Homo sapiens Protein: FGFR1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
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Summary | |||||||||||||||||||||||||||||||||||||||||||||||||||||
InnateDB Protein | IDBP-596957.3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Last Modified | 2014-10-13 [Report errors or provide feedback] | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Gene Symbol | FGFR1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Protein Name | fibroblast growth factor receptor 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Synonyms | bFGF-R-1; BFGFR; CD331; CEK; FGFBR; FGFR-1; FLG; FLT-2; FLT2; HBGFR; HH2; HRTFDS; KAL2; N-SAM; OGD; | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Species | Homo sapiens | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Ensembl Protein | ENSP00000433163 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
InnateDB Gene | IDBG-17796 (FGFR1) | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Protein Structure | |||||||||||||||||||||||||||||||||||||||||||||||||||||
UniProt Annotation | |||||||||||||||||||||||||||||||||||||||||||||||||||||
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. {ECO:0000269PubMed:10830168, ECO:0000269PubMed:11353842, ECO:0000269PubMed:12181353, ECO:0000269PubMed:1379697, ECO:0000269PubMed:1379698, ECO:0000269PubMed:15117958, ECO:0000269PubMed:16597617, ECO:0000269PubMed:17311277, ECO:0000269PubMed:17623664, ECO:0000269PubMed:18480409, ECO:0000269PubMed:19224897, ECO:0000269PubMed:19261810, ECO:0000269PubMed:19665973, ECO:0000269PubMed:20133753, ECO:0000269PubMed:20139426, ECO:0000269PubMed:21765395, ECO:0000269PubMed:8622701, ECO:0000269PubMed:8663044}. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Subcellular Localization | 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Disease Associations | Pfeiffer syndrome (PS) [MIM:101600]: 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). {ECO:0000269PubMed:7874169}. Note=The disease is caused by mutations affecting the gene represented in this entry.Hypogonadotropic hypogonadism 2 with or without anosmia (HH2) [MIM:147950]: 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). {ECO:0000269PubMed:12627230, ECO:0000269PubMed:15001591, ECO:0000269PubMed:15605412, ECO:0000269PubMed:15845591, ECO:0000269PubMed:16606836, ECO:0000269PubMed:16757108, ECO:0000269PubMed:16764984, ECO:0000269PubMed:16882753, ECO:0000269PubMed:17154279, ECO:0000269PubMed:19820032, ECO:0000269PubMed:21700882, ECO:0000269PubMed:22927827, ECO:0000269PubMed:23643382}. Note=The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. Some patients carrying mutations in FGFR1 also have a mutation other HH-associated genes including DUSP6, FGF8, FGF17, FLRT3, GNRH1, GNRHR, HS6ST1, IL17RD, KAL1, KISS1R, NSMF, PROKR2, SPRY4 and TACR3 (PubMed:23643382). {ECO:0000269PubMed:23643382}.Osteoglophonic dysplasia (OGD) [MIM:166250]: Characterized by craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as by rhizomelic dwarfism and nonossifying bone lesions. Inheritance is autosomal dominant. {ECO:0000269PubMed:15625620, ECO:0000269PubMed:16470795}. Note=The disease is caused by mutations affecting the gene represented in this entry.Hartsfield syndrome (HRTFDS) [MIM:615465]: 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. {ECO:0000269PubMed:23812909}. Note=The disease is caused by mutations affecting the gene represented in this entry.Trigonocephaly 1 (TRIGNO1) [MIM:190440]: A keel-shaped deformation of the forehead, caused by premature fusion of the metopic sutures. It results in a triangular shape of the head. {ECO:0000269PubMed:11173846}. Note=The disease is caused by mutations affecting the gene represented in this entry.Note=A chromosomal aberration involving FGFR1 may be a cause of stem cell leukemia lymphoma syndrome (SCLL). Translocation t(8;13)(p11;q12) with ZMYM2. SCLL usually presents as lymphoblastic lymphoma in association with a myeloproliferative disorder, often accompanied by pronounced peripheral eosinophilia and/or prominent eosinophilic infiltrates in the affected bone marrow.Note=A chromosomal aberration involving FGFR1 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(6;8)(q27;p11) with FGFR1OP. Insertion ins(12;8)(p11;p11p22) with FGFR1OP2. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion proteins FGFR1OP2-FGFR1, FGFR1OP-FGFR1 or FGFR1-FGFR1OP may exhibit constitutive kinase activity and be responsible for the transforming activity.Note=A chromosomal aberration involving FGFR1 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(8;9)(p12;q33) with CNTRL. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion protein CNTRL-FGFR1 is found in the cytoplasm, exhibits constitutive kinase activity and may be responsible for the transforming activity. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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. {ECO:0000269PubMed:1652059}. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||
Interactions | |||||||||||||||||||||||||||||||||||||||||||||||||||||
Number of Interactions |
This gene and/or its encoded proteins are associated with 82 experimentally validated interaction(s) in this database.
They are also associated with 6 interaction(s) predicted by orthology.
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Gene Ontology | |||||||||||||||||||||||||||||||||||||||||||||||||||||
Molecular Function |
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Biological Process |
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Cellular Component |
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Protein Structure and Domains | |||||||||||||||||||||||||||||||||||||||||||||||||||||
PDB ID | |||||||||||||||||||||||||||||||||||||||||||||||||||||
InterPro |
IPR003598
Immunoglobulin subtype 2 IPR003599 Immunoglobulin subtype IPR007110 Immunoglobulin-like domain IPR013098 Immunoglobulin I-set IPR013151 Immunoglobulin |
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PFAM |
PF07679
PF00047 |
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PRINTS | |||||||||||||||||||||||||||||||||||||||||||||||||||||
PIRSF | |||||||||||||||||||||||||||||||||||||||||||||||||||||
SMART |
SM00408
SM00409 |
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TIGRFAMs | |||||||||||||||||||||||||||||||||||||||||||||||||||||
Post-translational Modifications | |||||||||||||||||||||||||||||||||||||||||||||||||||||
Modification | |||||||||||||||||||||||||||||||||||||||||||||||||||||
Cross-References | |||||||||||||||||||||||||||||||||||||||||||||||||||||
SwissProt | P11362 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
PhosphoSite | PhosphoSite-P11362 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
TrEMBL | C9J205 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
UniProt Splice Variant | |||||||||||||||||||||||||||||||||||||||||||||||||||||
Entrez Gene | 2260 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
UniGene | Hs.690894 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
RefSeq | |||||||||||||||||||||||||||||||||||||||||||||||||||||
HUGO | HGNC:3688 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
OMIM | 136350 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
CCDS | |||||||||||||||||||||||||||||||||||||||||||||||||||||
HPRD | 00634 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
IMGT | |||||||||||||||||||||||||||||||||||||||||||||||||||||
EMBL | AB208919 AC087623 AK222718 AK291754 AK292470 AK309947 AY585209 BC015035 BC018128 BC091494 FJ809917 M34185 M34186 M34187 M34188 M34641 M37722 M60485 M63887 M63888 M63889 X51803 X52833 X57118 X57119 X57120 X57121 X57122 X66945 Y00665 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
GenPept | AAA35835 AAA35836 AAA35837 AAA35838 AAA35839 AAA35840 AAA35958 AAA35959 AAA35960 AAA75007 AAH15035 AAH18128 AAH91494 AAS79322 ACO38646 BAD92156 BAD96438 BAF84443 BAF85159 CAA36101 CAA37015 CAA40400 CAA40401 CAA40402 CAA40403 CAA40404 CAA47375 CAA68679 | ||||||||||||||||||||||||||||||||||||||||||||||||||||