UniProt:P21802-1 FGFR2

chain
  • signal peptide:1-21
  • chain:22-821
checksum 6CD5001C960ED82F
comment
  • FUNCTION Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1.ACTIVITY REGULATION 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.SUBUNIT 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).DOMAIN 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.PTM 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.PTM N-glycosylated in the endoplasmic reticulum. The N-glycan chains undergo further maturation to an Endo H-resistant form in the Golgi apparatus.PTM Ubiquitinated. FGFR2 is rapidly ubiquitinated after autophosphorylation, leading to internalization and degradation. Subject to degradation both in lysosomes and by the proteasome.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.
crossReference
databaseName UniProt
dbId 54816
description
  • recommendedName: Fibroblast growth factor receptor 2 shortName:FGFR-2 ecNumber evidence="30 36 41 42"2.7.10.1/ecNumber alternativeName: K-sam shortName:KGFR alternativeName: Keratinocyte growth factor receptor cdAntigenNameCD332/cdAntigenName
displayName UniProt:P21802-1 FGFR2
geneName
  • FGFR2
  • BEK
  • KGFR
  • KSAM
identifier P21802
isSequenceChanged false
isoformParent
keyword
  • 3D-structure
  • Alternative splicing
  • Apoptosis
  • ATP-binding
  • Cell membrane
  • Craniosynostosis
  • Cytoplasmic vesicle
  • Disease variant
  • Disulfide bond
  • Ectodermal dysplasia
  • Glycoprotein
  • Golgi apparatus
  • Heparin-binding
  • Immunoglobulin domain
  • Kinase
  • Lacrimo-auriculo-dento-digital syndrome
  • Membrane
  • Mental retardation
  • Nucleotide-binding
  • Phosphoprotein
  • Proto-oncogene
  • Receptor
  • Reference proteome
  • Repeat
  • Secreted
  • Signal
  • Transferase
  • Transmembrane
  • Transmembrane helix
  • Tyrosine-protein kinase
  • Ubl conjugation
modified [InstanceEdit:11703684] Shorser, Solomon, 2021-05-28
name
  • FGFR2
otherIdentifier
  • 0000730167
  • 0002470154
  • 1143_s_at
  • 1144_at
  • 1145_g_at
  • 11739249_a_at
  • 11740159_x_at
  • 11740394_a_at
  • 11740395_a_at
  • 11740409_a_at
  • 11751508_a_at
  • 11752116_a_at
  • 11753370_s_at
  • 11762105_at
  • 11762745_x_at
  • 11762987_x_at
  • 1363_at
  • 16719025
  • 1970_s_at
  • 203638_s_at
  • 203639_s_at
  • 208225_at
  • 208228_s_at
  • 208234_x_at
  • 211401_s_at
  • 2263
  • 3310109
  • 3310110
  • 3310111
  • 3310112
  • 3310113
  • 3310118
  • 3310120
  • 3310123
  • 3310125
  • 3310126
  • 3310128
  • 3310129
  • 3310132
  • 3310133
  • 3310137
  • 3310142
  • 3310143
  • 3310144
  • 3310146
  • 3310147
  • 3310149
  • 3310150
  • 3310164
  • 3310165
  • 3310166
  • 3310168
  • 3310173
  • 3310174
  • 3310176
  • 3310178
  • 3310203
  • 3310204
  • 3310205
  • 3310206
  • 3310209
  • 3310210
  • 3310211
  • 34354_at
  • 73572_at
  • 7936734
  • A_23_P303145
  • A_23_P303149
  • A_24_P206624
  • GE61433
  • GE798271
  • GO:0000003
  • GO:0000122
  • GO:0000165
  • GO:0000166
  • GO:0000902
  • GO:0001525
  • GO:0001657
  • GO:0001701
  • GO:0001837
  • GO:0002053
  • GO:0003148
  • GO:0003149
  • GO:0003416
  • GO:0003674
  • GO:0004672
  • GO:0004713
  • GO:0004714
  • GO:0005007
  • GO:0005515
  • GO:0005524
  • GO:0005575
  • GO:0005576
  • GO:0005622
  • GO:0005634
  • GO:0005737
  • GO:0005794
  • GO:0005886
  • GO:0005887
  • GO:0005938
  • GO:0006464
  • GO:0006468
  • GO:0006915
  • GO:0006950
  • GO:0007049
  • GO:0007165
  • GO:0007169
  • GO:0007267
  • GO:0007275
  • GO:0007409
  • GO:0008150
  • GO:0008201
  • GO:0008219
  • GO:0008283
  • GO:0008284
  • GO:0008543
  • GO:0008589
  • GO:0009058
  • GO:0009790
  • GO:0009791
  • GO:0009880
  • GO:0009887
  • GO:0009986
  • GO:0010518
  • GO:0010839
  • GO:0016020
  • GO:0016021
  • GO:0016301
  • GO:0016310
  • GO:0016331
  • GO:0016740
  • GO:0017134
  • GO:0018108
  • GO:0021769
  • GO:0021847
  • GO:0021860
  • GO:0022612
  • GO:0030154
  • GO:0030177
  • GO:0030282
  • GO:0030324
  • GO:0030855
  • GO:0030901
  • GO:0030916
  • GO:0031012
  • GO:0031069
  • GO:0031410
  • GO:0032496
  • GO:0032808
  • GO:0032991
  • GO:0033674
  • GO:0033688
  • GO:0034641
  • GO:0035265
  • GO:0035602
  • GO:0035603
  • GO:0035604
  • GO:0035607
  • GO:0040007
  • GO:0042060
  • GO:0042472
  • GO:0042476
  • GO:0042802
  • GO:0042803
  • GO:0043167
  • GO:0043226
  • GO:0043235
  • GO:0043410
  • GO:0044344
  • GO:0045165
  • GO:0045471
  • GO:0045667
  • GO:0045787
  • GO:0045944
  • GO:0046777
  • GO:0048286
  • GO:0048333
  • GO:0048557
  • GO:0048562
  • GO:0048565
  • GO:0048568
  • GO:0048608
  • GO:0048646
  • GO:0048661
  • GO:0048701
  • GO:0048705
  • GO:0048730
  • GO:0048755
  • GO:0048762
  • GO:0048856
  • GO:0050679
  • GO:0050680
  • GO:0051150
  • GO:0051301
  • GO:0051781
  • GO:0051897
  • GO:0055010
  • GO:0060045
  • GO:0060076
  • GO:0060174
  • GO:0060348
  • GO:0060349
  • GO:0060442
  • GO:0060445
  • GO:0060449
  • GO:0060463
  • GO:0060484
  • GO:0060501
  • GO:0060512
  • GO:0060523
  • GO:0060527
  • GO:0060529
  • GO:0060595
  • GO:0060601
  • GO:0060615
  • GO:0060664
  • GO:0060667
  • GO:0060670
  • GO:0060688
  • GO:0060915
  • GO:0060916
  • GO:0062023
  • GO:0070372
  • GO:0070374
  • GO:0071300
  • GO:0071560
  • GO:0090263
  • HMNXSV003001516
  • HMNXSV003003698
  • HMNXSV003045562
  • HMNXSV003050281
  • ILMN_1682270
  • M87770_at
  • PH_hs_0024624
  • TC10001711.hg
  • g13186252_3p_a_at
  • g13186256_3p_at
  • g13186266_3p_a_at
  • g186740_3p_a_at
  • g186781_3p_a_at
  • g6691454_3p_a_at
  • g6691454_3p_x_at
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceIsoform
secondaryIdentifier
  • FGFR2_HUMAN
  • B4DFC2
  • E7EVR6
  • E9PCR0
  • P18443
  • Q01742
  • Q12922
  • Q14300
  • Q14301
  • Q14302
  • Q14303
  • Q14304
  • Q14305
  • Q14672
  • Q14718
  • Q14719
  • Q1KHY5
  • Q86YI4
  • Q8IXC7
  • Q96KL9
  • Q96KM0
  • Q96KM1
  • Q96KM2
  • Q9NZU2
  • Q9NZU3
  • Q9UD01
  • Q9UD02
  • Q9UIH3
  • Q9UIH4
  • Q9UIH5
  • Q9UIH6
  • Q9UIH7
  • Q9UIH8
  • Q9UM87
  • Q9UMC6
  • Q9UNS7
  • Q9UQH7
  • Q9UQH8
  • Q9UQH9
  • Q9UQI0
sequenceLength 821
species [Species:48887] Homo sapiens
url http://purl.uniprot.org/uniprot/P21802-1
variantIdentifier P21802-1

Referrals

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(referenceSequence)
(interactor)
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