FGFR2_XENLA
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 03-AUG-2022, entry version 142.
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 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 PRIDE; Q03364; -.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0008284; P:positive regulation of cell population proliferation; IEA:InterPro.
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..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
