|CD334||FGFR4 (fibroblast growth factor receptor 4), JTK2, TKF|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
Type 1 glycoprotein
|110 / 110|
|CD334 is expressed on lymphocytes, macropages, fibroblasts, skeletal muscle cells and epithelial cells. Expression is in the liver, kidney, lung and pancreas.|
|MOLECULAR FAMILY NAME: Belongs to the tyrosine kinase protein family.|
CD334 is a single-pass type-1 781 aa glycoprotein. It contains a 348 aa extracellular domain which contains 3 Ig-like C2-type domains and 5 potential N-linked glycosylation sites, a 21 aa single hydrophobic membrane-spanning transmembrane domain and a 412 aa intracellular cytoplasmic tyrosine kinase domain which contains 2 APT binding sites and a 289 aa tyrosine kinase (TK) domain that is split by a short insert and lacks several lysines that are conserved in CD331, CD332 and CD333. The 3 Ig-like CD2-type domains (D1-D3), a stretch of residues in the linker connecting D1 and D2 known as the "acid box", a heparin binding site in D2. D2 and D3 form the primary binding pocket for fibroblast growth factor (FGF), whereas D1 and the acid box have an autoinhibitory role. Binding FGF induces dimerization of CD333 and results in a tetrameric complex. Essential cofactors associated with this complex are cell-surface heparin sulphate proteoglycans. The protein encoded by this gene (FGFR4) is a member of the fibroblast growth factor receptor subfamily within the Ig superfamily where expression is in K562 erythroleukemia cells and where the amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation.
Although alternative splicing has been observed, there is no evidence that the C-terminal half of the IgIII domain of this protein varies between 3 alternative forms.
CD333 has 5 potential N-linked glycosylation sites. Dimerization promotes autophosphorylation in trans of critical tyrosines in the activation loop that stablizes the receptor in an active conformation and leads to in cis phosphorylation of tyrosine residues within the TK domain. Intracellular phosphotyrosines serve as binding sites for signal transduction molecules such as SHC, FRS2 and phospholipase Cγ (PLCγ).
|LIGANDS AND MOLECULE ASSOCIATED WITH CD334|
CD334 is a high affinity receptor for acidic FGFs.
|CD334 serves as a high affinity receptor for fibroblast growth factors (FGFs). FGFs are mitogens that can activate a number of intracellular signalling pathways and exert numerous effects depending on the target cells. The protein encoded by this gene (FGFR4) is a member of the fibroblast growth factor receptor subfamily within the Ig superfamily where expression is in K562 erythroleukemia cells and where the amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. |
BIOCHEMICAL ACTIVITY: No information.
DISEASE RELEVANCE AND FUNCTION OF CD334 IN INTACT ANIMAL
CD334 signalling is also implicated in tumor growth and angiogenesis and is involved in endoderm and skeletal muscle development and cancer progression and metastasis. Disruption signaling interrups chick limb muscle. Knockout mice are phenotypically normal but demonstrate defective muscle regeneration. Bile acid synthesis in mice is regulated by signaling in hepatocytes. The Gly388Arg polymorphism in CD334 is associated with breast, colon, prostate cancer, head and neck squamous cell carcinoma and lung adenocarcinoma.
This particular family member preferentially binds acidic fibroblast growth factor and, although its specific function is unknown, it is overexpressed in gynecological tumor samples.
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD334: No information.
SUBSTRATES: No information.
ENZYMES WHICH MODIFY CD334: No information.
For further information see Walsh, S. et al (2000) Bone 27: 185-195.
Database accession numbers
Revised June 25, 2008