sujigwak/NVAR huggingface dataset:
UniProt ID: P22314
Variant: S -> G at position 547-547
Variant annotation: in SMAX2; dbSNP:rs80356546
Protein function: Catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation through the ubiquitin-proteasome system . Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP . Essential for the formation of radiation-induced foci, timely DNA repair and for response to replication stress. Promotes the recruitment of TP53BP1 and BRCA1 at DNA damage sites .
Reference sequence:
MSSSPLSKKRRVSGPDPKPGSNCSPAQSVLSEVPSVPTNGMAKNGSEADIDEGLYSRQLYVLGHEAMKRLQTSSVLVSGLRGLGVEIAKNIILGGVKAVTLHDQGTAQWADLSSQFYLREEDIGKNRAEVSQPRLAELNSYVPVTAYTGPLVEDFLSGFQVVVLTNTPLEDQLRVGEFCHNRGIKLVVADTRGLFGQLFCDFGEEMILTDSNGEQPLSAMVSMVTKDNPGVVTCLDEARHGFESGDFVSFSEVQGMVELNGNQPMEIKVLGPYTFSICDTSNFSDYIRGGIVSQVKVPKKISFKSLVASLAEPDFVVTDFAKFSRPAQLHIGFQALHQFCAQHGRPPRPRNEEDAAELVALAQAVNARALPAVQQNNLDEDLIRKLAYVAAGDLAPINAFIGGLAAQEVMKACSGKFMPIMQWLYFDALECLPEDKEVLTEDKCLQRQNRYDGQVAVFGSDLQEKLGKQKYFLVGAGAIGCELLKNFAMIGLGCGEGGEIIVTDMDTIEKSNLNRQFLFRPWDVTKLKSDTAAAAVRQMNPHIRVTSHQNRVGPDTERIYDDDFFQNLDGVANALDNVDARMYMDRRCVYYRKPLLESGTLGTKGNVQVVIPFLTESYSSSQDPPEKSIPICTLKNFPNAIEHTLQWARDEFEGLFKQPAENVNQYLTDPKFVERTLRLAGTQPLEVLEAVQRSLVLQRPQTWADCVTWACHHWHTQYSNNIRQLLHNFPPDQLTSSGAPFWSGPKRCPHPLTFDVNNPLHLDYVMAAANLFAQTYGLTGSQDRAAVATFLQSVQVPEFTPKSGVKIHVSDQELQSANASVDDSRLEELKATLPSPDKLPGFKMYPIDFEKDDDSNFHMDFIVAASNLRAENYDIPSADRHKSKLIAGKIIPAIATTTAAVVGLVCLELYKVVQGHRQLDSYKNGFLNLALPFFGFSEPLAAPRHQYYNQEWTLWDRFEVQGLQPNGEEMTLKQFLDYFKTEHKLEITMLSQGVSMLYSFFMPAAKLKERLDQPMTEIVSRVSKRKLGRHVRALVLELCCNDESGEDVEVPYVRYTIR
UniProt ID: P22314
Variant: E -> V at position 557-557
Variant annotation: in SMAX2
Protein function: Catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation through the ubiquitin-proteasome system . Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP . Essential for the formation of radiation-induced foci, timely DNA repair and for response to replication stress. Promotes the recruitment of TP53BP1 and BRCA1 at DNA damage sites .
Reference sequence:
MSSSPLSKKRRVSGPDPKPGSNCSPAQSVLSEVPSVPTNGMAKNGSEADIDEGLYSRQLYVLGHEAMKRLQTSSVLVSGLRGLGVEIAKNIILGGVKAVTLHDQGTAQWADLSSQFYLREEDIGKNRAEVSQPRLAELNSYVPVTAYTGPLVEDFLSGFQVVVLTNTPLEDQLRVGEFCHNRGIKLVVADTRGLFGQLFCDFGEEMILTDSNGEQPLSAMVSMVTKDNPGVVTCLDEARHGFESGDFVSFSEVQGMVELNGNQPMEIKVLGPYTFSICDTSNFSDYIRGGIVSQVKVPKKISFKSLVASLAEPDFVVTDFAKFSRPAQLHIGFQALHQFCAQHGRPPRPRNEEDAAELVALAQAVNARALPAVQQNNLDEDLIRKLAYVAAGDLAPINAFIGGLAAQEVMKACSGKFMPIMQWLYFDALECLPEDKEVLTEDKCLQRQNRYDGQVAVFGSDLQEKLGKQKYFLVGAGAIGCELLKNFAMIGLGCGEGGEIIVTDMDTIEKSNLNRQFLFRPWDVTKLKSDTAAAAVRQMNPHIRVTSHQNRVGPDTERIYDDDFFQNLDGVANALDNVDARMYMDRRCVYYRKPLLESGTLGTKGNVQVVIPFLTESYSSSQDPPEKSIPICTLKNFPNAIEHTLQWARDEFEGLFKQPAENVNQYLTDPKFVERTLRLAGTQPLEVLEAVQRSLVLQRPQTWADCVTWACHHWHTQYSNNIRQLLHNFPPDQLTSSGAPFWSGPKRCPHPLTFDVNNPLHLDYVMAAANLFAQTYGLTGSQDRAAVATFLQSVQVPEFTPKSGVKIHVSDQELQSANASVDDSRLEELKATLPSPDKLPGFKMYPIDFEKDDDSNFHMDFIVAASNLRAENYDIPSADRHKSKLIAGKIIPAIATTTAAVVGLVCLELYKVVQGHRQLDSYKNGFLNLALPFFGFSEPLAAPRHQYYNQEWTLWDRFEVQGLQPNGEEMTLKQFLDYFKTEHKLEITMLSQGVSMLYSFFMPAAKLKERLDQPMTEIVSRVSKRKLGRHVRALVLELCCNDESGEDVEVPYVRYTIR
UniProt ID: P22315
Variant: M -> K at position 98-98
Variant annotation: in Fechm1Pas
Protein function: Catalyzes the ferrous insertion into protoporphyrin IX.
Reference sequence:
MLSASANMAAALRAAGALLREPLVHGSSRACQPWRCQSGAAVAATTEKVHHAKTTKPQAQPERRKPKTGILMLNMGGPETLGEVQDFLQRLFLDRDLMTLPIQNKLAPFIAKRRTPKIQEQYRRIGGGSPIKMWTSKQGEGMVKLLDELSPATAPHKYYIGFRYVHPLTEEAIEEMERDGLERAIAFTQYPQYSCSTTGSSLNAIYRYYNEVGQKPTMKWSTIDRWPTHPLLIQCFADHILKELNHFPEEKRSEVVILFSAHSLPMSVVNRGDPYPQEVGATVHKVMEKLGYPNPYRLVWQSKVGPVPWLGPQTDEAIKGLCERGRKNILLVPIAFTSDHIETLYELDIEYSQVLAQKCGAENIRRAESLNGNPLFSKALADLVHSHIQSNKLCSTQLSLNCPLCVNPVCRKTKSFFTSQQL
UniProt ID: P22391
Variant: L -> P at position 262-262
Variant annotation: in strain: KH66
Protein function: Hydrolyzes broad-spectrum beta-lactam antibiotics. Active against cephalosporins.
Reference sequence:
MLKSSWRKTALMAAAAVPLLLASGSLWASADAIQQKLADLEKRSGGRLGVALINTADDSQTLYRGDERFAMCSTGKVMAAAAVLKQSESNPEVVNKRLEIKKSDLVVWSPITEKHLQSGMTLAELSAAALQYSDNTAMNKMISYLGGPEKVTAFAQSIGDVTFRLDRTEPALNSAIPGDKRDTTTPLAMAESLRKLTLGNALGEQQRAQLVTWLKGNTTGGQSIRAGLPASWAVGDKTGAGDYGTTNDIAVIWPENHAPLVLVTYFTQPQQDAKSRKEVLAAAAKIVTEGL
UniProt ID: P22391
Variant: E -> K at position 278-278
Variant annotation: in strain: KH66
Protein function: Hydrolyzes broad-spectrum beta-lactam antibiotics. Active against cephalosporins.
Reference sequence:
MLKSSWRKTALMAAAAVPLLLASGSLWASADAIQQKLADLEKRSGGRLGVALINTADDSQTLYRGDERFAMCSTGKVMAAAAVLKQSESNPEVVNKRLEIKKSDLVVWSPITEKHLQSGMTLAELSAAALQYSDNTAMNKMISYLGGPEKVTAFAQSIGDVTFRLDRTEPALNSAIPGDKRDTTTPLAMAESLRKLTLGNALGEQQRAQLVTWLKGNTTGGQSIRAGLPASWAVGDKTGAGDYGTTNDIAVIWPENHAPLVLVTYFTQPQQDAKSRKEVLAAAAKIVTEGL
UniProt ID: P22394
Variant: I -> V at position 46-46
Variant annotation: in strain: NRRLY-552
Protein function: Hydrolyzes all ester bonds in triglyceride and displays a high affinity for triolein. For unsaturated substrates having long fatty acyl chains (C18:2 cis-9, cis-12 and C18:3 cis-9, cis-12, cis-15) GCL I shows higher specific activity than GCL II, whereas GCL II shows higher specific activity against saturated substrates having short fatty acid chains (C8, C10, C12 and C14).
Reference sequence:
MVSKSLFLAAAVNLAGVLAQAPRPSLNGNEVISGVLEGKVDTFKGIPFADPPLNDLRFKHPQPFTGSYQGLKANDFSPACMQLDPGNSLTLLDKALGLAKVIPEEFRGPLYDMAKGTVSMNEDCLYLNVFRPAGTKPDAKLPVMVWIYGGAFVYGSSAAYPGNSYVKESINMGQPVVFVSINYRTGPFGFLGGDAITAEGNTNAGLHDQRKGLEWVSDNIANFGGDPDKVMIFGESAGAMSVAHQLIAYGGDNTYNGKKLFHSAILQSGGPLPYHDSSSVGPDISYNRFAQYAGCDTSASANDTLECLRSKSSSVLHDAQNSYDLKDLFGLLPQFLGFGPRPDGNIIPDAAYELFRSGRYAKVPYISGNQEDEGTAFAPVALNATTTPHVKKWLQYIFYDASEASIDRVLSLYPQTLSVGSPFRTGILNALTPQFKRVAAILSDMLFQSPRRVMLSATKDVNRWTYLSTHLHNLVPFLGTFHGNELIFQFNVNIGPANSYLRYFISFANHHDPNVGTNLLQWDQYTDEGKEMLEIHMTDNVMRTDDYRIEGISNFETDVNLYG
UniProt ID: P22394
Variant: I -> V at position 247-247
Variant annotation: in strain: NRRLY-553
Protein function: Hydrolyzes all ester bonds in triglyceride and displays a high affinity for triolein. For unsaturated substrates having long fatty acyl chains (C18:2 cis-9, cis-12 and C18:3 cis-9, cis-12, cis-15) GCL I shows higher specific activity than GCL II, whereas GCL II shows higher specific activity against saturated substrates having short fatty acid chains (C8, C10, C12 and C14).
Reference sequence:
MVSKSLFLAAAVNLAGVLAQAPRPSLNGNEVISGVLEGKVDTFKGIPFADPPLNDLRFKHPQPFTGSYQGLKANDFSPACMQLDPGNSLTLLDKALGLAKVIPEEFRGPLYDMAKGTVSMNEDCLYLNVFRPAGTKPDAKLPVMVWIYGGAFVYGSSAAYPGNSYVKESINMGQPVVFVSINYRTGPFGFLGGDAITAEGNTNAGLHDQRKGLEWVSDNIANFGGDPDKVMIFGESAGAMSVAHQLIAYGGDNTYNGKKLFHSAILQSGGPLPYHDSSSVGPDISYNRFAQYAGCDTSASANDTLECLRSKSSSVLHDAQNSYDLKDLFGLLPQFLGFGPRPDGNIIPDAAYELFRSGRYAKVPYISGNQEDEGTAFAPVALNATTTPHVKKWLQYIFYDASEASIDRVLSLYPQTLSVGSPFRTGILNALTPQFKRVAAILSDMLFQSPRRVMLSATKDVNRWTYLSTHLHNLVPFLGTFHGNELIFQFNVNIGPANSYLRYFISFANHHDPNVGTNLLQWDQYTDEGKEMLEIHMTDNVMRTDDYRIEGISNFETDVNLYG
UniProt ID: P22394
Variant: F -> Y at position 355-355
Variant annotation: in strain: NRRLY-553
Protein function: Hydrolyzes all ester bonds in triglyceride and displays a high affinity for triolein. For unsaturated substrates having long fatty acyl chains (C18:2 cis-9, cis-12 and C18:3 cis-9, cis-12, cis-15) GCL I shows higher specific activity than GCL II, whereas GCL II shows higher specific activity against saturated substrates having short fatty acid chains (C8, C10, C12 and C14).
Reference sequence:
MVSKSLFLAAAVNLAGVLAQAPRPSLNGNEVISGVLEGKVDTFKGIPFADPPLNDLRFKHPQPFTGSYQGLKANDFSPACMQLDPGNSLTLLDKALGLAKVIPEEFRGPLYDMAKGTVSMNEDCLYLNVFRPAGTKPDAKLPVMVWIYGGAFVYGSSAAYPGNSYVKESINMGQPVVFVSINYRTGPFGFLGGDAITAEGNTNAGLHDQRKGLEWVSDNIANFGGDPDKVMIFGESAGAMSVAHQLIAYGGDNTYNGKKLFHSAILQSGGPLPYHDSSSVGPDISYNRFAQYAGCDTSASANDTLECLRSKSSSVLHDAQNSYDLKDLFGLLPQFLGFGPRPDGNIIPDAAYELFRSGRYAKVPYISGNQEDEGTAFAPVALNATTTPHVKKWLQYIFYDASEASIDRVLSLYPQTLSVGSPFRTGILNALTPQFKRVAAILSDMLFQSPRRVMLSATKDVNRWTYLSTHLHNLVPFLGTFHGNELIFQFNVNIGPANSYLRYFISFANHHDPNVGTNLLQWDQYTDEGKEMLEIHMTDNVMRTDDYRIEGISNFETDVNLYG
UniProt ID: P22394
Variant: K -> R at position 391-391
Variant annotation: in strain: NRRLY-553
Protein function: Hydrolyzes all ester bonds in triglyceride and displays a high affinity for triolein. For unsaturated substrates having long fatty acyl chains (C18:2 cis-9, cis-12 and C18:3 cis-9, cis-12, cis-15) GCL I shows higher specific activity than GCL II, whereas GCL II shows higher specific activity against saturated substrates having short fatty acid chains (C8, C10, C12 and C14).
Reference sequence:
MVSKSLFLAAAVNLAGVLAQAPRPSLNGNEVISGVLEGKVDTFKGIPFADPPLNDLRFKHPQPFTGSYQGLKANDFSPACMQLDPGNSLTLLDKALGLAKVIPEEFRGPLYDMAKGTVSMNEDCLYLNVFRPAGTKPDAKLPVMVWIYGGAFVYGSSAAYPGNSYVKESINMGQPVVFVSINYRTGPFGFLGGDAITAEGNTNAGLHDQRKGLEWVSDNIANFGGDPDKVMIFGESAGAMSVAHQLIAYGGDNTYNGKKLFHSAILQSGGPLPYHDSSSVGPDISYNRFAQYAGCDTSASANDTLECLRSKSSSVLHDAQNSYDLKDLFGLLPQFLGFGPRPDGNIIPDAAYELFRSGRYAKVPYISGNQEDEGTAFAPVALNATTTPHVKKWLQYIFYDASEASIDRVLSLYPQTLSVGSPFRTGILNALTPQFKRVAAILSDMLFQSPRRVMLSATKDVNRWTYLSTHLHNLVPFLGTFHGNELIFQFNVNIGPANSYLRYFISFANHHDPNVGTNLLQWDQYTDEGKEMLEIHMTDNVMRTDDYRIEGISNFETDVNLYG
UniProt ID: P22394
Variant: A -> S at position 439-439
Variant annotation: in strain: NRRLY-553
Protein function: Hydrolyzes all ester bonds in triglyceride and displays a high affinity for triolein. For unsaturated substrates having long fatty acyl chains (C18:2 cis-9, cis-12 and C18:3 cis-9, cis-12, cis-15) GCL I shows higher specific activity than GCL II, whereas GCL II shows higher specific activity against saturated substrates having short fatty acid chains (C8, C10, C12 and C14).
Reference sequence:
MVSKSLFLAAAVNLAGVLAQAPRPSLNGNEVISGVLEGKVDTFKGIPFADPPLNDLRFKHPQPFTGSYQGLKANDFSPACMQLDPGNSLTLLDKALGLAKVIPEEFRGPLYDMAKGTVSMNEDCLYLNVFRPAGTKPDAKLPVMVWIYGGAFVYGSSAAYPGNSYVKESINMGQPVVFVSINYRTGPFGFLGGDAITAEGNTNAGLHDQRKGLEWVSDNIANFGGDPDKVMIFGESAGAMSVAHQLIAYGGDNTYNGKKLFHSAILQSGGPLPYHDSSSVGPDISYNRFAQYAGCDTSASANDTLECLRSKSSSVLHDAQNSYDLKDLFGLLPQFLGFGPRPDGNIIPDAAYELFRSGRYAKVPYISGNQEDEGTAFAPVALNATTTPHVKKWLQYIFYDASEASIDRVLSLYPQTLSVGSPFRTGILNALTPQFKRVAAILSDMLFQSPRRVMLSATKDVNRWTYLSTHLHNLVPFLGTFHGNELIFQFNVNIGPANSYLRYFISFANHHDPNVGTNLLQWDQYTDEGKEMLEIHMTDNVMRTDDYRIEGISNFETDVNLYG
UniProt ID: P22394
Variant: N -> D at position 484-484
Variant annotation: in strain: NRRLY-552
Protein function: Hydrolyzes all ester bonds in triglyceride and displays a high affinity for triolein. For unsaturated substrates having long fatty acyl chains (C18:2 cis-9, cis-12 and C18:3 cis-9, cis-12, cis-15) GCL I shows higher specific activity than GCL II, whereas GCL II shows higher specific activity against saturated substrates having short fatty acid chains (C8, C10, C12 and C14).
Reference sequence:
MVSKSLFLAAAVNLAGVLAQAPRPSLNGNEVISGVLEGKVDTFKGIPFADPPLNDLRFKHPQPFTGSYQGLKANDFSPACMQLDPGNSLTLLDKALGLAKVIPEEFRGPLYDMAKGTVSMNEDCLYLNVFRPAGTKPDAKLPVMVWIYGGAFVYGSSAAYPGNSYVKESINMGQPVVFVSINYRTGPFGFLGGDAITAEGNTNAGLHDQRKGLEWVSDNIANFGGDPDKVMIFGESAGAMSVAHQLIAYGGDNTYNGKKLFHSAILQSGGPLPYHDSSSVGPDISYNRFAQYAGCDTSASANDTLECLRSKSSSVLHDAQNSYDLKDLFGLLPQFLGFGPRPDGNIIPDAAYELFRSGRYAKVPYISGNQEDEGTAFAPVALNATTTPHVKKWLQYIFYDASEASIDRVLSLYPQTLSVGSPFRTGILNALTPQFKRVAAILSDMLFQSPRRVMLSATKDVNRWTYLSTHLHNLVPFLGTFHGNELIFQFNVNIGPANSYLRYFISFANHHDPNVGTNLLQWDQYTDEGKEMLEIHMTDNVMRTDDYRIEGISNFETDVNLYG
UniProt ID: P22439
Variant: P -> G at position 66-66
Protein function: Required for anchoring dihydrolipoamide dehydrogenase (E3) to the dihydrolipoamide transacetylase (E2) core of the pyruvate dehydrogenase complexes of eukaryotes. This specific binding is essential for a functional PDH complex.
Reference sequence:
MAASWRLGCDPRLLRCLLGFGSRRSPELVKGAARWSVGRGASWRWFHSTQWLRADPIKILMPSLSPTMEEGNIVKWLKKEGEAVSAGDALCEIETDKAVVTLDASDDGILAKIVVAEGSKNIRLGSLIGLLVEEGEDWKHVEIPKDTGPPPPAAKPSVPPPSAEPQIATPVKKEHPPGKVQFRLSPAARNILEKHALDANQGTATGPRGIFTKEDALKLVQLKQTGKITEPRPTAALPTTPAAPLPPQAAATASYPRPMIPPVSTPGQPNVEGTFTEIPASNIRRVIAKRLTESKSTIPHAYATTDCDLGAVLTARQNLVRDDIKVSVNDFIIKAAAVTLKQMPNVNASWDGEGAKQLPSIDISVAVATDRGLITPVIKDAAAKGLQEIADSVKALSKKARDGKLLPEEYQGGSFSISNLGMFGIDEFTAVINPPQACILAVGRFRPVLKLTQDEEGNAQLQQRQLITVTMSSDSRVVDDELATRFLESFKANLENPLRLA
UniProt ID: P22439
Variant: N -> G at position 72-72
Protein function: Required for anchoring dihydrolipoamide dehydrogenase (E3) to the dihydrolipoamide transacetylase (E2) core of the pyruvate dehydrogenase complexes of eukaryotes. This specific binding is essential for a functional PDH complex.
Reference sequence:
MAASWRLGCDPRLLRCLLGFGSRRSPELVKGAARWSVGRGASWRWFHSTQWLRADPIKILMPSLSPTMEEGNIVKWLKKEGEAVSAGDALCEIETDKAVVTLDASDDGILAKIVVAEGSKNIRLGSLIGLLVEEGEDWKHVEIPKDTGPPPPAAKPSVPPPSAEPQIATPVKKEHPPGKVQFRLSPAARNILEKHALDANQGTATGPRGIFTKEDALKLVQLKQTGKITEPRPTAALPTTPAAPLPPQAAATASYPRPMIPPVSTPGQPNVEGTFTEIPASNIRRVIAKRLTESKSTIPHAYATTDCDLGAVLTARQNLVRDDIKVSVNDFIIKAAAVTLKQMPNVNASWDGEGAKQLPSIDISVAVATDRGLITPVIKDAAAKGLQEIADSVKALSKKARDGKLLPEEYQGGSFSISNLGMFGIDEFTAVINPPQACILAVGRFRPVLKLTQDEEGNAQLQQRQLITVTMSSDSRVVDDELATRFLESFKANLENPLRLA
UniProt ID: P22455
Variant: V -> I at position 10-10
Variant annotation: in dbSNP:rs1966265
Protein function: Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4. Mutations that lead to constitutive kinase activation or impair normal FGFR4 inactivation lead to aberrant signaling.
Reference sequence:
MRLLLALLGVLLSVPGPPVLSLEASEEVELEPCLAPSLEQQEQELTVALGQPVRLCCGRAERGGHWYKEGSRLAPAGRVRGWRGRLEIASFLPEDAGRYLCLARGSMIVLQNLTLITGDSLTSSNDDEDPKSHRDPSNRHSYPQQAPYWTHPQRMEKKLHAVPAGNTVKFRCPAAGNPTPTIRWLKDGQAFHGENRIGGIRLRHQHWSLVMESVVPSDRGTYTCLVENAVGSIRYNYLLDVLERSPHRPILQAGLPANTTAVVGSDVELLCKVYSDAQPHIQWLKHIVINGSSFGADGFPYVQVLKTADINSSEVEVLYLRNVSAEDAGEYTCLAGNSIGLSYQSAWLTVLPEEDPTWTAAAPEARYTDIILYASGSLALAVLLLLAGLYRGQALHGRHPRPPATVQKLSRFPLARQFSLESGSSGKSSSSLVRGVRLSSSGPALLAGLVSLDLPLDPLWEFPRDRLVLGKPLGEGCFGQVVRAEAFGMDPARPDQASTVAVKMLKDNASDKDLADLVSEMEVMKLIGRHKNIINLLGVCTQEGPLYVIVECAAKGNLREFLRARRPPGPDLSPDGPRSSEGPLSFPVLVSCAYQVARGMQYLESRKCIHRDLAARNVLVTEDNVMKIADFGLARGVHHIDYYKKTSNGRLPVKWMAPEALFDRVYTHQSDVWSFGILLWEIFTLGGSPYPGIPVEELFSLLREGHRMDRPPHCPPELYGLMRECWHAAPSQRPTFKQLVEALDKVLLAVSEEYLDLRLTFGPYSPSGGDASSTCSSSDSVFSHDPLPLGSSSFPFGSGVQT
UniProt ID: P22455
Variant: P -> L at position 136-136
Variant annotation: in dbSNP:rs376618
Protein function: Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4. Mutations that lead to constitutive kinase activation or impair normal FGFR4 inactivation lead to aberrant signaling.
Reference sequence:
MRLLLALLGVLLSVPGPPVLSLEASEEVELEPCLAPSLEQQEQELTVALGQPVRLCCGRAERGGHWYKEGSRLAPAGRVRGWRGRLEIASFLPEDAGRYLCLARGSMIVLQNLTLITGDSLTSSNDDEDPKSHRDPSNRHSYPQQAPYWTHPQRMEKKLHAVPAGNTVKFRCPAAGNPTPTIRWLKDGQAFHGENRIGGIRLRHQHWSLVMESVVPSDRGTYTCLVENAVGSIRYNYLLDVLERSPHRPILQAGLPANTTAVVGSDVELLCKVYSDAQPHIQWLKHIVINGSSFGADGFPYVQVLKTADINSSEVEVLYLRNVSAEDAGEYTCLAGNSIGLSYQSAWLTVLPEEDPTWTAAAPEARYTDIILYASGSLALAVLLLLAGLYRGQALHGRHPRPPATVQKLSRFPLARQFSLESGSSGKSSSSLVRGVRLSSSGPALLAGLVSLDLPLDPLWEFPRDRLVLGKPLGEGCFGQVVRAEAFGMDPARPDQASTVAVKMLKDNASDKDLADLVSEMEVMKLIGRHKNIINLLGVCTQEGPLYVIVECAAKGNLREFLRARRPPGPDLSPDGPRSSEGPLSFPVLVSCAYQVARGMQYLESRKCIHRDLAARNVLVTEDNVMKIADFGLARGVHHIDYYKKTSNGRLPVKWMAPEALFDRVYTHQSDVWSFGILLWEIFTLGGSPYPGIPVEELFSLLREGHRMDRPPHCPPELYGLMRECWHAAPSQRPTFKQLVEALDKVLLAVSEEYLDLRLTFGPYSPSGGDASSTCSSSDSVFSHDPLPLGSSSFPFGSGVQT
UniProt ID: P22455
Variant: T -> A at position 179-179
Variant annotation: in dbSNP:rs55675160
Protein function: Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4. Mutations that lead to constitutive kinase activation or impair normal FGFR4 inactivation lead to aberrant signaling.
Reference sequence:
MRLLLALLGVLLSVPGPPVLSLEASEEVELEPCLAPSLEQQEQELTVALGQPVRLCCGRAERGGHWYKEGSRLAPAGRVRGWRGRLEIASFLPEDAGRYLCLARGSMIVLQNLTLITGDSLTSSNDDEDPKSHRDPSNRHSYPQQAPYWTHPQRMEKKLHAVPAGNTVKFRCPAAGNPTPTIRWLKDGQAFHGENRIGGIRLRHQHWSLVMESVVPSDRGTYTCLVENAVGSIRYNYLLDVLERSPHRPILQAGLPANTTAVVGSDVELLCKVYSDAQPHIQWLKHIVINGSSFGADGFPYVQVLKTADINSSEVEVLYLRNVSAEDAGEYTCLAGNSIGLSYQSAWLTVLPEEDPTWTAAAPEARYTDIILYASGSLALAVLLLLAGLYRGQALHGRHPRPPATVQKLSRFPLARQFSLESGSSGKSSSSLVRGVRLSSSGPALLAGLVSLDLPLDPLWEFPRDRLVLGKPLGEGCFGQVVRAEAFGMDPARPDQASTVAVKMLKDNASDKDLADLVSEMEVMKLIGRHKNIINLLGVCTQEGPLYVIVECAAKGNLREFLRARRPPGPDLSPDGPRSSEGPLSFPVLVSCAYQVARGMQYLESRKCIHRDLAARNVLVTEDNVMKIADFGLARGVHHIDYYKKTSNGRLPVKWMAPEALFDRVYTHQSDVWSFGILLWEIFTLGGSPYPGIPVEELFSLLREGHRMDRPPHCPPELYGLMRECWHAAPSQRPTFKQLVEALDKVLLAVSEEYLDLRLTFGPYSPSGGDASSTCSSSDSVFSHDPLPLGSSSFPFGSGVQT
UniProt ID: P22455
Variant: G -> R at position 388-388
Variant annotation: in cancer cells, may be associated with accelerated disease progression and increased tumor cell motility, possibly due to increased stability of the protease MMP14; leads to phosphorylation at residue Y-390, resulting in prolonged FGFR4 activity; increases interaction with STAT3, resulting in STAT3 phosphorylation and signaling activation.; dbSNP:rs351855
Protein function: Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4. Mutations that lead to constitutive kinase activation or impair normal FGFR4 inactivation lead to aberrant signaling.
Reference sequence:
MRLLLALLGVLLSVPGPPVLSLEASEEVELEPCLAPSLEQQEQELTVALGQPVRLCCGRAERGGHWYKEGSRLAPAGRVRGWRGRLEIASFLPEDAGRYLCLARGSMIVLQNLTLITGDSLTSSNDDEDPKSHRDPSNRHSYPQQAPYWTHPQRMEKKLHAVPAGNTVKFRCPAAGNPTPTIRWLKDGQAFHGENRIGGIRLRHQHWSLVMESVVPSDRGTYTCLVENAVGSIRYNYLLDVLERSPHRPILQAGLPANTTAVVGSDVELLCKVYSDAQPHIQWLKHIVINGSSFGADGFPYVQVLKTADINSSEVEVLYLRNVSAEDAGEYTCLAGNSIGLSYQSAWLTVLPEEDPTWTAAAPEARYTDIILYASGSLALAVLLLLAGLYRGQALHGRHPRPPATVQKLSRFPLARQFSLESGSSGKSSSSLVRGVRLSSSGPALLAGLVSLDLPLDPLWEFPRDRLVLGKPLGEGCFGQVVRAEAFGMDPARPDQASTVAVKMLKDNASDKDLADLVSEMEVMKLIGRHKNIINLLGVCTQEGPLYVIVECAAKGNLREFLRARRPPGPDLSPDGPRSSEGPLSFPVLVSCAYQVARGMQYLESRKCIHRDLAARNVLVTEDNVMKIADFGLARGVHHIDYYKKTSNGRLPVKWMAPEALFDRVYTHQSDVWSFGILLWEIFTLGGSPYPGIPVEELFSLLREGHRMDRPPHCPPELYGLMRECWHAAPSQRPTFKQLVEALDKVLLAVSEEYLDLRLTFGPYSPSGGDASSTCSSSDSVFSHDPLPLGSSSFPFGSGVQT
UniProt ID: P22455
Variant: G -> S at position 426-426
Variant annotation: in dbSNP:rs55879131
Protein function: Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4. Mutations that lead to constitutive kinase activation or impair normal FGFR4 inactivation lead to aberrant signaling.
Reference sequence:
MRLLLALLGVLLSVPGPPVLSLEASEEVELEPCLAPSLEQQEQELTVALGQPVRLCCGRAERGGHWYKEGSRLAPAGRVRGWRGRLEIASFLPEDAGRYLCLARGSMIVLQNLTLITGDSLTSSNDDEDPKSHRDPSNRHSYPQQAPYWTHPQRMEKKLHAVPAGNTVKFRCPAAGNPTPTIRWLKDGQAFHGENRIGGIRLRHQHWSLVMESVVPSDRGTYTCLVENAVGSIRYNYLLDVLERSPHRPILQAGLPANTTAVVGSDVELLCKVYSDAQPHIQWLKHIVINGSSFGADGFPYVQVLKTADINSSEVEVLYLRNVSAEDAGEYTCLAGNSIGLSYQSAWLTVLPEEDPTWTAAAPEARYTDIILYASGSLALAVLLLLAGLYRGQALHGRHPRPPATVQKLSRFPLARQFSLESGSSGKSSSSLVRGVRLSSSGPALLAGLVSLDLPLDPLWEFPRDRLVLGKPLGEGCFGQVVRAEAFGMDPARPDQASTVAVKMLKDNASDKDLADLVSEMEVMKLIGRHKNIINLLGVCTQEGPLYVIVECAAKGNLREFLRARRPPGPDLSPDGPRSSEGPLSFPVLVSCAYQVARGMQYLESRKCIHRDLAARNVLVTEDNVMKIADFGLARGVHHIDYYKKTSNGRLPVKWMAPEALFDRVYTHQSDVWSFGILLWEIFTLGGSPYPGIPVEELFSLLREGHRMDRPPHCPPELYGLMRECWHAAPSQRPTFKQLVEALDKVLLAVSEEYLDLRLTFGPYSPSGGDASSTCSSSDSVFSHDPLPLGSSSFPFGSGVQT