FGFR2_CHICK
ID FGFR2_CHICK Reviewed; 823 AA.
AC P18461;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Fibroblast growth factor receptor 2;
DE Short=FGFR-2;
DE EC=2.7.10.1;
DE AltName: Full=Tyrosine kinase receptor CEK3;
DE Flags: Precursor;
GN Name=FGFR2; Synonyms=CEK3;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2165604; DOI=10.1073/pnas.87.15.5812;
RA Pasquale E.B.;
RT "A distinctive family of embryonic protein-tyrosine kinase receptors.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:5812-5816(1990).
CC -!- FUNCTION: Tyrosine-protein kinase that acts as cell-surface receptor
CC for fibroblast growth factors and plays an essential role in the
CC regulation of cell proliferation, differentiation, migration and
CC apoptosis, and in the regulation of embryonic development. Required for
CC normal embryonic patterning, limb bud development, lung morphogenesis,
CC osteogenesis and skin development. Plays an essential role in the
CC regulation of osteoblast differentiation, proliferation and apoptosis,
CC and is required for normal skeleton development. Promotes cell
CC proliferation in keratinocytes and immature osteoblasts, but promotes
CC apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and
CC PAK4. Ligand binding leads to the activation of several signaling
CC cascades. Activation of PLCG1 leads to the production of the cellular
CC signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate.
CC Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and
CC SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the
CC MAP kinase signaling pathway, as well as of the AKT1 signaling pathway.
CC FGFR2 signaling is down-regulated by ubiquitination, internalization
CC and degradation. Mutations that lead to constitutive kinase activation
CC or impair normal FGFR2 maturation, internalization and degradation lead
CC to aberrant signaling. Over-expressed FGFR2 promotes activation of
CC STAT1 (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- ACTIVITY REGULATION: Present in an inactive conformation in the absence
CC of bound ligand. Ligand binding leads to dimerization and activation by
CC autophosphorylation on tyrosine residues (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Monomer. Homodimer after ligand binding (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein. Golgi apparatus {ECO:0000250}. Cytoplasmic vesicle
CC {ECO:0000250}. Note=Detected on osteoblast plasma membrane lipid rafts.
CC After ligand binding, the activated receptor is rapidly internalized
CC and degraded (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The second and third Ig-like domains directly interact with
CC fibroblast growth factors (FGF) and heparan sulfate proteoglycans.
CC {ECO:0000250}.
CC -!- PTM: Autophosphorylated. Binding of FGF family members together with
CC heparan sulfate proteoglycan or heparin promotes receptor dimerization
CC and autophosphorylation on tyrosine residues. Autophosphorylation
CC occurs in trans between the two FGFR molecules present in the dimer (By
CC similarity). {ECO:0000250}.
CC -!- PTM: N-glycosylated in the endoplasmic reticulum. The N-glycan chains
CC undergo further maturation to an Endo H-resistant form in the Golgi
CC apparatus (By similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated. FGFR2 is rapidly ubiquitinated after
CC autophosphorylation, leading to internalization and degradation.
CC Subject to degradation both in lysosomes and by the proteasome (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Fibroblast growth factor receptor subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; M35196; AAA48665.1; -; mRNA.
DR PIR; B35963; B35963.
DR RefSeq; NP_990650.1; NM_205319.2.
DR AlphaFoldDB; P18461; -.
DR SMR; P18461; -.
DR STRING; 9031.ENSGALP00000037940; -.
DR PaxDb; P18461; -.
DR Ensembl; ENSGALT00000038732; ENSGALP00000037940; ENSGALG00000009495.
DR GeneID; 396259; -.
DR KEGG; gga:396259; -.
DR CTD; 2263; -.
DR VEuPathDB; HostDB:geneid_396259; -.
DR eggNOG; KOG0200; Eukaryota.
DR GeneTree; ENSGT00940000155447; -.
DR HOGENOM; CLU_000288_74_3_1; -.
DR InParanoid; P18461; -.
DR OrthoDB; 220433at2759; -.
DR BRENDA; 2.7.10.1; 1306.
DR PRO; PR:P18461; -.
DR Proteomes; UP000000539; Chromosome 6.
DR Bgee; ENSGALG00000009495; Expressed in ovary and 11 other tissues.
DR ExpressionAtlas; P18461; baseline and differential.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0017134; F:fibroblast growth factor binding; IBA:GO_Central.
DR GO; GO:0005007; F:fibroblast growth factor receptor activity; IBA:GO_Central.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:InterPro.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR Gene3D; 2.60.40.10; -; 3.
DR InterPro; IPR016248; FGF_rcpt_fam.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF07679; I-set; 2.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PIRSF; PIRSF000628; FGFR; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00409; IG; 3.
DR SMART; SM00408; IGc2; 3.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 3.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50835; IG_LIKE; 3.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 2: Evidence at transcript level;
KW Apoptosis; ATP-binding; Cell membrane; Cytoplasmic vesicle; Disulfide bond;
KW Glycoprotein; Golgi apparatus; Immunoglobulin domain; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Repeat;
KW Signal; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase; Ubl conjugation.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..823
FT /note="Fibroblast growth factor receptor 2"
FT /id="PRO_0000016791"
FT TOPO_DOM 24..379
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 380..400
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 401..823
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 27..128
FT /note="Ig-like C2-type 1"
FT DOMAIN 156..249
FT /note="Ig-like C2-type 2"
FT DOMAIN 258..360
FT /note="Ig-like C2-type 3"
FT DOMAIN 483..772
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 163..180
FT /note="Heparin-binding"
FT /evidence="ECO:0000250"
FT ACT_SITE 628
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 489..497
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 519
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 567..569
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 573
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 468
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 588
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 658
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 659
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 771
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 86
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 126
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 148
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 230
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 243
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 267
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 299
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 320
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 333
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 65..110
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 181..233
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 280..344
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 823 AA; 92299 MW; 42BF3CC4EA02FD43 CRC64;
MVSWDSGCLI CLVVVTMAGL SLARPSFNLV VEDATLEPEE PPTKYQISQP DVHSALPGEP
LELRCQLKDA VMISWTKDGV PLGPDNRTVI IGEYLQIKDA SPRDSGLYAC TAIRTLDSDT
LYFIVNVTDA LSSGDDEDDN DGSEDFVNDS NQMRAPYWTH TDKMEKRLHA VPAANTVKFR
CPAMGNPTPT MRWLKNGKEF KQEHRIGGYK VRNQHWSLIM ESVVPSDKGN YTCIVENQYG
SINHTYHLDV VERSPHRPIL QAGLPANASA VVGGDVEFVC KVYSDAQPHI QWIKHVERNG
SKYGPDGLPY LQVLKAAGVN TTDKEIEVLY IRNVTFEDAG EYTCLAGNSI GISFHTAWLT
VLPAPEKEKE FPTSPDYLEI AIYCIGVFLI ACMVLTVILC RMKNTTKKPD FSSQPAVHKL
TKRIPLRRQV TVSADSSSSM NSNTPLVRIT TRLSSTADAP MLAGVSEYEL PEDPKWEFPR
DKLTLGKPLG EGCFGQVVMA EAVGIDKDRP KEAVTVAVKM LKDDATEKDL SDLVSEMEMM
KMIGKHKNII NLLGACTQDG PLYVIVEYAS KGNLREYLRA RRPPGMEYSF DINRVPEEQM
TFKDLVSCTY QLARGMEYLA SQKCIHRDLA ARNVLVTENN VMKIADFGLA RDINNIDYYK
KTTNGRLPVK WMAPEALFDR VYTHQSDVWS FGVLMWEIFT LGGSPYPGIP VEELFKLLKE
GHRMDKPANC TNELYMMMRD CWQAVPSQRP TFKQLVEDLD RILTLTTNEE YLDLSGPLEQ
YSPSYPDTRS SCSSGDDSVF SPDPMPYEPC LPKYQHMNGS VKT
