FGFR1

FGFR1, also known as CD331, belongs to the fibroblast growth factor receptor subfamily 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. Fibroblast growth factors (FGFs) (FGF1 - 10 and 16 - 23) are mitogenic signaling molecules that have roles in angiogenesis, wound healing, cell migration, neural outgrowth and embryonic development. FGFs bind heparan sulfate glycosaminoglycans, which facilitates dimerization (activation) of FGF receptors. FGFR1 is a full-length representative 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 of FGFR1 interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member binds both acidic and basic fibroblast growth factors and is involved in limb induction. CD331 can be detected in astrocytoma, neuroblastoma and adrenal cortex cell lines. Some isoforms are detected in foreskin fibroblast cell lines, however isoform 17, isoform 18 and isoform 19 are not detected in these cells. Defects in FGFR1 are a cause of Pfeiffer syndrome ，idiopathic hypogonadotropic hypogonadism， Kallmann syndrome type 2, osteoglophonic dysplasia and trigonocephaly non-syndromic.

FGFR1 Related Areas

Enzyme>>Protein Kinase>>Receptor Tyrosine Kinase>>FGFR1/CD331

Neuroscience>>Axon Guidance>>FGF & Receptor>>FGFR1/CD331

Signal Transduction>>Protein Kinase>>Receptor Tyrosine Kinase>>FGFR1/CD331

Stem Cell>>Neural Stem Cell (NSC)>>Glial Cell Markers>>FGFR1/CD331

Cancer>>Growth Factor & Receptor>>FGF & Receptor>>FGFR1/CD331

Cancer>>Growth Factor & Receptor>>Receptor Tyrosine Kinase>>FGFR1/CD331

Immunology>>Cluster of Differentiation>>Other>>FGFR1/CD331

FGFR1 Related Pathways

• EGFR dd

FGFR1 Alternative Names

FGFR1, CD331, FLT2, KAL2, BFGFR, CEK, FGFBR, FLG, FLJ99988, HBGFR, N-SAM, OGD [Homo sapiens]
Fgfr1, Flt-2, AW208770, FLG, Fgfr-1 [Mus musculus]

Summaries for FGFR1

Entrez Gene summary for FGFR1:

The protein encoded by this gene is a member of the fibroblast growth factor receptor (FGFR) 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 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 of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member binds both acidic and basic fibroblast growth factors and is involved in limb induction. Mutations in this gene have been associated with Pfeiffer syndrome, Jackson-Weiss syndrome, Antley-Bixler syndrome, osteoglophonic dysplasia, and autosomal dominant Kallmann syndrome 2. Chromosomal aberrations involving this gene are associated with stem cell myeloproliferative disorder and stem cell leukemia lymphoma syndrome. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized.

OMIM - description for FGFR1:

FGFR1 Ruta et al. (1988) isolated a novel gene from a human endothelial cell cDNA library by hybridizing at relaxed stringency using the v-fms oncogene as a probe. DNA sequence analysis of a 2-kb cDNA insert showed an open reading frame encoding a putative protein tyrosine kinase.

Human FGFR1 Protein General Information

 

• Protein names: Fibroblast growth factor receptor 1, Short name=FGFR1
• Sequence length: 822 AA.
• Domain: he second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans. Isoforms lacking the first Ig-like domain have higher affinity for fibroblast growth factors (FGF) and heparan sulfate proteoglycans than isoforms with all three Ig-like domains.
• 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.
• Post-translational modification: Autophosphorylated. 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 and proceeds in a highly ordered manner. Initial autophosphorylation at Tyr-653 increases the kinase activity by a factor of 50 to 100. After this, Tyr-583 becomes phosphorylated, followed by phosphorylation of Tyr-463, Tyr-766, Tyr-583 and Tyr-585. In a third stage, Tyr-654 is autophosphorylated, resulting in a further tenfold increase of kinase activity. Phosphotyrosine residues provide docking sites for interacting proteins and so are crucial for FGFR1 function and its regulation.
• Cofactor
• Subunit structure: Monomer. Homodimer after ligand binding. Interacts predominantly with FGF1 and FGF2, but can also interact with FGF3, FGF4, FGF5, FGF6, FGF8, FGF10, FGF19, FGF21, FGF22 and FGF23 (in vitro). Ligand specificity is determined by tissue-specific expression of isoforms, and differences in the third Ig-like domain are crucial for ligand specificity. Affinity for fibroblast growth factors (FGFs) is increased by heparan sulfate glycosaminoglycans that function as coreceptors. Likewise, KLB increases the affinity for FGF19, FGF21 and FGF23. Interacts (phosphorylated on Tyr-766) with PLCG1 (via SH2 domains). Interacts with FRS2. Interacts (via C-terminus) with NEDD4 (via WW3 domain). Interacts with KL By similarity. Interacts with SHB (via SH2 domain) and GRB10. Interacts with KAL1; this interaction does not interfere with FGF2-binding to FGFR1, but prevents binding of heparin-bound FGF2. Interacts with SOX2 and SOX3
• Subcellular location: Cell membrane; Single-pass type I membrane protein. Nucleus. Cytoplasm › cytosol. Cytoplasmic vesicle. Note: After ligand binding, both receptor and ligand are rapidly internalized. Can translocate to the nucleus after internalization, or by translocation from the endoplasmic reticulum or Golgi apparatus to the cytosol, and from there to the nucleus.
• Tissue specificity: Detected in astrocytoma, neuroblastoma and adrenal cortex cell lines. Some isoforms are detected in foreskin fibroblast cell lines, however isoform 17, isoform 18 and isoform 19 are not detected in these cells.
• Involvement in disease: Defects in FGFR1 are a cause of Pfeiffer syndrome (PS) [MIM:101600]; also known as acrocephalosyndactyly type V (ACS5). PS is characterized by craniosynostosis (premature fusion of the skull sutures) with deviation and enlargement of the thumbs and great toes, brachymesophalangy, with phalangeal ankylosis and a varying degree of soft tissue syndactyly.

General information above from UniProt

Function for FGFR1 Protein

UniProtKB:

Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. 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 phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation.

Genatlas:

• receptor tyrosine kinase, class IV, fibroblast growth factor receptor 1 (receptor for acidic FgF) involved in limb induction
• playing a role in the modulation of bone elongation
• mediate two independent signaling pathways in retinal pigment epithelial cells
• regulates proliferation, differentiation, and maintenance of normal myocardium
• playing a role in rhabdomyosarcoma tumorigenesis and a possible association with the deregulation of proliferation and differentiation of skeletal myoblasts in rhabdomyosarcoma
• negatively regulates endothelial cell function by altering the balance of modulatory cytokines

Homology for human FGFR1

• homolog to murine Fgfr1
• homolog to fibroblast growth factor receptor 1(flg/fms related gene)

Phenotype Information for FGFR1

• Gene/Locus: FGFR1, FLT2, KAL2, OGD
• Phenotype: Hypogonadotropic hypogonadism ,Jackson-Weiss syndrome ,Kallmann syndrome 2,Osteoglophonic dysplasia ,Pfeiffer syndrome ,Trigonocephaly 1

Phenotype Information for FGFR1 from OMIM (Online Mendelian Inheritance in Man)