FGFR-4/Fc Chimera, soluble Active Protein | FGFR-4/Fc Chimera active protein

Human FGFR-4/Fc Chimera, soluble

Cat. Num. AAA692006

• Gene Names: FGFR4; TKF; JTK2; CD334
• Reactivity: Human
• Purity: > 90% by SDS-PAGE & silver stain
• Synonyms: FGFR-4/Fc Chimera; soluble; Human FGFR-4/Fc Chimera; Recombinant Human Soluble FGFR-4/Fc Chimera; Fibroblast growth factor receptor 4; CD334; FGFR-4/Fc Chimera active protein

• Host: Insect Cells
• Reactivity: Human
• Purity/Purification: > 90% by SDS-PAGE & silver stain
• Form/Format: Lyophilized
• Sequence: LEASEEVELEPCLAPSLEQQEQELTVALGQPVRLCCGRAERGGHWYKEGS RLAPAGRVRGWRGRLEIASFLPEDAGRYLCLARGSMIVLQNLTLITGDSL TSSNDDEDPKSHRDPSNRHSYPQQAPYWTHPQRMEKKLHAVPAGNTVKFR CPAAGNPTPTIRWLKDGQAFHGENRIGGIRLRHQHWSLVMESVVPSDRGT YTCLVENAVGSIRYNYLLDVLERSPHRPILQAGLPANTTAVVGSDVELLC KVYSDAQPHIQWLKHIVINGSSFGADGFPYVQVLKTADINSSEVEVLYLR NVSAEDAGEYTCLAGNSIGLSYQSAWLTVLPEEDPTWTAAAPEARYTDTR SDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE DPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK
• Sequence Length: 578

• Buffer: PBS
• Preparation and Storage: Lyophilized samples are stable for greater than six months at -20 degree C to -70 degree C. Reconstituted sFGFR-4/Fc should be stored in working aliquots at -20 degree C. Avoid repeated freeze-thaw cycles!

Testing Data

Related Product Information for FGFR-4/Fc Chimera active protein

Recombinant human soluble FGFR-4 was fused with the Fc-part of human IgG1. Human recombinant soluble FGFR-4/Fc is a disulfide-linked heterodimeric protein. In the reduced form the glycosylated subunits of sFGFR-4 alpha/human Fc chimera display a molecular mass of 80-85 kDa. Fibroblast growth factors (FGFs) comprise a family of at least eighteen structurally related proteins that are involved in a multitude of physiological and pathological cellular processes, including cell growth, differentiation, angiogenesis, wound healing and tumorigenesis. The biological activities of the FGFs are mediated by a family of type I transmembrane tyrosine kinases which undergo dimerization and autophosphorylation after ligand binding. Four distinct genes encoding closely related FGF receptors, FGFR-1 to -4, are known. All four genes for FGF-receptors encode proteins with an N-terminal signal peptide, three immunoglobulin (Ig)-like domains, an acid-box region containing a run of acidic residues between the IgI and IgII domains, a transmembrane domain and the split tyrosine-kinase domain. Multiple forms of FGFR-1 to -3 are generated by alternative splicing of the mRNAs. A frequent splicing event involving FGFR-1 and -2 results in receptors containing all three Ig domains, referred to as the alpha isoform, or only IgII and IgIII, referred to as the beta isoform. Only the alpha isoform has been identified for FGFR-3 and FGFR-4. Additional splicing events for FGFR-1 to -3, involving the C-terminal half of the IgIII domain encoded by two mutually exclusive alternative exons, generate FGF receptors with alternative IgIII domains (IIIb and IIIc). A IIIa isoform which is a secreted FGF binding protein containing only the N-terminal half of the IgIII domain plus some intron sequences has also been reported for FGFR-1. Mutations in FGFR-1 to -3 have been found in patients with birth defects involving craniosynostosis. The complex patterns of expression of these receptors as well as the specificity of their interactions with the various FGF ligand family members are under investigation.

Product Categories/Family for FGFR-4/Fc Chimera active protein

Soluble receptors

References

1. Ezzat et al., Biochem Biophys Res Commun. 287:60, 2001 2. Takaishi et al., Biochem Biophys Res Commun. 267:658, 2000

NCBI and Uniprot Product Information

• NCBI GI #: 47524173
• NCBI GeneID: 2264
• NCBI Accession #: NP_002002
• NCBI GenBank Nucleotide #: NM_002011
• UniProt Accession #: P22455; O43785; Q14309; Q71TW8; Q8TDA0; Q96KE5; G3JVM2; G3JVM5; G3JVM7; G3JVM9; AAB25788
• Molecular Weight: ~170 kDa (Dimer)
• NCBI Official Full Name: fibroblast growth factor receptor 4 isoform 1
• NCBI Official Synonym Full Names: fibroblast growth factor receptor 4
• NCBI Official Symbol: FGFR4
• NCBI Official Synonym Symbols: TKF; JTK2; CD334
• NCBI Protein Information: fibroblast growth factor receptor 4; FGFR-4; tyrosylprotein kinase; protein-tyrosine kinase; hydroxyaryl-protein kinase; tyrosine kinase related to fibroblast growth factor receptor
• UniProt Protein Name: Fibroblast growth factor receptor 4
• UniProt Gene Name: FGFR4
• UniProt Synonym Gene Names: JTK2; TKF; FGFR-4
• UniProt Entry Name: FGFR4_HUMAN

NCBI Description

The protein encoded by this gene is a member of the fibroblast growth factor receptor family, where 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. A full-length representative protein would consist 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 of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. The genomic organization of this gene, compared to members 1-3, encompasses 18 exons rather than 19 or 20. Although alternative splicing has been observed, there is no evidence that the C-terminal half of the IgIII domain of this protein varies between three alternate forms, as indicated for members 1-3. This particular family member preferentially binds acidic fibroblast growth factor and, although its specific function is unknown, it is overexpressed in gynecological tumor samples, suggesting a role in breast and ovarian tumorigenesis. [provided by RefSeq, Jul 2008]

Uniprot Description

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. Ref.2 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.26 Ref.30

Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.16 Ref.19 Ref.20 Ref.21

Enzyme regulation: Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by autophosphorylation on tyrosine residues. Ref.20

Subunit structure: 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. Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.21 Ref.22 Ref.24 Ref.26

Subcellular location: 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. Ref.3 Ref.5 Ref.20 Ref.21 Ref.22Isoform 2: Secreted Ref.3 Ref.5 Ref.20 Ref.21 Ref.22. Isoform 3: Cytoplasm Ref.3 Ref.5 Ref.20 Ref.21 Ref.22.

Tissue specificity: Expressed in gastrointestinal epithelial cells, pancreas, and gastric and pancreatic cancer cell lines. Ref.3

Post-translational modification: N-glycosylated. Full maturation of the glycan chains in the Golgi is essential for high affinity interaction with FGF19. Ref.19 Ref.22Ubiquitinated. Subject to proteasomal degradation when not fully glycosylated. Ref.19 Ref.22Autophosphorylated. 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. Ref.14 Ref.19 Ref.21 Ref.22 Ref.24

Sequence similarities: Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.Contains 3 Ig-like C2-type (immunoglobulin-like) domains.Contains 1 protein kinase domain.