Fibroblast growth factor receptor 1

UniProt P11362 Organism Homo sapiens Gene BFGFR, CEK, FGFBR, FGFR1, FLG, FLT2, HBGFR EC 2.7.10.1

Also known as: BFGFR, CEK, FGFBR, FGFR1, FLG, FLT2, HBGFR

Function

Tyrosine-protein kinase that acts as a 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.

Classification

Family (Pfam): PF07679 I-set, PF00047 ig, PF07714 PK_Tyr_Ser-Thr
InterPro: FGF_rcpt_1, FGF_rcpt_fam, Ig-like_dom, Ig-like_dom_sf, Ig-like_fold, Ig_I-set, Ig_sub, Ig_sub2, Immunoglobulin_dom, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, RTK, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_AS, Tyr_kinase_cat_dom
Functional cluster: Immunoglobulin-Domain Cell Adhesion Proteins

Experimental structures · PDB · 81

1AGW X-ray 2.40A
1CVS X-ray 2.80A
1EVT X-ray 2.80A
1FGI X-ray 2.50A
1FGK X-ray 2.00A
1FQ9 X-ray 3.00A
1XR0 NMR
2CR3 NMR
2FGI X-ray 2.50A
3C4F X-ray 2.07A
3DPK X-ray 1.95A
3GQI X-ray 2.50A
… and 69 more

A predicted model is available from AlphaFold.

Gene Ontology · 52

Disease associations

Pfeiffer syndrome MONDO:0007043
Jackson-Weiss syndrome MONDO:0007400
hypogonadotropic hypogonadism 2 with or without anosmia MONDO:0007844
osteoglophonic dysplasia MONDO:0008150
trigonocephaly 1 MONDO:0008603
encephalocraniocutaneous lipomatosis MONDO:0013074
Hartsfield-Bixler-Demyer syndrome MONDO:0014196

Drugs targeting this protein · 24

PAZOPANIB HYDROCHLORIDE inhibitor
INFIGRATINIB PHOSPHATE inhibitor
INFIGRATINIB inhibitor
REGORAFENIB inhibitor
RG-1530 inhibitor
LUCITANIB inhibitor
BRIVANIB ALANINATE inhibitor
ORANTINIB inhibitor
NINTEDANIB ESYLATE inhibitor
FEXAGRATINIB inhibitor
PD-0166285 HYDROCHLORIDE inhibitor
ERDAFITINIB inhibitor
E-7090 inhibitor
FUTIBATINIB inhibitor
BRIVANIB inhibitor
LY-2874455 inhibitor
FGFR INHIBITOR DEBIO 1347 inhibitor
ROGARATINIB inhibitor
TG100-801 inhibitor
DERAZANTINIB inhibitor
SURUFATINIB inhibitor
PEMIGATINIB inhibitor
ENMD-981693 inhibitor
XL-999 inhibitor

Neighborhood · nearest proteins

Nearest neighbours of Fibroblast growth factor receptor 1: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

FGFR1 oncogene partner 2 3 shared papers
Anosmin-1 6 shared papers
Fibroblast growth factor 1 8 shared papers
Fibroblast growth factor receptor 2 9 shared papers
Zinc finger MYM-type protein 2 1 shared papers
Fibroblast growth factor receptor 4 7 shared papers
Centriolin 1 shared papers
Centrosomal protein 43 1 shared papers
Heparan-sulfate 6-O-sulfotransferase 1 2 shared papers
NMDA receptor synaptonuclear signaling and neuronal migration factor 2 shared papers
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 3 shared papers
Fibroblast growth factor receptor 1 1 shared papers

Literature · 84 cited papers

DISP1 deficiency: Monoallelic and biallelic variants cause a spectrum of midline craniofacial malformations. Genet. Med. · 2024
Mosaic activating mutations in FGFR1 cause encephalocraniocutaneous lipomatosis. Am. J. Hum. Genet. · 2016
Novel FGFR1 mutations in Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism: evidence for the involvement of an alternatively spliced isoform. Fertil. Steril. · 2015
The prevalence of CHD7 missense versus truncating mutations is higher in patients with Kallmann syndrome than in typical CHARGE patients. J. Clin. Endocrinol. Metab. · 2014
Novel de novo heterozygous FGFR1 mutation in two siblings with Hartsfield syndrome: A case of gonadal mosaicism. Am. J. Med. Genet. A · 2014
FGFR1 mutations cause Hartsfield syndrome, the unique association of holoprosencephaly and ectrodactyly. J. Med. Genet. · 2013
Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. Am. J. Hum. Genet. · 2013
A translocation t(2;8)(q12;p11) fuses FGFR1 to a novel partner gene, RANBP2/NUP358, in a myeloproliferative/myelodysplastic neoplasm. Leukemia · 2013
SEMA3A, a gene involved in axonal pathfinding, is mutated in patients with Kallmann syndrome. PLoS Genet. · 2012
Nedd4-1 binds and ubiquitylates activated FGFR1 to control its endocytosis and function. EMBO J. · 2011
Heparan sulfate 6-O-sulfotransferase 1, a gene involved in extracellular sugar modifications, is mutated in patients with idiopathic hypogonadotrophic hypogonadism. Proc. Natl. Acad. Sci. U.S.A. · 2011
A novel mode of protein kinase inhibition exploiting hydrophobic motifs of autoinhibited kinases: discovery of ATP-independent inhibitors of fibroblast growth factor receptor. J. Biol. Chem. · 2011
… and 72 more in the literature graph

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