lmmol · Proteins

Fibroblast growth factor receptor 4

UniProt P22455 Organism Homo sapiens Gene FGFR4, JTK2, TKF EC 2.7.10.1

Also known as: FGFR4, JTK2, TKF

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.

Classification

Family (Pfam)
PF07679 I-set, PF13927 Ig_3, PF07714 PK_Tyr_Ser-Thr
InterPro
FGF_rcpt_fam, Ig-like_dom, Ig-like_dom_sf, Ig-like_fold, Ig_I-set, Ig_sub, Ig_sub2, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, RTK, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_AS, Tyr_kinase_cat_dom
Functional cluster
Secreted Growth Factors & Cytokines

Experimental structures · PDB · 52

A predicted model is available from AlphaFold.

Gene Ontology · 27

Drugs targeting this protein · 15

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 36 cited papers

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