| Function: |
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. |
| 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: |
Pfeiffer syndrome: A syndrome characterized by the association of craniosynostosis, broad and deviated thumbs and big toes, and partial syndactyly of the fingers and toes. Three subtypes are known: mild autosomal dominant form (type 1); cloverleaf skull, elbow ankylosis, early death, sporadic (type 2); craniosynostosis, early demise, sporadic (type 3).
Hypogonadotropic hypogonadism 2 with or without anosmia: A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
Osteoglophonic dysplasia: Characterized by craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as by rhizomelic dwarfism and nonossifying bone lesions. Inheritance is autosomal dominant.
Hartsfield syndrome: A syndrome characterized by the triad of holoprosencephaly, ectrodactyly, and cleft/lip palate. Profound mental retardation is also present. Multiple other congenital anomalies usually occur.
Trigonocephaly 1: A keel-shaped deformation of the forehead, caused by premature fusion of the metopic sutures. It results in a triangular shape of the head.
Encephalocraniocutaneous lipomatosis: A sporadically occurring, neurocutaneous disorder characterized by ocular anomalies, skin lesions, and central nervous system anomalies. Clinical features include a well-demarcated hairless fatty nevus on the scalp, benign ocular tumors, intracranial and intraspinal lipomas, and congenital abnormalities of the meninges. Seizures, spasticity, and intellectual disability can be present.
Jackson-Weiss syndrome: An autosomal dominant craniosynostosis syndrome characterized by craniofacial abnormalities and abnormality of the feet: broad great toes with medial deviation and tarsal-metatarsal coalescence. |
| Sequence Similarities: |
Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily. |
| 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. |
| Cellular Location: |
Cell membrane. Nucleus. Cytoplasm > Cytosol. Cytoplasmic vesicle.
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. |
| Database Links: |
Entrez Gene: 3815?HumanOmim: 164920?HumanSwissProt: P10721?HumanUnigene: 479754?Human |
| Synonyms: |
C Kit Antibodyc-Kit Antibodyc-Kit Ligand AntibodyCD117 AntibodyKit AntibodyKit Ligand AntibodyKIT oncogene AntibodyKIT proto oncogene receptor tyrosine kinase AntibodyKIT_HUMAN AntibodyMast cell growth factor receptor AntibodyMast/stem cell growth factor receptor Kit AntibodyMast/stem cell growth factor receptor precursor AntibodyMGF Antibodyp145 c-kit AntibodyPBT AntibodyPiebald trait protein AntibodyProto oncogene c Kit AntibodyProto oncogene tyrosine protein kinase Kit AntibodyProto-oncogene c-Kit AntibodySCF Receptor AntibodySCFR Antibodysoluble KIT variant 1 AntibodySteel Factor Receptor AntibodyStem cell factor receptor Antibodytyrosine protein kinase Kit AntibodyTyrosine-protein kinase Kit Antibodyv kit Hardy Zuckerman 4 feline sarcoma viral oncogene homolog Antibodyv kit Hardy Zuckerman 4 feline sarcoma viral oncogene like protein Antibodyv-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog Antibody |
| Information: |
Target information shown above is from the UniProt Consortium. |
