FGFR1_XENLA
ID FGFR1_XENLA Reviewed; 812 AA.
AC P22182; Q03836;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1991, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Fibroblast growth factor receptor 1;
DE Short=FGFR-1;
DE EC=2.7.10.1;
DE Flags: Precursor;
GN Name=fgfr1; Synonyms=fgfra2;
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] (ISOFORM 1).
RX PubMed=2172985; DOI=10.1073/pnas.87.21.8365;
RA Musci T.J., Amaya E., Kirschner M.W.;
RT "Regulation of the fibroblast growth factor receptor in early Xenopus
RT embryos.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:8365-8369(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=1850097; DOI=10.1128/mcb.11.5.2481-2488.1991;
RA Friesel R.E., Dawid I.B.;
RT "cDNA cloning and developmental expression of fibroblast growth factor
RT receptors from Xenopus laevis.";
RL Mol. Cell. Biol. 11:2481-2488(1991).
RN [3]
RP INTERACTION WITH IL17RD.
RX PubMed=12604616; DOI=10.1074/jbc.c200606200;
RA Kovalenko D., Yang X., Nadeau R.J., Harkins L.K., Friesel R.;
RT "Sef inhibits fibroblast growth factor signaling by inhibiting FGFR1
RT tyrosine phosphorylation and subsequent ERK activation.";
RL J. Biol. Chem. 278:14087-14091(2003).
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 embryonic development, cell proliferation,
CC differentiation and migration. Required for normal mesoderm patterning
CC and normal skeletogenesis. Phosphorylates PLCG1, FRS2, GAB1 and SHB.
CC Ligand binding leads to the activation of several signaling cascades.
CC Activation of PLCG1 leads to the production of the cellular signaling
CC 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 Promotes phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the
CC nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the
CC regulation of transcription. FGFR1 signaling is down-regulated by
CC ubiquitination, internalization and degradation (By similarity).
CC {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 sequential autophosphorylation on tyrosine residues (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Monomer. Homodimer after ligand binding (By similarity).
CC Interacts with il17rd. {ECO:0000250, ECO:0000269|PubMed:12604616}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}. Nucleus {ECO:0000250}. Cytoplasm,
CC cytosol {ECO:0000250}. Cytoplasmic vesicle {ECO:0000250}. Note=After
CC ligand binding, both receptor and ligand are rapidly internalized. Can
CC translocate to the nucleus after internalization, or by translocation
CC from the endoplasmic reticulum or Golgi apparatus to the cytosol, and
CC from there to the nucleus (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P22182-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P22182-2; Sequence=VSP_011847;
CC -!- DOMAIN: The second and third Ig-like domains directly interact with
CC fibroblast growth factors (FGF) and heparan sulfate proteoglycans.
CC Isoforms lacking the first Ig-like domain have higher affinity for
CC fibroblast growth factors (FGF) and heparan sulfate proteoglycans than
CC isoforms with all three Ig-like domains (By similarity). {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 and
CC proceeds in a highly ordered manner. Phosphotyrosine residues provide
CC docking sites for interacting proteins and so are crucial for FGFR1
CC function and its regulation (By similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated. FGFR1 is rapidly ubiquitinated after
CC autophosphorylation, leading to internalization and degradation (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 -!- 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; U24491; AAA86868.1; -; mRNA.
DR EMBL; M62322; AAA49993.1; -; mRNA.
DR PIR; A36477; A36477.
DR RefSeq; NP_001081157.1; NM_001087688.1. [P22182-1]
DR RefSeq; NP_001081338.1; NM_001087869.1.
DR AlphaFoldDB; P22182; -.
DR SMR; P22182; -.
DR BioGRID; 99020; 2.
DR IntAct; P22182; 1.
DR MINT; P22182; -.
DR iPTMnet; P22182; -.
DR PRIDE; P22182; -.
DR GeneID; 394418; -.
DR GeneID; 397782; -.
DR KEGG; xla:397782; -.
DR CTD; 394418; -.
DR CTD; 397782; -.
DR Xenbase; XB-GENE-6254218; fgfr1.S.
DR OrthoDB; 220433at2759; -.
DR BRENDA; 2.7.10.1; 6725.
DR Proteomes; UP000186698; Chromosome 3S.
DR Bgee; 394418; Expressed in gastrula and 19 other tissues.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; 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; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:InterPro.
DR CDD; cd05098; PTKc_FGFR1; 1.
DR Gene3D; 2.60.40.10; -; 3.
DR InterPro; IPR028174; FGF_rcpt_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 Pfam; PF07679; I-set; 3.
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 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cell membrane; Cytoplasm;
KW Cytoplasmic vesicle; Disulfide bond; Glycoprotein; Immunoglobulin domain;
KW Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Receptor;
KW Reference proteome; Repeat; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation.
FT SIGNAL 1..20
FT /evidence="ECO:0000250"
FT CHAIN 21..812
FT /note="Fibroblast growth factor receptor 1"
FT /id="PRO_0000016792"
FT TOPO_DOM 21..371
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 372..393
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 394..812
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 25..118
FT /note="Ig-like C2-type 1"
FT DOMAIN 154..242
FT /note="Ig-like C2-type 2"
FT DOMAIN 251..353
FT /note="Ig-like C2-type 3"
FT DOMAIN 472..761
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 121..153
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 784..812
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 122..136
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 137..153
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 617
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 478..484
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 508
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 556..558
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 562
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 621
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 635
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 457
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 577
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 579
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 648
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 724
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 760
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 76
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 116
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 133
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 223
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 236
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 260
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 292
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 313
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 326
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 54..100
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 174..226
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 273..337
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 31..118
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:1850097"
FT /id="VSP_011847"
FT CONFLICT 190
FT /note="N -> G (in Ref. 2; AAA49993)"
FT /evidence="ECO:0000305"
FT CONFLICT 419
FT /note="V -> L (in Ref. 2; AAA49993)"
FT /evidence="ECO:0000305"
FT CONFLICT 637
FT /note="G -> R (in Ref. 2; AAA49993)"
FT /evidence="ECO:0000305"
FT CONFLICT 789
FT /note="M -> V (in Ref. 2; AAA49993)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 812 AA; 90502 MW; B06333BAFEAC5C9B CRC64;
MFSGMSLLLW GVLLGAALSV ARPPSTLPDE VAPKTKTEVE PYSAQPGDRI TLQCRLREDV
QSINWVKNGV QLSETNRTRI TGEEIQISNA GPEDNGVYAC VTNGPSRTYT VLCSVNVSDA
LPSAEDDDED DDNSSSEEKA AENSKPNRPL WSHPEKMEKK LHAVPAAKTV KFRCPANGTP
TPTLRWLKNN RAFQQDQRIG GYKVRSQTWS LIMDSVVPSD KGNYTCIVEN KYGAINHTYQ
LDVVERSPHR PILQAGLPAN TSVTVGTTAE FSCKVYSDPQ PHIQWLRHIE INGSRVASDG
FPYVEILKTA GVNTSDKDME VLHLRNVTFE DAGQYTCLAA NSIGISHHSA WLTVLKVEDN
KPALLASPLQ LEIIIYCTGA AFVSAMVVTI IIFKMKHPSK KSDFNSQLAV HKLAKSIPVR
RQVTVSGDSS SSMNSGVILV RRLSSSGTPM LSGLSEYELP EDPRWEVARD RLILGKPLGE
GCFGQVVMAE AIGLDKEKPN KVTKVAVKML KSDASEKDLS DLISEMEMMK MIGKHKNIIN
LLGACTQDGP LYVIVEYTSK GNLREYLRAR RPPAMEYCYN PTCVPDQLLS FKDLVSCAYQ
VARGMDYLAS KKCIHRDLAA RNVLVTEDNI MKIADFGLAR DIHHIDYYKK TTNGRLPVKW
MAPEALFDRI YTHQSDVWSF GVLLWEIFTL GGSPYPGVPM EELFKLLKEG HRMDKPTNCT
NELYMMMKDC WHAMPSQRPT FNQLVEDLDR ILALSSNQEY LDLSMPVNQY SPCFPDTRSS
TCSSGEDSMF SHDPLPDEPC LPKYSNGGLK KR
