InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: FGFR2

Summary

InnateDB Protein

IDBP-91365.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

FGFR2

Protein Name

fibroblast growth factor receptor 2

Synonyms

BBDS; BEK; BFR-1; CD332; CEK3; CFD1; ECT1; JWS; K-SAM; KGFR; TK14; TK25;

Species

Homo sapiens

Ensembl Protein

ENSP00000358056

InnateDB Gene

IDBG-91347 (FGFR2)

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 cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. 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. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1. {ECO:0000269PubMed:12529371, ECO:0000269PubMed:15190072, ECO:0000269PubMed:15629145, ECO:0000269PubMed:16384934, ECO:0000269PubMed:16597617, ECO:0000269PubMed:17311277, ECO:0000269PubMed:17623664, ECO:0000269PubMed:18374639, ECO:0000269PubMed:19103595, ECO:0000269PubMed:19387476, ECO:0000269PubMed:19410646, ECO:0000269PubMed:21596750, ECO:0000269PubMed:8663044}.

Subcellular Localization

Cell membrane; Single-pass type I membrane protein. Golgi apparatus. Cytoplasmic vesicle. Note=Detected on osteoblast plasma membrane lipid rafts. After ligand binding, the activated receptor is rapidly internalized and degraded.Isoform 1: Cell membrane; Single-pass type I membrane protein. Note=After ligand binding, the activated receptor is rapidly internalized and degraded.Isoform 3: Cell membrane; Single-pass type I membrane protein. Note=After ligand binding, the activated receptor is rapidly internalized and degraded.Isoform 14: Secreted.Isoform 19: Secreted.

Disease Associations

Crouzon syndrome (CS) [MIM:123500]: An autosomal dominant syndrome characterized by craniosynostosis, hypertelorism, exophthalmos and external strabismus, parrot-beaked nose, short upper lip, hypoplastic maxilla, and a relative mandibular prognathism. {ECO:0000269PubMed:10574673, ECO:0000269PubMed:11173845, ECO:0000269PubMed:11380921, ECO:0000269PubMed:11781872, ECO:0000269PubMed:7581378, ECO:0000269PubMed:7655462, ECO:0000269PubMed:7874170, ECO:0000269PubMed:7987400, ECO:0000269PubMed:8528214, ECO:0000269PubMed:8644708, ECO:0000269PubMed:8946174, ECO:0000269PubMed:8956050, ECO:0000269PubMed:9002682, ECO:0000269PubMed:9152842, ECO:0000269PubMed:9521581, ECO:0000269PubMed:9677057, ECO:0000269Ref.10}. Note=The disease is caused by mutations affecting the gene represented in this entry.Jackson-Weiss syndrome (JWS) [MIM:123150]: An autosomal dominant craniosynostosis syndrome characterized by craniofacial abnormalities and abnormality of the feet: broad great toes with medial deviation and tarsal-metatarsal coalescence. {ECO:0000269PubMed:7874170, ECO:0000269PubMed:8528214, ECO:0000269PubMed:8644708, ECO:0000269PubMed:9385368, ECO:0000269PubMed:9677057}. Note=The disease is caused by mutations affecting the gene represented in this entry.Apert syndrome (APRS) [MIM:101200]: A syndrome characterized by facio-cranio-synostosis, osseous and membranous syndactyly of the four extremities, and midface hypoplasia. The craniosynostosis is bicoronal and results in acrocephaly of brachysphenocephalic type. Syndactyly of the fingers and toes may be total (mitten hands and sock feet) or partial affecting the second, third, and fourth digits. Intellectual deficit is frequent and often severe, usually being associated with cerebral malformations. {ECO:0000269PubMed:11781872, ECO:0000269PubMed:7668257, ECO:0000269PubMed:7719344, ECO:0000269PubMed:9002682, ECO:0000269PubMed:9452027, ECO:0000269PubMed:9677057}. Note=The disease is caused by mutations affecting the gene represented in this entry.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:10394936, ECO:0000269PubMed:10945669, ECO:0000269PubMed:11173845, ECO:0000269PubMed:11781872, ECO:0000269PubMed:7719333, ECO:0000269PubMed:7719345, ECO:0000269PubMed:8644708, ECO:0000269PubMed:9002682, ECO:0000269PubMed:9150725, ECO:0000269PubMed:9693549, ECO:0000269PubMed:9719378}. Note=The disease is caused by mutations affecting the gene represented in this entry.Beare-Stevenson cutis gyrata syndrome (BSTVS) [MIM:123790]: An autosomal dominant disease characterized by craniofacial anomalies, particularly craniosynostosis, and ear defects, cutis gyrata, acanthosis nigricans, anogenital anomalies, skin tags, and prominent umbilical stump. The skin furrows have a corrugated appearance and are widespread. Cutis gyrata variably affects the scalp, forehead, face, preauricular area, neck, trunk, hands, and feet. {ECO:0000269PubMed:12000365, ECO:0000269PubMed:8696350}. Note=The disease is caused by mutations affecting the gene represented in this entry.Familial scaphocephaly syndrome (FSPC) [MIM:609579]: An autosomal dominant craniosynostosis syndrome characterized by scaphocephaly, macrocephaly, hypertelorism, maxillary retrusion, and mild intellectual disability. Scaphocephaly is the most common of the craniosynostosis conditions and is characterized by a long, narrow head. It is due to premature fusion of the sagittal suture or from external deformation. {ECO:0000269PubMed:16061565}. Note=The disease is caused by mutations affecting the gene represented in this entry.Lacrimo-auriculo-dento-digital syndrome (LADDS) [MIM:149730]: An autosomal dominant ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Lacrimo-auriculo-dento-digital syndrome is characterized by aplastic/hypoplastic lacrimal and salivary glands and ducts, cup-shaped ears, hearing loss, hypodontia and enamel hypoplasia, and distal limb segments anomalies. In addition to these cardinal features, facial dysmorphism, malformations of the kidney and respiratory system and abnormal genitalia have been reported. Craniosynostosis and severe syndactyly are not observed. {ECO:0000269PubMed:16501574}. Note=The disease is caused by mutations affecting the gene represented in this entry.Antley-Bixler syndrome, without genital anomalies or disordered steroidogenesis (ABS2) [MIM:207410]: A rare syndrome characterized by craniosynostosis, radiohumeral synostosis present from the perinatal period, midface hypoplasia, choanal stenosis or atresia, femoral bowing and multiple joint contractures. Arachnodactyly and/or camptodactyly have also been reported. {ECO:0000269PubMed:10633130}. Note=The disease is caused by mutations affecting the gene represented in this entry.Bent bone dysplasia syndrome (BBDS) [MIM:614592]: A perinatal lethal skeletal dysplasia characterized by poor mineralization of the calvarium, craniosynostosis, dysmorphic facial features, prenatal teeth, hypoplastic pubis and clavicles, osteopenia, and bent long bones. Dysmorphic facial features included low-set ears, hypertelorism, midface hypoplasia, prematurely erupted fetal teeth, and micrognathia. {ECO:0000269PubMed:22387015}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 47 experimentally validated interaction(s) in this database.
They are also associated with 2 interaction(s) predicted by orthology.

Experimentally validated
Total	47 [view]
Protein-Protein	44 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	2 [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:0042803	protein homodimerization activity

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0001525	angiogenesis
GO:0001657	ureteric bud development
GO:0001701	in utero embryonic development
GO:0002053	positive regulation of mesenchymal cell proliferation
GO:0003148	outflow tract septum morphogenesis
GO:0003149	membranous septum morphogenesis
GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007267	cell-cell signaling
GO:0007409	axonogenesis
GO:0008284	positive regulation of cell proliferation
GO:0008286	insulin receptor signaling pathway
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0008589	regulation of smoothened signaling pathway
GO:0009791	post-embryonic development
GO:0009880	embryonic pattern specification
GO:0009887	organ morphogenesis
GO:0010453	regulation of cell fate commitment
GO:0010518	positive regulation of phospholipase activity
GO:0016331	morphogenesis of embryonic epithelium
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0021769	orbitofrontal cortex development
GO:0021847	ventricular zone neuroblast division
GO:0021860	pyramidal neuron development
GO:0022612	gland morphogenesis
GO:0030177	positive regulation of Wnt signaling pathway
GO:0030282	bone mineralization
GO:0030324	lung development
GO:0030855	epithelial cell differentiation
GO:0030901	midbrain development
GO:0030916	otic vesicle formation
GO:0031069	hair follicle morphogenesis
GO:0032808	lacrimal gland development
GO:0033688	regulation of osteoblast proliferation
GO:0035264	multicellular organism growth
GO:0035265	organ growth
GO:0035602	fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow
GO:0035603	fibroblast growth factor receptor signaling pathway involved in hemopoiesis
GO:0035604	fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow
GO:0035607	fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0040014	regulation of multicellular organism growth
GO:0040036	regulation of fibroblast growth factor receptor signaling pathway
GO:0042472	inner ear morphogenesis
GO:0042476	odontogenesis
GO:0043410	positive regulation of MAPK cascade
GO:0045087	innate immune response
GO:0045165	cell fate commitment
GO:0045667	regulation of osteoblast differentiation
GO:0045787	positive regulation of cell cycle
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0046777	protein autophosphorylation
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048015	phosphatidylinositol-mediated signaling
GO:0048286	lung alveolus development
GO:0048557	embryonic digestive tract morphogenesis
GO:0048562	embryonic organ morphogenesis
GO:0048565	digestive tract development
GO:0048568	embryonic organ development
GO:0048608	reproductive structure development
GO:0048701	embryonic cranial skeleton morphogenesis
GO:0048705	skeletal system morphogenesis
GO:0048730	epidermis morphogenesis
GO:0048755	branching morphogenesis of a nerve
GO:0048762	mesenchymal cell differentiation
GO:0050679	positive regulation of epithelial cell proliferation
GO:0051150	regulation of smooth muscle cell differentiation
GO:0051781	positive regulation of cell division
GO:0055010	ventricular cardiac muscle tissue morphogenesis
GO:0060045	positive regulation of cardiac muscle cell proliferation
GO:0060174	limb bud formation
GO:0060348	bone development
GO:0060349	bone morphogenesis
GO:0060442	branching involved in prostate gland morphogenesis
GO:0060445	branching involved in salivary gland morphogenesis
GO:0060449	bud elongation involved in lung branching
GO:0060463	lung lobe morphogenesis
GO:0060484	lung-associated mesenchyme development
GO:0060501	positive regulation of epithelial cell proliferation involved in lung morphogenesis
GO:0060512	prostate gland morphogenesis
GO:0060523	prostate epithelial cord elongation
GO:0060527	prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis
GO:0060529	squamous basal epithelial stem cell differentiation involved in prostate gland acinus development
GO:0060595	fibroblast growth factor receptor signaling pathway involved in mammary gland specification
GO:0060601	lateral sprouting from an epithelium
GO:0060615	mammary gland bud formation
GO:0060664	epithelial cell proliferation involved in salivary gland morphogenesis
GO:0060667	branch elongation involved in salivary gland morphogenesis
GO:0060670	branching involved in labyrinthine layer morphogenesis
GO:0060687	regulation of branching involved in prostate gland morphogenesis
GO:0060688	regulation of morphogenesis of a branching structure
GO:0060915	mesenchymal cell differentiation involved in lung development
GO:0060916	mesenchymal cell proliferation involved in lung development
GO:0070372	regulation of ERK1 and ERK2 cascade
GO:0070374	positive regulation of ERK1 and ERK2 cascade
GO:0090263	positive regulation of canonical Wnt signaling pathway

Cellular Component

GO:0005576	extracellular region
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005794	Golgi apparatus
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0005938	cell cortex
GO:0009986	cell surface
GO:0016020	membrane
GO:0016021	integral component of membrane
GO:0016023	cytoplasmic membrane-bounded vesicle
GO:0031012	extracellular matrix
GO:0043231	intracellular membrane-bounded organelle
GO:0060076	excitatory synapse

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