Target Information
Target General Infomation | |||||
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Target ID |
T90989
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Former ID |
TTDNC00621
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Target Name |
FGF-4 receptor
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Gene Name |
FGFR4
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Synonyms |
CD334; Fibroblast growth factor receptor 4; FGFR4
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Target Type |
Clinical Trial
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Disease | Cancer [ICD9: 140-229; ICD10: C00-C96] | ||||
Obesity [ICD9: 278; ICD10: E66] | |||||
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48] | |||||
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. .
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BioChemical Class |
Kinase
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UniProt ID | |||||
EC Number |
EC 2.7.10.1
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Sequence |
MRLLLALLGVLLSVPGPPVLSLEASEEVELEPCLAPSLEQQEQELTVALGQPVRLCCGRA
ERGGHWYKEGSRLAPAGRVRGWRGRLEIASFLPEDAGRYLCLARGSMIVLQNLTLITGDS LTSSNDDEDPKSHRDPSNRHSYPQQAPYWTHPQRMEKKLHAVPAGNTVKFRCPAAGNPTP TIRWLKDGQAFHGENRIGGIRLRHQHWSLVMESVVPSDRGTYTCLVENAVGSIRYNYLLD VLERSPHRPILQAGLPANTTAVVGSDVELLCKVYSDAQPHIQWLKHIVINGSSFGADGFP YVQVLKTADINSSEVEVLYLRNVSAEDAGEYTCLAGNSIGLSYQSAWLTVLPEEDPTWTA AAPEARYTDIILYASGSLALAVLLLLAGLYRGQALHGRHPRPPATVQKLSRFPLARQFSL ESGSSGKSSSSLVRGVRLSSSGPALLAGLVSLDLPLDPLWEFPRDRLVLGKPLGEGCFGQ VVRAEAFGMDPARPDQASTVAVKMLKDNASDKDLADLVSEMEVMKLIGRHKNIINLLGVC TQEGPLYVIVECAAKGNLREFLRARRPPGPDLSPDGPRSSEGPLSFPVLVSCAYQVARGM QYLESRKCIHRDLAARNVLVTEDNVMKIADFGLARGVHHIDYYKKTSNGRLPVKWMAPEA LFDRVYTHQSDVWSFGILLWEIFTLGGSPYPGIPVEELFSLLREGHRMDRPPHCPPELYG LMRECWHAAPSQRPTFKQLVEALDKVLLAVSEEYLDLRLTFGPYSPSGGDASSTCSSSDS VFSHDPLPLGSSSFPFGSGVQT |
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Structure |
1QCT; 4QQ5; 4QQC; 4QQJ; 4QQT; 4QRC; 4R6V; 4TYE; 4TYG; 4TYI; 4TYJ; 4UXQ; 1QCT; 4QQ5; 4QQC; 4QQJ; 4QQT; 4QRC; 4R6V; 4TYE; 4TYG; 4TYI;4TYJ; 4UXQ
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Drugs and Mode of Action | |||||
Pathways | |||||
KEGG Pathway | MAPK signaling pathway | ||||
Ras signaling pathway | |||||
Rap1 signaling pathway | |||||
Endocytosis | |||||
PI3K-Akt signaling pathway | |||||
Signaling pathways regulating pluripotency of stem cells | |||||
Regulation of actin cytoskeleton | |||||
PANTHER Pathway | FGF signaling pathway | ||||
Pathway Interaction Database | FGF signaling pathway | ||||
Reactome | PI3K Cascade | ||||
PIP3 activates AKT signaling | |||||
FGFR4 ligand binding and activation | |||||
Constitutive Signaling by Aberrant PI3K in Cancer | |||||
Phospholipase C-mediated cascade | |||||
FRS-mediated FGFR4 signaling | |||||
FGFR4 | |||||
FGFR4 | |||||
Negative regulation of FGFR4 signaling | |||||
RAF/MAP kinase cascade | |||||
WikiPathways | Regulation of Actin Cytoskeleton | ||||
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) | |||||
PIP3 activates AKT signaling | |||||
Signaling by FGFR | |||||
References |
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