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P21802

- FGFR2_HUMAN

UniProt

P21802 - FGFR2_HUMAN

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Protein

Fibroblast growth factor receptor 2

Gene

FGFR2

Organism
Homo sapiens (Human)
Status
Reviewed - 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.4 PublicationsPROSITE-ProRule annotation

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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei517 – 5171ATP1 PublicationPROSITE-ProRule annotation
Binding sitei571 – 5711ATP1 PublicationPROSITE-ProRule annotation
Active sitei626 – 6261Proton acceptor1 PublicationPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi487 – 4959ATP1 PublicationPROSITE-ProRule annotation
Nucleotide bindingi565 – 5673ATP1 PublicationPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. fibroblast growth factor-activated receptor activity Source: UniProtKB
  3. fibroblast growth factor binding Source: UniProtKB
  4. heparin binding Source: UniProtKB-KW
  5. protein homodimerization activity Source: UniProtKB
  6. protein tyrosine kinase activity Source: UniProtKB

GO - Biological processi

  1. angiogenesis Source: UniProtKB
  2. apoptotic process Source: UniProtKB-KW
  3. axonogenesis Source: UniProtKB
  4. bone development Source: UniProtKB
  5. bone mineralization Source: UniProtKB
  6. bone morphogenesis Source: UniProtKB
  7. branch elongation involved in salivary gland morphogenesis Source: UniProtKB
  8. branching involved in labyrinthine layer morphogenesis Source: UniProtKB
  9. branching involved in prostate gland morphogenesis Source: UniProtKB
  10. branching involved in salivary gland morphogenesis Source: UniProtKB
  11. branching morphogenesis of a nerve Source: UniProtKB
  12. bud elongation involved in lung branching Source: UniProtKB
  13. cell-cell signaling Source: UniProtKB
  14. cell fate commitment Source: UniProtKB
  15. coronal suture morphogenesis Source: Ensembl
  16. digestive tract development Source: UniProtKB
  17. embryonic cranial skeleton morphogenesis Source: BHF-UCL
  18. embryonic digestive tract morphogenesis Source: UniProtKB
  19. embryonic organ development Source: UniProtKB
  20. embryonic organ morphogenesis Source: UniProtKB
  21. embryonic pattern specification Source: UniProtKB
  22. endodermal digestive tract morphogenesis Source: Ensembl
  23. epidermal growth factor receptor signaling pathway Source: Reactome
  24. epidermis morphogenesis Source: UniProtKB
  25. epithelial cell differentiation Source: UniProtKB
  26. epithelial cell proliferation involved in salivary gland morphogenesis Source: UniProtKB
  27. epithelial to mesenchymal transition Source: Ensembl
  28. Fc-epsilon receptor signaling pathway Source: Reactome
  29. fibroblast growth factor receptor signaling pathway Source: UniProtKB
  30. fibroblast growth factor receptor signaling pathway involved in hemopoiesis Source: UniProtKB
  31. fibroblast growth factor receptor signaling pathway involved in mammary gland specification Source: UniProtKB
  32. fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow Source: UniProtKB
  33. fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development Source: UniProtKB
  34. fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow Source: UniProtKB
  35. gland morphogenesis Source: UniProtKB
  36. hair follicle morphogenesis Source: UniProtKB
  37. innate immune response Source: Reactome
  38. inner ear morphogenesis Source: UniProtKB
  39. insulin receptor signaling pathway Source: Reactome
  40. in utero embryonic development Source: UniProtKB
  41. lacrimal gland development Source: UniProtKB
  42. lateral sprouting from an epithelium Source: UniProtKB
  43. lens fiber cell development Source: Ensembl
  44. limb bud formation Source: UniProtKB
  45. lung alveolus development Source: UniProtKB
  46. lung-associated mesenchyme development Source: UniProtKB
  47. lung development Source: UniProtKB
  48. lung lobe morphogenesis Source: UniProtKB
  49. mammary gland bud formation Source: UniProtKB
  50. membranous septum morphogenesis Source: UniProtKB
  51. mesenchymal cell differentiation Source: UniProtKB
  52. mesenchymal cell differentiation involved in lung development Source: UniProtKB
  53. mesenchymal cell proliferation involved in lung development Source: UniProtKB
  54. mesodermal cell differentiation Source: Ensembl
  55. midbrain development Source: UniProtKB
  56. morphogenesis of embryonic epithelium Source: UniProtKB
  57. multicellular organism growth Source: UniProtKB
  58. negative regulation of epithelial cell proliferation Source: Ensembl
  59. negative regulation of mitosis Source: Ensembl
  60. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  61. neuromuscular junction development Source: Ensembl
  62. neurotrophin TRK receptor signaling pathway Source: Reactome
  63. odontogenesis Source: UniProtKB
  64. orbitofrontal cortex development Source: UniProtKB
  65. organ growth Source: UniProtKB
  66. organ morphogenesis Source: UniProtKB
  67. otic vesicle formation Source: UniProtKB
  68. outflow tract septum morphogenesis Source: UniProtKB
  69. peptidyl-tyrosine phosphorylation Source: UniProtKB
  70. phosphatidylinositol-mediated signaling Source: Reactome
  71. positive regulation of canonical Wnt signaling pathway Source: UniProtKB
  72. positive regulation of cardiac muscle cell proliferation Source: UniProtKB
  73. positive regulation of cell cycle Source: UniProtKB
  74. positive regulation of cell division Source: UniProtKB
  75. positive regulation of cell proliferation Source: UniProtKB
  76. positive regulation of epithelial cell proliferation Source: UniProtKB
  77. positive regulation of epithelial cell proliferation involved in lung morphogenesis Source: UniProtKB
  78. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  79. positive regulation of MAPK cascade Source: UniProtKB
  80. positive regulation of mesenchymal cell proliferation Source: UniProtKB
  81. positive regulation of phospholipase activity Source: UniProtKB
  82. positive regulation of smooth muscle cell proliferation Source: Ensembl
  83. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  84. positive regulation of Wnt signaling pathway Source: UniProtKB
  85. post-embryonic development Source: UniProtKB
  86. prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis Source: UniProtKB
  87. prostate epithelial cord elongation Source: UniProtKB
  88. prostate gland morphogenesis Source: UniProtKB
  89. protein autophosphorylation Source: UniProtKB
  90. pyramidal neuron development Source: UniProtKB
  91. regulation of branching involved in prostate gland morphogenesis Source: UniProtKB
  92. regulation of cell fate commitment Source: UniProtKB
  93. regulation of ERK1 and ERK2 cascade Source: UniProtKB
  94. regulation of fibroblast growth factor receptor signaling pathway Source: UniProtKB
  95. regulation of morphogenesis of a branching structure Source: UniProtKB
  96. regulation of multicellular organism growth Source: UniProtKB
  97. regulation of osteoblast differentiation Source: UniProtKB
  98. regulation of osteoblast proliferation Source: UniProtKB
  99. regulation of smoothened signaling pathway Source: UniProtKB
  100. regulation of smooth muscle cell differentiation Source: UniProtKB
  101. reproductive structure development Source: UniProtKB
  102. skeletal system morphogenesis Source: UniProtKB
  103. squamous basal epithelial stem cell differentiation involved in prostate gland acinus development Source: UniProtKB
  104. synaptic vesicle transport Source: Ensembl
  105. ureteric bud development Source: UniProtKB
  106. ventricular cardiac muscle tissue morphogenesis Source: UniProtKB
  107. ventricular zone neuroblast division Source: UniProtKB
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

BRENDAi2.7.10.1. 2681.
ReactomeiREACT_111184. Negative regulation of FGFR signaling.
REACT_120863. Activated point mutants of FGFR2.
REACT_121255. Signaling by FGFR2 amplification mutants.
REACT_121398. Signaling by FGFR mutants.
REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
REACT_21247. FRS2-mediated cascade.
REACT_21270. PI-3K cascade.
REACT_21310. Phospholipase C-mediated cascade.
REACT_21374. SHC-mediated cascade.
REACT_75829. PIP3 activates AKT signaling.
REACT_9413. FGFR2c ligand binding and activation.
REACT_9416. FGFR2b ligand binding and activation.
REACT_976. PI3K Cascade.
SignaLinkiP21802.

Protein family/group databases

MEROPSiI43.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Fibroblast growth factor receptor 2 (EC:2.7.10.1)
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
ProteomesiUP000005640: Chromosome 10

Organism-specific databases

HGNCiHGNC:3689. FGFR2.

Subcellular locationi

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.

GO - Cellular componenti

  1. cell cortex Source: UniProtKB
  2. cell surface Source: UniProtKB
  3. cytoplasm Source: UniProtKB
  4. cytoplasmic vesicle Source: UniProtKB-KW
  5. excitatory synapse Source: UniProtKB
  6. extracellular region Source: UniProtKB-KW
  7. Golgi apparatus Source: UniProtKB-KW
  8. integral component of membrane Source: UniProtKB
  9. integral component of plasma membrane Source: UniProtKB
  10. intracellular membrane-bounded organelle Source: HPA
  11. membrane Source: UniProtKB
  12. nucleus Source: UniProtKB
  13. 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) [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.17 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti105 – 1051Y → C in CS. 2 Publications
VAR_004112
Natural varianti252 – 2521S → L in CS. 1 Publication
VAR_004113
Natural varianti263 – 2631P → L in CS. 1 Publication
VAR_017261
Natural varianti267 – 2671S → P in CS. 1 Publication
VAR_004118
Natural varianti268 – 2681T → TG in CS. 1 Publication
VAR_004119
Natural varianti276 – 2761F → V in CS. 3 Publications
VAR_004120
Natural varianti278 – 2781C → 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. 4 Publications
VAR_004121
Natural varianti278 – 2781C → Y in CS. 1 Publication
VAR_017263
Natural varianti281 – 2811Y → C in CS. 2 Publications
VAR_017264
Natural varianti287 – 2893Missing in CS.
VAR_004122
Natural varianti288 – 2881I → S in CS. 1 Publication
VAR_017265
Natural varianti289 – 2891Q → P in CS and JWS. 5 Publications
VAR_004123
Natural varianti290 – 2901W → G in CS. 1 Publication
VAR_017266
Natural varianti290 – 2901W → R in CS.
VAR_004125
Natural varianti292 – 2921K → E in CS. 1 Publication
VAR_004126
Natural varianti301 – 3011Y → C in CS. 1 Publication
VAR_004127
Natural varianti328 – 3281Y → C in CS. 1 Publication
VAR_004130
Natural varianti331 – 3311N → I in CS. 1 Publication
VAR_004131
Natural varianti337 – 3371A → ANA in CS.
VAR_004132
Natural varianti337 – 3371A → P in CS. 1 Publication
VAR_017268
Natural varianti338 – 3381G → E in CS. 1 Publication
VAR_004133
Natural varianti338 – 3381G → R in CS. 3 Publications
VAR_015011
Natural varianti340 – 3401Y → H in CS. 2 Publications
VAR_004134
Natural varianti341 – 3411T → P in PS and CS. 3 Publications
VAR_004135
Natural varianti342 – 3421C → F in CS. 3 Publications
VAR_004136
Natural varianti342 – 3421C → R in CS, JWS, PS and ABS2. 9 Publications
VAR_004137
Natural varianti342 – 3421C → S in CS, JWS, PS and ABS2. 8 Publications
VAR_004138
Natural varianti342 – 3421C → W in CS. 3 Publications
VAR_017271
Natural varianti342 – 3421C → Y in CS and PS. 8 Publications
VAR_004139
Natural varianti344 – 3441A → G in CS and JWS. 2 Publications
VAR_004140
Natural varianti344 – 3441A → P in CS and PS. 1 Publication
VAR_004141
Natural varianti347 – 3471S → C in CS. 2 Publications
VAR_004142
Natural varianti351 – 3511S → C in CS, PS and ABS2. 3 Publications
VAR_004143
Natural varianti354 – 3541S → C in CS. 5 Publications
VAR_004144
Natural varianti354 – 3541S → Y in CS. 1 Publication
VAR_017272
Natural varianti356 – 3583Missing in CS. 1 Publication
VAR_004145
Natural varianti359 – 3591V → F in CS and PS. 2 Publications
VAR_004146
Natural varianti362 – 3621A → S in CS. 1 Publication
VAR_017273
Natural varianti384 – 3841G → R in CS. 1 Publication
VAR_004147
Natural varianti549 – 5491N → H in CS; constitutive kinase activity. 1 Publication
VAR_017276
Natural varianti678 – 6781R → G in CS. 1 Publication
VAR_017281
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.5 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti278 – 2781C → 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. 4 Publications
VAR_004121
Natural varianti289 – 2891Q → P in CS and JWS. 5 Publications
VAR_004123
Natural varianti342 – 3421C → R in CS, JWS, PS and ABS2. 9 Publications
VAR_004137
Natural varianti342 – 3421C → S in CS, JWS, PS and ABS2. 8 Publications
VAR_004138
Natural varianti344 – 3441A → G in CS and JWS. 2 Publications
VAR_004140
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.6 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti252 – 2521S → F in APRS; requires 2 nucleotide substitutions. 1 Publication
VAR_004114
Natural varianti252 – 2521S → W in APRS and PS; common mutation. 6 Publications
VAR_004115
Natural varianti253 – 2531P → R in APRS; common mutation. 5 Publications
VAR_004117
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).11 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti172 – 1721A → F in PS; requires 2 nucleotide substitutions. 1 Publication
VAR_017259
Natural varianti252 – 2532SP → FS in PS.
VAR_004116
Natural varianti252 – 2521S → W in APRS and PS; common mutation. 6 Publications
VAR_004115
Natural varianti273 – 2731Missing in PS; type 2. 1 Publication
VAR_017262
Natural varianti278 – 2781C → 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. 4 Publications
VAR_004121
Natural varianti290 – 2901W → C in PS; severe; also in a lung squamous cell carcinoma sample; somatic mutation. 3 Publications
VAR_004124
Natural varianti321 – 3211D → A in PS. 1 Publication
VAR_004129
Natural varianti340 – 3401Y → C in PS. 2 Publications
VAR_017269
Natural varianti341 – 3411T → P in PS and CS. 3 Publications
VAR_004135
Natural varianti342 – 3421C → G in PS. 1 Publication
VAR_017270
Natural varianti342 – 3421C → R in CS, JWS, PS and ABS2. 9 Publications
VAR_004137
Natural varianti342 – 3421C → S in CS, JWS, PS and ABS2. 8 Publications
VAR_004138
Natural varianti342 – 3421C → Y in CS and PS. 8 Publications
VAR_004139
Natural varianti344 – 3441A → P in CS and PS. 1 Publication
VAR_004141
Natural varianti351 – 3511S → C in CS, PS and ABS2. 3 Publications
VAR_004143
Natural varianti359 – 3591V → F in CS and PS. 2 Publications
VAR_004146
Natural varianti375 – 3751Y → C in PS and BSTVS. 3 Publications
VAR_017275
Natural varianti565 – 5651E → G in PS; constitutive kinase activity. 1 Publication
VAR_017277
Natural varianti641 – 6411K → R in PS; constitutive kinase activity. 1 Publication
VAR_017278
Natural varianti663 – 6631G → E in PS. 1 Publication
VAR_017280
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.2 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti372 – 3721S → C in BSTVS. 1 Publication
VAR_017274
Natural varianti375 – 3751Y → C in PS and BSTVS. 3 Publications
VAR_017275
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.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti526 – 5261K → E in FSPC; constitutive kinase activity. 1 Publication
VAR_023788
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.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti628 – 6281A → T in LADDS; strongly reduced kinase activity. 1 Publication
VAR_029884
Natural varianti648 – 6481A → T in LADDS. 1 Publication
VAR_029885
Natural varianti649 – 6502RD → S in LADDS. 1 Publication
VAR_029886
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.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti342 – 3421C → R in CS, JWS, PS and ABS2. 9 Publications
VAR_004137
Natural varianti342 – 3421C → S in CS, JWS, PS and ABS2. 8 Publications
VAR_004138
Natural varianti351 – 3511S → C in CS, PS and ABS2. 3 Publications
VAR_004143
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.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti381 – 3811Y → D in BBDS. 1 Publication
VAR_067977
Natural varianti391 – 3911M → R in BBDS; the mutation selectively reduces plasma-membrane levels of the protein and markedly diminishes the receptor's responsiveness to extracellular FGF. 1 Publication
VAR_067978

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi265 – 2651N → Q: Reduced N-glycosylation. Reduced expression at the cell surface. 1 Publication
Mutagenesisi549 – 5491N → T: Constitutive kinase activity. 1 Publication
Mutagenesisi565 – 5651E → A: Constitutive kinase activity. 1 Publication
Mutagenesisi656 – 6572Missing: Loss of kinase activity. 1 Publication
Mutagenesisi769 – 7691Y → F: Increases fibroblast proliferation. Decreases phosphorylation of PLCG1 and FRS2. Decreases activation of MAP kinases. 2 Publications

Keywords - Diseasei

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

Organism-specific databases

MIMi101200. phenotype.
101600. phenotype.
123150. phenotype.
123500. phenotype.
123790. phenotype.
149730. phenotype.
207410. phenotype.
609579. phenotype.
614592. phenotype.
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.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence AnalysisAdd
BLAST
Chaini22 – 821800Fibroblast growth factor receptor 2PRO_0000016783Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi62 ↔ 107PROSITE-ProRule annotation
Glycosylationi83 – 831N-linked (GlcNAc...)Sequence Analysis
Glycosylationi123 – 1231N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi179 ↔ 2311 PublicationPROSITE-ProRule annotation
Glycosylationi228 – 2281N-linked (GlcNAc...)Sequence Analysis
Glycosylationi241 – 2411N-linked (GlcNAc...)Sequence Analysis
Glycosylationi265 – 2651N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi278 ↔ 3421 PublicationPROSITE-ProRule annotation
Glycosylationi297 – 2971N-linked (GlcNAc...)Sequence Analysis
Glycosylationi318 – 3181N-linked (GlcNAc...)Sequence Analysis
Glycosylationi331 – 3311N-linked (GlcNAc...)Sequence Analysis
Modified residuei466 – 4661Phosphotyrosine; by autocatalysis2 Publications
Modified residuei586 – 5861Phosphotyrosine; by autocatalysis3 Publications
Modified residuei588 – 5881Phosphotyrosine; by autocatalysis2 Publications
Modified residuei656 – 6561Phosphotyrosine; by autocatalysis3 Publications
Modified residuei657 – 6571Phosphotyrosine; by autocatalysis3 Publications
Modified residuei769 – 7691Phosphotyrosine; by autocatalysis2 Publications

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

MaxQBiP21802.
PaxDbiP21802.
PRIDEiP21802.

PTM databases

PhosphoSiteiP21802.

Expressioni

Gene expression databases

BgeeiP21802.
ExpressionAtlasiP21802. baseline and differential.
GenevestigatoriP21802.

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 PAK4.21 Publications

Binary interactionsi

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

Protein-protein interaction databases

BioGridi108554. 21 interactions.
DIPiDIP-3788N.
IntActiP21802. 16 interactions.
MINTiMINT-118359.

Structurei

Secondary structure

1
821
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi152 – 1576
Turni159 – 1624
Beta strandi166 – 1705
Beta strandi175 – 1784
Beta strandi181 – 1855
Beta strandi188 – 1936
Helixi200 – 2023
Beta strandi208 – 2103
Helixi211 – 2133
Beta strandi215 – 2184
Helixi223 – 2253
Beta strandi227 – 2359
Beta strandi238 – 24912
Beta strandi266 – 2694
Beta strandi274 – 2774
Beta strandi287 – 2937
Beta strandi296 – 2983
Beta strandi299 – 3013
Beta strandi309 – 3135
Beta strandi315 – 3195
Turni321 – 3255
Beta strandi326 – 3294
Helixi334 – 3363
Beta strandi338 – 3458
Beta strandi350 – 3578
Turni463 – 4653
Turni472 – 4743
Helixi478 – 4803
Beta strandi481 – 4899
Beta strandi494 – 5007
Beta strandi504 – 5063
Beta strandi513 – 5186
Helixi525 – 54117
Beta strandi550 – 5545
Beta strandi556 – 5583
Beta strandi561 – 5655
Beta strandi568 – 5714
Helixi572 – 5776
Turni582 – 5854
Helixi594 – 5963
Helixi600 – 61920
Helixi629 – 6313
Beta strandi632 – 6343
Turni636 – 6383
Beta strandi640 – 6423
Helixi645 – 6473
Turni652 – 6543
Beta strandi655 – 6584
Turni659 – 6646
Helixi667 – 6693
Helixi672 – 6776
Helixi682 – 69716
Helixi709 – 71810
Beta strandi726 – 7283
Helixi730 – 73910
Helixi744 – 7463
Helixi750 – 76415

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1DJSX-ray2.40A32-362[»]
1E0OX-ray2.80B/D148-366[»]
1EV2X-ray2.20E/F/G/H147-366[»]
1GJOX-ray2.40A456-768[»]
1II4X-ray2.70E/F/G/H147-366[»]
1IILX-ray2.30E/F/G/H147-366[»]
1NUNX-ray2.90B140-368[»]
1OECX-ray2.40A456-768[»]
1WVZNMR-A147-249[»]
2FDBX-ray2.28P/R149-368[»]
2PSQX-ray2.40A/B413-768[»]
2PVFX-ray1.80A458-778[»]
B764-778[»]
2PVYX-ray2.20A/B/C/D458-768[»]
2PWLX-ray2.40A/B458-768[»]
2PY3X-ray2.30A/B458-768[»]
2PZ5X-ray2.40A/B458-768[»]
2PZPX-ray2.40A/B458-768[»]
2PZRX-ray3.00A/B458-768[»]
2Q0BX-ray2.90A/B458-768[»]
3B2TX-ray1.80A/B458-766[»]
3CAFX-ray1.96A150-249[»]
3CLYX-ray2.00A458-778[»]
3CU1X-ray2.60A/C150-249[»]
3DARX-ray2.20A/B146-249[»]
3EUUX-ray2.34A/B150-249[»]
3OJ2X-ray2.20C/D140-313[»]
3OJMX-ray2.10B140-313[»]
3RI1X-ray2.10A/B458-768[»]
4J23X-ray3.88A147-366[»]
4J95X-ray2.38A/B/C/D458-768[»]
4J96X-ray2.30A/B458-768[»]
4J97X-ray2.55A/B/C/D458-768[»]
4J98X-ray2.31A/B458-768[»]
4J99X-ray1.85A/B/C/D458-768[»]
ProteinModelPortaliP21802.
SMRiP21802. Positions 5-364, 462-801.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP21802.

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini22 – 377356ExtracellularSequence AnalysisAdd
BLAST
Topological domaini399 – 821423CytoplasmicSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei378 – 39821HelicalSequence AnalysisAdd
BLAST

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini25 – 125101Ig-like C2-type 1Add
BLAST
Domaini154 – 24794Ig-like C2-type 2Add
BLAST
Domaini256 – 358103Ig-like C2-type 3Add
BLAST
Domaini481 – 770290Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni161 – 17818Heparin-bindingAdd
BLAST

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
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118923.
HOGENOMiHOG000263410.
HOVERGENiHBG000345.
InParanoidiP21802.
KOiK05093.
OMAiLELRCQL.
OrthoDBiEOG7NGQ9N.
PhylomeDBiP21802.
TreeFamiTF316307.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
InterProiIPR028175. FGF_rcpt_2.
IPR016248. FGF_rcpt_fam.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
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.
[Graphical view]
PANTHERiPTHR24416:SF130. PTHR24416:SF130. 1 hit.
PfamiPF07679. I-set. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF000628. FGFR. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00408. IGc2. 3 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50835. IG_LIKE. 3 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]

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. Align

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.

« Hide

        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