InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: FGFR4

Summary

InnateDB Protein

IDBP-59462.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

FGFR4

Protein Name

fibroblast growth factor receptor 4

Synonyms

CD334; JTK2; TKF;

Species

Homo sapiens

Ensembl Protein

ENSP00000292408

InnateDB Gene

IDBG-59460 (FGFR4)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:11433297, ECO:0000269PubMed:16597617, ECO:0000269PubMed:17311277, ECO:0000269PubMed:17623664, ECO:0000269PubMed:18480409, ECO:0000269PubMed:18670643, ECO:0000269PubMed:20018895, ECO:0000269PubMed:20683963, ECO:0000269PubMed:20798051, ECO:0000269PubMed:20876804, ECO:0000269PubMed:21653700, ECO:0000269PubMed:7518429, ECO:0000269PubMed:7680645, ECO:0000269PubMed:8663044}.

Subcellular Localization

Cell membrane; Single-pass type I membrane protein. Endosome. Endoplasmic reticulum. Note=Internalized from the cell membrane to recycling endosomes, and from there back to the cell membrane.Isoform 2: Secreted.Isoform 3: Cytoplasm {ECO:0000269PubMed:11781352}.

Disease Associations

Tissue Specificity

Expressed in gastrointestinal epithelial cells, pancreas, and gastric and pancreatic cancer cell lines. {ECO:0000269PubMed:10631118}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 11 experimentally validated interaction(s) in this database.
They are also associated with 2 interaction(s) predicted by orthology.

Experimentally validated
Total	11 [view]
Protein-Protein	9 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	2 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005007	fibroblast growth factor-activated receptor activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008201	heparin binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0017134	fibroblast growth factor binding

Biological Process

GO:0001759	organ induction
GO:0006468	protein phosphorylation
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0008284	positive regulation of cell proliferation
GO:0008286	insulin receptor signaling pathway
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0010715	regulation of extracellular matrix disassembly
GO:0016477	cell migration
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0019216	regulation of lipid metabolic process
GO:0030324	lung development
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0042593	glucose homeostasis
GO:0045087	innate immune response
GO:0045862	positive regulation of proteolysis
GO:0046777	protein autophosphorylation
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048015	phosphatidylinositol-mediated signaling
GO:0048554	positive regulation of metalloenzyme activity
GO:0055062	phosphate ion homeostasis
GO:0061144	alveolar secondary septum development
GO:0070374	positive regulation of ERK1 and ERK2 cascade
GO:0070857	regulation of bile acid biosynthetic process
GO:2000188	regulation of cholesterol homeostasis
GO:2000573	positive regulation of DNA biosynthetic process

Cellular Component

GO:0005576	extracellular region
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005768	endosome
GO:0005783	endoplasmic reticulum
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0005911	cell-cell junction
GO:0016021	integral component of membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR003598 Immunoglobulin subtype 2
IPR003599 Immunoglobulin subtype
IPR007110 Immunoglobulin-like domain
IPR011009 Protein kinase-like domain
IPR013098 Immunoglobulin I-set
IPR013151 Immunoglobulin
IPR016248 Fibroblast growth factor receptor family
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF07679
PF00047

PRINTS

PR00109

PIRSF

PIRSF000628

SMART

SM00220
SM00408
SM00409
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References