDMWTIGLQDRELTCWEEVAQSGEIPPSCCNFPVAVCRDKMFVFSGQSGAKITNNLFQFEFKDKTWTRIPTEHLLRGSPPPPQRRYGHTMVAFDRHLYVFGGAADNTLPNELHCYDVDFQTWEVVQPSSDSEVGGAEVPERACASEEVPTLTYEERVGFKKSRDVFGLDFGTTSAKQPTQPASELPSGRLFHAAAVISDAMYIFGGTVDNNIRSGEMYRFQFSCYPKCTLHEDYGRLWESRQFCDVEFVLGEKEECVQGHVAIVTARSRWLRRKITQARERLAQKLEQEAAPVPREAPGVAAGGARPPLLHVAIREAEARPFEVLMQFLYTDKIKYPRKGHVEDVLLIMDVYKLALSFQLCRLEQLCRQYIEASVDLQNVLVVCESAARLQLSQLKEHCLNFVVKESHFNQVIMMKEFEHLSSPLIVEIVRRKQQPPPRTPLDQPVDIGTSLIQDMKAYLEGAGAEFCDITLLLDGHPRPAHKAILAARSSYFEAMFRSFMPEDGQVNISIGEMVPSRQAFESMLRYIYYGEVNMPPEDSLYLFAAPYYYGFYNNRLQAYCKQNLEMNVTVQNVLQILEAADKTQALDMKRHCLHIIVHQFTKVSKLPTLRSLSQQLLLDIIDSLASHISDKQCAELGADI,Has not effect on protein abundance; does not affect localization to Golgi apparatus; does not affect function in regulation of RAS-MAPK signaling.,,MAGPGSTGGQIGAAALAGGARSKVAPSVDFDHSCSDSVEYLTLNFGPFETVHRWRRLPPCDEFVGARRSKHTVVAYKDAIYVFGGDNGKTMLNDLLRFDVKDCSWCRAFTTGTPPAPRYHHSAVVYGSSMFVFGGYTGDIYSNSNLKNKNDLFEYKFATGQWTEWKIEGRLPVARSAHGATVYSDKLWIFAGYDGNARLNDMWTIGLQDRELTCWEEVAQSGEIPPSCCNFPVAVCRDKMFVFSGQSGAKITNNLFQFEFKDKTWTRIPTEHLLRGSPPPPQRRYGHTMVAFDRHLYVFGGAADNTLPNELHCYDVDFQTWEVVQPSSDSEVGGAEVPERACASEEVPTLTYEERVGFKKSRDVFGLDFGTTSAKQPTQPASELPSGRLFHAAAVISDAMYIFGGTVDNNIRSGEMYRFQFSCYPKCTLHEDYGRLWESRQFCDVEFVLGEKEECVQGHVAIVTARSRWLRRKITQARERLAQKLEQEAAPVPREAPGVAAGGARPPLLHVAIREAEARPFEVLMQFLYTDKIKYPRKGHVEDVLLIMDVYKLALSFQLCRLEQLCRQYIEASVDLQNVLVVCESAARLQLSQLKEHCLNFVVKESHFNQVIMMKEFERLSSPLIVEIVRRKQQPPPRTPLDQPVDIGTSLIQDMKAYLEGAGAEFCDITLLLDGHPRPAHKAILAARSSYFEAMFRSFMPEDGQVNISIGEMVPSRQAFESMLRYIYYGEVNMPPEDSLYLFAAPYYYGFYNNRLQAYCKQNLEMNVTVQNVLQILEAADKTQALDMKRHCLHIIVHQFTKVSKLPTLRSLSQQLLLDIIDSLASHISDKQCAELGADI,Leucine-zipper-like transcriptional regulator 1,"Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates ubiquitination of Ras (K-Ras/KRAS, N-Ras/NRAS and H-Ras/HRAS). Is a negative regulator of RAS-MAPK signaling that acts by controlling Ras levels and decreasing Ras association with membranes.",,Has not effect on protein abundance; does not affect localization to Golgi apparatus; does not affect function in regulation of RAS-MAPK signaling.
42,42,Q3E991-D234A,MAAAVLNPGFFLLILLLSFSISPSLQYVSESEPLVRFKNSVKITKGDLNSWREGTDPCSGKWFGIYCQKGLTVSGIHVTRLGLSGTITVDDLKDLPNLKTIRLDNNLLSGPLPHFFKLRGLKSLMLSNNSFSGEIRDDFFKDMSKLKRLFLDHNKFEGSIPSSITQLPQLEELHMQSNNLTGEIPPEFGSMKNLKVLDLSTNSLDGIVPQSIADKKNLAVNLTENEYLCGPVVAVGCENIELNDPQEGQPPSKPSSSVPETSNKAAINAIMVSISLLLLFFIIVGVIKRRNKKKNPDFRMLANNRENDVVEVRISESSSTTAKRSTDSSRKRGGHSDDGSTKKGVSNIGKGGNGGGGGALGGGMGDIIMVNTDKGSFGLPDLMKAAAEVLGNGSLGSAYKAVMTTGLSVVVKRIRDMNQLAREPFDVEMRRFGKLRHPNILTPLAYHYRREEKLVVSEYMPKSSLLYVLHGDRGIYHSELTWATRLKIIQGVAHGMKFLHEEFASYDLPHGNLKSSNVLLSETYEPLISDYAFLPLLQPSNASQALFAFKTPEFAQTQQVSHKSDVYCLGIIILEILTGKFPSQYLNNGKGGTDIVQWVQSSVAEQKEEELIDPEIVNNTESMRQMVELLRVGAACIASNPDERLDMREAVRRIEQVKT,Compromised interaction with LURE1.2. Reduced pollen tube attraction.,,MAAAVLNPGFFLLILLLSFSISPSLQYVSESEPLVRFKNSVKITKGDLNSWREGTDPCSGKWFGIYCQKGLTVSGIHVTRLGLSGTITVDDLKDLPNLKTIRLDNNLLSGPLPHFFKLRGLKSLMLSNNSFSGEIRDDFFKDMSKLKRLFLDHNKFEGSIPSSITQLPQLEELHMQSNNLTGEIPPEFGSMKNLKVLDLSTNSLDGIVPQSIADKKNLAVNLTENEYLCGPVVDVGCENIELNDPQEGQPPSKPSSSVPETSNKAAINAIMVSISLLLLFFIIVGVIKRRNKKKNPDFRMLANNRENDVVEVRISESSSTTAKRSTDSSRKRGGHSDDGSTKKGVSNIGKGGNGGGGGALGGGMGDIIMVNTDKGSFGLPDLMKAAAEVLGNGSLGSAYKAVMTTGLSVVVKRIRDMNQLAREPFDVEMRRFGKLRHPNILTPLAYHYRREEKLVVSEYMPKSSLLYVLHGDRGIYHSELTWATRLKIIQGVAHGMKFLHEEFASYDLPHGNLKSSNVLLSETYEPLISDYAFLPLLQPSNASQALFAFKTPEFAQTQQVSHKSDVYCLGIIILEILTGKFPSQYLNNGKGGTDIVQWVQSSVAEQKEEELIDPEIVNNTESMRQMVELLRVGAACIASNPDERLDMREAVRRIEQVKT,Pollen receptor-like kinase 6,Key receptor for sensing species-specific attractants in cooperation with other pollen receptor-like kinases. Essential for pollen tube reorientation toward attractant peptides.,,Compromised interaction with LURE1.2. Reduced pollen tube attraction.
43,43,P02768-D389V,MKWVTFISLLFLFSSAYSRGVFRRDAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAAVPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGKKLVAASQAALGL,In Iowa city-1.,,MKWVTFISLLFLFSSAYSRGVFRRDAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGKKLVAASQAALGL,Albumin,"Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc. Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma. Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner. The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood. The rank order of affinity is zinc > calcium > magnesium. Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli. Does not prevent iron uptake by the bacterial siderophore aerobactin.",,In Iowa city-1.
44,44,Q96C86-K138D,MADAAPQLGKRKRELDVEEAHAASTEEKEAGVGNGTCAPVRLPFSGFRLQKVLRESARDKIIFLHGKVNEASGDGDGEDAVVILEKTPFQVEQVAQLLTGSPELQLQFSNDIYSTYHLFPPRQLNDVKTTVVYPATEDHLQKYLRQDLRLIRETGDDYRNITLPHLESQSLSIQWVYNILDKKAEADRIVFENPDPSDGFVLIPDLKWNQQQLDDLYLIAICHRRGIRSLRDLTPEHLPLLRNILHQGQEAILQRYRMKGDHLRVYLHYLPSYYHLHVHFTALGFEAPGSGVERAHLLAEVIENLECDPRHYQQRTLTFALRADDPLLKLLQEAQQS,Increases decapping activity to 250% of wild-type.,,MADAAPQLGKRKRELDVEEAHAASTEEKEAGVGNGTCAPVRLPFSGFRLQKVLRESARDKIIFLHGKVNEASGDGDGEDAVVILEKTPFQVEQVAQLLTGSPELQLQFSNDIYSTYHLFPPRQLNDVKTTVVYPATEKHLQKYLRQDLRLIRETGDDYRNITLPHLESQSLSIQWVYNILDKKAEADRIVFENPDPSDGFVLIPDLKWNQQQLDDLYLIAICHRRGIRSLRDLTPEHLPLLRNILHQGQEAILQRYRMKGDHLRVYLHYLPSYYHLHVHFTALGFEAPGSGVERAHLLAEVIENLECDPRHYQQRTLTFALRADDPLLKLLQEAQQS,m7GpppX diphosphatase,"Decapping scavenger enzyme that catalyzes the cleavage of a residual cap structure following the degradation of mRNAs by the 3'->5' exosome-mediated mRNA decay pathway. Hydrolyzes cap analog structures like 7-methylguanosine nucleoside triphosphate (m7GpppG) with up to 10 nucleotide substrates (small capped oligoribonucleotides) and specifically releases 5'-phosphorylated RNA fragments and 7-methylguanosine monophosphate (m7GMP). Cleaves cap analog structures like tri-methyl guanosine nucleoside triphosphate (m3(2,2,7)GpppG) with very poor efficiency. Does not hydrolyze unmethylated cap analog (GpppG) and shows no decapping activity on intact m7GpppG-capped mRNA molecules longer than 25 nucleotides. Does not hydrolyze 7-methylguanosine diphosphate (m7GDP) to m7GMP. May also play a role in the 5'->3 mRNA decay pathway; m7GDP, the downstream product released by the 5'->3' mRNA mediated decapping activity, may be also converted by DCPS to m7GMP. Binds to m7GpppG and strongly to m7GDP. Plays a role in first intron splicing of pre-mRNAs. Inhibits activation-induced cell death.",,Increases decapping activity to 250% of wild-type.
45,45,P93830-D187A,MMGSVELNLRETELCLGLPGGDTVAPVTGNKRGFSETVDLKLNLNNEPANKEGSTTHDVVTFDSKEKSACPKDPAKPPAKAQVVGWPPVRSYRKNVMVSCQKSSGGPEAAAFVKVSMDGAPYLRKIDLRMYKSYDELSNALSNMFSSFTMGKHGGEEGMIDFMNERKLMDLVNSWDYVPSYEDKDGAWMLVGDVPWPMFVDTCKRLRLMKGSDAIGLAPRAMEKCKSRA,No effect on interaction with ARF7; when associated with A-183. Loss of interaction with ARF7; when associated with A-114 and A-183.,,MMGSVELNLRETELCLGLPGGDTVAPVTGNKRGFSETVDLKLNLNNEPANKEGSTTHDVVTFDSKEKSACPKDPAKPPAKAQVVGWPPVRSYRKNVMVSCQKSSGGPEAAAFVKVSMDGAPYLRKIDLRMYKSYDELSNALSNMFSSFTMGKHGGEEGMIDFMNERKLMDLVNSWDYVPSYEDKDGDWMLVGDVPWPMFVDTCKRLRLMKGSDAIGLAPRAMEKCKSRA,Auxin-responsive protein IAA17,"Aux/IAA proteins are short-lived transcriptional factors that function as repressors of early auxin response genes at low auxin concentrations. Repression is thought to result from the interaction with auxin response factors (ARFs), proteins that bind to the auxin-responsive promoter element (AuxRE). Formation of heterodimers with ARF proteins may alter their ability to modulate early auxin response genes expression.",Mutation of interface residues in the ARF7 PB1 domain yields monomeric protein and abolishes interaction with both itself and IAA17.,No effect on interaction with ARF7; when associated with A-183. Loss of interaction with ARF7; when associated with A-114 and A-183. Mutation of interface residues in the ARF7 PB1 domain yields monomeric protein and abolishes interaction with both itself and IAA17.
46,46,P26769-S490A,MRRRRYLRDRAEAAAAAAAGGGEGLQRSRDWLYESYYCMSQQHPLIVFLLLIVMGACLALLAVFFALGLEVEDHVAFLITVPTALAIFFAIFILVCIESVFKKLLRVFSLVIWICLVAMGYLFMCFGGTVSAWDQVSFFLFIIFVVYTMLPFNMRDAIIASILTSSSHTIVLSVYLSATPGAKEHLFWQILANVIIFICGNLAGAYHKHLMELALQQTYRDTCNCIKSRIKLEFEKRQQERLLLSLLPAHIAMEMKAEIIQRLQGPKAGQMENTNNFHNLYVKRHTNVSILYADIVGFTRLASDCSPGELVHMLNELFGKFDQIAKENECMRIKILGDCYYCVSGLPISLPNHAKNCVKMGLDMCEAIKKVRDATGVDINMRVGVHSGNVLCGVIGLQKWQYDVWSHDVTLANHMEAGGVPGRVHISSVTLEHLNGAYKVEEGDGEIRDPYLKQHLVKTYFVINPKGERRSPQHLFRPRHTLDGAKMRAAVRMTRYLESWGAAKPFAHLHHRDSMTTENGKISTTDVPMGQHNFQNRTLRTKSQKKRFEEELNERMIQAIDGINAQKQWLKSEDIQRISLLFYNKNIEKEYRATALPAFKYYVTCACLIFLCIFIVQILVLPKTSILGFSFGAAFLSLIFILFVCFAGQLLQCSKKASTSLMWLLKSSGIIANRPWPRISLTIVTTAIILTMAVFNMFFLSNSEETTLPTANTSNANVSVPDNQASILHARNLFFLPYFIYSCILGLISCSVFLRVNYELKMLIMMVALVGYNTILLHTHAHVLDAYSQVLFQRPGIWKDLKTMGSVSLSIFFITLLVLGRQSEYYCRLDFLWKNKFKKEREEIETMENLNRVLLENVLPAHVAEHFLARSLKNEELYHQSYDCVCVMFASIPDFKEFYTESDVNKEGLECLRLLNEIIADFDDLLSKPKFSGVEKIKTIGSTYMAATGLSAIPSQEHAQEPERQYMHIGTMVEFAYALVGKLDAINKHSFNDFKLRVGINHGPVIAGVIGAQKPQYDIWGNTV,Reduces activation by PKC. Abolishes activation by PKC; when associated with A-543.,,MRRRRYLRDRAEAAAAAAAGGGEGLQRSRDWLYESYYCMSQQHPLIVFLLLIVMGACLALLAVFFALGLEVEDHVAFLITVPTALAIFFAIFILVCIESVFKKLLRVFSLVIWICLVAMGYLFMCFGGTVSAWDQVSFFLFIIFVVYTMLPFNMRDAIIASILTSSSHTIVLSVYLSATPGAKEHLFWQILANVIIFICGNLAGAYHKHLMELALQQTYRDTCNCIKSRIKLEFEKRQQERLLLSLLPAHIAMEMKAEIIQRLQGPKAGQMENTNNFHNLYVKRHTNVSILYADIVGFTRLASDCSPGELVHMLNELFGKFDQIAKENECMRIKILGDCYYCVSGLPISLPNHAKNCVKMGLDMCEAIKKVRDATGVDINMRVGVHSGNVLCGVIGLQKWQYDVWSHDVTLANHMEAGGVPGRVHISSVTLEHLNGAYKVEEGDGEIRDPYLKQHLVKTYFVINPKGERRSPQHLFRPRHTLDGAKMRASVRMTRYLESWGAAKPFAHLHHRDSMTTENGKISTTDVPMGQHNFQNRTLRTKSQKKRFEEELNERMIQAIDGINAQKQWLKSEDIQRISLLFYNKNIEKEYRATALPAFKYYVTCACLIFLCIFIVQILVLPKTSILGFSFGAAFLSLIFILFVCFAGQLLQCSKKASTSLMWLLKSSGIIANRPWPRISLTIVTTAIILTMAVFNMFFLSNSEETTLPTANTSNANVSVPDNQASILHARNLFFLPYFIYSCILGLISCSVFLRVNYELKMLIMMVALVGYNTILLHTHAHVLDAYSQVLFQRPGIWKDLKTMGSVSLSIFFITLLVLGRQSEYYCRLDFLWKNKFKKEREEIETMENLNRVLLENVLPAHVAEHFLARSLKNEELYHQSYDCVCVMFASIPDFKEFYTESDVNKEGLECLRLLNEIIADFDDLLSKPKFSGVEKIKTIGSTYMAATGLSAIPSQEHAQEPERQYMHIGTMVEFAYALVGKLDAINKHSFNDFKLRVGINHGPVIAGVIGAQKPQYDIWGNTV,Adenylate cyclase type 2,Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Down-stream signaling cascades mediate changes in gene expression patterns and lead to increased IL6 production. Functions in signaling cascades downstream of the muscarinic acetylcholine receptors.,The double phosphorylation-deficient mutant (S490/543A) of AC2 was insensitive to PMA and CCh stimulation.,Reduces activation by PKC. Abolishes activation by PKC; when associated with A-543. The double phosphorylation-deficient mutant (S490/543A) of AC2 was insensitive to PMA and CCh stimulation.
47,47,P07204-D486Y,MLGVLVLGALALAGLGFPAPAEPQPGGSQCVEHDCFALYPGPATFLNASQICDGLRGHLMTVRSSVAADVISLLLNGDGGVGRRRLWIGLQLPPGCGDPKRLGPLRGFQWVTGDNNTSYSRWARLDLNGAPLCGPLCVAVSAAEATVPSEPIWEEQQCEVKADGFLCEFHFPATCRPLAVEPGAAAAAVSITYGTPFAARGADFQALPVGSSAAVAPLGLQLMCTAPPGAVQGHWAREAPGAWDCSVENGGCEHACNAIPGAPRCQCPAGAALQADGRSCTASATQSCNDLCEHFCVPNPDQPGSYSCMCETGYRLAADQHRCEDVDDCILEPSPCPQRCVNTQGGFECHCYPNYDLVDGECVEPVDPCFRANCEYQCQPLNQTSYLCVCAEGFAPIPHEPHRCQMFCNQTACPADCDPNTQASCECPEGYILDDGFICTDIDECENGGFCSGVCHNLPGTFECICGPDSALARHIGTDCDSGKVYGGDSGSGEPPPSPTPGSTLTPPAVGLVHSGLLIGISIASLCLVVALLALLCHLRKKQGAARAKMEYKCAAPSKEVVLQHVRTERTPQRL,In THPH12 and AHUS6; cells transfected with the mutant are less effective in converting C3b to iC3b on the cell surface after complement activation.,,MLGVLVLGALALAGLGFPAPAEPQPGGSQCVEHDCFALYPGPATFLNASQICDGLRGHLMTVRSSVAADVISLLLNGDGGVGRRRLWIGLQLPPGCGDPKRLGPLRGFQWVTGDNNTSYSRWARLDLNGAPLCGPLCVAVSAAEATVPSEPIWEEQQCEVKADGFLCEFHFPATCRPLAVEPGAAAAAVSITYGTPFAARGADFQALPVGSSAAVAPLGLQLMCTAPPGAVQGHWAREAPGAWDCSVENGGCEHACNAIPGAPRCQCPAGAALQADGRSCTASATQSCNDLCEHFCVPNPDQPGSYSCMCETGYRLAADQHRCEDVDDCILEPSPCPQRCVNTQGGFECHCYPNYDLVDGECVEPVDPCFRANCEYQCQPLNQTSYLCVCAEGFAPIPHEPHRCQMFCNQTACPADCDPNTQASCECPEGYILDDGFICTDIDECENGGFCSGVCHNLPGTFECICGPDSALARHIGTDCDSGKVDGGDSGSGEPPPSPTPGSTLTPPAVGLVHSGLLIGISIASLCLVVALLALLCHLRKKQGAARAKMEYKCAAPSKEVVLQHVRTERTPQRL,Thrombomodulin,"Thrombomodulin is a specific endothelial cell receptor that forms a 1:1 stoichiometric complex with thrombin. This complex is responsible for the conversion of protein C to the activated protein C (protein Ca). Once evolved, protein Ca scissions the activated cofactors of the coagulation mechanism, factor Va and factor VIIIa, and thereby reduces the amount of thrombin generated.","This mutation is located between the transmembrane domain and the sixth epidermal growth factor-like domain. The change is predicted to cause significant structural changes in the protein, potentially preventing its expression or causing a non-functional conformation.","In THPH12 and AHUS6; cells transfected with the mutant are less effective in converting C3b to iC3b on the cell surface after complement activation. This mutation is located between the transmembrane domain and the sixth epidermal growth factor-like domain. The change is predicted to cause significant structural changes in the protein, potentially preventing its expression or causing a non-functional conformation."
48,48,Q15392-Y471S,MEPAVSLAVCALLFLLWVRLKGLEFVLIHQRWVFVCLFLLPLSLIFDIYYYVRAWVVFKLSSAPRLHEQRVRDIQKQVREWKEQGSKTFMCTGRPGWLTVSLRVGKYKKTHKNIMINLMDILEVDTKKQIVRVEPLVTMGQVTALLTSIGWTLPVLPELDDLTVGGLIMGTGIESSSHKYGLFQHICTAYELVLADGSFVRCTPSENSDLFYAVPWSCGTLGFLVAAEIRIIPAKKYVKLRFEPVRGLEAICAKFTHESQRQENHFVEGLLYSLDEAVIMTGVMTDEAEPSKLNSIGNYYKPWFFKHVENYLKTNREGLEYIPLRHYYHRHTRSIFWELQDIIPFGNNPIFRYLFGWMVPPKISLLKLTQGETLRKLYEQHHVVQDMLVPMKCLQQALHTFQNDIHVYPIWLCPFILPSQPGLVHPKGNEAELYIDIGAYGEPRVKHFEARSCMRQLEKFVRSVHGFQMLSADCYMNREEFWEMFDGSLYHKLREKLGCQDAFPEVYDKICKAARH,In DESMOS; complete loss of ability to convert desmosterol to cholesterol.,,MEPAVSLAVCALLFLLWVRLKGLEFVLIHQRWVFVCLFLLPLSLIFDIYYYVRAWVVFKLSSAPRLHEQRVRDIQKQVREWKEQGSKTFMCTGRPGWLTVSLRVGKYKKTHKNIMINLMDILEVDTKKQIVRVEPLVTMGQVTALLTSIGWTLPVLPELDDLTVGGLIMGTGIESSSHKYGLFQHICTAYELVLADGSFVRCTPSENSDLFYAVPWSCGTLGFLVAAEIRIIPAKKYVKLRFEPVRGLEAICAKFTHESQRQENHFVEGLLYSLDEAVIMTGVMTDEAEPSKLNSIGNYYKPWFFKHVENYLKTNREGLEYIPLRHYYHRHTRSIFWELQDIIPFGNNPIFRYLFGWMVPPKISLLKLTQGETLRKLYEQHHVVQDMLVPMKCLQQALHTFQNDIHVYPIWLCPFILPSQPGLVHPKGNEAELYIDIGAYGEPRVKHFEARSCMRQLEKFVRSVHGFQMLYADCYMNREEFWEMFDGSLYHKLREKLGCQDAFPEVYDKICKAARH,Delta,"Catalyzes the reduction of the delta-24 double bond of sterol intermediates during cholesterol biosynthesis. In addition to its cholesterol-synthesizing activity, can protect cells from oxidative stress by reducing caspase 3 activity during apoptosis induced by oxidative stress. Also protects against amyloid-beta peptide-induced apoptosis.",The missense mutation in DHCR24 has been shown to be disease causing in patients with desmosterolosis.,In DESMOS; complete loss of ability to convert desmosterol to cholesterol. The missense mutation in DHCR24 has been shown to be disease causing in patients with desmosterolosis.
49,49,Q99JB6-T114A,MPNPRPAKPMAPSLALGPSPGVLPSWKTAPKGSELLGTRGSGGPFQGRDLRSGAHTSSSLNPLPPSQLQLPTVPLVMVAPSGARLGPSPHLQALLQDRPHFMHQLSTVDAHAQAPVLQVRPLDNPAMISLPPPSAATGVFSLKARPGLPPGINVASLEWVSREPALLCTFPRSGTPRKDSNLLAAPQGSYPLLANGVCKWPGCEKVFEEPEEFLKHCQADHLLDEKGKAQCLLQREVVQSLEQQLELEKEKLGAMQAHLAGKMALAKAPSVASMDKSSCCIVATSTQGSVLPAWSAPREAPDGGLFAVRRHLWGSHGNSSFPEFFHNMDYFKYHNMRPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRVESEKGAVWTVDEFEFRKKRSQRPNKCSNPCP,"Increase in protein stability, transcriptional activity and the ability to suppress the proliferation of conventional T-cells in vitro; when associated with A-19; A-88 and A-175.",,MPNPRPAKPMAPSLALGPSPGVLPSWKTAPKGSELLGTRGSGGPFQGRDLRSGAHTSSSLNPLPPSQLQLPTVPLVMVAPSGARLGPSPHLQALLQDRPHFMHQLSTVDAHAQTPVLQVRPLDNPAMISLPPPSAATGVFSLKARPGLPPGINVASLEWVSREPALLCTFPRSGTPRKDSNLLAAPQGSYPLLANGVCKWPGCEKVFEEPEEFLKHCQADHLLDEKGKAQCLLQREVVQSLEQQLELEKEKLGAMQAHLAGKMALAKAPSVASMDKSSCCIVATSTQGSVLPAWSAPREAPDGGLFAVRRHLWGSHGNSSFPEFFHNMDYFKYHNMRPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRVESEKGAVWTVDEFEFRKKRSQRPNKCSNPCP,Forkhead box protein P3,"Transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg). Plays an essential role in maintaining homeostasis of the immune system by allowing the acquisition of full suppressive function and stability of the Treg lineage, and by directly modulating the expansion and function of conventional T-cells. Can act either as a transcriptional repressor or a transcriptional activator depending on its interactions with other transcription factors, histone acetylases and deacetylases. The suppressive activity of Treg involves the coordinate activation of many genes, including CTLA4 and TNFRSF18 by FOXP3 along with repression of genes encoding cytokines such as interleukin-2 (IL2) and interferon-gamma (IFNG). Inhibits cytokine production and T-cell effector function by repressing the activity of two key transcription factors, RELA and NFATC2. Mediates transcriptional repression of IL2 via its association with histone acetylase KAT5 and histone deacetylase HDAC7. Can activate the expression of TNFRSF18, IL2RA and CTLA4 and repress the expression of IL2 and IFNG via its association with transcription factor RUNX1. Inhibits the differentiation of IL17 producing helper T-cells (Th17) by antagonizing RORC function, leading to down-regulation of IL17 expression, favoring Treg development. Inhibits the transcriptional activator activity of RORA. Can repress the expression of IL2 and IFNG via its association with transcription factor IKZF4.","T cells expressing the mutant of Foxp3 showed enhanced induction (e. g. CD25) and repression (e. g. IL2) of canonical Foxp3-responsive genes, exhibited an increased capacity to suppress conventional T cell proliferation in vitro, and were highly effective at ameliorating colitis in an in vivo model of inflammatory bowel disease.","Increase in protein stability, transcriptional activity and the ability to suppress the proliferation of conventional T-cells in vitro; when associated with A-19; A-88 and A-175. T cells expressing the mutant of Foxp3 showed enhanced induction (e. g. CD25) and repression (e. g. IL2) of canonical Foxp3-responsive genes, exhibited an increased capacity to suppress conventional T cell proliferation in vitro, and were highly effective at ameliorating colitis in an in vivo model of inflammatory bowel disease."
50,50,O75840-T137M,MDVLASYSIFQELQLVHDTGYFSALPSLEETWQQTCLELERYLQTEPRRISETFGEDLDCFLHASPPPCIEESFRRLDPLLLPVEAAICEKSSAVDILLSRDKLLSETCLSLQPASSSLDSYTAVNQAQLNAVTSLMPPSSPELSRHLVKTSQTLSAVDGTVTLKLVAKKAALSSVKVGGVATAAAAVTAAGAVKSGQSDSDQGGLGAEACPENKKRVHRCQFNGCRKVYTKSSHLKAHQRTHTGEKPYKCSWEGCEWRFARSDELTRHYRKHTGAKPFKCNHCDRCFSRSDHLALHMKRHI,"Found in two patients with developmental delay/intellectual disability, neuromuscular and psychiatric symptoms; unknown pathological significance.",,MDVLASYSIFQELQLVHDTGYFSALPSLEETWQQTCLELERYLQTEPRRISETFGEDLDCFLHASPPPCIEESFRRLDPLLLPVEAAICEKSSAVDILLSRDKLLSETCLSLQPASSSLDSYTAVNQAQLNAVTSLTPPSSPELSRHLVKTSQTLSAVDGTVTLKLVAKKAALSSVKVGGVATAAAAVTAAGAVKSGQSDSDQGGLGAEACPENKKRVHRCQFNGCRKVYTKSSHLKAHQRTHTGEKPYKCSWEGCEWRFARSDELTRHYRKHTGAKPFKCNHCDRCFSRSDHLALHMKRHI,Krueppel-like factor 7,"Transcriptional factor. Plays a critical role in neuronal morphogenesis and survival of sensory neurons. Represses the corneal epithelium differentiation. Acts also as a metabolic regulator, by modulating insulin sensitivity in pancreatic beta cells and skeletal muscle cells. Inhibits transcriptional inducers of adipogenesis and has a repressive role in the expression of several adipokines, including leptin.",,"Found in two patients with developmental delay/intellectual disability, neuromuscular and psychiatric symptoms; unknown pathological significance."
51,51,O76082-N91Q,MRDYDEVTAFLGEWGPFQRLIFFLLSASIIPNGFTGLSSVFLIATPEHRCRVPDAANLSSAWRNHTVPLRLRDGREVPHSCRRYRLATIAQFSALGLEPGRDVDLGQLEQESCLDGWEFSQDVYLSTIVTEWNLVCEDDWKAPLTISLFFVGVLLGSFISGQLSDRFGRKNVLFVTMGMQTGFSFLQIFSKNFEMFVVLFVLVGMGQISNYVAAFVLGTEILGKSVRIIFSTLGVCIFYAFGYMVLPLFAYFIRDWRMLLVALTMPGVLCVALWWFIPESPRWLISQGRFEEAEVIIRKAAKANGIVVPSTIFDPSELQDLSSKKQQSHNILDLLRTWNIRMVTIMSIMLWMTISVGYFGLSLDTPNLHGDIFVNCFLSAMVEVPAYVLAWLLLQYLPRRYSMATALFLGGSVLLFMQLVPPDLYYLATVLVMVGKFGVTAAFSMVYVYTAELYPTVVRNMGVGVSSTASRLGSILSPYFVYLGAYDRFLPYILMGSLTILTAILTLFLPESFGTPLPDTIDQMLRVKGMKHRKTPSHTRMLKDGQERPTILKSTAF,Reduces expression to 50%. No effect on carnitine transporter activity.,,MRDYDEVTAFLGEWGPFQRLIFFLLSASIIPNGFTGLSSVFLIATPEHRCRVPDAANLSSAWRNHTVPLRLRDGREVPHSCRRYRLATIANFSALGLEPGRDVDLGQLEQESCLDGWEFSQDVYLSTIVTEWNLVCEDDWKAPLTISLFFVGVLLGSFISGQLSDRFGRKNVLFVTMGMQTGFSFLQIFSKNFEMFVVLFVLVGMGQISNYVAAFVLGTEILGKSVRIIFSTLGVCIFYAFGYMVLPLFAYFIRDWRMLLVALTMPGVLCVALWWFIPESPRWLISQGRFEEAEVIIRKAAKANGIVVPSTIFDPSELQDLSSKKQQSHNILDLLRTWNIRMVTIMSIMLWMTISVGYFGLSLDTPNLHGDIFVNCFLSAMVEVPAYVLAWLLLQYLPRRYSMATALFLGGSVLLFMQLVPPDLYYLATVLVMVGKFGVTAAFSMVYVYTAELYPTVVRNMGVGVSSTASRLGSILSPYFVYLGAYDRFLPYILMGSLTILTAILTLFLPESFGTPLPDTIDQMLRVKGMKHRKTPSHTRMLKDGQERPTILKSTAF,Organic cation/carnitine transporter 2,"Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Relative uptake activity ratio of carnitine to TEA is 11.3. In intestinal epithelia, transports the quorum-sensing pentapeptide CSF (competence and sporulation factor) from Bacillus Subtilis wich induces cytoprotective heat shock proteins contributing to intestinal homeostasis. May also contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable).Retained in the ER, unable to perform carnitine uptake.","The insertion of 24 amino acids in the first extracellular loop of OCTN2 caused by the mutation leads to distinct biochemical and functional characteristics of OCTN2VT compared to OCTN2. OCTN2VT is retained in the endoplasmic reticulum with poor N-glycosylation, resulting in no carnitine uptake into the cells.","Reduces expression to 50%. No effect on carnitine transporter activity. The insertion of 24 amino acids in the first extracellular loop of OCTN2 caused by the mutation leads to distinct biochemical and functional characteristics of OCTN2VT compared to OCTN2. OCTN2VT is retained in the endoplasmic reticulum with poor N-glycosylation, resulting in no carnitine uptake into the cells."
52,52,Q9UK23-H84Q,MATSTGRWLLLRLALFGFLWEASGGLDSGASRDDDLLLPYPRARARLPRDCTRVRAGNREHESWPPPPATPGAGGLAVRTFVSQFRDRAVAGHLTRAVEPLRTFSVLEPGGPGGCAARRRATVEETARAADCRVAQNGGFFRMNSGECLGNVVSDERRVSSSGGLQNAQFGIRRDGTLVTGYLSEEEVLDTENPFVQLLSGVVWLIRNGSIYINESQATECDETQETGSFSKFVNVISARTAIGHDRKGQLVLFHADGQTEQRGINLWEMAEFLLKQDVVNAINLDGGGSATFVLNGTLASYPSDHCQDNMWRCPRQVSTVVCVHEPRCQPPDCHGHGTCVDGHCQCTGHFWRGPGCDELDCGPSNCSQHGLCTETGCRCDAGWTGSNCSEECPLGWHGPGCQRPCKCEHHCPCDPKTGNCSVSRVKQCLQPPEATLRAGELSFFTRTAWLALTLALAFLLLISTAANLSLLLSRAERNRRLHGDYAYHPLQEMNGEPLAAEKEQPGGAHNPFKD,Rare variant; found in individuals suffering from stuttering; unknown pathological significance.,,MATSTGRWLLLRLALFGFLWEASGGLDSGASRDDDLLLPYPRARARLPRDCTRVRAGNREHESWPPPPATPGAGGLAVRTFVSHFRDRAVAGHLTRAVEPLRTFSVLEPGGPGGCAARRRATVEETARAADCRVAQNGGFFRMNSGECLGNVVSDERRVSSSGGLQNAQFGIRRDGTLVTGYLSEEEVLDTENPFVQLLSGVVWLIRNGSIYINESQATECDETQETGSFSKFVNVISARTAIGHDRKGQLVLFHADGQTEQRGINLWEMAEFLLKQDVVNAINLDGGGSATFVLNGTLASYPSDHCQDNMWRCPRQVSTVVCVHEPRCQPPDCHGHGTCVDGHCQCTGHFWRGPGCDELDCGPSNCSQHGLCTETGCRCDAGWTGSNCSEECPLGWHGPGCQRPCKCEHHCPCDPKTGNCSVSRVKQCLQPPEATLRAGELSFFTRTAWLALTLALAFLLLISTAANLSLLLSRAERNRRLHGDYAYHPLQEMNGEPLAAEKEQPGGAHNPFKD,N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase,"Catalyzes the second step in the formation of the mannose 6-phosphate targeting signal on lysosomal enzyme oligosaccharides by removing GlcNAc residues from GlcNAc-alpha-P-mannose moieties, which are formed in the first step. Also hydrolyzes UDP-GlcNAc, a sugar donor for Golgi N-acetylglucosaminyltransferases.",,Rare variant; found in individuals suffering from stuttering; unknown pathological significance.
53,53,Q15233-W271A,MQSNKTFNLEKQNHTPRKHHQHHHQQQHHQQQQQQPPPPPIPANGQQASSQNEGLTIDLKNFRKPGEKTFTQRSRLFVGNLPPDITEEEMRKLFEKYGKAGEVFIHKDKGFGFIRLETRTLAEIAKVELDNMPLRGKQLRVRFACHSASLTVRNLPQYVSNELLEEAFSVFGQVERAVVIVDDRGRPSGKGIVEFSGKPAARKALDRCSEGSFLLTTFPRPVTVEPMDQLDDEEGLPEKLVIKNQQFHKEREQPPRFAQPGSFEYEYAMRAKALIEMEKQQQDQVDRNIKEAREKLEMEMEAARHEHQVMLMRQDLMRRQEELRRMEELHNQEVQKRKQLELRQEEERRRREEEMRRQQEEMMRRQQEGFKGTFPDAREQEIRMGQMAMGGAMGINNRGAMPPAPVPAGTPAPPGPATMMPDGTLGLTPPTTERFGQAATMEGIGAIGGTPPAFNRAAPGAEFAPNKRRRY,Abolishes interaction with PSPC1 and localization in nuclear paraspeckles; when associated with A-267.,,MQSNKTFNLEKQNHTPRKHHQHHHQQQHHQQQQQQPPPPPIPANGQQASSQNEGLTIDLKNFRKPGEKTFTQRSRLFVGNLPPDITEEEMRKLFEKYGKAGEVFIHKDKGFGFIRLETRTLAEIAKVELDNMPLRGKQLRVRFACHSASLTVRNLPQYVSNELLEEAFSVFGQVERAVVIVDDRGRPSGKGIVEFSGKPAARKALDRCSEGSFLLTTFPRPVTVEPMDQLDDEEGLPEKLVIKNQQFHKEREQPPRFAQPGSFEYEYAMRWKALIEMEKQQQDQVDRNIKEAREKLEMEMEAARHEHQVMLMRQDLMRRQEELRRMEELHNQEVQKRKQLELRQEEERRRREEEMRRQQEEMMRRQQEGFKGTFPDAREQEIRMGQMAMGGAMGINNRGAMPPAPVPAGTPAPPGPATMMPDGTLGLTPPTTERFGQAATMEGIGAIGGTPPAFNRAAPGAEFAPNKRRRY,Non-POU domain-containing octamer-binding protein,"DNA- and RNA binding protein, involved in several nuclear processes. Binds the conventional octamer sequence in double-stranded DNA. Also binds single-stranded DNA and RNA at a site independent of the duplex site. Involved in pre-mRNA splicing, probably as a heterodimer with SFPQ. Interacts with U5 snRNA, probably by binding to a purine-rich sequence located on the 3' side of U5 snRNA stem 1b. Together with PSPC1, required for the formation of nuclear paraspeckles. The SFPQ-NONO heteromer associated with MATR3 may play a role in nuclear retention of defective RNAs. The SFPQ-NONO heteromer may be involved in DNA unwinding by modulating the function of topoisomerase I/TOP1. The SFPQ-NONO heteromer may be involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination and may stabilize paired DNA ends. In vitro, the complex strongly stimulates DNA end joining, binds directly to the DNA substrates and cooperates with the Ku70/G22P1-Ku80/XRCC5 (Ku) dimer to establish a functional preligation complex. NONO is involved in transcriptional regulation. The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional activity. NONO binds to an enhancer element in long terminal repeats of endogenous intracisternal A particles (IAPs) and activates transcription. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer. Important for the functional organization of GABAergic synapses. Plays a specific and important role in the regulation of synaptic RNAs and GPHN/gephyrin scaffold structure, through the regulation of GABRA2 transcript. Plays a key role during neuronal differentiation by recruiting TET1 to genomic loci and thereby regulating 5-hydroxymethylcytosine levels. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway. Promotes activation of the cGAS-STING pathway in response to HIV-2 infection: acts by interacting with HIV-2 Capsid protein p24, thereby promoting detection of viral DNA by CGAS, leading to CGAS-mediated inmmune activation. In contrast, the weak interaction with HIV-1 Capsid protein p24 does not allow activation of the cGAS-STING pathway.","The mutation in the PSPC1 protein causes a change in its structure, which is important for the formation of paraspeckle subnuclear bodies.","Abolishes interaction with PSPC1 and localization in nuclear paraspeckles; when associated with A-267. The mutation in the PSPC1 protein causes a change in its structure, which is important for the formation of paraspeckle subnuclear bodies."
54,54,P83887-S131D,MPREIITLQLGQCGNQIGFEFWKQLCAEHGISPEGIVEEFATEGTDRKDVFFYQADDEHYIPRAVLLDLEPRVIHSILNSSYAKLYNPENIYLSEHGGGAGNNWASGFSQGEKIHEDIFDIIDREADGSDDLEGFVLCHSIAGGTGSGLGSYLLERLNDRYPKKLVQTYSVFPNQDEMSDVVVQPYNSLLTLKRLTQNADCVVVLDNTALNLIATDRLHIQNPSFSQINQLVSTIMSASTTTLRYPGYMNNDLIGLIASLIPTPRLHFLMTGYTPLTTDQSVASVRKTTVLDVMRRLLQPKNVMVSTGRDRQTNHCYIAILNIIQGEVDPTQVHKSLQRIRERKLANFIPWGPASIQVALSRKSPYLPSAHRVSGLMMANHTSISSLFERTCRQFDKLRKREAFMEQFRKEDIFKDNFDEMDTSREIVQQLIDEYHAATRPDYISWGTQEQ,Phosphomimetic mutant that lead to increased centrosome number.,,MPREIITLQLGQCGNQIGFEFWKQLCAEHGISPEGIVEEFATEGTDRKDVFFYQADDEHYIPRAVLLDLEPRVIHSILNSSYAKLYNPENIYLSEHGGGAGNNWASGFSQGEKIHEDIFDIIDREADGSDSLEGFVLCHSIAGGTGSGLGSYLLERLNDRYPKKLVQTYSVFPNQDEMSDVVVQPYNSLLTLKRLTQNADCVVVLDNTALNLIATDRLHIQNPSFSQINQLVSTIMSASTTTLRYPGYMNNDLIGLIASLIPTPRLHFLMTGYTPLTTDQSVASVRKTTVLDVMRRLLQPKNVMVSTGRDRQTNHCYIAILNIIQGEVDPTQVHKSLQRIRERKLANFIPWGPASIQVALSRKSPYLPSAHRVSGLMMANHTSISSLFERTCRQFDKLRKREAFMEQFRKEDIFKDNFDEMDTSREIVQQLIDEYHAATRPDYISWGTQEQ,Tubulin gamma-1 chain,"Tubulin is the major constituent of microtubules. The gamma chain is found at microtubule organizing centers (MTOC) such as the spindle poles or the centrosome. Pericentriolar matrix component that regulates alpha/beta chain minus-end nucleation, centrosome duplication and spindle formation.",Expression of a phosphomimetic S 131-to-D gamma-tubulin mutant increased centrosome numbers.,Phosphomimetic mutant that lead to increased centrosome number. Expression of a phosphomimetic S 131-to-D gamma-tubulin mutant increased centrosome numbers.
55,55,Q14190-P372A,MKEKSKNAAKTRREKENGEFYELAKLLPLPSAITSQLDKASIIRLTTSYLKMRAVFPEGLGDAWGQPSRAGPLDGVAKELGSHLLQTLDGFVFVVASDGKIMYISETASVHLGLSQVELTGNSIYEYIHPSDHDEMTAVLTAHQPLHHHLLQEYEIERSFFLRMKCVLAKRNAGLTCSGYKVIHCSGYLKIRQYMLDMSLYDSCYQIVGLVAVGQSLPPSAITEIKLYSNMFMFRASLDLKLIFLDSRVTEVTGYEPQDLIEKTLYHHVHGCDVFHLRYAHHLLLVKGQVTTKYYRLLSKRGGWVWVQSYATVVHNSRSSRPHCIVSVNYVLTEIEYKELQLSLEQVSTAKSQDSWRTALSTSQETRKLVKAKNTKMKTKLRTNPYPPQQYSSFQMDKLECGQLGNWRASPPASAAAPPELQPHSESSDLLYTPSYSLPFSYHYGHFPLDSHVFSSKKPMLPAKFGQPQGSPCEVARFFLSTLPASGECQWHYANPLVPSSSSPAKNPPEPPANTARHSLVPSYEAPAAAVRRFGEDTAPPSFPSCGHYREEPALGPAKAARQAARDGARLALARAAPECCAPPTPEAPGAPAQLPFVLLNYHRVLARRGPLGGAAPAASGLACAPGGPEAATGALRLRHPSPAATSPPGAPLPHYLGASVIITNGR,No effect on nuclear translocation.,,MKEKSKNAAKTRREKENGEFYELAKLLPLPSAITSQLDKASIIRLTTSYLKMRAVFPEGLGDAWGQPSRAGPLDGVAKELGSHLLQTLDGFVFVVASDGKIMYISETASVHLGLSQVELTGNSIYEYIHPSDHDEMTAVLTAHQPLHHHLLQEYEIERSFFLRMKCVLAKRNAGLTCSGYKVIHCSGYLKIRQYMLDMSLYDSCYQIVGLVAVGQSLPPSAITEIKLYSNMFMFRASLDLKLIFLDSRVTEVTGYEPQDLIEKTLYHHVHGCDVFHLRYAHHLLLVKGQVTTKYYRLLSKRGGWVWVQSYATVVHNSRSSRPHCIVSVNYVLTEIEYKELQLSLEQVSTAKSQDSWRTALSTSQETRKLVKPKNTKMKTKLRTNPYPPQQYSSFQMDKLECGQLGNWRASPPASAAAPPELQPHSESSDLLYTPSYSLPFSYHYGHFPLDSHVFSSKKPMLPAKFGQPQGSPCEVARFFLSTLPASGECQWHYANPLVPSSSSPAKNPPEPPANTARHSLVPSYEAPAAAVRRFGEDTAPPSFPSCGHYREEPALGPAKAARQAARDGARLALARAAPECCAPPTPEAPGAPAQLPFVLLNYHRVLARRGPLGGAAPAASGLACAPGGPEAATGALRLRHPSPAATSPPGAPLPHYLGASVIITNGR,Single-minded homolog 2,Transcription factor that may be a master gene of CNS development in cooperation with Arnt. It may have pleiotropic effects in the tissues expressed during development.,,No effect on nuclear translocation.
56,56,P62736-R212Q,MCEEEDSTALVCDNGSGLCKAGFAGDDAPRAVFPSIVGRPRHQGVMVGMGQKDSYVGDEAQSKRGILTLKYPIEHGIITNWDDMEKIWHHSFYNELRVAPEEHPTLLTEAPLNPKANREKMTQIMFETFNVPAMYVAIQAVLSLYASGRTTGIVLDSGDGVTHNVPIYEGYALPHAIMRLDLAGRDLTDYLMKILTERGYSFVTTAEREIVQDIKEKLCYVALDFENEMATAASSSSLEKSYELPDGQVITIGNERFRCPETLFQPSFIGMESAGIHETTYNSIMKCDIDIRKDLYANNVLSGGTTMYPGIADRMQKEITALAPSTMKIKIIAPPERKYSVWIGGSILASLSTFQQMWISKQEYDEAGPSIVHRKCF,In AAT6.,,MCEEEDSTALVCDNGSGLCKAGFAGDDAPRAVFPSIVGRPRHQGVMVGMGQKDSYVGDEAQSKRGILTLKYPIEHGIITNWDDMEKIWHHSFYNELRVAPEEHPTLLTEAPLNPKANREKMTQIMFETFNVPAMYVAIQAVLSLYASGRTTGIVLDSGDGVTHNVPIYEGYALPHAIMRLDLAGRDLTDYLMKILTERGYSFVTTAEREIVRDIKEKLCYVALDFENEMATAASSSSLEKSYELPDGQVITIGNERFRCPETLFQPSFIGMESAGIHETTYNSIMKCDIDIRKDLYANNVLSGGTTMYPGIADRMQKEITALAPSTMKIKIIAPPERKYSVWIGGSILASLSTFQQMWISKQEYDEAGPSIVHRKCF,"Actin, aortic smooth muscle",Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.,"Heterozygous ACTA2 mutations cause familial thoracic aortic aneurysms and dissections (TAAD), premature onset of coronary artery disease (CAD), premature ischemic strokes (including Moyamoya disease [MMD]), as well as previously defined TAAD. The mutation in the ACTA2 gene is considered to be causative for familial thoracic AAD (TAAD). Some of the clinical features of patients with this mutation were the same as previously reported, whereas others were different.","In AAT6. Heterozygous ACTA2 mutations cause familial thoracic aortic aneurysms and dissections (TAAD), premature onset of coronary artery disease (CAD), premature ischemic strokes (including Moyamoya disease [MMD]), as well as previously defined TAAD. The mutation in the ACTA2 gene is considered to be causative for familial thoracic AAD (TAAD). Some of the clinical features of patients with this mutation were the same as previously reported, whereas others were different."
57,57,P23942-N244K,MALLKVKFDQKKRVKLAQGLWLMNWFSVLAGIIIFSLGLFLKIELRKRSDVMNNSESHFVPNSLIGMGVLSCVFNSLAGKICYDALDPAKYARWKPWLKPYLAICVLFNIILFLVALCCFLLRGSLENTLGQGLKNGMKYYRDTDTPGRCFMKKTIDMLQIEFKCCGNNGFRDWFEIQWISNRYLDFSSKEVKDRIKSNVDGRYLVDGVPFSCCNPSSPRPCIQYQITNNSAHYSYDHQTEELKLWVRGCRAALLSYYSSLMNSMGVVTLLIWLFEVTITIGLRYLQTSLDGVSNPEESESESQGWLLERSVPETWKAFLESVKKLGKGNQVEAEGADAGQAPEAG,In RP7; with bulls-eye maculopathy.,,MALLKVKFDQKKRVKLAQGLWLMNWFSVLAGIIIFSLGLFLKIELRKRSDVMNNSESHFVPNSLIGMGVLSCVFNSLAGKICYDALDPAKYARWKPWLKPYLAICVLFNIILFLVALCCFLLRGSLENTLGQGLKNGMKYYRDTDTPGRCFMKKTIDMLQIEFKCCGNNGFRDWFEIQWISNRYLDFSSKEVKDRIKSNVDGRYLVDGVPFSCCNPSSPRPCIQYQITNNSAHYSYDHQTEELNLWVRGCRAALLSYYSSLMNSMGVVTLLIWLFEVTITIGLRYLQTSLDGVSNPEESESESQGWLLERSVPETWKAFLESVKKLGKGNQVEAEGADAGQAPEAG,Peripherin-2,"Essential for retina photoreceptor outer segment disk morphogenesis, may also play a role with ROM1 in the maintenance of outer segment disk structure. Required for the maintenance of retinal outer nuclear layer thickness. Required for the correct development and organization of the photoreceptor inner segment.",,In RP7; with bulls-eye maculopathy.
58,58,P09211-D99A,MPPYTVVYFPVRGRCAALRMLLADQGQSWKEEVVTVETWQEGSLKASCLYGQLPKFQDGDLTLYQSNTILRHLGRTLGLYGKDQQEAALVDMVNDGVEALRCKYISLIYTNYEAGKDDYVKALPGQLKPFETLLSQNQGGKTFIVGDQISFADYNLLDLLLIHEVLAPGCLDAFPLLSAYVGRLSARPKLKAFLASPEYVNLPINGNGKQ,Reduces affinity for glutathione. Slightly reduced catalytic activity.,,MPPYTVVYFPVRGRCAALRMLLADQGQSWKEEVVTVETWQEGSLKASCLYGQLPKFQDGDLTLYQSNTILRHLGRTLGLYGKDQQEAALVDMVNDGVEDLRCKYISLIYTNYEAGKDDYVKALPGQLKPFETLLSQNQGGKTFIVGDQISFADYNLLDLLLIHEVLAPGCLDAFPLLSAYVGRLSARPKLKAFLASPEYVNLPINGNGKQ,Glutathione S-transferase P,Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2). Participates in the formation of novel hepoxilin regioisomers. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration.,,Reduces affinity for glutathione. Slightly reduced catalytic activity.
59,59,P35290-S67Q,MSGQRVDVKVVMLGKEYVGKTSLVERYVHDRFLVGPYQNTIGAAFVAKVMCVGDRTVTLGIWDTAGQERYEAMSRIYYRGAKAAIVCYDLTDSSSFERAKFWVKELRSLEEGCQIYLCGTKSDLLEEDRRRRRVDFHDVQDYADNIKAQLFETSSKTGQSVDELFQKVAEDYVSVAAFQVMTEDKGVDLSQKANPYFYSCCHH,"Increase in GTPase activity. No effect neither on prenylation, nor on subcellular location.",,MSGQRVDVKVVMLGKEYVGKTSLVERYVHDRFLVGPYQNTIGAAFVAKVMCVGDRTVTLGIWDTAGSERYEAMSRIYYRGAKAAIVCYDLTDSSSFERAKFWVKELRSLEEGCQIYLCGTKSDLLEEDRRRRRVDFHDVQDYADNIKAQLFETSSKTGQSVDELFQKVAEDYVSVAAFQVMTEDKGVDLSQKANPYFYSCCHH,Ras-related protein Rab-24,May be involved in autophagy-related processes.,,"Increase in GTPase activity. No effect neither on prenylation, nor on subcellular location."
60,60,P53264-W170R,MFKSTLNSIIRRPLKGFQLLRGADSSNTRPQSPRASARDVTEKQILRTPSAPTAIPLREIIYRVPSLFPRPLEDSVKDFRDFIKNEDAFQTELLKTLPFYPTPSESKTARLIRTVVDDEGNYINEFCIRPRKTSVPEADLKHLVFIHGYGAGLGFFIKNFEDIPLLDNERCIHAIDLPGYGFSSRPKFPFEYPRDNIHSVQDWFHERIHTWFSKRNLLNRPEKNIVMAHSLGSYLMALYLQKYKESPSFKKLILCSPAGVSYRDFNNTASEVEKWKPPPWWYVKLWDRNISPFTLVRNFRQLGSKITSGWSYRRFKHILNGDPEQSKRFEALHRYAYAIFNKRGSGEYLLSFALKCGGEPRLSLEQQLFDGKKSDILKNSNCDWLWLYGDDDWMDVNGGLRVSRFLKEKLKQKSNVIIVPHSGHHLYLDNYKFFNNILTKEMQKI,Loss of function.,,MFKSTLNSIIRRPLKGFQLLRGADSSNTRPQSPRASARDVTEKQILRTPSAPTAIPLREIIYRVPSLFPRPLEDSVKDFRDFIKNEDAFQTELLKTLPFYPTPSESKTARLIRTVVDDEGNYINEFCIRPRKTSVPEADLKHLVFIHGYGAGLGFFIKNFEDIPLLDNEWCIHAIDLPGYGFSSRPKFPFEYPRDNIHSVQDWFHERIHTWFSKRNLLNRPEKNIVMAHSLGSYLMALYLQKYKESPSFKKLILCSPAGVSYRDFNNTASEVEKWKPPPWWYVKLWDRNISPFTLVRNFRQLGSKITSGWSYRRFKHILNGDPEQSKRFEALHRYAYAIFNKRGSGEYLLSFALKCGGEPRLSLEQQLFDGKKSDILKNSNCDWLWLYGDDDWMDVNGGLRVSRFLKEKLKQKSNVIIVPHSGHHLYLDNYKFFNNILTKEMQKI,"Cardiolipin-specific deacylase 1, mitochondrial","Mitochondrial cardiolipin-specific phospholipase which deacylates de novo synthesized cardiolipin (CL). Part of the remodeling process of cardiolipin, which involves deacylation-reacylation of premature cardiolipin. Has a strong substrate preference for palmitic acid residues and generates monolysocardiolipin (MLCL) for TAZ1-dependent reacylation with unsaturated fatty acids. The hydrolytic selectivity of the enzyme toward C16-CL substrates contributes to the preservation of C18:1-containing CL species. Has high specificity towards peroxidized cardiolipids CL(OX). Required to mitigate oxidative stress by removing CL(OX).","The mutation in tafazzin leads to growth and respiration defects. In humans, this mutation results in the life-threatening disorder Barth syndrome. Tafazzin deficiency causes a decrease in the CL/MLCL ratio and decreased unsaturated CL species.","Loss of function. The mutation in tafazzin leads to growth and respiration defects. In humans, this mutation results in the life-threatening disorder Barth syndrome. Tafazzin deficiency causes a decrease in the CL/MLCL ratio and decreased unsaturated CL species."
61,61,Q96CV9-E50K,MSHQPLSCLTEKEDSPSESTGNGPPHLAHPNLDTFTPEELLQQMKELLTKNHQLKEAMKLNNQAMKGRFEELSAWTEKQKEERQFFEIQSKEAKERLMALSHENEKLKEELGKLKGKSERSSEDPTDDSRLPRAEAEQEKDQLRTQVVRLQAEKADLLGIVSELQLKLNSSGSSEDSFVEIRMAEGEAEGSVKEIKHSPGPTRTVSTGTALSKYRSRSADGAKNYFEHEELTVSQLLLCLREGNQKVERLEVALKEAKERVSDFEKKTSNRSEIETQTEGSTEKENDEEKGPETVGSEVEALNLQVTSLFKELQEAHTKLSEAELMKKRLQEKCQALERKNSAIPSELNEKQELVYTNKKLELQVESMLSEIKMEQAKTEDEKSKLTVLQMTHNKLLQEHNNALKTIEELTRKESEKVDRAVLKELSEKLELAEKALASKQLQMDEMKQTIAKQEEDLETMTILRAQMEVYCSDFHAERAAREKIHEEKEQLALQLAVLLKENDAFEDGGRQSLMEMQSRHGARTSDSDQQAYLVQRGAEDRDWRQQRNIPIHSCPKCGEVLPDIDTLQIHVMDCII,"No effect on retinal ganglion cell death, decreased interaction with TFRC, loss of localization to recycling endosomes, loss of ubiquitin-binding; when associated with N-474.",,MSHQPLSCLTEKEDSPSESTGNGPPHLAHPNLDTFTPEELLQQMKELLTENHQLKEAMKLNNQAMKGRFEELSAWTEKQKEERQFFEIQSKEAKERLMALSHENEKLKEELGKLKGKSERSSEDPTDDSRLPRAEAEQEKDQLRTQVVRLQAEKADLLGIVSELQLKLNSSGSSEDSFVEIRMAEGEAEGSVKEIKHSPGPTRTVSTGTALSKYRSRSADGAKNYFEHEELTVSQLLLCLREGNQKVERLEVALKEAKERVSDFEKKTSNRSEIETQTEGSTEKENDEEKGPETVGSEVEALNLQVTSLFKELQEAHTKLSEAELMKKRLQEKCQALERKNSAIPSELNEKQELVYTNKKLELQVESMLSEIKMEQAKTEDEKSKLTVLQMTHNKLLQEHNNALKTIEELTRKESEKVDRAVLKELSEKLELAEKALASKQLQMDEMKQTIAKQEEDLETMTILRAQMEVYCSDFHAERAAREKIHEEKEQLALQLAVLLKENDAFEDGGRQSLMEMQSRHGARTSDSDQQAYLVQRGAEDRDWRQQRNIPIHSCPKCGEVLPDIDTLQIHVMDCII,Optineurin,"Plays an important role in the maintenance of the Golgi complex, in membrane trafficking, in exocytosis, through its interaction with myosin VI and Rab8. Links myosin VI to the Golgi complex and plays an important role in Golgi ribbon formation. Plays a role in the activation of innate immune response during viral infection. Mechanistically, recruits TBK1 at the Golgi apparatus, promoting its trans-phosphorylation after RLR or TLR3 stimulation. In turn, activated TBK1 phosphorylates its downstream partner IRF3 to produce IFN-beta/IFNB1. Plays a neuroprotective role in the eye and optic nerve. May act by regulating membrane trafficking and cellular morphogenesis via a complex that contains Rab8 and hungtingtin (HD). Mediates the interaction of Rab8 with the probable GTPase-activating protein TBC1D17 during Rab8-mediated endocytic trafficking, such as that of transferrin receptor (TFRC/TfR); regulates Rab8 recruitment to tubules emanating from the endocytic recycling compartment. Autophagy receptor that interacts directly with both the cargo to become degraded and an autophagy modifier of the MAP1 LC3 family; targets ubiquitin-coated bacteria (xenophagy), such as cytoplasmic Salmonella enterica, and appears to function in the same pathway as SQSTM1 and CALCOCO2/NDP52.(Microbial infection) May constitute a cellular target for various viruses, such as adenovirus E3 14.7 or Bluetongue virus, to inhibit innate immune response. During RNA virus infection, such as that of Sendai virus, negatively regulates the induction of IFNB1.",,"No effect on retinal ganglion cell death, decreased interaction with TFRC, loss of localization to recycling endosomes, loss of ubiquitin-binding; when associated with N-474."
62,62,Q9X519-R261L,MSKKPVALIILDGFALRDETYGNAVAQANKPNFDRYWNEYPHTTLKACGEAVGLPEGQMGNSEVGHLNIGAGRIVYQSLTRINIAIREGEFDRNETFLAAMNHVKQHGTSLHLFGLLSDGGVHSHIHHLYALLRLAAKEGVKRVYIHGFLDGRDVGPQTAPQYIKELQEKIKEYGVGEIATLSGRYYSMDRDKRWDRVEKAYRAMVYGEGPTYRDPLECIEDSYKHGIYDEFVLPSVIVREDGRPVATIQDNDAIIFYNFLPDRAIQISNTFTNEDFREFDRGPKHPKHLFFVCLTHFSETVKGYVAFKPTNLDNTIGEVLSQHGLRQLRIAETEKYPHVTFFMSGGREEKFPGEDRILINSPKVPTYDLKPEMSAYEVTDALLKEIEADKYDAIILNYANPDMVGHSGKLEPTIKAVEAVDECLGKVVDAILAKGGIAIITADHGNADEVLTPDGKPQTAHTTNPVPVIVTKKGIKLRDGGILGDLAPTMLDLLGLPQPKEMTGKSLIVK,Loss of mutase activity.,,MSKKPVALIILDGFALRDETYGNAVAQANKPNFDRYWNEYPHTTLKACGEAVGLPEGQMGNSEVGHLNIGAGRIVYQSLTRINIAIREGEFDRNETFLAAMNHVKQHGTSLHLFGLLSDGGVHSHIHHLYALLRLAAKEGVKRVYIHGFLDGRDVGPQTAPQYIKELQEKIKEYGVGEIATLSGRYYSMDRDKRWDRVEKAYRAMVYGEGPTYRDPLECIEDSYKHGIYDEFVLPSVIVREDGRPVATIQDNDAIIFYNFRPDRAIQISNTFTNEDFREFDRGPKHPKHLFFVCLTHFSETVKGYVAFKPTNLDNTIGEVLSQHGLRQLRIAETEKYPHVTFFMSGGREEKFPGEDRILINSPKVPTYDLKPEMSAYEVTDALLKEIEADKYDAIILNYANPDMVGHSGKLEPTIKAVEAVDECLGKVVDAILAKGGIAIITADHGNADEVLTPDGKPQTAHTTNPVPVIVTKKGIKLRDGGILGDLAPTMLDLLGLPQPKEMTGKSLIVK,"2,3-bisphosphoglycerate-independent phosphoglycerate mutase",Essential for rapid growth and for sporulation. Catalyzes the interconversion of 2-phosphoglycerate (2-PGA) and 3-phosphoglycerate (3-PGA).,,Loss of mutase activity.
63,63,Q8WVQ1-D169N,MPVQLSEHPEWNESMHSLRISVGGLPVLASMTKAADPRFRPRWKVILTFFVGAAILWLLCSHRPAPGRPPTHNAHNWRLGQAPANWYNDTYPLSPPQRTPAGIRYRIAVIADLDTESRAQEENTWFSYLKKGYLTLSDSGDKVAVEWDKDHGVLESHLAEKGRGMELSNLIVFNGKLYSVDDRTGVVYQIEGSKAVPWVILSDGDGTVEKGFKAEWLAVKDERLYVGGLGKEWTTTTGDVVNENPEWVKVVGYKGSVDHENWVSNYNALRAAAGIQPPGYLIHESACWSDTLQRWFFLPRRASQERYSEKDDERKGANLLLSASPDFGDIAVSHVGAVVPTHGFSSFKFIPNTDDQIIVALKSEEDSGRVASYIMAFTLDGRFLLPETKIGSVKYEGIEFI,Reduces activity by 96%.,,MPVQLSEHPEWNESMHSLRISVGGLPVLASMTKAADPRFRPRWKVILTFFVGAAILWLLCSHRPAPGRPPTHNAHNWRLGQAPANWYNDTYPLSPPQRTPAGIRYRIAVIADLDTESRAQEENTWFSYLKKGYLTLSDSGDKVAVEWDKDHGVLESHLAEKGRGMELSDLIVFNGKLYSVDDRTGVVYQIEGSKAVPWVILSDGDGTVEKGFKAEWLAVKDERLYVGGLGKEWTTTTGDVVNENPEWVKVVGYKGSVDHENWVSNYNALRAAAGIQPPGYLIHESACWSDTLQRWFFLPRRASQERYSEKDDERKGANLLLSASPDFGDIAVSHVGAVVPTHGFSSFKFIPNTDDQIIVALKSEEDSGRVASYIMAFTLDGRFLLPETKIGSVKYEGIEFI,Soluble calcium-activated nucleotidase 1,Calcium-dependent nucleotidase with a preference for UDP. The order of activity with different substrates is UDP > GDP > UTP > GTP. Has very low activity towards ADP and even lower activity towards ATP. Does not hydrolyze AMP and GMP. Involved in proteoglycan synthesis.,,Reduces activity by 96%.
64,64,Q13153-D393A,MSNNGLDIQDKPPAPPMRNTSTMIGAGSKDAGTLNHGSKPLPPNPEEKKKKDRFYRSILPGDKTNKKKEKERPEISLPSDFEHTIHVGFDAVTGEFTGMPEQWARLLQTSNITKSEQKKNPQAVLDVLEFYNSKKTSNSQKYMSFTDKSAEDYNSSNALNVKAVSETPAVPPVSEDEDDDDDDATPPPVIAPRPEHTKSVYTRSVIEPLPVTPTRDVATSPISPTENNTTPPDALTRNTEKQKKKPKMSDEEILEKLRSIVSVGDPKKKYTRFEKIGQGASGTVYTAMDVATGQEVAIKQMNLQQQPKKELIINEILVMRENKNPNIVNYLDSYLVGDELWVVMEYLAGGSLTDVVTETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSANILLGMDGSVKLTDFGFCAQITPEQSKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMIEGEPPYLNENPLRALYLIATNGTPELQNPEKLSAIFRDFLNRCLEMDVEKRGSAKELLQHQFLKIAKPLSSLTPLIAAAKEATKNNH,Abolishes autophosphorylation at Thr-423.,,MSNNGLDIQDKPPAPPMRNTSTMIGAGSKDAGTLNHGSKPLPPNPEEKKKKDRFYRSILPGDKTNKKKEKERPEISLPSDFEHTIHVGFDAVTGEFTGMPEQWARLLQTSNITKSEQKKNPQAVLDVLEFYNSKKTSNSQKYMSFTDKSAEDYNSSNALNVKAVSETPAVPPVSEDEDDDDDDATPPPVIAPRPEHTKSVYTRSVIEPLPVTPTRDVATSPISPTENNTTPPDALTRNTEKQKKKPKMSDEEILEKLRSIVSVGDPKKKYTRFEKIGQGASGTVYTAMDVATGQEVAIKQMNLQQQPKKELIINEILVMRENKNPNIVNYLDSYLVGDELWVVMEYLAGGSLTDVVTETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQSKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMIEGEPPYLNENPLRALYLIATNGTPELQNPEKLSAIFRDFLNRCLEMDVEKRGSAKELLQHQFLKIAKPLSSLTPLIAAAKEATKNNH,Serine/threonine-protein kinase PAK 1,"Protein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes. Can directly phosphorylate BAD and protects cells against apoptosis. Activated by interaction with CDC42 and RAC1. Functions as GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway. Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases. Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes. Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton. Plays a role in the regulation of insulin secretion in response to elevated glucose levels. Part of a ternary complex that contains PAK1, DVL1 and MUSK that is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ). Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2. Phosphorylates MYL9/MLC2. Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2. Phosphorylates SNAI1 at 'Ser-246' promoting its transcriptional repressor activity by increasing its accumulation in the nucleus. In podocytes, promotes NR3C2 nuclear localization. Required for atypical chemokine receptor ACKR2-induced phosphorylation of LIMK1 and cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3, maybe through CFL1 phosphorylation and inactivation. Plays a role in RUFY3-mediated facilitating gastric cancer cells migration and invasion. In response to DNA damage, phosphorylates MORC2 which activates its ATPase activity and facilitates chromatin remodeling. In neurons, plays a crucial role in regulating GABA(A) receptor synaptic stability and hence GABAergic inhibitory synaptic transmission through its role in F-actin stabilization. In hippocampal neurons, necessary for the formation of dendritic spines and excitatory synapses; this function is dependent on kinase activity and may be exerted by the regulation of actomyosin contractility through the phosphorylation of myosin II regulatory light chain (MLC). Along with GIT1, positively regulates microtubule nucleation during interphase. Phosphorylates FXR1, promoting its localization to stress granules and activity.",This mutation may lead to functional changes in the PAK1 protein.,Abolishes autophosphorylation at Thr-423. This mutation may lead to functional changes in the PAK1 protein.
65,65,O75874-R132S,MSKKISGGSVVEMQGDEMTRIIWELIKEKLIFPYVELDLHSYDLGIENRDATNDQVTKDAAEAIKKHNVGVKCATITPDEKRVEEFKLKQMWKSPNGTIRNILGGTVFREAIICKNIPRLVSGWVKPIIIGSHAYGDQYRATDFVVPGPGKVEITYTPSDGTQKVTYLVHNFEEGGGVAMGMYNQDKSIEDFAHSSFQMALSKGWPLYLSTKNTILKKYDGRFKDIFQEIYDKQYKSQFEAQKIWYEHRLIDDMVAQAMKSEGGFIWACKNYDGDVQSDSVAQGYGSLGMMTSVLVCPDGKTVEAEAAHGTVTRHYRMYQKGQETSTNPIASIFAWTRGLAHRAKLDNNKELAFFANALEEVSIETIEAGFMTKDLAACIKGLPNVQRSDYLNTFEFMDKLGENLKIKLAQAKL,In a glioma sample; glioblastoma multiforme; somatic mutation; abolishes magnesium binding and alters enzyme activity so that isocitrate is no longer converted to alpha-ketoglutarate but instead alpha-ketoglutarate is converted to R(-)-2-hydroxyglutarate.,,MSKKISGGSVVEMQGDEMTRIIWELIKEKLIFPYVELDLHSYDLGIENRDATNDQVTKDAAEAIKKHNVGVKCATITPDEKRVEEFKLKQMWKSPNGTIRNILGGTVFREAIICKNIPRLVSGWVKPIIIGRHAYGDQYRATDFVVPGPGKVEITYTPSDGTQKVTYLVHNFEEGGGVAMGMYNQDKSIEDFAHSSFQMALSKGWPLYLSTKNTILKKYDGRFKDIFQEIYDKQYKSQFEAQKIWYEHRLIDDMVAQAMKSEGGFIWACKNYDGDVQSDSVAQGYGSLGMMTSVLVCPDGKTVEAEAAHGTVTRHYRMYQKGQETSTNPIASIFAWTRGLAHRAKLDNNKELAFFANALEEVSIETIEAGFMTKDLAACIKGLPNVQRSDYLNTFEFMDKLGENLKIKLAQAKL,Isocitrate dehydrogenase [NADP] cytoplasmic,"Catalyzes the NADP(+)-dependent oxidative decarboxylation of isocitrate (D-threo-isocitrate) to 2-ketoglutarate (2-oxoglutarate), which is required by other enzymes such as the phytanoyl-CoA dioxygenase. Plays a critical role in the generation of NADPH, an important cofactor in many biosynthesis pathways. May act as a corneal epithelial crystallin and may be involved in maintaining corneal epithelial transparency.",,In a glioma sample; glioblastoma multiforme; somatic mutation; abolishes magnesium binding and alters enzyme activity so that isocitrate is no longer converted to alpha-ketoglutarate but instead alpha-ketoglutarate is converted to R(-)-2-hydroxyglutarate.
66,66,P27623-W74A,MKKVITYGTFDLLHWGHIKLLERAKQLGDYLVVAISTDEFNLQKQKKAYHSYEHRKLILETIRYVDEVIPEKNAEQKKQDIIDHNIDVFVMGDDWEGKFDFLKDQCEVVYLPRTEGISTTKIKEEIAGL,"50% of wild-type activity, but 9-fold decrease in substrate affinity.",,MKKVITYGTFDLLHWGHIKLLERAKQLGDYLVVAISTDEFNLQKQKKAYHSYEHRKLILETIRYVDEVIPEKNWEQKKQDIIDHNIDVFVMGDDWEGKFDFLKDQCEVVYLPRTEGISTTKIKEEIAGL,Glycerol-3-phosphate cytidylyltransferase,"Catalyzes the transfer of the cytidylyl group of CTP to sn-glycerol 3-phosphate so the activated glycerol 3-phosphate can be used for teichoic acid synthesis, via incorporation into both the linkage unit and the teichoic acid polymer by TagB and TagF.",Residue W74 is important for activity,"50% of wild-type activity, but 9-fold decrease in substrate affinity. Residue W74 is important for activity"
67,67,Q8TAP8-S47A,MMMGCGESELKSADGEEAAAVPGPPPEPQVPQLRAPVPEPGLDLSLAPRPDSPQPRHGSPGRRKGRAERRGAARQRRQVRFRLTPPSPVRSEPQPAVPQELEMPVLKSSLALGLELRAAAGSHFDAAKAVEEQLRKSFQIRCGLEESVSEGLNVPRSKRLFRDLVSLQVPEEQVLNAALREKLALLPPQARAPHPKEPPGPGPDMTILCDPETLFYESPHLTLDGLPPLRLQLRPRPSEDTFLMHRTLRRWEA,Does not affect centrosome localization; when associated with A-45 and A-52. Does not affect interaction with RTTN; when associated with A-45 and A-52.,,MMMGCGESELKSADGEEAAAVPGPPPEPQVPQLRAPVPEPGLDLSLSPRPDSPQPRHGSPGRRKGRAERRGAARQRRQVRFRLTPPSPVRSEPQPAVPQELEMPVLKSSLALGLELRAAAGSHFDAAKAVEEQLRKSFQIRCGLEESVSEGLNVPRSKRLFRDLVSLQVPEEQVLNAALREKLALLPPQARAPHPKEPPGPGPDMTILCDPETLFYESPHLTLDGLPPLRLQLRPRPSEDTFLMHRTLRRWEA,Protein phosphatase 1 regulatory subunit 35,"During centriole duplication, plays a role in the centriole elongation by promoting the recruitment of the microtubule-binding elongation machinery through its interaction with RTTN, leading to the centriole to centrosome conversion. In addition, may play a role in the primary cilia assembly.",Loss of PPP1R35 function results in decreased centrosome number and shortened centrioles that lack centriolar distal and microtubule wall associated proteins required for centriole elongation.,Does not affect centrosome localization; when associated with A-45 and A-52. Does not affect interaction with RTTN; when associated with A-45 and A-52. Loss of PPP1R35 function results in decreased centrosome number and shortened centrioles that lack centriolar distal and microtubule wall associated proteins required for centriole elongation.
68,68,Q8RZ35-S44D,MASEMSKNVKVTDDQEVTSQERDQSGGTKVGGEEEIAPLARQSDILSLTLEELQNSLCEPGRNFGSMNMDEFVANIWNAEEFQATTGGCKGAMEEAKVVDSGSGSGDAGGSGLCRQGSFSLPLPLCQKTVEEVWTEINQAPAHTSAPASALQPHAGSGGVAANDRQVTLGEMTLEDFLVKAGVVRGSFTGQAAMGSGMVNGPVNPMQQGQGGPMMFPVGPVNAMYPVMGDGMGYPGGYNGMAIVPPPPPAQGAMVVVSPGSSDGMSAMTHADMMNCIGNGMMIENGTRKRPHREDGCAEKTVERRQRRMIKNRESAARSRARKQAYTVELEAELNYLKQENARLKEAEKTVLLTKKQMLVEKMMEQSKEKMNANRGGSQLRRSGSCMW,Reduces transactivation activity 4-fold; when associated with D-43 and D-47.,,MASEMSKNVKVTDDQEVTSQERDQSGGTKVGGEEEIAPLARQSSILSLTLEELQNSLCEPGRNFGSMNMDEFVANIWNAEEFQATTGGCKGAMEEAKVVDSGSGSGDAGGSGLCRQGSFSLPLPLCQKTVEEVWTEINQAPAHTSAPASALQPHAGSGGVAANDRQVTLGEMTLEDFLVKAGVVRGSFTGQAAMGSGMVNGPVNPMQQGQGGPMMFPVGPVNAMYPVMGDGMGYPGGYNGMAIVPPPPPAQGAMVVVSPGSSDGMSAMTHADMMNCIGNGMMIENGTRKRPHREDGCAEKTVERRQRRMIKNRESAARSRARKQAYTVELEAELNYLKQENARLKEAEKTVLLTKKQMLVEKMMEQSKEKMNANRGGSQLRRSGSCMW,bZIP transcription factor ABI5 homolog,"Transcription factor that possesses transactivation activity in yeast. Involved in abscisic acid (ABA) signaling pathway. Binds to the G-box motif 5'-CACGTG-3' of TRAB1 gene promoter. Involved in the regulation of pollen maturation. May act as negative regulator of salt stress response. Together with PYL5, PP2C30 and SAPK2, is part of an ABA signaling unit that modulates seed germination and early seedling growth.",Mutation of S 44 of the C1 domain to aspartates decreased OREB1 activity.,Reduces transactivation activity 4-fold; when associated with D-43 and D-47. Mutation of S 44 of the C1 domain to aspartates decreased OREB1 activity.
69,69,Q9NXW9-H169A,MAAAAAETPEVLRECGCKGIRTCLICERQRGSDPPWELPPAKTYRFIYCSDTGWAVGTEESDFEGWAFPFPGVMLIEDFVTREEEAELVRLMDRDPWKLSQSGRRKQDYGPKVNFRKQKLKTEGFCGLPSFSREVVRRMGLYPGLEGFRPVEQCNLDYCPERGSAIDPALDDAWLWGERLVSLNLLSPTVLSMCREAPGSLLLCSAPSAAPEALVDSVIAPSRSVLCQEVEVAIPLPARSLLVLTGAARHQWKHAIHRRHIEARRVCVTFRELSAEFGPGGRQQELGQELLRIALSFQGRPV,"Loss of function mutant that acts as a dominant-negative mutant when overexpressed, leading to multinucleation and cleavage furrow disorganization; when associated with A-171 and A-254.",,MAAAAAETPEVLRECGCKGIRTCLICERQRGSDPPWELPPAKTYRFIYCSDTGWAVGTEESDFEGWAFPFPGVMLIEDFVTREEEAELVRLMDRDPWKLSQSGRRKQDYGPKVNFRKQKLKTEGFCGLPSFSREVVRRMGLYPGLEGFRPVEQCNLDYCPERGSAIDPHLDDAWLWGERLVSLNLLSPTVLSMCREAPGSLLLCSAPSAAPEALVDSVIAPSRSVLCQEVEVAIPLPARSLLVLTGAARHQWKHAIHRRHIEARRVCVTFRELSAEFGPGGRQQELGQELLRIALSFQGRPV,Alpha-ketoglutarate-dependent dioxygenase alkB homolog 4,"Dioxygenase that mediates demethylation of actin monomethylated at 'Lys-84' (K84me1), thereby acting as a regulator of actomyosin-processes. Demethylation of actin K84me1 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration. In addition to proteins, also demethylates DNA: specifically demethylates DNA methylated on the 6th position of adenine (N(6)-methyladenosine) DNA, thereby regulating Polycomb silencing.",,"Loss of function mutant that acts as a dominant-negative mutant when overexpressed, leading to multinucleation and cleavage furrow disorganization; when associated with A-171 and A-254."
70,70,Q14739-R583Q,MPSRKFADGEVVRGRWPGSSLYYEVEILSHDSTSQLYTVKYKDGTELELKENDIKPLTSFRQRKGGSTSSSPSRRRGSRSRSRSRSPGRPPKSARRSASASHQADIKEARREVEVKLTPLILKPFGNSISRYNGEPEHIERNDAPHKNTQEKFSLSQESSYIATQYSLRPRREEVKLKEIDSKEEKYVAKELAVRTFEVTPIRAKDLEFGGVPGVFLIMFGLPVFLFLLLLMCKQKDPSLLNFPPPLPALYELWETRVFGVYLLWFLIQVLFYLLPIGKVVEGTPLIDGRRLKYRLNGFYAFILTSAVIGTSLFQGVEFHYVYSHFLQFALAATVFCVVLSVYLYMRSLKAPRNDLSPASSGNAVYDFFIGRELNPRIGTFDLKYFCELRPGLIGWVVINLVMLLAEMKIQDRAVPSLAMILVNSFQLLYVVDALWNEEALLTTMDIIHDGFGFMLAFGDLVWVPFIYSFQAFYLVSHPNEVSWPMASLIIVLKLCGYVIFRGANSQKNAFRKNPSDPKLAHLKTIHTSTGKNLLVSGWWGFVRHPNYLGDLIMALAWSLPCGFNHILPYFYIIYFTMLLVHQEARDEYHCKKKYGVAWEKYCQRVPYRIFPYIY,In GRBGD; significant reduction in affinity for NADPH; loss of cholesterol biosynthesis; does not affect protein stability.,,MPSRKFADGEVVRGRWPGSSLYYEVEILSHDSTSQLYTVKYKDGTELELKENDIKPLTSFRQRKGGSTSSSPSRRRGSRSRSRSRSPGRPPKSARRSASASHQADIKEARREVEVKLTPLILKPFGNSISRYNGEPEHIERNDAPHKNTQEKFSLSQESSYIATQYSLRPRREEVKLKEIDSKEEKYVAKELAVRTFEVTPIRAKDLEFGGVPGVFLIMFGLPVFLFLLLLMCKQKDPSLLNFPPPLPALYELWETRVFGVYLLWFLIQVLFYLLPIGKVVEGTPLIDGRRLKYRLNGFYAFILTSAVIGTSLFQGVEFHYVYSHFLQFALAATVFCVVLSVYLYMRSLKAPRNDLSPASSGNAVYDFFIGRELNPRIGTFDLKYFCELRPGLIGWVVINLVMLLAEMKIQDRAVPSLAMILVNSFQLLYVVDALWNEEALLTTMDIIHDGFGFMLAFGDLVWVPFIYSFQAFYLVSHPNEVSWPMASLIIVLKLCGYVIFRGANSQKNAFRKNPSDPKLAHLKTIHTSTGKNLLVSGWWGFVRHPNYLGDLIMALAWSLPCGFNHILPYFYIIYFTMLLVHREARDEYHCKKKYGVAWEKYCQRVPYRIFPYIY,Delta,"Catalyzes the reduction of the C14-unsaturated bond of lanosterol, as part of the metabolic pathway leading to cholesterol biosynthesis. Plays a critical role in myeloid cell cholesterol biosynthesis which is essential to both myeloid cell growth and functional maturation. Mediates the activation of NADPH oxidases, perhaps by maintaining critical levels of cholesterol required for membrane lipid raft formation during neutrophil differentiation. Anchors the lamina and the heterochromatin to the inner nuclear membrane.","The mutation in LBR also causes Greenberg dysplasia. This mutation affects a residue that is evolutionarily conserved among sterol reductases. Similar to the mutation, it results in an enzymatic defect and fails to rescue C14 sterol reductase deficient yeast. The mutation does not cause Pelger anomaly in the carrier parent, indicating no marked effects on nuclear structure. LBR expression in mouse embryos is consistent with sites of histological changes in Greenberg dysplasia. Additionally, cytoplasmatic LBR localization is observed in disease-relevant cell types, co-localizing with ER-markers and sites of endogenous sterol synthesis. The findings suggest that the mutation abolishes sterol reductase activity, leading to lethal Greenberg dysplasia. The mutation in the LBR protein is implicated in Greenberg skeletal dysplasia or Pelger-Huët anomaly, leading to a loss-of-function mechanism for these congenital disorders.","In GRBGD; significant reduction in affinity for NADPH; loss of cholesterol biosynthesis; does not affect protein stability. The mutation in LBR also causes Greenberg dysplasia. This mutation affects a residue that is evolutionarily conserved among sterol reductases. Similar to the mutation, it results in an enzymatic defect and fails to rescue C14 sterol reductase deficient yeast. The mutation does not cause Pelger anomaly in the carrier parent, indicating no marked effects on nuclear structure. LBR expression in mouse embryos is consistent with sites of histological changes in Greenberg dysplasia. Additionally, cytoplasmatic LBR localization is observed in disease-relevant cell types, co-localizing with ER-markers and sites of endogenous sterol synthesis. The findings suggest that the mutation abolishes sterol reductase activity, leading to lethal Greenberg dysplasia. The mutation in the LBR protein is implicated in Greenberg skeletal dysplasia or Pelger-Huët anomaly, leading to a loss-of-function mechanism for these congenital disorders."
71,71,P50985-L54A,MGMRMMFTVFLLVVLATTVVSFTSDRASDDGNAAASDLIALTIKGCCSLPPCAASNPDYCG,28-fold decrease in inhibition potency of nAChr alpha-7 subunits and 8-fold increase in inhibition potency of nAChr alpha-3-beta-2 subunits.,,MGMRMMFTVFLLVVLATTVVSFTSDRASDDGNAAASDLIALTIKGCCSLPPCALSNPDYCG,Alpha-conotoxin PnIB,"Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin blocks mammalian nAChRs (alpha-7 > alpha-3/beta-2).",,28-fold decrease in inhibition potency of nAChr alpha-7 subunits and 8-fold increase in inhibition potency of nAChr alpha-3-beta-2 subunits.
72,72,B9DFK5-G328R,MAGCAMNLQFSSVVKVRNEISSFGICNRDFVFRDLAKAMKVPVLRIRGGSGRQRSRLFVVNMSQSPIEPQSGGFAATEQIKGEGDNSILGKDNVRNLGTDQLENLDIDGNVGDGFNGSDGNGGGGGGGNGGEGDGEGEDYEEKEFGPILKFEEVMKETEARGATLPSDMLEAAKNYGIRKVLLLRYLDLQSSAGLLGFAIRSWAMLRNRMLADPSFLFKIGAEIVIDSCCATVAEVQKRGKDFWAEFELYVADLLVGTVVNIALVGMLAPYVRFGQPSASPGFLGRMVFAYNALPSSVFEAERPGCRFSAQQRLATYFYKGIMYGAVRFGCGIVGQGIANLIMTAKRNINKSEENIPVPPLIKSAALWGVFLSVSSNTRYQIINGLERVVEASPFAKKFPPAAMAFTVGVRLANNIYGGMQFVDWARLSGCQ,In re-3; pale interveinal phenotype.,,MAGCAMNLQFSSVVKVRNEISSFGICNRDFVFRDLAKAMKVPVLRIRGGSGRQRSRLFVVNMSQSPIEPQSGGFAATEQIKGEGDNSILGKDNVRNLGTDQLENLDIDGNVGDGFNGSDGNGGGGGGGNGGEGDGEGEDYEEKEFGPILKFEEVMKETEARGATLPSDMLEAAKNYGIRKVLLLRYLDLQSSAGLLGFAIRSWAMLRNRMLADPSFLFKIGAEIVIDSCCATVAEVQKRGKDFWAEFELYVADLLVGTVVNIALVGMLAPYVRFGQPSASPGFLGRMVFAYNALPSSVFEAERPGCRFSAQQRLATYFYKGIMYGAVGFGCGIVGQGIANLIMTAKRNINKSEENIPVPPLIKSAALWGVFLSVSSNTRYQIINGLERVVEASPFAKKFPPAAMAFTVGVRLANNIYGGMQFVDWARLSGCQ,"Protein RETICULATA, chloroplastic",May play a role in leaf development. Required for leaf mesophyll cell division in the early stages of leaf organogenesis. Acts in a developmental pathway that involves PPT1/CUE1 but does not include ASE2/DOV1.,,In re-3; pale interveinal phenotype.
73,73,Q05776-W77D,MVLLHKSTHIFPTDFASVSRAFFNRYPNPYSPHVLSIDTISRNVDQEGNLRTTRLLKKSGKLPTWVKPFLRGITETDIIEVSVVNPANSTMKTYTRNLDHTGIMKVEEYTTYQFDSATSSTIADSRVKFSSGFNMGIKSKVEDWSRTKFDENVKKSRMGMAFVIQKLEEARNPQF,Impairs interaction with MDM35. Reduces ability to complement the mitochondrial defects of UPS1-deficient cells.,,MVLLHKSTHIFPTDFASVSRAFFNRYPNPYSPHVLSIDTISRNVDQEGNLRTTRLLKKSGKLPTWVKPFLRGITETWIIEVSVVNPANSTMKTYTRNLDHTGIMKVEEYTTYQFDSATSSTIADSRVKFSSGFNMGIKSKVEDWSRTKFDENVKKSRMGMAFVIQKLEEARNPQF,"Protein UPS1, mitochondrial","Required for maintenance of normal mitochondrial morphology. Required for PCP1-dependent processing of MGM1. The UPS1:MDM35 complex mediates the transfer of phosphatidic acid (PA) between liposomes and probably functions as a PA transporter across the mitochondrion intermembrane space. Phosphatidic acid release requires dissociation of the UPS1:MDM35 complex. Phosphatidic acid import is required for cardiolipin (CL) synthesis in the mitochondrial inner membrane. With UPS2, controls the level of cardiolipin in mitochondria. Cardiolipin is a unique phospholipid with four fatty acid chains and is present mainly in the mitochondrial inner membrane where it stabilizes the electron transport chain supercomplex between complexes III and IV through direct interaction of their subunits.",The mutation in Ups1 is critical for PA binding and transfer.,Impairs interaction with MDM35. Reduces ability to complement the mitochondrial defects of UPS1-deficient cells. The mutation in Ups1 is critical for PA binding and transfer.
74,74,Q6UX46-C66Y,MRGPGHPLLLGLLLVLGAAGRGRGGAEPREPADGQALLRLVVELVQELRKHHSAEHKGLQLLGRDYALGRAEAAGLGPSPEQRVEIVPRDLRMKDKFLKHLTGPLYFSPKCSKHFHRLYHNTRDCTIPAYYKRCARLLTRLAVSPVCMEDKQ,Abolished interchain disulfide bond without affecting homodimerization.,,MRGPGHPLLLGLLLVLGAAGRGRGGAEPREPADGQALLRLVVELVQELRKHHSAEHKGLQLLGRDCALGRAEAAGLGPSPEQRVEIVPRDLRMKDKFLKHLTGPLYFSPKCSKHFHRLYHNTRDCTIPAYYKRCARLLTRLAVSPVCMEDKQ,ALK and LTK ligand 2,"Cytokine that acts as a physiological ligand for receptor tyrosine kinases LTK and ALK, leading to their activation. Cytokine-binding is sufficient to activate LTK. In contrast, ALKAL2-driven activation of ALK is coupled with heparin-binding to ALK. Stimulation of ALK signaling is involved in neural development and regulation of energy expenditure.",,Abolished interchain disulfide bond without affecting homodimerization.
75,75,Q8WZ75-Y280S,MGSGGDSLLGGRGSLPLLLLLIMGGMAQDSPPQILVHPQDQLFQGPGPARMSCQASGQPPPTIRWLLNGQPLSMVPPDPHHLLPDGTLLLLQPPARGHAHDGQALSTDLGVYTCEASNRLGTAVSRGARLSVAVLREDFQIQPRDMVAVVGEQFTLECGPPWGHPEPTVSWWKDGKPLALQPGRHTVSGGSLLMARAEKSDEGTYMCVATNSAGHRESRAARVSIQEPQDYTEPVELLAVRIQLENVTLLNPDPAEGPKPRPAVWLSWKVSGPAAPAQSSTALFRTQTAPGGQGAPWAEELLAGWQSAELGGLHWGQDYEFKVRPSSGRARGPDSNVLLLRLPEKVPSAPPQEVTLKPGNGTVFVSWVPPPAENHNGIIRGYQVWSLGNTSLPPANWTVVGEQTQLEIATHMPGSYCVQVAAVTGAGAGEPSRPVCLLLEQAMERATQEPSEHGPWTLEQLRATLKRPEVIATCGVALWLLLLGTAVCIHRRRRARVHLGPGLYRYTSEDAILKHRMDHSDSQWLADTWRSTSGSRDLSSSSSLSSRLGADARDPLDCRRSLLSWDSRSPGVPLLPDTSTFYGSLIAELPSSTPARPSPQVPAVRRLPPQLAQLSSPCSSSDSLCSRRGLSSPRLSLAPAEAWKAKKKQELQHANSSPLLRGSHSLELRACELGNRGSKNLSQSPGAVPQALVAWRALGPKLLSSSNELVTRHLPPAPLFPHETPPTQSQQTQPPVAPQAPSSILLPAAPIPILSPCSPPSPQASSLSGPSPASSRLSSSSLSSLGEDQDSVLTPEEVALCLELSEGEETPRNSVSPMPRAPSPPTTYGYISVPTASEFTDMGRTGGGVGPKGGVLLCPPRPCLTPTPSEGSLANGWGSASEDNAASARASLVSSSDGSFLADAHFARALAVAVDSFGFGLEPREADCVFIDASSPPSPRDEIFLTPNLSLPLWEWRPDWLEDMEVSHTQRLGRGMPPWPPDSQISSQRSQLHCRMPKAGASPVDYS,In AOVD3; unknown pathological significance.,,MGSGGDSLLGGRGSLPLLLLLIMGGMAQDSPPQILVHPQDQLFQGPGPARMSCQASGQPPPTIRWLLNGQPLSMVPPDPHHLLPDGTLLLLQPPARGHAHDGQALSTDLGVYTCEASNRLGTAVSRGARLSVAVLREDFQIQPRDMVAVVGEQFTLECGPPWGHPEPTVSWWKDGKPLALQPGRHTVSGGSLLMARAEKSDEGTYMCVATNSAGHRESRAARVSIQEPQDYTEPVELLAVRIQLENVTLLNPDPAEGPKPRPAVWLSWKVSGPAAPAQSYTALFRTQTAPGGQGAPWAEELLAGWQSAELGGLHWGQDYEFKVRPSSGRARGPDSNVLLLRLPEKVPSAPPQEVTLKPGNGTVFVSWVPPPAENHNGIIRGYQVWSLGNTSLPPANWTVVGEQTQLEIATHMPGSYCVQVAAVTGAGAGEPSRPVCLLLEQAMERATQEPSEHGPWTLEQLRATLKRPEVIATCGVALWLLLLGTAVCIHRRRRARVHLGPGLYRYTSEDAILKHRMDHSDSQWLADTWRSTSGSRDLSSSSSLSSRLGADARDPLDCRRSLLSWDSRSPGVPLLPDTSTFYGSLIAELPSSTPARPSPQVPAVRRLPPQLAQLSSPCSSSDSLCSRRGLSSPRLSLAPAEAWKAKKKQELQHANSSPLLRGSHSLELRACELGNRGSKNLSQSPGAVPQALVAWRALGPKLLSSSNELVTRHLPPAPLFPHETPPTQSQQTQPPVAPQAPSSILLPAAPIPILSPCSPPSPQASSLSGPSPASSRLSSSSLSSLGEDQDSVLTPEEVALCLELSEGEETPRNSVSPMPRAPSPPTTYGYISVPTASEFTDMGRTGGGVGPKGGVLLCPPRPCLTPTPSEGSLANGWGSASEDNAASARASLVSSSDGSFLADAHFARALAVAVDSFGFGLEPREADCVFIDASSPPSPRDEIFLTPNLSLPLWEWRPDWLEDMEVSHTQRLGRGMPPWPPDSQISSQRSQLHCRMPKAGASPVDYS,Roundabout homolog 4,"Receptor for Slit proteins, at least for SLIT2, and seems to be involved in angiogenesis and vascular patterning. May mediate the inhibition of primary endothelial cell migration by Slit proteins. Involved in the maintenance of endothelial barrier organization and function.",,In AOVD3; unknown pathological significance.
76,76,Q8NBK3-W179S,MAAPALGLVCGRCPELGLVLLLLLLSLLCGAAGSQEAGTGAGAGSLAGSCGCGTPQRPGAHGSSAAAHRYSREANAPGPVPGERQLAHSKMVPIPAGVFTMGTDDPQIKQDGEAPARRVTIDAFYMDAYEVSNTEFEKFVNSTGYLTEAEKFGDSFVFEGMLSEQVKTNIQQAVAAAPSWLPVKGANWRHPEGPDSTILHRPDHPVLHVSWNDAVAYCTWAGKRLPTEAEWEYSCRGGLHNRLFPWGNKLQPKGQHYANIWQGEFPVTNTGEDGFQGTAPVDAFPPNGYGLYNIVGNAWEWTSDWWTVHHSVEETLNPKGPPSGKDRVKKGGSYMCHRSYCYRYRCAARSQNTPDSSASNLGFRCAADRLPTMD,In MSD; decreases its specific enzyme activity to less than 3%; does not affect localization of the protein in the endoplasmic reticulum of MSD fibroblasts; protein stability is almost comparable to wild-type.,,MAAPALGLVCGRCPELGLVLLLLLLSLLCGAAGSQEAGTGAGAGSLAGSCGCGTPQRPGAHGSSAAAHRYSREANAPGPVPGERQLAHSKMVPIPAGVFTMGTDDPQIKQDGEAPARRVTIDAFYMDAYEVSNTEFEKFVNSTGYLTEAEKFGDSFVFEGMLSEQVKTNIQQAVAAAPWWLPVKGANWRHPEGPDSTILHRPDHPVLHVSWNDAVAYCTWAGKRLPTEAEWEYSCRGGLHNRLFPWGNKLQPKGQHYANIWQGEFPVTNTGEDGFQGTAPVDAFPPNGYGLYNIVGNAWEWTSDWWTVHHSVEETLNPKGPPSGKDRVKKGGSYMCHRSYCYRYRCAARSQNTPDSSASNLGFRCAADRLPTMD,Formylglycine-generating enzyme,"Oxidase that catalyzes the conversion of cysteine to 3-oxoalanine on target proteins, using molecular oxygen and an unidentified reducing agent. 3-oxoalanine modification, which is also named formylglycine (fGly), occurs in the maturation of arylsulfatases and some alkaline phosphatases that use the hydrated form of 3-oxoalanine as a catalytic nucleophile. Known substrates include GALNS, ARSA, STS and ARSE.",The missense mutation p. in the SUMF1 gene encoding the formylglycine-generating enzyme (FGE) resulted in a decrease in specific enzymatic activity to 3%.,In MSD; decreases its specific enzyme activity to less than 3%; does not affect localization of the protein in the endoplasmic reticulum of MSD fibroblasts; protein stability is almost comparable to wild-type. The missense mutation p. in the SUMF1 gene encoding the formylglycine-generating enzyme (FGE) resulted in a decrease in specific enzymatic activity to 3%.
77,77,Q9ZWJ9-D655G,MVNPGHGRGPDSGTAAGGSNSDPFPANLRVLVVDDDPTCLMILERMLMTCLYRVTKCNRAESALSLLRKNKNGFDIVISDVHMPDMDGFKLLEHVGLEMDLPVIMMSADDSKSVVLKGVTHGAVDYLIKPVRIEALKNIWQHVVRKKRNEWNVSEHSGGSIEDTGGDRDRQQQHREDADNNSSSVNEGNGRSSRKRKEEEVDDQGDDKEDSSSLKKPRVVWSVELHQQFVAAVNQLGVDKAVPKKILEMMNVPGLTRENVASHLQKYRIYLRRLGGVSQHQGNMNHSFMTGQDQSFGPLSSLNGFDLQSLAVTGQLPPQSLAQLQAAGLGRPTLAKPGMSVSPLVDQRSIFNFENPKIRFGDGHGQTMNNGNLLHGVPTGSHMRLRPGQNVQSSGMMLPVADQLPRGGPSMLPSLGQQPILSSSVSRRSDLTGALAVRNSIPETNSRVLPTTHSVFNNFPADLPRSSFPLASAPGISVPVSVSYQEEVNSSDAKGGSSAATAGFGNPSYDIFNDFPQHQQHNKNISNKLNDWDLRNMGLVFSSNQDAATATATAAFSTSEAYSSSSTQRKRRETDATVVGEHGQNLQSPSRNLYHLNHVFMDGGSVRVKSERVAETVTCPPANTLFHEQYNQEDLMSAFLKQEGIPSVDNEFEFGGYSIDNIQV,In strain: cv. Landsberg erecta.,,MVNPGHGRGPDSGTAAGGSNSDPFPANLRVLVVDDDPTCLMILERMLMTCLYRVTKCNRAESALSLLRKNKNGFDIVISDVHMPDMDGFKLLEHVGLEMDLPVIMMSADDSKSVVLKGVTHGAVDYLIKPVRIEALKNIWQHVVRKKRNEWNVSEHSGGSIEDTGGDRDRQQQHREDADNNSSSVNEGNGRSSRKRKEEEVDDQGDDKEDSSSLKKPRVVWSVELHQQFVAAVNQLGVDKAVPKKILEMMNVPGLTRENVASHLQKYRIYLRRLGGVSQHQGNMNHSFMTGQDQSFGPLSSLNGFDLQSLAVTGQLPPQSLAQLQAAGLGRPTLAKPGMSVSPLVDQRSIFNFENPKIRFGDGHGQTMNNGNLLHGVPTGSHMRLRPGQNVQSSGMMLPVADQLPRGGPSMLPSLGQQPILSSSVSRRSDLTGALAVRNSIPETNSRVLPTTHSVFNNFPADLPRSSFPLASAPGISVPVSVSYQEEVNSSDAKGGSSAATAGFGNPSYDIFNDFPQHQQHNKNISNKLNDWDLRNMGLVFSSNQDAATATATAAFSTSEAYSSSSTQRKRRETDATVVGEHGQNLQSPSRNLYHLNHVFMDGGSVRVKSERVAETVTCPPANTLFHEQYNQEDLMSAFLKQEGIPSVDNEFEFDGYSIDNIQV,Two-component response regulator ARR2,Transcriptional activator that binds specifically to the DNA sequence 5'-[AG]GATT-3'. Functions as a response regulator involved in His-to-Asp phosphorelay signal transduction system. Phosphorylation of the Asp residue in the receiver domain activates the ability of the protein to promote the transcription of target genes. Could directly activate some type-A response regulators in response to cytokinins. Involved in the expression of nuclear genes for components of mitochondrial complex I. Promotes cytokinin-mediated leaf longevity. Involved in the ethylene signaling pathway in an ETR1-dependent manner and in the cytokinin signaling pathway.,,In strain: cv. Landsberg erecta.
78,78,P28700-S75A,MDTKHFLPLDFSTQVNSSSLNSPTGRGSMAVPSLHPSLGPGIGSPLGSPGQLHSPISTLSSPINGMGPPFSVISAPMGPHSMSVPTTPTLGFGTGSPQLNSPMNPVSSTEDIKPPLGLNGVLKVPAHPSGNMASFTKHICAICGDRSSGKHYGVYSCEGCKGFFKRTVRKDLTYTCRDNKDCLIDKRQRNRCQYCRYQKCLAMGMKREAVQEERQRGKDRNENEVESTSSANEDMPVEKILEAELAVEPKTETYVEANMGLNPSSPNDPVTNICQAADKQLFTLVEWAKRIPHFSELPLDDQVILLRAGWNELLIASFSHRSIAVKDGILLATGLHVHRNSAHSAGVGAIFDRVLTELVSKMRDMQMDKTELGCLRAIVLFNPDSKGLSNPAEVEALREKVYASLEAYCKHKYPEQPGRFAKLLLRLPALRSIGLKCLEHLFFFKLIGDTPIDTFLMEMLEAPHQAT,"No effect on constituitive phosphorylation, decreased stress-induced phosphorylation but no effect on RXRA transcriptional activity. Abolishes stress-induced phosphorylation but no effect on RXRA transcriptional activity; when associated with A-61 and A-87.",,MDTKHFLPLDFSTQVNSSSLNSPTGRGSMAVPSLHPSLGPGIGSPLGSPGQLHSPISTLSSPINGMGPPFSVISSPMGPHSMSVPTTPTLGFGTGSPQLNSPMNPVSSTEDIKPPLGLNGVLKVPAHPSGNMASFTKHICAICGDRSSGKHYGVYSCEGCKGFFKRTVRKDLTYTCRDNKDCLIDKRQRNRCQYCRYQKCLAMGMKREAVQEERQRGKDRNENEVESTSSANEDMPVEKILEAELAVEPKTETYVEANMGLNPSSPNDPVTNICQAADKQLFTLVEWAKRIPHFSELPLDDQVILLRAGWNELLIASFSHRSIAVKDGILLATGLHVHRNSAHSAGVGAIFDRVLTELVSKMRDMQMDKTELGCLRAIVLFNPDSKGLSNPAEVEALREKVYASLEAYCKHKYPEQPGRFAKLLLRLPALRSIGLKCLEHLFFFKLIGDTPIDTFLMEMLEAPHQAT,Retinoic acid receptor RXR-alpha,"Receptor for retinoic acid that acts as a transcription factor. Forms homo- or heterodimers with retinoic acid receptors (RARs) and binds to target response elements in response to their ligands, all-trans or 9-cis retinoic acid, to regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 to regulate transcription. The high affinity ligand for retinoid X receptors (RXRs) is 9-cis retinoic acid. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and coactivators are recruited leading to transcriptional activation. Serves as a common heterodimeric partner for a number of nuclear receptors, such as RARA, RARB and PPARA. The RXRA/RARB heterodimer can act as a transcriptional repressor or transcriptional activator, depending on the RARE DNA element context. The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes. Together with RARA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells. Acts as an enhancer of RARA binding to RARE DNA element. May facilitate the nuclear import of heterodimerization partners such as VDR and NR4A1. Promotes myelin debris phagocytosis and remyelination by macrophages. Plays a role in the attenuation of the innate immune system in response to viral infections, possibly by negatively regulating the transcription of antiviral genes such as type I IFN genes. Involved in the regulation of calcium signaling by repressing ITPR2 gene expression, thereby controlling cellular senescence.",Hyperphosphorylation at S75 occurs in the B region of RXRalpha.,"No effect on constituitive phosphorylation, decreased stress-induced phosphorylation but no effect on RXRA transcriptional activity. Abolishes stress-induced phosphorylation but no effect on RXRA transcriptional activity; when associated with A-61 and A-87. Hyperphosphorylation at S75 occurs in the B region of RXRalpha."
79,79,Q6ZQE4-S420E,MAGGIKVSVWSAVGPGPRCWGAGGGGGATWLLLVVAGCVVCGSADVNVVMLQESQVDMNSSQQFCYKNVLIPKWHDIWTRIQVRVNSSKLVRVTQVDNEEKLKELEQFSIWNFFSSFLKEKLNDTYVNVGLYSTKTCLKVEMIEKDTTYSVTVTRRFDPKLFLVFLLGLTLFFCGDLLSRSQIFYYSTGMSVGIVASLLIVIFMISKFMPKRSPIYVILVGGWSFSLYLIQLVFKNLQEIWRSYWHYLLSYILTVGFMSFAVCYKYGPLENERSINLLTWTLQLLGLGLMYSSIQIPHVAFALIVIALCTKNLEYPIHWLCSTYRRMCKASGKPVPPRLLTEEEYRIQGEVETQKALQELREFCNSPECSAWKTISRIQSPKRFADFVEGSFHLTPNEVSVHEQEYGLGSIFTQDEELSEEEEGSEYPTFTQNNFLT,Partial loss of phosphorylation and loss of interaction with RAN-GTP; when associated with A/E-366; A/E-376; A/E-380 and A/E-419.,,MAGGIKVSVWSAVGPGPRCWGAGGGGGATWLLLVVAGCVVCGSADVNVVMLQESQVDMNSSQQFCYKNVLIPKWHDIWTRIQVRVNSSKLVRVTQVDNEEKLKELEQFSIWNFFSSFLKEKLNDTYVNVGLYSTKTCLKVEMIEKDTTYSVTVTRRFDPKLFLVFLLGLTLFFCGDLLSRSQIFYYSTGMSVGIVASLLIVIFMISKFMPKRSPIYVILVGGWSFSLYLIQLVFKNLQEIWRSYWHYLLSYILTVGFMSFAVCYKYGPLENERSINLLTWTLQLLGLGLMYSSIQIPHVAFALIVIALCTKNLEYPIHWLCSTYRRMCKASGKPVPPRLLTEEEYRIQGEVETQKALQELREFCNSPECSAWKTISRIQSPKRFADFVEGSFHLTPNEVSVHEQEYGLGSIFTQDEELSSEEEGSEYPTFTQNNFLT,Nuclear envelope integral membrane protein 1,"Together with EMD, contributes to nuclear envelope stiffness in germ cells. Required for female fertility.",The mutation in Nemp1/TMEM194A causes a functional change in the protein.,Partial loss of phosphorylation and loss of interaction with RAN-GTP; when associated with A/E-366; A/E-376; A/E-380 and A/E-419. The mutation in Nemp1/TMEM194A causes a functional change in the protein.
80,80,P82251-R250K,MGDTGLRKRREDEKSIQSQEPKTTSLQKELGLISGISIIVGTIIGSGIFVSPKSVLSNTEAVGPCLIIWAACGVLATLGALCFAELGTMITKSGGEYPYLMEAYGPIPAYLFSWASLIVIKPTSFAIICLSFSEYVCAPFYVGCKPPQIVVKCLAAAAILFISTVNSLSVRLGSYVQNIFTAAKLVIVAIIIISGLVLLAQGNTKNFDNSFEGAQLSVGAISLAFYNGLWAYDGWNQLNYITEELRNPYKNLPLAIIIGIPLVTACYILMNVSYFTVMTATELLQSQAVAVTFGDRVLYPASWIVPLFVAFSTIGAANGTCFTAGRLIYVAGREGHMLKVLSYISVRRLTPAPAIIFYGIIATIYIIPGDINSLVNYFSFAAWLFYGLTILGLIVMRFTRKELERPIKVPVVIPVLMTLISVFLVLAPIISKPTWEYLYCVLFILSGLLFYFLFVHYKFGWAQKISKPITMHLQMLMEVVPPEEDPE,In CSNU.,,MGDTGLRKRREDEKSIQSQEPKTTSLQKELGLISGISIIVGTIIGSGIFVSPKSVLSNTEAVGPCLIIWAACGVLATLGALCFAELGTMITKSGGEYPYLMEAYGPIPAYLFSWASLIVIKPTSFAIICLSFSEYVCAPFYVGCKPPQIVVKCLAAAAILFISTVNSLSVRLGSYVQNIFTAAKLVIVAIIIISGLVLLAQGNTKNFDNSFEGAQLSVGAISLAFYNGLWAYDGWNQLNYITEELRNPYRNLPLAIIIGIPLVTACYILMNVSYFTVMTATELLQSQAVAVTFGDRVLYPASWIVPLFVAFSTIGAANGTCFTAGRLIYVAGREGHMLKVLSYISVRRLTPAPAIIFYGIIATIYIIPGDINSLVNYFSFAAWLFYGLTILGLIVMRFTRKELERPIKVPVVIPVLMTLISVFLVLAPIISKPTWEYLYCVLFILSGLLFYFLFVHYKFGWAQKISKPITMHLQMLMEVVPPEEDPE,b,"Associates with SLC3A1 to form a functional transporter complex that mediates the electrogenic exchange between cationic amino acids and neutral amino acids, with a stoichiometry of 1:1. Has system b(0,+)-like activity with high affinity for extracellular cationic amino acids and L-cystine and lower affinity for intracellular neutral amino acids. Substrate exchange is driven by high concentration of intracellular neutral amino acids and the intracellular reduction of L-cystine to L-cysteine. Required for reabsorption of L-cystine and dibasic amino acids across the brush border membrane in renal proximal tubules.",The document mentions a novel point mutation in the SLC7A9 gene.,In CSNU. The document mentions a novel point mutation in the SLC7A9 gene.
81,81,P51168-G37S,MHVKKYLLKGLHRLQKGPGYTYKELLVWYCDNTNTHSPKRIICEGPKKKAMWFLLTLLFAALVCWQWGIFIRTYLSWEVSVSLSVGFKTMDFPAVTICNASPFKYSKIKHLLKDLDELMEAVLERILAPELSHANATRNLNFSIWNHTPLVLIDERNPHHPMVLDLFGDNHNGLTSSSASEKICNAHGCKMAMRLCSLNRTQCTFRNFTSATQALTEWYILQATNIFAQVPQQELVEMSYPGEQMILACLFGAEPCNYRNFTSIFYPHYGNCYIFNWGMTEKALPSANPGTEFGLKLILDIGQEDYVPFLASTAGVRLMLHEQRSYPFIRDEGIYAMSGTETSIGVLVDKLQRMGEPYSPCTVNGSEVPVQNFYSDYNTTYSIQACLRSCFQDHMIRNCNCGHYLYPLPRGEKYCNNRDFPDWAHCYSDLQMSVAQRETCIGMCKESCNDTQYKMTISMADWPSEASEDWIFHVLSQERDQSTNITLSRKGIVKLNIYFQEFNYRTIEESAANNIVWLLSNLGGQFGFWMGGSVLCLIEFGEIIIDFVWITIIKLVALAKSLRQRRAQASYAGPPPTVAELVEAHTNFGFQPDTAPRSPNTGPYPSEQALPIPGTPPPNYDSLRLQPLDVIESDSEGDAI,In PHA1B2.,,MHVKKYLLKGLHRLQKGPGYTYKELLVWYCDNTNTHGPKRIICEGPKKKAMWFLLTLLFAALVCWQWGIFIRTYLSWEVSVSLSVGFKTMDFPAVTICNASPFKYSKIKHLLKDLDELMEAVLERILAPELSHANATRNLNFSIWNHTPLVLIDERNPHHPMVLDLFGDNHNGLTSSSASEKICNAHGCKMAMRLCSLNRTQCTFRNFTSATQALTEWYILQATNIFAQVPQQELVEMSYPGEQMILACLFGAEPCNYRNFTSIFYPHYGNCYIFNWGMTEKALPSANPGTEFGLKLILDIGQEDYVPFLASTAGVRLMLHEQRSYPFIRDEGIYAMSGTETSIGVLVDKLQRMGEPYSPCTVNGSEVPVQNFYSDYNTTYSIQACLRSCFQDHMIRNCNCGHYLYPLPRGEKYCNNRDFPDWAHCYSDLQMSVAQRETCIGMCKESCNDTQYKMTISMADWPSEASEDWIFHVLSQERDQSTNITLSRKGIVKLNIYFQEFNYRTIEESAANNIVWLLSNLGGQFGFWMGGSVLCLIEFGEIIIDFVWITIIKLVALAKSLRQRRAQASYAGPPPTVAELVEAHTNFGFQPDTAPRSPNTGPYPSEQALPIPGTPPPNYDSLRLQPLDVIESDSEGDAI,Amiloride-sensitive sodium channel subunit beta,"Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Plays an essential role in electrolyte and blood pressure homeostasis, but also in airway surface liquid homeostasis, which is important for proper clearance of mucus. Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. Also plays a role in taste perception.","The mutation in either the alpha or beta subunits of the amiloride-sensitive epithelial sodium channel results in loss of channel activity, leading to severe neonatal salt wasting, hyperkalaemia, metabolic acidosis, and unresponsiveness to mineralocorticoid hormones. This mutation is homozygous in affected subjects and co-segregates with the disease.","In PHA1B2. The mutation in either the alpha or beta subunits of the amiloride-sensitive epithelial sodium channel results in loss of channel activity, leading to severe neonatal salt wasting, hyperkalaemia, metabolic acidosis, and unresponsiveness to mineralocorticoid hormones. This mutation is homozygous in affected subjects and co-segregates with the disease."
82,82,A6QIG7-F31A,MKKKLATTVLALSFLTAGISTHHHSAKAFTAEPFPTNEEIESNKKMLEKEKAYKESFKNSGLPTTLGKLDERLRNYLKKGTKNSAQFEKMVILTENKGYYTVYLNTPLAEDRKNVELLGKMYKTYFFKKGESKSSYVINGPGKTNEYAY,Decreases FPR-blocking activity. No effect on C5aR-blocking activity.,,MKKKLATTVLALSFLTAGISTHHHSAKAFTFEPFPTNEEIESNKKMLEKEKAYKESFKNSGLPTTLGKLDERLRNYLKKGTKNSAQFEKMVILTENKGYYTVYLNTPLAEDRKNVELLGKMYKTYFFKKGESKSSYVINGPGKTNEYAY,Chemotaxis inhibitory protein,"Involved in countering the first line of host defense mechanisms. Specifically inhibits the response of human neutrophils and monocytes to complement anaphylatoxin C5a and formylated peptides, like N-formyl-methionyl-leucyl-phenylalanine (fMLP). Acts by binding directly to the C5a receptor (C5aR) and formylated peptide receptor (FPR), thereby blocking the C5a- and fMLP-induced calcium responses. Prevents phagocytosis of the bacterium.","The mutant CHIPS protein with the mutation has impaired or absent FPR-blocking activity, indicating that the loss of the FPR-blocking activity is not caused by any structural impairment.","Decreases FPR-blocking activity. No effect on C5aR-blocking activity. The mutant CHIPS protein with the mutation has impaired or absent FPR-blocking activity, indicating that the loss of the FPR-blocking activity is not caused by any structural impairment."
83,83,O43272-A472T,MALRRALPALRPCIPRFVQLSTAPASREQPAAGPAAVPGGGSATAVRPPVPAVDFGNAQEAYRSRRTWELARSLLVLRLCAWPALLARHEQLLYVSRKLLGQRLFNKLMKMTFYGHFVAGEDQESIQPLLRHYRAFGVSAILDYGVEEDLSPEEAEHKEMESCTSAAERDGSGTNKRDKQYQAHRAFGDRRNGVISARTYFYANEAKCDSHMETFLRCIEASGRVSDDGFIAIKLTALGRPQFLLQFSEVLAKWRCFFHQMAVEQGQAGLAAMDTKLEVAVLQESVAKLGIASRAEIEDWFTAETLGVSGTMDLLDWSSLIDSRTKLSKHLVVPNAQTGQLEPLLSRFTEEEELQMTRMLQRMDVLAKKATEMGVRLMVDAEQTYFQPAISRLTLEMQRKFNVEKPLIFNTYQCYLKDAYDNVTLDVELARREGWCFGAKLVRGAYLAQERARAAEIGYEDPINPTYEATNTMYHRCLDYVLEELKHNAKAKVMVASHNEDTVRFALRRMEELGLHPADHQVYFGQLLGMCDQISFPLGQAGYPVYKYVPYGPVMEVLPYLSRRALENSSLMKGTHRERQLLWLELLRRLRTGNLFHRPA,In HYRPRO1 and SCZD4; associated with disease susceptibility; mild decrease of enzymatic activity.,,MALRRALPALRPCIPRFVQLSTAPASREQPAAGPAAVPGGGSATAVRPPVPAVDFGNAQEAYRSRRTWELARSLLVLRLCAWPALLARHEQLLYVSRKLLGQRLFNKLMKMTFYGHFVAGEDQESIQPLLRHYRAFGVSAILDYGVEEDLSPEEAEHKEMESCTSAAERDGSGTNKRDKQYQAHRAFGDRRNGVISARTYFYANEAKCDSHMETFLRCIEASGRVSDDGFIAIKLTALGRPQFLLQFSEVLAKWRCFFHQMAVEQGQAGLAAMDTKLEVAVLQESVAKLGIASRAEIEDWFTAETLGVSGTMDLLDWSSLIDSRTKLSKHLVVPNAQTGQLEPLLSRFTEEEELQMTRMLQRMDVLAKKATEMGVRLMVDAEQTYFQPAISRLTLEMQRKFNVEKPLIFNTYQCYLKDAYDNVTLDVELARREGWCFGAKLVRGAYLAQERARAAEIGYEDPINPTYEATNAMYHRCLDYVLEELKHNAKAKVMVASHNEDTVRFALRRMEELGLHPADHQVYFGQLLGMCDQISFPLGQAGYPVYKYVPYGPVMEVLPYLSRRALENSSLMKGTHRERQLLWLELLRRLRTGNLFHRPA,"Proline dehydrogenase 1, mitochondrial",Converts proline to delta-1-pyrroline-5-carboxylate.,severe reduction in POX activity,In HYRPRO1 and SCZD4; associated with disease susceptibility; mild decrease of enzymatic activity. severe reduction in POX activity
84,84,Q5AQ33-S570A,MIMNMTTDYRDPLLDLFGTESNSGNETSSPSDIPVINRSGTFNQQQFSPLLTQQSLYNTPNSGSTPNIFDPNYTQMQEEQTSPSSNKLQPEDPPRKKRNTRSQTKIHQQSEGDEYNSNDYKDSIDLDKPPVVEPSPPFFVESDTTPEFVIPTPTSEQQQQQHHELIAQDYQRSNNSNQFGNLTHYEPNLPPLPPLSESILPQTNTFHPLVLPHDPRHAITAGPANNSQQQQQQQQQDSSIPSDGISSKIQQLHAPSLSNNQSASQRKKKESSGPKTRPAFVMKIWSMVNDPANHEYIRWNDDGKTFQVFHREDFMKVILPKYFKHNNFASFVRQLNMYGWHKVQDVANGTLNQNSDKNGQDEIWQFENPNFIKDREDLLDKIVRNKSSSNQDDVSGVSFNGINNSANLSLILQELETIKMNQYVISEDLRRVRQDNKMLWQENYLNRERNQVQGRTLDKILKFLSVVYGNNANKILNGHGFADFNDSNNIMTQYRPSPMGSPLLSRPQTQPPPSNSRFARDNNQTAQPTYESPLSTSDTNNNNNNTFEYQQAVNRPRLMLTNRAHSRRPAMSRTKSTPEGSIEEIIRSYSNDKAAESNVNRMYEQLVGHQPGATTNNNNHSSSTAISAPSPRHSFLQELNLPGTPRNLDDLEKHINKEGQSIQQVQDWIDKLAQEQHEKQQQQQGNDDDDDFDVNEFLKDATTTPSSNVPNGGHYNNGNISFVGSPIAMTPGSNVSSNINDSDGNEKKSKKRSIEEVSDH,"Decreases thermotolerance; when associated with A-574, A-576 and A-577.",,MIMNMTTDYRDPLLDLFGTESNSGNETSSPSDIPVINRSGTFNQQQFSPLLTQQSLYNTPNSGSTPNIFDPNYTQMQEEQTSPSSNKLQPEDPPRKKRNTRSQTKIHQQSEGDEYNSNDYKDSIDLDKPPVVEPSPPFFVESDTTPEFVIPTPTSEQQQQQHHELIAQDYQRSNNSNQFGNLTHYEPNLPPLPPLSESILPQTNTFHPLVLPHDPRHAITAGPANNSQQQQQQQQQDSSIPSDGISSKIQQLHAPSLSNNQSASQRKKKESSGPKTRPAFVMKIWSMVNDPANHEYIRWNDDGKTFQVFHREDFMKVILPKYFKHNNFASFVRQLNMYGWHKVQDVANGTLNQNSDKNGQDEIWQFENPNFIKDREDLLDKIVRNKSSSNQDDVSGVSFNGINNSANLSLILQELETIKMNQYVISEDLRRVRQDNKMLWQENYLNRERNQVQGRTLDKILKFLSVVYGNNANKILNGHGFADFNDSNNIMTQYRPSPMGSPLLSRPQTQPPPSNSRFARDNNQTAQPTYESPLSTSDTNNNNNNTFEYQQAVNRPRLMLTNRAHSRRPSMSRTKSTPEGSIEEIIRSYSNDKAAESNVNRMYEQLVGHQPGATTNNNNHSSSTAISAPSPRHSFLQELNLPGTPRNLDDLEKHINKEGQSIQQVQDWIDKLAQEQHEKQQQQQGNDDDDDFDVNEFLKDATTTPSSNVPNGGHYNNGNISFVGSPIAMTPGSNVSSNINDSDGNEKKSKKRSIEEVSDH,Heat shock transcription factor,"DNA-binding transcription factor that specifically binds heat shock promoter elements (HSE) and activates transcription. With HSP90, is required for the modulation of the chaperone levels in response to growth temperature, rather than the activation of acute responses to sudden thermal transitions. Activated during infection and contributes to full virulence.",This mutation affects the activation of Hsf1 and its ability to activate HSE-containing genes in response to heat shock. The mutant is thermosensitive and unable to contribute to the thermal adaptation and virulence of Candida albicans.,"Decreases thermotolerance; when associated with A-574, A-576 and A-577. This mutation affects the activation of Hsf1 and its ability to activate HSE-containing genes in response to heat shock. The mutant is thermosensitive and unable to contribute to the thermal adaptation and virulence of Candida albicans."
85,85,Q99972-V426F,MRFFCARCCSFGPEMPAVQLLLLACLVWDVGARTAQLRKANDQSGRCQYTFSVASPNESSCPEQSQAMSVIHNLQRDSSTQRLDLEATKARLSSLESLLHQLTLDQAARPQETQEGLQRELGTLRRERDQLETQTRELETAYSNLLRDKSVLEEEKKRLRQENENLARRLESSSQEVARLRRGQCPQTRDTARAVPPGSREVSTWNLDTLAFQELKSELTEVPASRILKESPSGYLRSGEGDTGCGELVWVGEPLTLRTAETITGKYGVWMRDPKPTYPYTQETTWRIDTVGTDVRQVFEYDLISQFMQGYPSKVHILPRPLESTGAVVYSGSLYFQGAESRTVIRYELNTETVKAEKEIPGAGYHGQFPYSWGGYTDIDLAVDEAGLWVIYSTDEAKGAIVLSKLNPENLELEQTWETNIRKQSFANAFIICGTLYTVSSYTSADATVNFAYDTGTGISKTLTIPFKNRYKYSSMIDYNPLEKKLFAWDNLNMVTYDIKLSKM,In GLC1A.,,MRFFCARCCSFGPEMPAVQLLLLACLVWDVGARTAQLRKANDQSGRCQYTFSVASPNESSCPEQSQAMSVIHNLQRDSSTQRLDLEATKARLSSLESLLHQLTLDQAARPQETQEGLQRELGTLRRERDQLETQTRELETAYSNLLRDKSVLEEEKKRLRQENENLARRLESSSQEVARLRRGQCPQTRDTARAVPPGSREVSTWNLDTLAFQELKSELTEVPASRILKESPSGYLRSGEGDTGCGELVWVGEPLTLRTAETITGKYGVWMRDPKPTYPYTQETTWRIDTVGTDVRQVFEYDLISQFMQGYPSKVHILPRPLESTGAVVYSGSLYFQGAESRTVIRYELNTETVKAEKEIPGAGYHGQFPYSWGGYTDIDLAVDEAGLWVIYSTDEAKGAIVLSKLNPENLELEQTWETNIRKQSVANAFIICGTLYTVSSYTSADATVNFAYDTGTGISKTLTIPFKNRYKYSSMIDYNPLEKKLFAWDNLNMVTYDIKLSKM,Myocilin,"Secreted glycoprotein regulating the activation of different signaling pathways in adjacent cells to control different processes including cell adhesion, cell-matrix adhesion, cytoskeleton organization and cell migration. Promotes substrate adhesion, spreading and formation of focal contacts. Negatively regulates cell-matrix adhesion and stress fiber assembly through Rho protein signal transduction. Modulates the organization of actin cytoskeleton by stimulating the formation of stress fibers through interactions with components of Wnt signaling pathways. Promotes cell migration through activation of PTK2 and the downstream phosphatidylinositol 3-kinase signaling. Plays a role in bone formation and promotes osteoblast differentiation in a dose-dependent manner through mitogen-activated protein kinase signaling. Mediates myelination in the peripheral nervous system through ERBB2/ERBB3 signaling. Plays a role as a regulator of muscle hypertrophy through the components of dystrophin-associated protein complex. Involved in positive regulation of mitochondrial depolarization. Plays a role in neurite outgrowth. May participate in the obstruction of fluid outflow in the trabecular meshwork.",A G-T transversion at the first base of codon 426 in the TIGR gene results in a valine to phenylalanine amino acid substitution.,In GLC1A. A G-T transversion at the first base of codon 426 in the TIGR gene results in a valine to phenylalanine amino acid substitution.
86,86,Q46896-E141A,MTWLPLNPIPLKDRVSMIFLQYGQIDVIDGAFVLIDKTGIRTHIPVGSVACIMLEPGTRVSHAAVRLAAQVGTLLVWVGEAGVRVYASGQPGGARSDKLLYQAKLALDEDLRLKVVRKMFELRFGEPAPARRSVEQLRGIAGSRVRATYALLAKQYGVTWNGRRYDPKDWEKGDTINQCISAATSCLYGVTEAAILAAGYAPAIGFVHTGKPLSFVYDIADIIKFDTVVPKAFEIARRNPGEPDREVRLACRDIFRSSKTLAKLIPLIEDVLAAGEIQPPAPPEDAQPVAIPLPVSLGDAGHRSS,"No cleavage of any substrates, no restoration of UV or mitomycin C (MMC) resistance (PubMed:21219465). Loss of spacer acquisition in vivo (PubMed:24793649).",,MTWLPLNPIPLKDRVSMIFLQYGQIDVIDGAFVLIDKTGIRTHIPVGSVACIMLEPGTRVSHAAVRLAAQVGTLLVWVGEAGVRVYASGQPGGARSDKLLYQAKLALDEDLRLKVVRKMFELRFGEPAPARRSVEQLRGIEGSRVRATYALLAKQYGVTWNGRRYDPKDWEKGDTINQCISAATSCLYGVTEAAILAAGYAPAIGFVHTGKPLSFVYDIADIIKFDTVVPKAFEIARRNPGEPDREVRLACRDIFRSSKTLAKLIPLIEDVLAAGEIQPPAPPEDAQPVAIPLPVSLGDAGHRSS,CRISPR-associated endonuclease Cas1,"CRISPR (clustered regularly interspaced short palindromic repeat), is an adaptive immune system that provides protection against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain sequences complementary to antecedent mobile elements and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA). The Cas1-Cas2 complex is involved in CRISPR adaptation, the first stage of CRISPR immunity, being required for the addition/removal of CRISPR spacers at the leader end of the CRISPR locus. The Cas1-Cas2 complex introduces staggered nicks into both strands of the CRISPR array near the leader repeat and joins the 5'-ends of the repeat strands with the 3'-ends of the new spacer sequence. Spacer DNA integration requires supercoiled target DNA and 3'-OH ends on the inserted (spacer) DNA and probably initiates with a nucleophilic attack of the C 3'-OH end of the protospacer on the minus strand of the first repeat sequence. Expression of Cas1-Cas2 in a strain lacking both genes permits spacer acquisition. Non-specifically binds DNA; the Cas1-Cas2 complex preferentially binds CRISPR-locus DNA. Highest binding is seen to a dual forked DNA complex with 3'-overhangs and a protospacer-adjacent motif-complement specifically positioned. The protospacer DNA lies across a flat surface extending from 1 Cas1 dimer, across the Cas2 dimer and contacting the other Cas1 dimer; the 23 bp-long ds section of the DNA is bracketed by 1 Tyr-22 from each of the Cas1 dimers. Cas1 cuts within the 3'-overhang, to generate a 33-nucleotide DNA that is probably incorporated into the CRISPR leader by a cut-and-paste mechanism. Cas1 alone endonucleolytically cleaves linear ssRNA, ssDNA and short (34 base) dsDNA as well as branched DNA substrates such as Holliday junctions, replication forks and 5'-flap DNA substrates. In vitro catalyzes a concerted transesterification reaction on branched DNA, as would be expected during integration of protospacers into the CRISPR leader sequence; Cas2 is not required in vitro. This reaction requires a 3'-OH group at the branch point. Genetic interactions suggest Cas1 interacts with components of the RecBC and RuvB DNA repair systems.",,"No cleavage of any substrates, no restoration of UV or mitomycin C (MMC) resistance (PubMed:21219465). Loss of spacer acquisition in vivo (PubMed:24793649)."
87,87,P51460-N110K,MDPRLPAWALVLLGPALVFALGPAPTPEMREKLCGHHFVRALVRVCGGPRWSTEARRPATGGDRELLQWLERRHLLHGLVADSNLTLGPGLQPLPQTSHHHRHHRAAATKPARYCCLSGCTQQDLLTLCPY,In CRYPTO.,,MDPRLPAWALVLLGPALVFALGPAPTPEMREKLCGHHFVRALVRVCGGPRWSTEARRPATGGDRELLQWLERRHLLHGLVADSNLTLGPGLQPLPQTSHHHRHHRAAATNPARYCCLSGCTQQDLLTLCPY,Insulin-like 3,Seems to play a role in testicular function. May be a trophic hormone with a role in testicular descent in fetal life. Is a ligand for LGR8 receptor.,"The N-into-K change is likely deleterious because it leads to a nonconservative amino acid substitution, changing a highly conserved residue. This mutation, located in the A-chain of the INSL3 protein, is the first mutation reported in this region. This finding provides new evidence that INSL3 is involved in testicular descent in humans; however, mutations of this gene are not a frequent cause of cryptorchidism.","In CRYPTO. The N-into-K change is likely deleterious because it leads to a nonconservative amino acid substitution, changing a highly conserved residue. This mutation, located in the A-chain of the INSL3 protein, is the first mutation reported in this region. This finding provides new evidence that INSL3 is involved in testicular descent in humans; however, mutations of this gene are not a frequent cause of cryptorchidism."
88,88,Q9VAW5-T828D,MSSKEETPSTGGAAPVATVAASGSATTSYANVVQNLETKKSGTSNTTTTTARATVDNKENQPNLKSFKSWSEEAAAAEAAGESPIVGSVSLAQTGEKRAAASGGDNTAENSSELDDNNDFVPVLSHHRRDRKKARKEKPRDQQPAGGRGDGQKPQQAGGRRVPGSSDTERKSVRPRAPRGGSPRKSAAGAAGAAGSNAGAVSSAVPGGPKVHKDRKDTSPSASIEGAGSSGNEAKSADGDQQAGEKGAAGAAPPPKRFIAAPPPKVNAWKISAKQSGSPKAGTSPLDKRVLQPKAQQQQQQTKQTASQNNNAQNTASNKKTQQQQQPQQGATTTTQTTTAAAAAATAAAAATAATTSAAAATSSAAAVPAATTETATTTTVDASQADALAKVVVKDKKKVNQKASDFSNVGDWPTLIGGTSGSGKATSNEPKRNPTKKQQSAKTAAAVAASSNTTSSEVATESNVAGTTSSSNSNPSSSTTTTNTTTNSQATTAPVASTSHDAKAQRDAEPAANSAAGTTGTAAGPALTKKIPKHKWRPLPIDLAKSSRPKPIGGRPNRRFSDDIADQRRPPRVYHDRQPGAGGAGVESRHPHAGRHPYGSRPATATSERVDSWRSSSSTTTAAFDEQRSGAAGGAGAAGTGVGSATRGPRRYRTPYRGGRQGRGGFSRQGPGRPTYRIPRHLLASGEYANYLPADAAGADSQSSYVLMGTHYFGNVPAAYIELDANSIKEAIKKQVEYYFSVDNLTGDFFLRRKMDPEGYIPVTLIASFHRVLALTTDVAVIVNAIKESDKLELFEGYKVRTKTTPTTWPITEVPEVNEGEPKAIGDLEQEQLEQNDGQEKLEEQTEADSPPPILTSAMATKPLNSIPPPPMPRNPQNLVPKMLQDKQQSRSSTIAALNSVNAISALTQQVEGGAAELAGHLSGLAESVKPKSTSTPDKRNAASAGNGAGSAAALVAEPEGIWKEVKRRSKTNAIKENATTPPQQQQPPLSQTLNNNNDNVKTNNTSSKSKSSSNNAPSNASS,"Phosphomimetic mutant, partially rescues mtDNA levels and hatching rate in spoon null mutants.",,MSSKEETPSTGGAAPVATVAASGSATTSYANVVQNLETKKSGTSNTTTTTARATVDNKENQPNLKSFKSWSEEAAAAEAAGESPIVGSVSLAQTGEKRAAASGGDNTAENSSELDDNNDFVPVLSHHRRDRKKARKEKPRDQQPAGGRGDGQKPQQAGGRRVPGSSDTERKSVRPRAPRGGSPRKSAAGAAGAAGSNAGAVSSAVPGGPKVHKDRKDTSPSASIEGAGSSGNEAKSADGDQQAGEKGAAGAAPPPKRFIAAPPPKVNAWKISAKQSGSPKAGTSPLDKRVLQPKAQQQQQQTKQTASQNNNAQNTASNKKTQQQQQPQQGATTTTQTTTAAAAAATAAAAATAATTSAAAATSSAAAVPAATTETATTTTVDASQADALAKVVVKDKKKVNQKASDFSNVGDWPTLIGGTSGSGKATSNEPKRNPTKKQQSAKTAAAVAASSNTTSSEVATESNVAGTTSSSNSNPSSSTTTTNTTTNSQATTAPVASTSHDAKAQRDAEPAANSAAGTTGTAAGPALTKKIPKHKWRPLPIDLAKSSRPKPIGGRPNRRFSDDIADQRRPPRVYHDRQPGAGGAGVESRHPHAGRHPYGSRPATATSERVDSWRSSSSTTTAAFDEQRSGAAGGAGAAGTGVGSATRGPRRYRTPYRGGRQGRGGFSRQGPGRPTYRIPRHLLASGEYANYLPADAAGADSQSSYVLMGTHYFGNVPAAYIELDANSIKEAIKKQVEYYFSVDNLTGDFFLRRKMDPEGYIPVTLIASFHRVLALTTDVAVIVNAIKESDKLELFEGYKVRTKTTPTTWPITEVPEVNEGEPKAIGTLEQEQLEQNDGQEKLEEQTEADSPPPILTSAMATKPLNSIPPPPMPRNPQNLVPKMLQDKQQSRSSTIAALNSVNAISALTQQVEGGAAELAGHLSGLAESVKPKSTSTPDKRNAASAGNGAGSAAALVAEPEGIWKEVKRRSKTNAIKENATTPPQQQQPPLSQTLNNNNDNVKTNNTSSKSKSSSNNAPSNASS,La-related protein 1,"RNA-binding protein that regulates the translation of specific target mRNA species downstream of the mTORC1 complex, in function of growth signals and nutrient availability. Interacts on the one hand with the 3' poly-A tails that are present in all mRNA molecules, and on the other hand with the 7-methylguanosine cap structure of mRNAs containing a 5' terminal oligopyrimidine (5'TOP) motif, which is present in mRNAs encoding ribosomal proteins and several components of the translation machinery. The interaction with the 5' end of mRNAs containing a 5'TOP motif leads to translational repression. Associates with actively translating ribosomes and stimulates translation of mRNAs containing a 5'TOP motif, thereby regulating protein synthesis, and as a consequence, cell growth and proliferation.",,"Phosphomimetic mutant, partially rescues mtDNA levels and hatching rate in spoon null mutants."
89,89,P10088-H9A,MSVVANPLAPLFAAGVEDIDLREALGSTEVREIERLMDEKSVLVFRGQPLSQDQQIAFARNFGPLEGGFIKVNQRPSRFKYAELADISNVSLDGKVAQRDAREVVGNFANQLWHSDSSFQQPAARYSMLSAVVVPPSGGDTEFCDMRAAYDALPRDLQSELEGLRAEHYALNSRFLLGDTDYSEAQRNAMPPVNWPLVRTHAGSGRKFLFIGAHASHVEGLPVAEGRMLLAELLEHATQREFVYRHRWNVGDLVMWDNRCVLHRGRRYDISARRELRRATTLDDAVV,No change in activity and substrate affinity.,,MSVVANPLHPLFAAGVEDIDLREALGSTEVREIERLMDEKSVLVFRGQPLSQDQQIAFARNFGPLEGGFIKVNQRPSRFKYAELADISNVSLDGKVAQRDAREVVGNFANQLWHSDSSFQQPAARYSMLSAVVVPPSGGDTEFCDMRAAYDALPRDLQSELEGLRAEHYALNSRFLLGDTDYSEAQRNAMPPVNWPLVRTHAGSGRKFLFIGAHASHVEGLPVAEGRMLLAELLEHATQREFVYRHRWNVGDLVMWDNRCVLHRGRRYDISARRELRRATTLDDAVV,"Alpha-ketoglutarate-dependent 2,4-dichlorophenoxyacetate dioxygenase","Involved in degradation of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). Is also able to degrade 2-methyl-4-chlorophenoxyacetic acid and 3-chlorobenzoic acid.",,No change in activity and substrate affinity.
90,90,Q8FJ36-E11A,MFVPFLIILRAGLEAALIVSLIASYLTRTQRGRWIGVMWIGVLLAAALCLGLGIFINETTGEFPQKEQELFEGIVAVIAVVILTWMVFWMRKVSRNVKVQLEQAVDSALQRGNHHGWALVMMVFFAVAREGLESVFFLLAAFQQDVGIWPPLGAMLGLATAVVLGFLLYWGGIRLNLGAFFKWTSLFILFVAAGLAAGAIRAFHEAGLWNHFQEIAFDMSAVLSTHSLFGTLMEGIFGYQEAPSVSEVAVWFIYLIPALVAFVLPPRAGATASRSM,Loss of activity in vivo.,,MFVPFLIILREGLEAALIVSLIASYLTRTQRGRWIGVMWIGVLLAAALCLGLGIFINETTGEFPQKEQELFEGIVAVIAVVILTWMVFWMRKVSRNVKVQLEQAVDSALQRGNHHGWALVMMVFFAVAREGLESVFFLLAAFQQDVGIWPPLGAMLGLATAVVLGFLLYWGGIRLNLGAFFKWTSLFILFVAAGLAAGAIRAFHEAGLWNHFQEIAFDMSAVLSTHSLFGTLMEGIFGYQEAPSVSEVAVWFIYLIPALVAFVLPPRAGATASRSM,Ferrous iron permease EfeU,Uptake of Fe(2+) ions across the membrane.,,Loss of activity in vivo.
91,91,O74859-C130A,MSVHKTNDAFKVLMNSAKEPIVEDIPKKYRKQSFRDNLKVYIESPESYKNVIYYDDDVVLVRDMFPKSKMHLLLMTRDPHLTHVHPLEIMMKHRSLVEKLVSYVQGDLSGLIFDEARNCLSQQLTNEALANYIKVGFHAGPSMNNLHLHIMTLDHVSPSLKNSAHYISFTSPFFVKIDTPTSNLPTRGTLTSLFQEDLKCWRCGETFGRHFTKLKAHLQEEYDDWLDKSVSM,Decreased affinity for DNA.,,MSVHKTNDAFKVLMNSAKEPIVEDIPKKYRKQSFRDNLKVYIESPESYKNVIYYDDDVVLVRDMFPKSKMHLLLMTRDPHLTHVHPLEIMMKHRSLVEKLVSYVQGDLSGLIFDEARNCLSQQLTNEALCNYIKVGFHAGPSMNNLHLHIMTLDHVSPSLKNSAHYISFTSPFFVKIDTPTSNLPTRGTLTSLFQEDLKCWRCGETFGRHFTKLKAHLQEEYDDWLDKSVSM,Aprataxin-like protein,"DNA-binding protein involved in single-strand DNA break repair, double-strand DNA break repair and base excision repair. Resolves abortive DNA ligation intermediates formed either at base excision sites, or when DNA ligases attempt to repair non-ligatable breaks induced by reactive oxygen species. Catalyzes the release of adenylate groups covalently linked to 5'-phosphate termini, resulting in the production of 5'-phosphate termini that can be efficiently rejoined. Likewise, catalyzes the release of 3'-linked guanosine (DNAppG) and inosine (DNAppI) from DNA, but has higher specific activity with 5'-linked adenosine (AppDNA).",This mutation may result in altered DNA deadenylase activity and affect the ability of aprataxin to resolve DNA 5'-AMP termini and reverse abortive DNA ligation.,Decreased affinity for DNA. This mutation may result in altered DNA deadenylase activity and affect the ability of aprataxin to resolve DNA 5'-AMP termini and reverse abortive DNA ligation.
92,92,O54992-T182A,MSEDSDMEKAIKETSILEEYSINWTQKLGAGISGPVRVCVKKSTQERFALKILLDRPKARNEVRLHMMCATHPNIVQIIEVFANSVQFPHESSPRARLLIVMEMMEGGELFHRISQHRHFTEKQASQVTKQIALALQHCHLLNIAHRDLKPENLLFKDNSLDAPVKLCDFGFAKVDQGDLMAPQFTPYYVAPQVLEAQRRHQKEKSGIIPTSPTPYTYNKSCDLWSLGVIIYVMLCGYPPFYSKHHSRTIPKDMRKKIMTGSFEFPEEEWSQISEMAKDVVRKLLKVKPEERLTIEGVLDHPWLNSTEALDNVLPSAQLMMDKAVVAGIQQAHAEQLANMRIQDLKVSLKPLHSVNNPILRKRKLLGTKPKDGIYIHDHENGTEDSNVALEKLRDVIAQCILPQAGKGENEDEKLNEVMQEAWKYNRECKLLRDALQSFSWNGRGFTDKVDRLKLAEVVKQVIEEQTLPHEPQ,Impairs protein kinase activity and shuttling to the cytoplasm.,,MSEDSDMEKAIKETSILEEYSINWTQKLGAGISGPVRVCVKKSTQERFALKILLDRPKARNEVRLHMMCATHPNIVQIIEVFANSVQFPHESSPRARLLIVMEMMEGGELFHRISQHRHFTEKQASQVTKQIALALQHCHLLNIAHRDLKPENLLFKDNSLDAPVKLCDFGFAKVDQGDLMTPQFTPYYVAPQVLEAQRRHQKEKSGIIPTSPTPYTYNKSCDLWSLGVIIYVMLCGYPPFYSKHHSRTIPKDMRKKIMTGSFEFPEEEWSQISEMAKDVVRKLLKVKPEERLTIEGVLDHPWLNSTEALDNVLPSAQLMMDKAVVAGIQQAHAEQLANMRIQDLKVSLKPLHSVNNPILRKRKLLGTKPKDGIYIHDHENGTEDSNVALEKLRDVIAQCILPQAGKGENEDEKLNEVMQEAWKYNRECKLLRDALQSFSWNGRGFTDKVDRLKLAEVVKQVIEEQTLPHEPQ,MAP kinase-activated protein kinase 5,"Tumor suppressor serine/threonine-protein kinase involved in mTORC1 signaling and post-transcriptional regulation. Phosphorylates FOXO3, ERK3/MAPK6, ERK4/MAPK4, HSP27/HSPB1, p53/TP53 and RHEB. Acts as a tumor suppressor by mediating Ras-induced senescence and phosphorylating p53/TP53. Involved in post-transcriptional regulation of MYC by mediating phosphorylation of FOXO3: phosphorylation of FOXO3 leads to promote nuclear localization of FOXO3, enabling expression of miR-34b and miR-34c, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent MYC translation. Acts as a negative regulator of mTORC1 signaling by mediating phosphorylation and inhibition of RHEB. Part of the atypical MAPK signaling via its interaction with ERK3/MAPK6 or ERK4/MAPK4: the precise role of the complex formed with ERK3/MAPK6 or ERK4/MAPK4 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPK (ERK3/MAPK6 or ERK4/MAPK4), ERK3/MAPK6 (or ERK4/MAPK4) is phosphorylated and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6 (or ERK4/MAPK4). Mediates phosphorylation of HSP27/HSPB1 in response to PKA/PRKACA stimulation, inducing F-actin rearrangement.","This mutation has been shown to inhibit the catalytic activity of MK5 in vitro and prevent PKA-induced nuclear export of MK5. Additionally, noroxoaconitine, a diterpenoid alkaloid, has been identified as an ATP competitor that binds more strongly to MK5 than to MK3, suggesting that it may be a potential therapeutic for targeting MK5.","Impairs protein kinase activity and shuttling to the cytoplasm. This mutation has been shown to inhibit the catalytic activity of MK5 in vitro and prevent PKA-induced nuclear export of MK5. Additionally, noroxoaconitine, a diterpenoid alkaloid, has been identified as an ATP competitor that binds more strongly to MK5 than to MK3, suggesting that it may be a potential therapeutic for targeting MK5."
93,93,Q9SRH5-P223H,MVKGPGLYTEIGKKARDLLYKDHNSDQKFSITTFSPAGVAITSTGTKKGDLLLGDVAFQSRRKNITTDLKVCTDSTFLITATVDEAAPGLRSIFSFKVPDQNSGKVELQYLHEYAGISTSMGLTQNPTVNFSGVIGSNVLAVGTDVSFDTKSGNFTKINAGLSFTKEDLIASLTVNDKGDLLNASYYHIVNPLFNTAVGAEVSHKLSSKDSTITVGTQHSLDHLTSVKARVNSAGIASALIQHEWKPKSFFTISGEVDTKSIDKSAKVGLALALKP,Alteration of subcellular localization.,,MVKGPGLYTEIGKKARDLLYKDHNSDQKFSITTFSPAGVAITSTGTKKGDLLLGDVAFQSRRKNITTDLKVCTDSTFLITATVDEAAPGLRSIFSFKVPDQNSGKVELQYLHEYAGISTSMGLTQNPTVNFSGVIGSNVLAVGTDVSFDTKSGNFTKINAGLSFTKEDLIASLTVNDKGDLLNASYYHIVNPLFNTAVGAEVSHKLSSKDSTITVGTQHSLDPLTSVKARVNSAGIASALIQHEWKPKSFFTISGEVDTKSIDKSAKVGLALALKP,Mitochondrial outer membrane protein porin 1,"Forms a channel through the mitochondrial outer membrane that allows diffusion of small hydrophilic molecules. The channel adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV. The open state has a weak anion selectivity whereas the closed state is cation-selective. Involved in plant development at reproductive stage, is important for pollen development and may regulate hydrogen peroxide generation during disease resistance.",,Alteration of subcellular localization.
94,94,Q9Y320-A178T,MAVLAPLIALVYSVPRLSRWLAQPYYLLSALLSAAFLLVRKLPPLCHGLPTQREDGNPCDFDWREVEILMFLSAIVMMKNRRSITVEQHIGNIFMFSKVANTILFFRLDIRMGLLYITLCIVFLMTCKPPLYMGPEYIKYFNDKTIDEELERDKRVTWIVEFFANWSNDCQSFAPIYTDLSLKYNCTGLNFGKVDVGRYTDVSTRYKVSTSPLTKQLPTLILFQGGKEAMRRPQIDKKGRAVSWTFSEENVIREFNLNELYQRAKKLSKAGDNIPEEQPVASTPTTVSDGENKKDK,In NEDMCMS; unknown pathological significance.,,MAVLAPLIALVYSVPRLSRWLAQPYYLLSALLSAAFLLVRKLPPLCHGLPTQREDGNPCDFDWREVEILMFLSAIVMMKNRRSITVEQHIGNIFMFSKVANTILFFRLDIRMGLLYITLCIVFLMTCKPPLYMGPEYIKYFNDKTIDEELERDKRVTWIVEFFANWSNDCQSFAPIYADLSLKYNCTGLNFGKVDVGRYTDVSTRYKVSTSPLTKQLPTLILFQGGKEAMRRPQIDKKGRAVSWTFSEENVIREFNLNELYQRAKKLSKAGDNIPEEQPVASTPTTVSDGENKKDK,Thioredoxin-related transmembrane protein 2,"Endoplasmic reticulum and mitochondria-associated protein that probably functions as a regulator of cellular redox state and thereby regulates protein post-translational modification, protein folding and mitochondrial activity. Indirectly regulates neuronal proliferation, migration, and organization in the developing brain.",,In NEDMCMS; unknown pathological significance.
95,95,P11086-E185Q,MSGADRSPNAGAAPDSAPGQAAVASAYQRFEPRAYLRNNYAPPRGDLCNPNGVGPWKLRCLAQTFATGEVSGRTLIDIGSGPTVYQLLSACSHFEDITMTDFLEVNRQELGRWLQEEPGAFNWSMYSQHACLIEGKGECWQDKERQLRARVKRVLPIDVHQPQPLGAGSPAPLPADALVSAFCLQAVSPDLASFQRALDHITTLLRPGGHLLLIGALEESWYLAGEARLTVVPVSEEEVREALVRSGYKVRDLRTYIMPAHLQTGVDDVKGVFFAWAQKVGL,Strongly reduced enzyme activity towards phenylethanolamine. Increases affinity for S-adenosyl-L-methionine.,,MSGADRSPNAGAAPDSAPGQAAVASAYQRFEPRAYLRNNYAPPRGDLCNPNGVGPWKLRCLAQTFATGEVSGRTLIDIGSGPTVYQLLSACSHFEDITMTDFLEVNRQELGRWLQEEPGAFNWSMYSQHACLIEGKGECWQDKERQLRARVKRVLPIDVHQPQPLGAGSPAPLPADALVSAFCLEAVSPDLASFQRALDHITTLLRPGGHLLLIGALEESWYLAGEARLTVVPVSEEEVREALVRSGYKVRDLRTYIMPAHLQTGVDDVKGVFFAWAQKVGL,Phenylethanolamine N-methyltransferase,"Catalyzes the transmethylation of nonepinephrine (noradrenaline) to form epinephrine (adrenaline), using S-adenosyl-L-methionine as the methyl donor. Other substrates include phenylethanolamine and octopamine. Also methylates normetanephrine.",,Strongly reduced enzyme activity towards phenylethanolamine. Increases affinity for S-adenosyl-L-methionine.
96,96,Q9QUH6-S842A,MSRSRASIHRGSIPAMSYAPFRDVRGPPMHRTQYVHSPYDRPGWNPRFCIISGNQLLMLDEDEIHPLLIRDRRSESSRNKLLRRTVSVPVEGRPHGEHEYHLGRSRRKSVPGGKQYSMEAAPAAPFRPSQGFLSRRLKSSIKRTKSQPKLDRTSSFRQILPRFRSADHDRARLMQSFKESHSHESLLSPSSAAEALELNLDEDSIIKPVHSSILGQEFCFEVTTSSGTKCFACRSAAERDKWIENLQRAVKPNKDNSRRVDNVLKLWIIEARELPPKKRYYCELCLDDMLYARTTSKPRSASGDTVFWGEHFEFNNLPAVRALRLHLYRDSDKKRKKDKAGYVGLVTVPVATLAGRHFTEQWYPVTLPTGSGGSGGMGSGGGGGSGGGSGGKGKGGCPAVRLKARYQTMSILPMELYKEFAEYVTNHYRMLCAVLEPALNVKGKEEVASALVHILQSTGKAKDFLSDMAMSEVDRFMEREHLIFRENTLATKAIEEYMRLIGQKYLKDAIGEFIRALYESEENCEVDPIKCTASSLAEHQANLRMCCELALCKVVNSHCVFPRELKEVFASWRLRCAERGREDIADRLISASLFLRFLCPAIMSPSLFGLMQEYPDEQTSRTLTLIAKVIQNLANFSKFTSKEDFLGFMNEFLELEWGSMQQFLYEISNLDTLTNSSSFEGYIDLGRELSTLHALLWEVLPQLSKEALLKLGPLPRLLSDISTALRNPNIQRQPSRQSERARSQPMVLRGPSAEMQGYMMRDLNSSIDLQSFMARGLNSSMDMARLPSPTKEKPPPPPPGGGKDLFYVSRPPLARSSPAYCTSSSDITEPEQKMLSVNKSVAMLDLQGDGPGGRLNSSSVSNLAAVGDLLHSSQASLTAALGLRPAPAGRLSQGSGSSITAAGMRLSQMGVTTDGVPAQQLRIPLSFQNPLFHMAADGPGPPAGHGGSSGHGPPSSHHHHHHHHHHRGGEPPGDTFAPFHGYSKSEDLSTGVPKPPAASILHSHSYSDEFGPSGTDFTRRQLSL,Blocks the gel mobility shift induced by PLK2.,,MSRSRASIHRGSIPAMSYAPFRDVRGPPMHRTQYVHSPYDRPGWNPRFCIISGNQLLMLDEDEIHPLLIRDRRSESSRNKLLRRTVSVPVEGRPHGEHEYHLGRSRRKSVPGGKQYSMEAAPAAPFRPSQGFLSRRLKSSIKRTKSQPKLDRTSSFRQILPRFRSADHDRARLMQSFKESHSHESLLSPSSAAEALELNLDEDSIIKPVHSSILGQEFCFEVTTSSGTKCFACRSAAERDKWIENLQRAVKPNKDNSRRVDNVLKLWIIEARELPPKKRYYCELCLDDMLYARTTSKPRSASGDTVFWGEHFEFNNLPAVRALRLHLYRDSDKKRKKDKAGYVGLVTVPVATLAGRHFTEQWYPVTLPTGSGGSGGMGSGGGGGSGGGSGGKGKGGCPAVRLKARYQTMSILPMELYKEFAEYVTNHYRMLCAVLEPALNVKGKEEVASALVHILQSTGKAKDFLSDMAMSEVDRFMEREHLIFRENTLATKAIEEYMRLIGQKYLKDAIGEFIRALYESEENCEVDPIKCTASSLAEHQANLRMCCELALCKVVNSHCVFPRELKEVFASWRLRCAERGREDIADRLISASLFLRFLCPAIMSPSLFGLMQEYPDEQTSRTLTLIAKVIQNLANFSKFTSKEDFLGFMNEFLELEWGSMQQFLYEISNLDTLTNSSSFEGYIDLGRELSTLHALLWEVLPQLSKEALLKLGPLPRLLSDISTALRNPNIQRQPSRQSERARSQPMVLRGPSAEMQGYMMRDLNSSIDLQSFMARGLNSSMDMARLPSPTKEKPPPPPPGGGKDLFYVSRPPLARSSPAYCTSSSDITEPEQKMLSVNKSVSMLDLQGDGPGGRLNSSSVSNLAAVGDLLHSSQASLTAALGLRPAPAGRLSQGSGSSITAAGMRLSQMGVTTDGVPAQQLRIPLSFQNPLFHMAADGPGPPAGHGGSSGHGPPSSHHHHHHHHHHRGGEPPGDTFAPFHGYSKSEDLSTGVPKPPAASILHSHSYSDEFGPSGTDFTRRQLSL,Ras/Rap GTPase-activating protein SynGAP,"Major constituent of the PSD essential for postsynaptic signaling. Inhibitory regulator of the Ras-cAMP pathway. Member of the NMDAR signaling complex in excitatory synapses, it may play a role in NMDAR-dependent control of AMPAR potentiation, AMPAR membrane trafficking and synaptic plasticity. Regulates AMPAR-mediated miniature excitatory postsynaptic currents. Exhibits dual GTPase-activating specificity for Ras and Rap. May be involved in certain forms of brain injury, leading to long-term learning and memory deficits.",Phosphorylation of Plk2 at stimulates Ras inhibitor SynGAP and Rap activator PDZGEF1.,Blocks the gel mobility shift induced by PLK2. Phosphorylation of Plk2 at stimulates Ras inhibitor SynGAP and Rap activator PDZGEF1.
97,97,P38398-S186Y,MDLSALRVEEVQNVINAMQKILECPICLELIKEPVSTKCDHIFCKFCMLKLLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVEELLKIICAFQLDTGLEYANSYNFAKKENNSPEHLKDEVSIIQSMGYRNRAKRLLQSEPENPSLQETSLSVQLSNLGTVRTLRTKQRIQPQKTSVYIELGSDYSEDTVNKATYCSVGDQELLQITPQGTRDEISLDSAKKAACEFSETDVTNTEHHQPSNNDLNTTEKRAAERHPEKYQGSSVSNLHVEPCGTNTHASSLQHENSSLLLTKDRMNVEKAEFCNKSKQPGLARSQHNRWAGSKETCNDRRTPSTEKKVDLNADPLCERKEWNKQKLPCSENPRDTEDVPWITLNSSIQKVNEWFSRSDELLGSDDSHDGESESNAKVADVLDVLNEVDEYSGSSEKIDLLASDPHEALICKSERVHSKSVESNIEDKIFGKTYRKKASLPNLSHVTENLIIGAFVTEPQIIQERPLTNKLKRKRRPTSGLHPEDFIKKADLAVQKTPEMINQGTNQTEQNGQVMNITNSGHENKTKGDSIQNEKNPNPIESLEKESAFKTKAEPISSSISNMELELNIHNSKAPKKNRLRRKSSTRHIHALELVVSRNLSPPNCTELQIDSCSSSEEIKKKKYNQMPVRHSRNLQLMEGKEPATGAKKSNKPNEQTSKRHDSDTFPELKLTNAPGSFTKCSNTSELKEFVNPSLPREEKEEKLETVKVSNNAEDPKDLMLSGERVLQTERSVESSSISLVPGTDYGTQESISLLEVSTLGKAKTEPNKCVSQCAAFENPKGLIHGCSKDNRNDTEGFKYPLGHEVNHSRETSIEMEESELDAQYLQNTFKVSKRQSFAPFSNPGNAEEECATFSAHSGSLKKQSPKVTFECEQKEENQGKNESNIKPVQTVNITAGFPVVGQKDKPVDNAKCSIKGGSRFCLSSQFRGNETGLITPNKHGLLQNPYRIPPLFPIKSFVKTKCKKNLLEENFEEHSMSPEREMGNENIPSTVS,In BC; unknown pathological significance; functionally neutral in vitro.,,MDLSALRVEEVQNVINAMQKILECPICLELIKEPVSTKCDHIFCKFCMLKLLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVEELLKIICAFQLDTGLEYANSYNFAKKENNSPEHLKDEVSIIQSMGYRNRAKRLLQSEPENPSLQETSLSVQLSNLGTVRTLRTKQRIQPQKTSVYIELGSDSSEDTVNKATYCSVGDQELLQITPQGTRDEISLDSAKKAACEFSETDVTNTEHHQPSNNDLNTTEKRAAERHPEKYQGSSVSNLHVEPCGTNTHASSLQHENSSLLLTKDRMNVEKAEFCNKSKQPGLARSQHNRWAGSKETCNDRRTPSTEKKVDLNADPLCERKEWNKQKLPCSENPRDTEDVPWITLNSSIQKVNEWFSRSDELLGSDDSHDGESESNAKVADVLDVLNEVDEYSGSSEKIDLLASDPHEALICKSERVHSKSVESNIEDKIFGKTYRKKASLPNLSHVTENLIIGAFVTEPQIIQERPLTNKLKRKRRPTSGLHPEDFIKKADLAVQKTPEMINQGTNQTEQNGQVMNITNSGHENKTKGDSIQNEKNPNPIESLEKESAFKTKAEPISSSISNMELELNIHNSKAPKKNRLRRKSSTRHIHALELVVSRNLSPPNCTELQIDSCSSSEEIKKKKYNQMPVRHSRNLQLMEGKEPATGAKKSNKPNEQTSKRHDSDTFPELKLTNAPGSFTKCSNTSELKEFVNPSLPREEKEEKLETVKVSNNAEDPKDLMLSGERVLQTERSVESSSISLVPGTDYGTQESISLLEVSTLGKAKTEPNKCVSQCAAFENPKGLIHGCSKDNRNDTEGFKYPLGHEVNHSRETSIEMEESELDAQYLQNTFKVSKRQSFAPFSNPGNAEEECATFSAHSGSLKKQSPKVTFECEQKEENQGKNESNIKPVQTVNITAGFPVVGQKDKPVDNAKCSIKGGSRFCLSSQFRGNETGLITPNKHGLLQNPYRIPPLFPIKSFVKTKCKKNLLEENFEEHSMSPEREMGNENIPSTVS,Breast cancer type 1 susceptibility protein,"E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Required for FANCD2 targeting to sites of DNA damage. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8. Acts as a transcriptional activator.",,In BC; unknown pathological significance; functionally neutral in vitro.
98,98,P07902-V168L,MSRSGTDPQQRQQASEADAAAATFRANDHQHIRYNPLQDEWVLVSAHRMKRPWQGQVEPQLLKTVPRHDPLNPLCPGAIRANGEVNPQYDSTFLFDNDFPALQPDAPSPGPSDHPLFQAKSARGVCKVMCFHPWSDVTLPLMSVPEIRAVVDAWASVTEELGAQYPWLQIFENKGAMMGCSNPHPHCQVWASSFLPDIAQREERSQQAYKSQHGEPLLMEYSRQELLRKERLVLTSEHWLVLVPFWATWPYQTLLLPRRHVRRLPELTPAERDDLASIMKKLLTKYDNLFETSFPYSMGWHGAPTGSEAGANWNHWQLHAHYYPPLLRSATVRKFMVGYEMLAQAQRDLTPEQAAERLRALPEVHYHLGQKDRETATIA,In GALAC1; loss of activity.,,MSRSGTDPQQRQQASEADAAAATFRANDHQHIRYNPLQDEWVLVSAHRMKRPWQGQVEPQLLKTVPRHDPLNPLCPGAIRANGEVNPQYDSTFLFDNDFPALQPDAPSPGPSDHPLFQAKSARGVCKVMCFHPWSDVTLPLMSVPEIRAVVDAWASVTEELGAQYPWVQIFENKGAMMGCSNPHPHCQVWASSFLPDIAQREERSQQAYKSQHGEPLLMEYSRQELLRKERLVLTSEHWLVLVPFWATWPYQTLLLPRRHVRRLPELTPAERDDLASIMKKLLTKYDNLFETSFPYSMGWHGAPTGSEAGANWNHWQLHAHYYPPLLRSATVRKFMVGYEMLAQAQRDLTPEQAAERLRALPEVHYHLGQKDRETATIA,Galactose-1-phosphate uridylyltransferase,Plays an important role in galactose metabolism.,"The variant showed decreased levels of expression and decreased abundance in the soluble fraction of the Escherichia coli cell extracts, suggesting altered stability and solubility. It also had a significantly decreased V(max) in kinetic studies.","In GALAC1; loss of activity. The variant showed decreased levels of expression and decreased abundance in the soluble fraction of the Escherichia coli cell extracts, suggesting altered stability and solubility. It also had a significantly decreased V(max) in kinetic studies."
99,99,Q62219-C91S,MEDLDALLSDLETTTSHMSRLGAPKERPPETLTPPPPYGHQPQTGSGESSGTTGDKDHLYSTVCKPRSPKPVAPVAPPFSSSSGVLGNGLSELDRLLQELNATQFNITDEIMSQFPSSKMAEGEEKEDQSEDKSSPTVPPSPFPAPSKPSATSATQELDRLMASLSDFRVQNHLPASGPPQPPAASPTREGCPSPPGQTSKGSLDTMLGLLQSDLSRRGVPTQAKGLCGSCNKPIAGQVVTALGRAWHPEHFLCSGCSTTLGGSSFFEKDGAPFCPECYFERFSPRCGFCNQPIRHKMVTALGTHWHPEHFCCVSCGEPFGEEGFHEREGRPYCRRDFLQLFAPRCQGCQGPILDNYISALSALWHPDCFVCRECLAPFSGGSFFEHEGRPLCENHFHAQRGSLCATCGLPVTGRCVSALGRRFHPDHFTCTFCLRPLTKGSFQERASKPYCQPCFLKLFG,Increase in nuclear localization.,,MEDLDALLSDLETTTSHMSRLGAPKERPPETLTPPPPYGHQPQTGSGESSGTTGDKDHLYSTVCKPRSPKPVAPVAPPFSSSSGVLGNGLCELDRLLQELNATQFNITDEIMSQFPSSKMAEGEEKEDQSEDKSSPTVPPSPFPAPSKPSATSATQELDRLMASLSDFRVQNHLPASGPPQPPAASPTREGCPSPPGQTSKGSLDTMLGLLQSDLSRRGVPTQAKGLCGSCNKPIAGQVVTALGRAWHPEHFLCSGCSTTLGGSSFFEKDGAPFCPECYFERFSPRCGFCNQPIRHKMVTALGTHWHPEHFCCVSCGEPFGEEGFHEREGRPYCRRDFLQLFAPRCQGCQGPILDNYISALSALWHPDCFVCRECLAPFSGGSFFEHEGRPLCENHFHAQRGSLCATCGLPVTGRCVSALGRRFHPDHFTCTFCLRPLTKGSFQERASKPYCQPCFLKLFG,Transforming growth factor beta-1-induced transcript 1 protein,"Functions as a molecular adapter coordinating multiple protein-protein interactions at the focal adhesion complex and in the nucleus. Links various intracellular signaling modules to plasma membrane receptors and regulates the Wnt and TGFB signaling pathways. May also regulate SLC6A3 and SLC6A4 targeting to the plasma membrane hence regulating their activity. In the nucleus, functions as a nuclear receptor coactivator regulating glucocorticoid, androgen, mineralocorticoid and progesterone receptor transcriptional activity. May play a role in the processes of cell growth, proliferation, migration, differentiation and senescence. May have a zinc-dependent DNA-binding activity.","Mutation at site regulates the nuclear accumulation of Hic-5 by affecting the nuclear export signal (NES) in the N-terminal, which is sensitive to oxidants.","Increase in nuclear localization. Mutation at site regulates the nuclear accumulation of Hic-5 by affecting the nuclear export signal (NES) in the N-terminal, which is sensitive to oxidants."
