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UniProtKB - P21802 (FGFR2_HUMAN)

Protein

Fibroblast growth factor receptor 2

Gene

FGFR2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Activity 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

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionHeparin-binding, Kinase, Receptor, Transferase, Tyrosine-protein kinase
Biological processApoptosis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000066468.20
HGNCiHGNC:3689 FGFR2
MIMi176943 gene
neXtProtiNX_P21802

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

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 PublicationsCorresponds to variant dbSNP:rs1434545235Ensembl.1
Natural variantiVAR_017261263P → L in CS. 1 PublicationCorresponds to variant dbSNP:rs779326224Ensembl.1
Natural variantiVAR_004118267S → P in CS. 1 PublicationCorresponds to variant dbSNP:rs121918505EnsemblClinVar.1
Natural variantiVAR_004119268T → TG in CS. 1 Publication1
Natural variantiVAR_004120276F → V in CS. 3 PublicationsCorresponds to variant dbSNP:rs1057519036Ensembl.1
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 dbSNP:rs776587763EnsemblClinVar.1
Natural variantiVAR_017263278C → Y in CS. 1 Publication1
Natural variantiVAR_017264281Y → C in CS. 2 PublicationsCorresponds to variant dbSNP:rs1057519038Ensembl.1
Natural variantiVAR_004122287 – 289Missing in CS. 3
Natural variantiVAR_017265288I → S in CS. 1 Publication1
Natural variantiVAR_017266290W → G in CS. 1 PublicationCorresponds to variant dbSNP:rs121918501EnsemblClinVar.1
Natural variantiVAR_004125290W → R in CS. Corresponds to variant dbSNP:rs121918501EnsemblClinVar.1
Natural variantiVAR_004126292K → E in CS. 1 PublicationCorresponds to variant dbSNP:rs121918500EnsemblClinVar.1
Natural variantiVAR_004127301Y → C in CS. 1 Publication1
Natural variantiVAR_004130328Y → C in CS. 1 PublicationCorresponds to variant dbSNP:rs121918493EnsemblClinVar.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 dbSNP:rs387906676EnsemblClinVar.1
Natural variantiVAR_004133338G → E in CS. 1 PublicationCorresponds to variant dbSNP:rs1057519044Ensembl.1
Natural variantiVAR_015011338G → R in CS. 3 PublicationsCorresponds to variant dbSNP:rs1057519043Ensembl.1
Natural variantiVAR_004134340Y → H in CS. 2 PublicationsCorresponds to variant dbSNP:rs121918489EnsemblClinVar.1
Natural variantiVAR_004136342C → F in CS. 3 PublicationsCorresponds to variant dbSNP:rs121918487EnsemblClinVar.1
Natural variantiVAR_004137342C → R in CS, JWS, PS and ABS2. 9 PublicationsCorresponds to variant dbSNP:rs121918488EnsemblClinVar.1
Natural variantiVAR_004138342C → S in CS, JWS, PS and ABS2. 8 PublicationsCorresponds to variant dbSNP:rs121918488EnsemblClinVar.1
Natural variantiVAR_017271342C → W in CS. 3 PublicationsCorresponds to variant dbSNP:rs121918496EnsemblClinVar.1
Natural variantiVAR_004142347S → C in CS. 2 PublicationsCorresponds to variant dbSNP:rs121918494EnsemblClinVar.1
Natural variantiVAR_004143351S → C in CS, PS and ABS2. 3 PublicationsCorresponds to variant dbSNP:rs121918502EnsemblClinVar.1
Natural variantiVAR_004144354S → C in CS. 5 PublicationsCorresponds to variant dbSNP:rs121918490EnsemblClinVar.1
Natural variantiVAR_017272354S → Y in CS. 1 Publication1
Natural variantiVAR_004145356 – 358Missing in CS. 1 Publication3
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 PublicationsCorresponds to variant dbSNP:rs1057519045Ensembl.1
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
Apert syndrome (APRS)8 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 dbSNP:rs121918498EnsemblClinVar.1
Natural variantiVAR_004117253P → R in APRS; common mutation. 5 PublicationsCorresponds to variant dbSNP:rs77543610EnsemblClinVar.1
Pfeiffer syndrome (PS)13 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 dbSNP:rs281865420Ensembl.2
Natural variantiVAR_017262273Missing in PS; type 2. 1 Publication1
Natural variantiVAR_004124290W → C in PS; severe; also in a lung squamous cell carcinoma sample; somatic mutation. 3 PublicationsCorresponds to variant dbSNP:rs121918499EnsemblClinVar.1
Natural variantiVAR_004129321D → A in PS. 1 PublicationCorresponds to variant dbSNP:rs121918510EnsemblClinVar.1
Natural variantiVAR_017269340Y → C in PS. 2 Publications1
Natural variantiVAR_017270342C → G in PS. 1 PublicationCorresponds to variant dbSNP:rs121918488EnsemblClinVar.1
Natural variantiVAR_017277565E → G in PS; constitutive kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs121918506EnsemblClinVar.1
Natural variantiVAR_017278641K → R in PS; constitutive kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs1057519047Ensembl.1
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 dbSNP:rs121913477EnsemblClinVar.1
Familial scaphocephaly syndrome (FSPC)2 Publications
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 dbSNP:rs121918507EnsemblClinVar.1
Lacrimo-auriculo-dento-digital syndrome (LADDS)2 Publications
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 dbSNP:rs121918509EnsemblClinVar.1
Natural variantiVAR_029885648A → T in LADDS. 1 PublicationCorresponds to variant dbSNP:rs121918508EnsemblClinVar.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
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 dbSNP:rs387906678EnsemblClinVar.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 dbSNP:rs387906677EnsemblClinVar.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
GeneReviewsiFGFR2
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
DrugBankiDB02491 4-[4-(1-Amino-1-Methylethyl)Phenyl]-5-Chloro-N-[4-(2-Morpholin-4-Ylethyl)Phenyl]Pyrimidin-2-Amine
DB09078 Lenvatinib
DB09079 Nintedanib
DB00039 Palifermin
DB08901 Ponatinib
DB08896 Regorafenib
DB02058 SU4984
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...) asparagineSequence analysis1
Glycosylationi123N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi179 ↔ 231PROSITE-ProRule annotation1 Publication
Glycosylationi228N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi241N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi265N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi278 ↔ 342PROSITE-ProRule annotation1 Publication
Glycosylationi297N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi318N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi331N-linked (GlcNAc...) asparagineSequence 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
ProteomicsDBi53905
53906 [P21802-10]
53907 [P21802-11]
53908 [P21802-12]
53909 [P21802-13]
53910 [P21802-14]
53911 [P21802-15]
53912 [P21802-16]
53913 [P21802-17]
53914 [P21802-18]
53915 [P21802-19]
53916 [P21802-2]
53917 [P21802-20]
53918 [P21802-21]
53919 [P21802-22]
53920 [P21802-23]
53921 [P21802-3]
53922 [P21802-4]
53923 [P21802-5]
53924 [P21802-6]
53925 [P21802-7]
53926 [P21802-8]
53927 [P21802-9]
TopDownProteomicsiP21802-8 [P21802-8]

PTM databases

iPTMnetiP21802
PhosphoSitePlusiP21802

Expressioni

Gene expression databases

BgeeiENSG00000066468 Expressed in 222 organ(s), highest expression level in C1 segment of cervical spinal cord
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

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi108554, 91 interactors
CORUMiP21802
DIPiDIP-3788N
IntActiP21802, 30 interactors
MINTiP21802
STRINGi9606.ENSP00000410294

Chemistry databases

BindingDBiP21802

Structurei

Secondary structure

1821
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP21802
SMRiP21802
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP21802

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini25 – 125Ig-like C2-type 1Add BLAST101
Domaini154 – 247Ig-like C2-type 2Add BLAST94
Domaini256 – 358Ig-like C2-type 3Add BLAST103
Domaini481 – 770Protein kinasePROSITE-ProRule annotationAdd BLAST290

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni161 – 178Heparin-bindingAdd BLAST18

Domaini

The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans. Alternative splicing events affecting the third Ig-like domain are crucial for ligand selectivity.3 Publications

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0200 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118923
HOGENOMiHOG000263410
HOVERGENiHBG000345
InParanoidiP21802
KOiK05093
OrthoDBiEOG091G0CQZ
PhylomeDBiP21802
TreeFamiTF316307

Family and domain databases

Gene3Di2.60.40.10, 3 hits
InterProiView protein in InterPro
IPR016248 FGF_rcpt_fam
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR013098 Ig_I-set
IPR003599 Ig_sub
IPR003598 Ig_sub2
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
PfamiView protein in Pfam
PF07679 I-set, 2 hits
PF07714 Pkinase_Tyr, 1 hit
PIRSFiPIRSF000628 FGFR, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00409 IG, 3 hits
SM00408 IGc2, 3 hits
SM00219 TyrKc, 1 hit
SUPFAMiSSF48726 SSF48726, 3 hits
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 3 hits
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00109 PROTEIN_KINASE_TYR, 1 hit

Sequences (23+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 23 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 23 described isoforms and 11 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P21802-1) [UniParc]FASTAAdd to basket
Also known as: BEK, FGFR2IIIc

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

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        10         20         30         40         50
MVSWGRFICL VVVTMATLSL ARPSFSLVED TTLEPEEPPT KYQISQPEVY 
        60         70         80         90        100
VAAPGESLEV RCLLKDAAVI SWTKDGVHLG PNNRTVLIGE YLQIKGATPR 
       110        120        130        140        150
DSGLYACTAS RTVDSETWYF MVNVTDAISS GDDEDDTDGA EDFVSENSNN 
       160        170        180        190        200
KRAPYWTNTE KMEKRLHAVP AANTVKFRCP AGGNPMPTMR WLKNGKEFKQ 
       210        220        230        240        250
EHRIGGYKVR NQHWSLIMES VVPSDKGNYT CVVENEYGSI NHTYHLDVVE 
       260        270        280        290        300
RSPHRPILQA GLPANASTVV GGDVEFVCKV YSDAQPHIQW IKHVEKNGSK 
       310        320        330        340        350
YGPDGLPYLK VLKAAGVNTT DKEIEVLYIR NVTFEDAGEY TCLAGNSIGI 
       360        370        380        390        400
SFHSAWLTVL PAPGREKEIT ASPDYLEIAI YCIGVFLIAC MVVTVILCRM 
       410        420        430        440        450
KNTTKKPDFS SQPAVHKLTK RIPLRRQVTV SAESSSSMNS NTPLVRITTR 
       460        470        480        490        500
LSSTADTPML AGVSEYELPE DPKWEFPRDK LTLGKPLGEG CFGQVVMAEA 
       510        520        530        540        550
VGIDKDKPKE AVTVAVKMLK DDATEKDLSD LVSEMEMMKM IGKHKNIINL 
       560        570        580        590        600
LGACTQDGPL YVIVEYASKG NLREYLRARR PPGMEYSYDI NRVPEEQMTF 
       610        620        630        640        650
KDLVSCTYQL ARGMEYLASQ KCIHRDLAAR NVLVTENNVM KIADFGLARD 
       660        670        680        690        700
INNIDYYKKT TNGRLPVKWM APEALFDRVY THQSDVWSFG VLMWEIFTLG 
       710        720        730        740        750
GSPYPGIPVE ELFKLLKEGH RMDKPANCTN ELYMMMRDCW HAVPSQRPTF 
       760        770        780        790        800
KQLVEDLDRI LTLTTNEEYL DLSQPLEQYS PSYPDTRSSC SSGDDSVFSP 
       810        820 
DPMPYEPCLP QYPHINGSVK T
Length:821
Mass (Da):92,025
Last modified:May 1, 1991 - v1
Checksum:i6CD5001C960ED82F
GO
Isoform 2 (identifier: P21802-2) [UniParc]FASTAAdd to basket
Also known as: Short

The sequence of this isoform differs from the canonical sequence as follows:
     768-821: EYLDLSQPLEQYSPSYPDTRSSCSSGDDSVFSPDPMPYEPCLPQYPHINGSVKT → I

Show »
Length:768
Mass (Da):86,130
Checksum:i8D4734CBEA8E8C8F
GO
Isoform 3 (identifier: P21802-3) [UniParc]FASTAAdd to basket
Also known as: BFR-1, FGFR2IIIb, KGFR

The sequence of this isoform differs from the canonical sequence as follows:
     314-330: AAGVNTTDKEIEVLYIR → HSGINSSNAEVLALF
     334-335: FE → EA
     341-353: TCLAGNSIGISFH → ICKVSNYIGQANQ
     361-361: P → PKQQ

Show »
Length:822
Mass (Da):92,118
Checksum:i288CF737673BA4AB
GO
Isoform 4 (identifier: P21802-4) [UniParc]FASTAAdd to basket
Also known as: K-sam

The sequence of this isoform differs from the canonical sequence as follows:
     37-125: Missing.
     314-330: AAGVNTTDKEIEVLYIR → HSGINSSNAEVLALF
     334-335: FE → EA
     341-353: TCLAGNSIGISFH → ICKVSNYIGQANQ
     361-361: P → PKQQ
     428-429: Missing.
     761-821: LTLTTNEEYLDLSQPLEQYSPSYPDTRSSCSSGDDSVFSPDPMPYEPCLPQYPHINGSVKT → PPNPSLMSIFRK

Show »
Length:682
Mass (Da):76,705
Checksum:iD56050B4385A6635
GO
Isoform 5 (identifier: P21802-5) [UniParc]FASTAAdd to basket
Also known as: K-sam-I, BEK, IgIIIc

The sequence of this isoform differs from the canonical sequence as follows:
     428-429: Missing.

Show »
Length:819
Mass (Da):91,825
Checksum:i4746938783A1D94F
GO
Isoform 6 (identifier: P21802-6) [UniParc]FASTAAdd to basket
Also known as: K-sam-IIC2

The sequence of this isoform differs from the canonical sequence as follows:
     428-429: Missing.
     778-821: QYSPSYPDTRSSCSSGDDSVFSPDPMPYEPCLPQYPHINGSVKT → PYSPCYPDPR

Show »
Length:785
Mass (Da):88,181
Checksum:i042BF83F92CE97F5
GO
Isoform 7 (identifier: P21802-7) [UniParc]FASTAAdd to basket
Also known as: K-sam-IIO2

The sequence of this isoform differs from the canonical sequence as follows:
     314-330: AAGVNTTDKEIEVLYIR → HSGINSSNAEVLALF
     334-335: FE → EA
     341-353: TCLAGNSIGISFH → ICKVSNYIGQANQ
     361-361: P → PKQQ
     768-821: EYLDLSQPLE...YPHINGSVKT → RYKLLPCPDK...RVRQEKISTG

Show »
Length:817
Mass (Da):91,620
Checksum:i46BA78E51DB700CD
GO
Isoform 8 (identifier: P21802-8) [UniParc]FASTAAdd to basket
Also known as: K-sam-IIC3

The sequence of this isoform differs from the canonical sequence as follows:
     428-429: Missing.
     768-821: EYLDLSQPLEQYSPSYPDTRSSCSSGDDSVFSPDPMPYEPCLPQYPHINGSVKT → I

Show »
Length:766
Mass (Da):85,929
Checksum:iFE97A413B085D31E
GO
Isoform 9 (identifier: P21802-9) [UniParc]FASTAAdd to basket
Also known as: K-sam-IIH1

The sequence of this isoform differs from the canonical sequence as follows:
     314-330: AAGVNTTDKEIEVLYIR → HSGINSSNAEVLALF
     334-335: FE → EA
     341-353: TCLAGNSIGISFH → ICKVSNYIGQANQ
     361-361: P → PKQQ
     768-821: EYLDLSQPLE...YPHINGSVKT → RILTLTTNEN...LADTGSKVPN

Show »
Length:819
Mass (Da):91,566
Checksum:iC60FE09EC1BE0654
GO
Isoform 10 (identifier: P21802-10) [UniParc]FASTAAdd to basket
Also known as: K-sam-IIH2

The sequence of this isoform differs from the canonical sequence as follows:
     314-330: AAGVNTTDKEIEVLYIR → HSGINSSNAEVLALF
     334-335: FE → EA
     341-353: TCLAGNSIGISFH → ICKVSNYIGQANQ
     361-361: P → PKQQ
     768-821: EYLDLSQPLE...YPHINGSVKT → SFQSSLKSSS...CAGSKKIYDI

Show »
Length:819
Mass (Da):91,641
Checksum:i467E9BAAD07C5463
GO
Isoform 11 (identifier: P21802-11) [UniParc]FASTAAdd to basket
Also known as: K-sam-IIH3, K-sam-IIO4

The sequence of this isoform differs from the canonical sequence as follows:
     314-330: AAGVNTTDKEIEVLYIR → HSGINSSNAEVLALF
     334-335: FE → EA
     341-353: TCLAGNSIGISFH → ICKVSNYIGQANQ
     361-361: P → PKQQ
     768-821: EYLDLSQPLE...YPHINGSVKT → GRLPAWASQE...SQGLPQSVVP

Show »
Length:830
Mass (Da):92,733
Checksum:iE726FA4235995586
GO
Isoform 12 (identifier: P21802-12) [UniParc]FASTAAdd to basket
Also known as: K-sam-IIO1

The sequence of this isoform differs from the canonical sequence as follows:
     314-330: AAGVNTTDKEIEVLYIR → HSGINSSNAEVLALF
     334-335: FE → EA
     341-353: TCLAGNSIGISFH → ICKVSNYIGQANQ
     361-361: P → PKQQ
     768-821: EYLDLSQPLEQYSPSYPDTRSSCSSGDDSVFSPDPMPYEPCLPQYPHINGSVKT → PLS

Show »
Length:771
Mass (Da):86,407
Checksum:i881C475B4771CA5C
GO
Isoform 13 (identifier: P21802-13) [UniParc]FASTAAdd to basket
Also known as: K-sam-IIO3

The sequence of this isoform differs from the canonical sequence as follows:
     314-330: AAGVNTTDKEIEVLYIR → HSGINSSNAEVLALF
     334-335: FE → EA
     341-353: TCLAGNSIGISFH → ICKVSNYIGQANQ
     361-361: P → PKQQ
     768-821: Missing.

Show »
Length:768
Mass (Da):86,110
Checksum:iBB4771CA5CBEEFAA
GO
Isoform 14 (identifier: P21802-14) [UniParc]FASTAAdd to basket
Also known as: K-sam-IV, Soluble KGFR

The sequence of this isoform differs from the canonical sequence as follows:
     250-254: ERSPH → GSQGL
     255-821: Missing.

Show »
Length:254
Mass (Da):28,299
Checksum:i1855113266C85F4F
GO
Isoform 15 (identifier: P21802-15) [UniParc]FASTAAdd to basket
Also known as: K-sam-III

The sequence of this isoform differs from the canonical sequence as follows:
     314-429: Missing.

Show »
Length:705
Mass (Da):79,212
Checksum:i590967DCBF5DA25D
GO
Isoform 16 (identifier: P21802-16) [UniParc]FASTAAdd to basket
Also known as: TK14

The sequence of this isoform differs from the canonical sequence as follows:
     313-313: K → KVTK
     428-429: Missing.

Show »
Length:822
Mass (Da):92,153
Checksum:i15D08A6D66AC4EA0
GO
Isoform 17 (identifier: P21802-17) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     314-330: AAGVNTTDKEIEVLYIR → HSGINSSNAEVLALF
     334-335: FE → EA
     341-353: TCLAGNSIGISFH → ICKVSNYIGQANQ
     361-361: P → PKQQ
     768-821: EYLDLSQPLEQYSPSYPDTRSSCSSGDDSVFSPDPMPYEPCLPQYPHINGSVKT → I

Show »
Length:769
Mass (Da):86,223
Checksum:i806B4771CA5CBEEF
GO
Isoform 18 (identifier: P21802-18) [UniParc]FASTAAdd to basket
Also known as: K-sam-IIC1, KGFR, IgIIIb

The sequence of this isoform differs from the canonical sequence as follows:
     314-330: AAGVNTTDKEIEVLYIR → HSGINSSNAEVLALF
     334-335: FE → EA
     341-353: TCLAGNSIGISFH → ICKVSNYIGQANQ
     361-361: P → PKQQ
     428-429: Missing.

Show »
Length:820
Mass (Da):91,918
Checksum:i806D62B2FF25AFF6
GO
Isoform 19 (identifier: P21802-19) [UniParc]FASTAAdd to basket
Also known as: Soluble KGFR

The sequence of this isoform differs from the canonical sequence as follows:
     314-330: AAGVNTTDKEIEVLYIR → HSGINSSNAEVLALF
     334-335: FE → EA
     341-353: TCLAGNSIGISFH → ICKVSNYIGQANQ
     361-361: P → PKQQ
     362-365: APGR → GRRC
     366-821: Missing.

Show »
Length:366
Mass (Da):40,614
Checksum:iC02708836203465F
GO
Isoform 20 (identifier: P21802-20) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     37-152: EPPTKYQISQ...FVSENSNNKR → G
     429-430: Missing.

Show »
Length:704
Mass (Da):79,197
Checksum:i287F39DCF95B9312
GO
Isoform 21 (identifier: P21802-21) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     37-125: Missing.
     769-821: YLDLSQPLEQ...YPHINGSVKT → EKKVSGAVDCHKPPCNPSHLPCVLAVDQ

Show »
Length:707
Mass (Da):79,300
Checksum:i01DF22CD5B50092A
GO
Isoform 22 (identifier: P21802-22) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     37-125: Missing.
     314-330: AAGVNTTDKEIEVLYIR → HSGINSSNAEVLALF
     334-335: FE → EA
     341-353: TCLAGNSIGISFH → ICKVSNYIGQANQ
     361-361: P → PKQQ
     768-821: EYLDLSQPLEQYSPSYPDTRSSCSSGDDSVFSPDPMPYEPCLPQYPHINGSVKT → I

Show »
Length:680
Mass (Da):76,423
Checksum:iA6FF9BEBABCCE931
GO
Isoform 23 (identifier: P21802-23) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     250-361: Missing.

Show »
Length:709
Mass (Da):79,833
Checksum:i7F37AAB82F8B7A48
GO

Computationally mapped potential isoform sequencesi

There are 11 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D2CGD1D2CGD1_HUMAN
Fibroblast growth factor receptor
FGFR2
732Annotation score:
A0A0A0MR25A0A0A0MR25_HUMAN
Fibroblast growth factor receptor
FGFR2
821Annotation score:
H7BXU9H7BXU9_HUMAN
Receptor protein-tyrosine kinase
FGFR2
669Annotation score:
E7EVR7E7EVR7_HUMAN
Fibroblast growth factor receptor
FGFR2
707Annotation score:
S4R381S4R381_HUMAN
Fibroblast growth factor receptor 2
FGFR2
593Annotation score:
H7C265H7C265_HUMAN
Fibroblast growth factor receptor 2
FGFR2
371Annotation score:
S4R3B2S4R3B2_HUMAN
Fibroblast growth factor receptor 2
FGFR2
251Annotation score:
A0A087X2D1A0A087X2D1_HUMAN
Fibroblast growth factor receptor 2
FGFR2
64Annotation score:
A0A1B0GWF4A0A1B0GWF4_HUMAN
Fibroblast growth factor receptor 2
FGFR2
144Annotation score:
A0A1W2PQT9A0A1W2PQT9_HUMAN
Fibroblast growth factor receptor 2
FGFR2
86Annotation score:
There is more potential isoformShow all

Sequence cautioni

The sequence BAG57383 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti246L → P in BAG57383 (PubMed:14702039).Curated1
Sequence conflicti310K → N in BAG57383 (PubMed:14702039).Curated1
Isoform 16 (identifier: P21802-16)
Sequence conflicti315T → L in AAA61188 (PubMed:2172978).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0172586R → P1 PublicationCorresponds to variant dbSNP:rs3750819EnsemblClinVar.1
Natural variantiVAR_04220457S → L Polymorphism. 2 PublicationsCorresponds to variant dbSNP:rs56226109EnsemblClinVar.1
Natural variantiVAR_004112105Y → C in CS. 2 PublicationsCorresponds to variant dbSNP:rs1434545235Ensembl.1
Natural variantiVAR_017259172A → F in PS; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_017260186M → T3 PublicationsCorresponds to variant dbSNP:rs755793EnsemblClinVar.1
Natural variantiVAR_036380203R → C in breast cancer samples; infiltrating ductal carcinoma; somatic mutation. 2 Publications1
Natural variantiVAR_004116252 – 253SP → FS in PS. Corresponds to variant dbSNP:rs281865420Ensembl.2
Natural variantiVAR_004114252S → F in APRS; requires 2 nucleotide substitutions. 1 PublicationCorresponds to variant dbSNP:rs121918498EnsemblClinVar.1
Natural variantiVAR_004113252S → L1 PublicationCorresponds to variant dbSNP:rs79184941EnsemblClinVar.1
Natural variantiVAR_004115252S → W in APRS and PS; common mutation. 7 PublicationsCorresponds to variant dbSNP:rs79184941EnsemblClinVar.1
Natural variantiVAR_004117253P → R in APRS; common mutation. 5 PublicationsCorresponds to variant dbSNP:rs77543610EnsemblClinVar.1
Natural variantiVAR_017261263P → L in CS. 1 PublicationCorresponds to variant dbSNP:rs779326224Ensembl.1
Natural variantiVAR_004118267S → P in CS. 1 Publication