InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: FGFR1

Summary

InnateDB Protein

IDBP-236024.6

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

ENSP00000380280

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.

Experimentally validated
Total	82 [view]
Protein-Protein	80 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	6 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005007	fibroblast growth factor-activated receptor activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008201	heparin binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0017134	fibroblast growth factor binding
GO:0042802	identical protein binding
GO:0042803	protein homodimerization activity

Biological Process

GO:0000165	MAPK cascade
GO:0001501	skeletal system development
GO:0001764	neuron migration
GO:0006351	transcription, DNA-templated
GO:0006468	protein phosphorylation
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007411	axon guidance
GO:0008284	positive regulation of cell proliferation
GO:0008286	insulin receptor signaling pathway
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0010518	positive regulation of phospholipase activity
GO:0010863	positive regulation of phospholipase C activity
GO:0014068	positive regulation of phosphatidylinositol 3-kinase signaling
GO:0016477	cell migration
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0043009	chordate embryonic development
GO:0043406	positive regulation of MAP kinase activity
GO:0043410	positive regulation of MAPK cascade
GO:0045087	innate immune response
GO:0045595	regulation of cell differentiation
GO:0045666	positive regulation of neuron differentiation
GO:0046777	protein autophosphorylation
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048015	phosphatidylinositol-mediated signaling
GO:0048705	skeletal system morphogenesis

Cellular Component

GO:0005576	extracellular region
GO:0005634	nucleus
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0016021	integral component of membrane
GO:0016023	cytoplasmic membrane-bounded vesicle
GO:0043235	receptor complex

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR003598 Immunoglobulin subtype 2
IPR003599 Immunoglobulin subtype
IPR007110 Immunoglobulin-like domain
IPR011009 Protein kinase-like domain
IPR013098 Immunoglobulin I-set
IPR013151 Immunoglobulin
IPR016248 Fibroblast growth factor receptor family
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF07679
PF00047

PRINTS

PR00109

PIRSF

PIRSF000628

SMART

SM00220
SM00408
SM00409
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References