Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Fibroblast growth factor receptor 2

Gene

FGFR2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 STAT1.13 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation4 Publications

Enzyme regulationi

Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by ARQ 523 and ARQ 069; these compounds maintain the kinase in an inactive conformation and inhibit autophosphorylation.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei517ATPPROSITE-ProRule annotation1 Publication1
Binding sitei571ATPPROSITE-ProRule annotation1 Publication1
Active sitei626Proton acceptorPROSITE-ProRule annotation1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi487 – 495ATPPROSITE-ProRule annotation1 Publication9
Nucleotide bindingi565 – 567ATPPROSITE-ProRule annotation1 Publication3

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Apoptosis

Keywords - Ligandi

ATP-binding, Heparin-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS00881-MONOMER.
BRENDAi2.7.10.1. 2681.
ReactomeiR-HSA-109704. PI3K Cascade.
R-HSA-1257604. PIP3 activates AKT signaling.
R-HSA-190375. FGFR2c ligand binding and activation.
R-HSA-190377. FGFR2b ligand binding and activation.
R-HSA-2023837. Signaling by FGFR2 amplification mutants.
R-HSA-2033519. Activated point mutants of FGFR2.
R-HSA-2219530. Constitutive Signaling by Aberrant PI3K in Cancer.
R-HSA-5654221. Phospholipase C-mediated cascade, FGFR2.
R-HSA-5654695. PI-3K cascade:FGFR2.
R-HSA-5654699. SHC-mediated cascade:FGFR2.
R-HSA-5654700. FRS-mediated FGFR2 signaling.
R-HSA-5654727. Negative regulation of FGFR2 signaling.
R-HSA-5655253. Signaling by FGFR2 in disease.
R-HSA-5673001. RAF/MAP kinase cascade.
R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-HSA-8851708. Signaling by FGFR2 IIIa TM.
R-HSA-8853333. Signaling by FGFR2 fusions.
SignaLinkiP21802.
SIGNORiP21802.

Names & Taxonomyi

Protein namesi
Recommended name:
Fibroblast growth factor receptor 2 (EC:2.7.10.14 Publications)
Short name:
FGFR-2
Alternative name(s):
K-sam
Short name:
KGFR
Keratinocyte growth factor receptor
CD_antigen: CD332
Gene namesi
Name:FGFR2
Synonyms:BEK, KGFR, KSAM
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:3689. FGFR2.

Subcellular locationi

Isoform 1 :
Isoform 3 :

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini22 – 377ExtracellularSequence analysisAdd BLAST356
Transmembranei378 – 398HelicalSequence analysisAdd BLAST21
Topological domaini399 – 821CytoplasmicSequence analysisAdd BLAST423

GO - Cellular componenti

  • cell cortex Source: UniProtKB
  • cell surface Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytoplasmic, membrane-bounded vesicle Source: UniProtKB-SubCell
  • excitatory synapse Source: UniProtKB
  • extracellular region Source: UniProtKB-SubCell
  • Golgi apparatus Source: UniProtKB-SubCell
  • integral component of membrane Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • intracellular membrane-bounded organelle Source: HPA
  • membrane Source: UniProtKB
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Golgi apparatus, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Crouzon syndrome (CS)17 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant syndrome characterized by craniosynostosis, hypertelorism, exophthalmos and external strabismus, parrot-beaked nose, short upper lip, hypoplastic maxilla, and a relative mandibular prognathism.
See also OMIM:123500
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_004112105Y → C in CS. 2 Publications1
Natural variantiVAR_004113252S → L in CS. 1 PublicationCorresponds to variant rs79184941dbSNPEnsembl.1
Natural variantiVAR_017261263P → L in CS. 1 PublicationCorresponds to variant rs779326224dbSNPEnsembl.1
Natural variantiVAR_004118267S → P in CS. 1 PublicationCorresponds to variant rs121918505dbSNPEnsembl.1
Natural variantiVAR_004119268T → TG in CS. 1 Publication1
Natural variantiVAR_075856269 – 270Missing in SCS. 1 Publication2
Natural variantiVAR_004120276F → V in CS. 3 Publications1
Natural variantiVAR_004121278C → F in CS, JWS and PS; forms disulfide-linked dimers with constitutive kinase activity, is retained in an intracellular compartment and not detected at the cell surface. 5 PublicationsCorresponds to variant rs776587763dbSNPEnsembl.1
Natural variantiVAR_017263278C → Y in CS. 1 Publication1
Natural variantiVAR_017264281Y → C in CS. 2 Publications1
Natural variantiVAR_004122287 – 289Missing in CS. 3
Natural variantiVAR_017265288I → S in CS. 1 Publication1
Natural variantiVAR_004123289Q → P in CS and JWS. 5 PublicationsCorresponds to variant rs121918497dbSNPEnsembl.1
Natural variantiVAR_017266290W → G in CS. 1 PublicationCorresponds to variant rs121918501dbSNPEnsembl.1
Natural variantiVAR_004125290W → R in CS. Corresponds to variant rs121918501dbSNPEnsembl.1
Natural variantiVAR_004126292K → E in CS. 1 PublicationCorresponds to variant rs121918500dbSNPEnsembl.1
Natural variantiVAR_004127301Y → C in CS. 1 Publication1
Natural variantiVAR_004130328Y → C in CS. 1 PublicationCorresponds to variant rs121918493dbSNPEnsembl.1
Natural variantiVAR_004131331N → I in CS. 1 Publication1
Natural variantiVAR_004132337A → ANA in CS. 1
Natural variantiVAR_017268337A → P in CS. 1 PublicationCorresponds to variant rs387906676dbSNPEnsembl.1
Natural variantiVAR_004133338G → E in CS. 1 Publication1
Natural variantiVAR_015011338G → R in CS. 3 Publications1
Natural variantiVAR_004134340Y → H in CS. 2 PublicationsCorresponds to variant rs121918489dbSNPEnsembl.1
Natural variantiVAR_004135341T → P in PS and CS. 3 PublicationsCorresponds to variant rs121918495dbSNPEnsembl.1
Natural variantiVAR_004136342C → F in CS. 3 Publications1
Natural variantiVAR_004137342C → R in CS, JWS, PS and ABS2. 9 PublicationsCorresponds to variant rs121918488dbSNPEnsembl.1
Natural variantiVAR_004138342C → S in CS, JWS, PS and ABS2. 8 PublicationsCorresponds to variant rs121918488dbSNPEnsembl.1
Natural variantiVAR_017271342C → W in CS. 3 PublicationsCorresponds to variant rs121918496dbSNPEnsembl.1
Natural variantiVAR_004139342C → Y in CS and PS. 8 PublicationsCorresponds to variant rs121918487dbSNPEnsembl.1
Natural variantiVAR_004140344A → G in CS and JWS. 2 PublicationsCorresponds to variant rs121918492dbSNPEnsembl.1
Natural variantiVAR_004141344A → P in CS and PS. 1 Publication1
Natural variantiVAR_004142347S → C in CS. 2 PublicationsCorresponds to variant rs121918494dbSNPEnsembl.1
Natural variantiVAR_004143351S → C in CS, PS and ABS2. 3 PublicationsCorresponds to variant rs121918502dbSNPEnsembl.1
Natural variantiVAR_004144354S → C in CS. 5 PublicationsCorresponds to variant rs121918490dbSNPEnsembl.1
Natural variantiVAR_017272354S → Y in CS. 1 Publication1
Natural variantiVAR_004145356 – 358Missing in CS. 1 Publication3
Natural variantiVAR_004146359V → F in CS and PS. 2 Publications1
Natural variantiVAR_017273362A → S in CS. 1 Publication1
Natural variantiVAR_004147384G → R in CS. 1 Publication1
Natural variantiVAR_017276549N → H in CS; constitutive kinase activity. 2 Publications1
Natural variantiVAR_017281678R → G in CS. 1 Publication1
Jackson-Weiss syndrome (JWS)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant craniosynostosis syndrome characterized by craniofacial abnormalities and abnormality of the feet: broad great toes with medial deviation and tarsal-metatarsal coalescence.
See also OMIM:123150
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_004121278C → F in CS, JWS and PS; forms disulfide-linked dimers with constitutive kinase activity, is retained in an intracellular compartment and not detected at the cell surface. 5 PublicationsCorresponds to variant rs776587763dbSNPEnsembl.1
Natural variantiVAR_004123289Q → P in CS and JWS. 5 PublicationsCorresponds to variant rs121918497dbSNPEnsembl.1
Natural variantiVAR_004137342C → R in CS, JWS, PS and ABS2. 9 PublicationsCorresponds to variant rs121918488dbSNPEnsembl.1
Natural variantiVAR_004138342C → S in CS, JWS, PS and ABS2. 8 PublicationsCorresponds to variant rs121918488dbSNPEnsembl.1
Natural variantiVAR_004140344A → G in CS and JWS. 2 PublicationsCorresponds to variant rs121918492dbSNPEnsembl.1
Apert syndrome (APRS)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:101200
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_004114252S → F in APRS; requires 2 nucleotide substitutions. 1 PublicationCorresponds to variant rs121918498dbSNPEnsembl.1
Natural variantiVAR_004115252S → W in APRS and PS; common mutation. 7 PublicationsCorresponds to variant rs79184941dbSNPEnsembl.1
Natural variantiVAR_004117253P → R in APRS; common mutation. 5 PublicationsCorresponds to variant rs77543610dbSNPEnsembl.1
Pfeiffer syndrome (PS)11 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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).
See also OMIM:101600
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_017259172A → F in PS; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_004116252 – 253SP → FS in PS. Corresponds to variant rs281865420dbSNPEnsembl.2
Natural variantiVAR_004115252S → W in APRS and PS; common mutation. 7 PublicationsCorresponds to variant rs79184941dbSNPEnsembl.1
Natural variantiVAR_017262273Missing in PS; type 2. 1 Publication1
Natural variantiVAR_004121278C → F in CS, JWS and PS; forms disulfide-linked dimers with constitutive kinase activity, is retained in an intracellular compartment and not detected at the cell surface. 5 PublicationsCorresponds to variant rs776587763dbSNPEnsembl.1
Natural variantiVAR_004124290W → C in PS; severe; also in a lung squamous cell carcinoma sample; somatic mutation. 3 PublicationsCorresponds to variant rs121918499dbSNPEnsembl.1
Natural variantiVAR_004129321D → A in PS. 1 PublicationCorresponds to variant rs121918510dbSNPEnsembl.1
Natural variantiVAR_017269340Y → C in PS. 2 Publications1
Natural variantiVAR_004135341T → P in PS and CS. 3 PublicationsCorresponds to variant rs121918495dbSNPEnsembl.1
Natural variantiVAR_017270342C → G in PS. 1 Publication1
Natural variantiVAR_004137342C → R in CS, JWS, PS and ABS2. 9 PublicationsCorresponds to variant rs121918488dbSNPEnsembl.1
Natural variantiVAR_004138342C → S in CS, JWS, PS and ABS2. 8 PublicationsCorresponds to variant rs121918488dbSNPEnsembl.1
Natural variantiVAR_004139342C → Y in CS and PS. 8 PublicationsCorresponds to variant rs121918487dbSNPEnsembl.1
Natural variantiVAR_004141344A → P in CS and PS. 1 Publication1
Natural variantiVAR_004143351S → C in CS, PS and ABS2. 3 PublicationsCorresponds to variant rs121918502dbSNPEnsembl.1
Natural variantiVAR_004146359V → F in CS and PS. 2 Publications1
Natural variantiVAR_017275375Y → C in PS and BSTVS. 3 PublicationsCorresponds to variant rs121913478dbSNPEnsembl.1
Natural variantiVAR_017277565E → G in PS; constitutive kinase activity. 2 Publications1
Natural variantiVAR_017278641K → R in PS; constitutive kinase activity. 2 Publications1
Natural variantiVAR_017280663G → E in PS. 1 Publication1
Beare-Stevenson cutis gyrata syndrome (BSTVS)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:123790
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_017274372S → C in BSTVS. 1 PublicationCorresponds to variant rs121913477dbSNPEnsembl.1
Natural variantiVAR_017275375Y → C in PS and BSTVS. 3 PublicationsCorresponds to variant rs121913478dbSNPEnsembl.1
Familial scaphocephaly syndrome (FSPC)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:609579
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_023788526K → E in FSPC; constitutive kinase activity. 2 PublicationsCorresponds to variant rs121918507dbSNPEnsembl.1
Lacrimo-auriculo-dento-digital syndrome (LADDS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:149730
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_029884628A → T in LADDS; strongly reduced kinase activity. 1 PublicationCorresponds to variant rs121918509dbSNPEnsembl.1
Natural variantiVAR_029885648A → T in LADDS. 1 PublicationCorresponds to variant rs121918508dbSNPEnsembl.1
Natural variantiVAR_029886649 – 650RD → S in LADDS. 1 Publication2
Antley-Bixler syndrome, without genital anomalies or disordered steroidogenesis (ABS2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:207410
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_004137342C → R in CS, JWS, PS and ABS2. 9 PublicationsCorresponds to variant rs121918488dbSNPEnsembl.1
Natural variantiVAR_004138342C → S in CS, JWS, PS and ABS2. 8 PublicationsCorresponds to variant rs121918488dbSNPEnsembl.1
Natural variantiVAR_004143351S → C in CS, PS and ABS2. 3 PublicationsCorresponds to variant rs121918502dbSNPEnsembl.1
Bent bone dysplasia syndrome (BBDS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:614592
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067977381Y → D in BBDS. 1 PublicationCorresponds to variant rs387906678dbSNPEnsembl.1
Natural variantiVAR_067978391M → R in BBDS; the mutation selectively reduces plasma-membrane levels of the protein and markedly diminishes the receptor's responsiveness to extracellular FGF. 1 PublicationCorresponds to variant rs387906677dbSNPEnsembl.1
Saethre-Chotzen syndrome (SCS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA craniosynostosis syndrome characterized by coronal synostosis, brachycephaly, low frontal hairline, facial asymmetry, hypertelorism, broad halluces, and clinodactyly.
See also OMIM:101400
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_075856269 – 270Missing in SCS. 1 Publication2

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi265N → Q: Reduced N-glycosylation. Reduced expression at the cell surface. 1 Publication1
Mutagenesisi549N → T: Constitutive kinase activity. 1 Publication1
Mutagenesisi565E → A: Constitutive kinase activity. 1 Publication1
Mutagenesisi656 – 657Missing : Loss of kinase activity. 1 Publication2
Mutagenesisi769Y → F: Increases fibroblast proliferation. Decreases phosphorylation of PLCG1 and FRS2. Decreases activation of MAP kinases. 2 Publications1

Keywords - Diseasei

Craniosynostosis, Disease mutation, Ectodermal dysplasia, Lacrimo-auriculo-dento-digital syndrome, Mental retardation, Proto-oncogene

Organism-specific databases

DisGeNETi2263.
MalaCardsiFGFR2.
MIMi101200. phenotype.
101400. phenotype.
101600. phenotype.
123150. phenotype.
123500. phenotype.
123790. phenotype.
149730. phenotype.
207410. phenotype.
609579. phenotype.
614592. phenotype.
OpenTargetsiENSG00000066468.
Orphaneti83. Antley-Bixler syndrome.
87. Apert syndrome.
207. Crouzon disease.
1555. Cutis gyrata - acanthosis nigricans - craniosynostosis.
168624. Familial scaphocephaly syndrome, McGillivray type.
313855. FGFR2-related bent bone dysplasia.
1540. Jackson-Weiss syndrome.
2363. Lacrimoauriculodentodigital syndrome.
93258. Pfeiffer syndrome type 1.
93259. Pfeiffer syndrome type 2.
93260. Pfeiffer syndrome type 3.
794. Saethre-Chotzen syndrome.
PharmGKBiPA28128.

Chemistry databases

ChEMBLiCHEMBL4142.
DrugBankiDB09078. Lenvatinib.
DB09079. Nintedanib.
DB00039. Palifermin.
DB08901. Ponatinib.
DB08896. Regorafenib.
DB01041. Thalidomide.
GuidetoPHARMACOLOGYi1809.

Polymorphism and mutation databases

BioMutaiFGFR2.
DMDMi120049.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000001678322 – 821Fibroblast growth factor receptor 2Add BLAST800

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi62 ↔ 107PROSITE-ProRule annotation
Glycosylationi83N-linked (GlcNAc...)Sequence analysis1
Glycosylationi123N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi179 ↔ 231PROSITE-ProRule annotation1 Publication
Glycosylationi228N-linked (GlcNAc...)Sequence analysis1
Glycosylationi241N-linked (GlcNAc...)Sequence analysis1
Glycosylationi265N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi278 ↔ 342PROSITE-ProRule annotation1 Publication
Glycosylationi297N-linked (GlcNAc...)Sequence analysis1
Glycosylationi318N-linked (GlcNAc...)Sequence analysis1
Glycosylationi331N-linked (GlcNAc...)Sequence analysis1
Modified residuei466Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei586Phosphotyrosine; by autocatalysis3 Publications1
Modified residuei588Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei656Phosphotyrosine; by autocatalysis3 Publications1
Modified residuei657Phosphotyrosine; by autocatalysis3 Publications1
Modified residuei769Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei780PhosphoserineCombined sources1

Post-translational modificationi

Autophosphorylated. Binding of FGF family members together with heparan sulfate proteoglycan or heparin promotes receptor dimerization and autophosphorylation on several tyrosine residues. Autophosphorylation occurs in trans between the two FGFR molecules present in the dimer. Phosphorylation at Tyr-769 is essential for interaction with PLCG1.2 Publications
N-glycosylated in the endoplasmic reticulum. The N-glycan chains undergo further maturation to an Endo H-resistant form in the Golgi apparatus.2 Publications
Ubiquitinated. FGFR2 is rapidly ubiquitinated after autophosphorylation, leading to internalization and degradation. Subject to degradation both in lysosomes and by the proteasome.3 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP21802.
PeptideAtlasiP21802.
PRIDEiP21802.
TopDownProteomicsiP21802-8. [P21802-8]

PTM databases

iPTMnetiP21802.
PhosphoSitePlusiP21802.

Expressioni

Gene expression databases

BgeeiENSG00000066468.
ExpressionAtlasiP21802. baseline and differential.
GenevisibleiP21802. HS.

Organism-specific databases

HPAiCAB010886.
HPA035305.
HPA056562.

Interactioni

Subunit structurei

Monomer. Homodimer after ligand binding. Interacts predominantly with FGF1 and FGF2, but can also interact with FGF3, FGF4, FGF6, FGF7, FGF8, FGF9, FGF10, FGF17, FGF18 and FGF22 (in vitro). Ligand specificity is determined by tissue-specific expression of isoforms, and differences in the third Ig-like domain are crucial for ligand specificity. Isoform 1 has high affinity for FGF1 and FGF2, but low affinity for FGF7. Isoform 3 has high affinity for FGF1 and FGF7, and has much higher affinity for FGF7 than isoform 1 (in vitro). Affinity for fibroblast growth factors (FGFs) is increased by heparan sulfate glycosaminoglycans that function as coreceptors. Likewise, KLB increases the affinity for FGF19 and FGF21. Interacts with PLCG1, GRB2 and PAK4. Interacts with FLRT2 (By similarity).By similarity21 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
FGF1P039682EBI-1028658,EBI-6358090From a different organism.
FGF1P052303EBI-1028658,EBI-698068
FGF10O155202EBI-1028658,EBI-1035684
FGF2P090383EBI-1028658,EBI-977447
FGF2P09038-22EBI-1028658,EBI-11122080
FGF7P217812EBI-6354683,EBI-3937699
GRB2P629935EBI-1028658,EBI-401755

GO - Molecular functioni

  • fibroblast growth factor binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi108554. 71 interactors.
DIPiDIP-3788N.
IntActiP21802. 28 interactors.
MINTiMINT-118359.
STRINGi9606.ENSP00000410294.

Chemistry databases

BindingDBiP21802.

Structurei

Secondary structure

1821
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi152 – 157Combined sources6
Turni159 – 162Combined sources4
Beta strandi166 – 170Combined sources5
Beta strandi175 – 178Combined sources4
Beta strandi181 – 185Combined sources5
Beta strandi188 – 193Combined sources6
Helixi200 – 202Combined sources3
Beta strandi203 – 205Combined sources3
Beta strandi208 – 210Combined sources3
Helixi211 – 213Combined sources3
Beta strandi215 – 218Combined sources4
Helixi223 – 225Combined sources3
Beta strandi227 – 235Combined sources9
Beta strandi238 – 249Combined sources12
Beta strandi266 – 269Combined sources4
Beta strandi274 – 277Combined sources4
Beta strandi287 – 293Combined sources7
Beta strandi296 – 298Combined sources3
Beta strandi299 – 301Combined sources3
Beta strandi303 – 305Combined sources3
Beta strandi309 – 313Combined sources5
Beta strandi315 – 319Combined sources5
Turni321 – 325Combined sources5
Beta strandi326 – 329Combined sources4
Helixi334 – 336Combined sources3
Beta strandi338 – 345Combined sources8
Beta strandi350 – 357Combined sources8
Turni463 – 465Combined sources3
Turni472 – 474Combined sources3
Helixi478 – 480Combined sources3
Beta strandi481 – 489Combined sources9
Beta strandi494 – 500Combined sources7