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P21802

- FGFR2_HUMAN

UniProt

P21802 - FGFR2_HUMAN

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
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    • History
      Entry version 197 (01 Oct 2014)
      Sequence version 1 (01 May 1991)
      Previous versions | rss
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    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 binding Source: IntAct
    6. protein homodimerization activity Source: UniProtKB
    7. 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

    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 membrane-bounded vesicle Source: UniProtKB-SubCell
    5. excitatory synapse Source: UniProtKB
    6. extracellular region Source: UniProtKB-SubCell
    7. Golgi apparatus Source: UniProtKB-SubCell
    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

    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.
    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.
    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.
    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. Lacrimo-auriculo-dento-digital 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 autocatalysis3 Publications
    Modified residuei586 – 5861Phosphotyrosine; by autocatalysis4 Publications
    Modified residuei588 – 5881Phosphotyrosine; by autocatalysis3 Publications
    Modified residuei656 – 6561Phosphotyrosine; by autocatalysis4 Publications
    Modified residuei657 – 6571Phosphotyrosine; by autocatalysis4 Publications
    Modified residuei769 – 7691Phosphotyrosine; by autocatalysis3 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

    ArrayExpressiP21802.
    BgeeiP21802.
    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. 19 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.
    HOGENOMiHOG000263410.
    HOVERGENiHBG000345.
    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

    MVSWGRFICL VVVTMATLSL ARPSFSLVED TTLEPEEPPT KYQISQPEVY    50
    VAAPGESLEV RCLLKDAAVI SWTKDGVHLG PNNRTVLIGE YLQIKGATPR 100
    DSGLYACTAS RTVDSETWYF MVNVTDAISS GDDEDDTDGA EDFVSENSNN 150
    KRAPYWTNTE KMEKRLHAVP AANTVKFRCP AGGNPMPTMR WLKNGKEFKQ 200
    EHRIGGYKVR NQHWSLIMES VVPSDKGNYT CVVENEYGSI NHTYHLDVVE 250
    RSPHRPILQA GLPANASTVV GGDVEFVCKV YSDAQPHIQW IKHVEKNGSK 300
    YGPDGLPYLK VLKAAGVNTT DKEIEVLYIR NVTFEDAGEY TCLAGNSIGI 350
    SFHSAWLTVL PAPGREKEIT ASPDYLEIAI YCIGVFLIAC MVVTVILCRM 400
    KNTTKKPDFS SQPAVHKLTK RIPLRRQVTV SAESSSSMNS NTPLVRITTR 450
    LSSTADTPML AGVSEYELPE DPKWEFPRDK LTLGKPLGEG CFGQVVMAEA 500
    VGIDKDKPKE AVTVAVKMLK DDATEKDLSD LVSEMEMMKM IGKHKNIINL 550
    LGACTQDGPL YVIVEYASKG NLREYLRARR PPGMEYSYDI NRVPEEQMTF 600
    KDLVSCTYQL ARGMEYLASQ KCIHRDLAAR NVLVTENNVM KIADFGLARD 650
    INNIDYYKKT TNGRLPVKWM APEALFDRVY THQSDVWSFG VLMWEIFTLG 700
    GSPYPGIPVE ELFKLLKEGH RMDKPANCTN ELYMMMRDCW HAVPSQRPTF 750
    KQLVEDLDRI LTLTTNEEYL DLSQPLEQYS PSYPDTRSSC SSGDDSVFSP 800
    DPMPYEPCLP QYPHINGSVK T 821
    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.