ID   FGFR2_XENLA             Reviewed;         813 AA.
AC   Q03364;
DT   01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1994, sequence version 1.
DT   27-MAR-2024, entry version 149.
DE   RecName: Full=Fibroblast growth factor receptor 2;
DE            Short=FGFR-2;
DE            EC=2.7.10.1;
DE   Flags: Precursor;
GN   Name=fgfr2;
OS   Xenopus laevis (African clawed frog).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX   NCBI_TaxID=8355;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=1284237; DOI=10.1242/dev.116.4.1051;
RA   Friesel R., Brown S.A.N.;
RT   "Spatially restricted expression of fibroblast growth factor receptor-2
RT   during Xenopus development.";
RL   Development 116:1051-1058(1992).
CC   -!- FUNCTION: Tyrosine-protein kinase that acts as a 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   -!- TISSUE SPECIFICITY: Expressed in the anterior neural plate in early
CC       neurula stage embryos. Later in development, the protein is also
CC       expressed in the eye anlagen, midbrain-hindbrain boundary and otic
CC       vesicle.
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; X65943; CAA46758.1; -; mRNA.
DR   PIR; A49123; A49123.
DR   AlphaFoldDB; Q03364; -.
DR   SMR; Q03364; -.
DR   GlyCosmos; Q03364; 7 sites, No reported glycans.
DR   AGR; Xenbase:XB-GENE-1018301; -.
DR   Xenbase; XB-GENE-1018301; fgfr2.L.
DR   BRENDA; 2.7.10.1; 6725.
DR   Proteomes; UP000186698; Genome assembly.
DR   GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR   GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0005007; F:fibroblast growth factor receptor activity; IEA:InterPro.
DR   GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:InterPro.
DR   CDD; cd05857; IgI_2_FGFR; 1.
DR   CDD; cd05101; PTKc_FGFR2; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 3.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
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   PANTHER; PTHR24416:SF130; FIBROBLAST GROWTH FACTOR RECEPTOR 2; 1.
DR   PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1.
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; Immunoglobulin; 3.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 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..14
FT   CHAIN           15..813
FT                   /note="Fibroblast growth factor receptor 2"
FT                   /id="PRO_0000016793"
FT   TOPO_DOM        18..367
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        368..388
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        389..813
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          21..117
FT                   /note="Ig-like C2-type 1"
FT   DOMAIN          145..237
FT                   /note="Ig-like C2-type 2"
FT   DOMAIN          246..348
FT                   /note="Ig-like C2-type 3"
FT   DOMAIN          471..760
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          119..143
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          152..169
FT                   /note="Heparin-binding"
FT                   /evidence="ECO:0000250"
FT   REGION          771..801
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        771..789
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        616
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10028"
FT   BINDING         477..485
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         507
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         555..557
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         561
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         456
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         576
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         646
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         647
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         759
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        79
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        115
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        231
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        255
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        287
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        308
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        321
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        58..103
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        170..221
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        268..332
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ   SEQUENCE   813 AA;  91340 MW;  815436569892A565 CRC64;
     MLLLALLAFL LVSRTIARPS YSMVDDTTPE PEEPPAKYQI SKADVFPVLP GEPLDLRCPL
     ADGPLVTWTK DGAKLEVNNR TLIVRTYLQI KESTTRDSGL YACSVLKNSH FFHVNVTEAS
     SSGDDEDDND GSEDFTNDNN NIRAPYWTNT EKMEKKLHAV SAANTVKLRC PAREPHPSNE
     WLKNGKEFKQ EHRIGGYKVR NQHWSLIMES VVPSDKGIYT CIVENEHGSI NHTYHLDVIE
     RSSHRPILQA GLPANTTAVV GGDAEFVCKV YSDAQPHIRW VRYIEKNGSR FGVDGLPYFK
     VLKAAGVNVT DEEIEVLYVR NVSFEDAGEY TCIAGNSIGI SQHSAWLTVH PAPVNPLEDN
     PVPYYMEIGI YSTGIFIIFC MVVVCVVCRM RQGAKKKKNF TGPPVHKLTK RIPLHRQVTV
     SADSSSSMNS TTPLVRITTR LLNSTDAMPL ANVSEYELPH DPMWEFSRDK LTLGKPLGEG
     CFGQVVMAEA LGIDKERPKE SVTVAVKMLK DNATEKDLAD LVSEMEMMKM IGKHKNIINL
     LGACTQGGTL YVIVEYAAKG NLRQYLRARR PLEMEYSFDV TRVPDEQMTF KDLVSCTYQI
     ARGMEYLASQ KCIHRDLAAR NVLVTENNVM KIADFGLARD VNNIDYYKKT SNGRLPVKWM
     APEALFDRVY THQSDVWSFG VLMWEIFTLG GSPYPGIPVE ELFKLLKEGH RMDKPANCTN
     ELYMMMRDCW HAIPSHRPTF KQLVEDLDRI LTLTTNEEYL DLSAPLEQYS PSFPDSSCSA
     SSSSGDDSVF SPDPMPHDPC LPKFQHVNGV VKT
//