FGFR1_CHICK
ID FGFR1_CHICK Reviewed; 819 AA.
AC P21804;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Fibroblast growth factor receptor 1;
DE Short=FGFR-1;
DE Short=bFGF-R-1;
DE EC=2.7.10.1;
DE AltName: Full=Basic fibroblast growth factor receptor 1;
DE AltName: Full=Tyrosine kinase receptor CEK1;
DE Flags: Precursor;
GN Name=FGFR1; Synonyms=CEK1;
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=2473471; DOI=10.1073/pnas.86.14.5449;
RA Pasquale E.B., Singer S.J.;
RT "Identification of a developmentally regulated protein-tyrosine kinase by
RT using anti-phosphotyrosine antibodies to screen a cDNA expression
RT library.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:5449-5453(1989).
RN [2]
RP SEQUENCE REVISION.
RA Pasquale E.B.;
RL Submitted (MAY-1989) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2544996; DOI=10.1126/science.2544996;
RA Lee P.L., Johnson D.E., Cousens L.S., Fried V.A., Williams L.T.;
RT "Purification and complementary DNA cloning of a receptor for basic
RT fibroblast growth factor.";
RL Science 245:57-60(1989).
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 {ECO:0000250}.
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 -!- 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; M24637; AAA48663.1; -; mRNA.
DR PIR; A41345; TVCHFG.
DR RefSeq; NP_990841.1; NM_205510.1.
DR AlphaFoldDB; P21804; -.
DR SMR; P21804; -.
DR STRING; 9031.ENSGALP00000005237; -.
DR Ensembl; ENSGALT00000066938; ENSGALP00000046610; ENSGALG00000039786.
DR GeneID; 396516; -.
DR KEGG; gga:396516; -.
DR CTD; 2260; -.
DR VEuPathDB; HostDB:geneid_396516; -.
DR eggNOG; KOG0200; Eukaryota.
DR GeneTree; ENSGT00940000155860; -.
DR InParanoid; P21804; -.
DR OMA; YACVTNS; -.
DR OrthoDB; 220433at2759; -.
DR PhylomeDB; P21804; -.
DR BRENDA; 2.7.10.1; 1306.
DR PRO; PR:P21804; -.
DR Proteomes; UP000000539; Chromosome 22.
DR Bgee; ENSGALG00000039786; Expressed in cerebellum and 10 other tissues.
DR ExpressionAtlas; P21804; baseline and differential.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0005007; F:fibroblast growth factor receptor activity; ISS:UniProtKB.
DR GO; GO:0008201; F:heparin binding; ISS:UniProtKB.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0003347; P:epicardial cell to mesenchymal cell transition; TAS:DFLAT.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:0045597; P:positive regulation of cell differentiation; IBA:GO_Central.
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:0043406; P:positive regulation of MAP kinase activity; ISS:UniProtKB.
DR GO; GO:0010863; P:positive regulation of phospholipase C activity; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; TAS:DFLAT.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
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; IPR013151; Immunoglobulin.
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; PF00047; ig; 1.
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 ATP-binding; Cell membrane; Cytoplasm; Cytoplasmic vesicle; Disulfide bond;
KW Glycoprotein; Immunoglobulin domain; Kinase; Membrane; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Receptor; Reference proteome; Repeat; Signal;
KW Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase;
KW Ubl conjugation.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..819
FT /note="Fibroblast growth factor receptor 1"
FT /id="PRO_0000016789"
FT TOPO_DOM 22..374
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 375..395
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 396..819
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 25..118
FT /note="Ig-like C2-type 1"
FT DOMAIN 145..244
FT /note="Ig-like C2-type 2"
FT DOMAIN 253..355
FT /note="Ig-like C2-type 3"
FT DOMAIN 476..765
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 121..150
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 780..801
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 ACT_SITE 621
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 482..488
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 512
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 560..562
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 566
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 625
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 639
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 461
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 581
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 583
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 651
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 652
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 728
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 764
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 225
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 238
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 262
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 294
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 315
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 328
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 54..100
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 176..228
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 275..339
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT CONFLICT 90
FT /note="A -> R (in Ref. 3; no nucleotide entry)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 819 AA; 91577 MW; 7E030B7AE5181DDC CRC64;
MFTWRCLILW AVLVTATLSA ARPAPTLPDQ ALPKANIEVE SHSAHPGDLL QLRCRLRDDV
QSINWVRDGV QLPENNRTRI TGEEVEVRDA VPEDSGLYAC MTNSPSGSET TYFSVNVSDA
LPSAEDDDDE DDSSSEEKEA DNTKPNQAVA PYWTYPEKME KKLHAVPAAK TVKFKCPSGG
TPNPTLRWLK NGKEFKPDHR IGGYKVRYAT WSIIMDSVVP SDKGNYTCIV ENKYGSINHT
YQLDVVERSP HRPILQAGLP ANKTVALGSN VEFVCKVYSD PQPHIQWLKH IEVNGSKIGP
DNLPYVQILK TAGVNTTDKE MEVLHLRNVS FEDAGEYTCL AGNSIGISHH SAWLTVLEAT
EQSPAMMTSP LYLEIIIYCT GAFLISCMVV TVIIYKMKST TKKTDFNSQL AVHKLAKSIP
LRRQVTVSAD SSSSMNSGVM LVRPSRLSSS GTPMLAGVSE YELPEDPRWE LPRDRLILGK
PLGEGCFGQV VLAEAIGLDK DKPNRVTKVA VKMLKSDATE KDLSDLISEM EMMKMIGKHK
NIINLLGACT QDGPLYVIVE YASKGNLREY LQARRPPGME YCYNPTRIPE EQLSFKDLVS
CAYQVARGME YLASKKCIHR DLAARNVLVT EDNVMKIADF GLARDIHHID YYKKTTNGRL
PVKWMAPEAL FDRIYTHQSD VWSFGVLLWE IFTLGGSPYP GVPVEELFKL LKEGHRMDKP
SNCTNELYMM MRDCWHAVPS QRPTFKQLVE DLDRIVAMTS NQEYLDLSVP LDQYSPGFPA
TRSSTCSSGE DSVFSHDPLP DEPCLPRCPP HSHGALKRH
