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Details on Person UniProt:P22455 FGFR4
| Class:Id | ReferenceGeneProduct:54820 |
|---|---|
| _chainChangeLog | signal peptide:1-21 added on Sat February 7 2015;chain:22-802 added on Sat February 7 2015 |
| _displayName | UniProt:P22455 FGFR4 |
| _timestamp | 2025-02-21 19:06:43 |
| chain | signal peptide:1-21 chain:22-802 |
| checksum | B22B259831BB889F |
| comment | FUNCTION Tyrosine-protein kinase that acts as a 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.CATALYTIC ACTIVITY L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)ACTIVITY REGULATION Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by autophosphorylation on tyrosine residues.SUBUNIT Monomer. Homodimer after ligand binding. Interacts with FGF1, FGF2, FGF4, FGF6, FGF8, FGF9, FGF16, FGF17, FGF18, FGF19, FGF21 and FGF23 (in vitro). Binding affinity for FGF family members is enhanced by interactions between FGFs and heparan sulfate proteoglycans. Interacts with KLB; this strongly increases the affinity for FGF19 and FGF23. Affinity for FGF19 is strongly increased by KLB and sulfated glycosaminoglycans. KLB and KL both interact with the core-glycosylated FGFR4 in the endoplasmic reticulum and promote its degradation, so that only FGFR4 with fully mature N-glycans is expressed at the cell surface. Identified in a complex with NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN. Interacts with MMP14 and HIP1 (PubMed:11433297, PubMed:16597617, PubMed:17623664, PubMed:18670643, PubMed:20683963, PubMed:20798051, PubMed:21653700, PubMed:7518429, PubMed:8663044). Interacts with STAT3 (PubMed:26675719).INTERACTION Internalized from the cell membrane to recycling endosomes, and from there back to the cell membrane.SUBCELLULAR LOCATION Expressed in gastrointestinal epithelial cells, pancreas, and gastric and pancreatic cancer cell lines.PTM N-glycosylated. Full maturation of the glycan chains in the Golgi is essential for high affinity interaction with FGF19.PTM Ubiquitinated. Subject to proteasomal degradation when not fully glycosylated.PTM Autophosphorylated. Binding of FGF family members together with heparan sulfate proteoglycan or heparin promotes receptor dimerization and autophosphorylation on tyrosine residues. Autophosphorylation occurs in trans between the two FGFR molecules present in the dimer.DISEASE FGFR4 variants may be involved in the pathogenesis of various cancers. Variant Arg-388 predisposes cancer patients to accelerated disease progression and may be associated with poor prognosis. It has been found in prostate cancer as well as cancers of the breast, colon, head and neck, larynx, lung, skin.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.CAUTION An additional N-terminally truncated cytoplasmic isoform was previously reported to exist. However, the paper was subsequently retracted due to concerns regarding duplication of panels in some figures. |
| description | recommendedName: Fibroblast growth factor receptor 4 shortName: FGFR-4 ecNumber: 2.7.10.1 cdAntigenNameCD334/cdAntigenName |
| geneName | FGFR4 JTK2 TKF |
| identifier | P22455 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing ATP-binding Cell membrane Direct protein sequencing Disulfide bond Endoplasmic reticulum Endosome Glycoprotein Immunoglobulin domain Kinase Membrane Nucleotide-binding Phosphoprotein Proteomics identification Receptor Reference proteome Repeat Secreted Signal Transferase Transmembrane Transmembrane helix Tyrosine-protein kinase Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 |
| name | FGFR4 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8995434] ENSEMBL:ENSG00000160867 FGFR4 [Homo sapiens] |
| secondaryIdentifier | FGFR4_HUMAN G3JVM2 G3JVM5 G3JVM7 G3JVM9 O43785 Q14309 Q71TW8 Q8TDA0 Q96KE5 |
| sequenceLength | 802 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:385067] UniProt:P22455-2 FGFR4 [Homo sapiens] [ReferenceIsoform:403333] UniProt:P22455-1 FGFR4 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:189921] FGFR4 [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:190330] p-5Y-FGFR4 [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:1614427] FGFR4 N535D [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:1614430] FGFR4 N535K [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:1614433] FGFR4 V550E [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:1614436] FGFR4 V550L [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:1614439] FGFR4 Y367C [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:2011873] p5Y-FGFR4 Y367C mutant [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:2038931] p-5Y-FGFR4 N535K [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:2038932] p-5Y-FGFR4 V550E [plasma membrane] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:190327] O4'-phospho-L-tyrosine at 643 [ModifiedResidue:190957] O4'-phospho-L-tyrosine at 719 [ModifiedResidue:190958] O4'-phospho-L-tyrosine at 642 [ModifiedResidue:190960] O4'-phospho-L-tyrosine at 754 [ModifiedResidue:1307893] O4'-phospho-L-tyrosine at 764 [ReplacedResidue:1614426] L-asparagine 535 replaced with L-aspartic acid [ReplacedResidue:1614431] L-asparagine 535 replaced with L-lysine [ReplacedResidue:1614434] L-valine 550 replaced with L-glutamic acid [ReplacedResidue:1614435] L-valine 550 replaced with L-leucine [ReplacedResidue:1614438] L-tyrosine 367 replaced with L-cysteine |
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No pathways have been reviewed or authored by UniProt:P22455 FGFR4 (54820)
