Tclin FGFR4 Fibroblast growth factor receptor 4

Protein Summary

Description

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. The protein encoded by this gene is a tyrosine kinase and cell surface receptor for fibroblast growth factors. The encoded protein is involved in the regulation of several pathways, including cell proliferation, cell differentiation, cell migration, lipid metabolism, bile acid biosynthesis, vitamin D metabolism, glucose uptake, and phosphate homeostasis. This protein consists of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment, and a cytoplasmic tyrosine kinase domain. The extracellular portion interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. [provided by RefSeq, Aug 2017]

Uniprot Accession IDs

• P22455
• G3JVM2
• G3JVM5
• G3JVM7
• G3JVM9
• O43785
• Q14309
• Q71TW8
• Q8TDA0
• Q96KE5
• FGFR-4

Gene Name

• FGFR4

Ensembl ID

• ENST00000292408
• ENSP00000292408
• ENSG00000160867
• ENST00000393637
• ENSP00000377254
• ENST00000502906
• ENSP00000424960

Symbol

• JTK2
• TKF
• TKF
• JTK2
• CD334

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	1
molecular function	0.99
biological process	0.95
PubMedID	0.9
transcription factor perturbation	0.88

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Tk Group / Fgfr Family / Fibroblast Growth Factor Receptor 4

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 495.05   (req: < 5)

Gene RIFs: 178   (req: <= 3)

Antibodies: 736   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 495.05   (req: >= 5)

Gene RIFs: 178   (req: > 3)

Antibodies: 736   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 32

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 592

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 4