FGFR1_PLEWA
ID FGFR1_PLEWA Reviewed; 816 AA.
AC Q91285;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Fibroblast growth factor receptor 1;
DE Short=FGFR-1;
DE EC=2.7.10.1;
DE AltName: Full=PFR1;
DE Flags: Precursor;
GN Name=FGFR1;
OS Pleurodeles waltl (Iberian ribbed newt).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Caudata; Salamandroidea; Salamandridae; Pleurodelinae;
OC Pleurodeles.
OX NCBI_TaxID=8319;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RC TISSUE=Embryo;
RX PubMed=1483392; DOI=10.1242/dev.116.1.261;
RA Shi D.-L., Feige J.-J., Riou J.-F., DeSimone D.W., Boucaut J.-C.;
RT "Differential expression and regulation of two distinct fibroblast growth
RT factor receptors during early development of the urodele amphibian
RT Pleurodeles waltl.";
RL Development 116:261-273(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 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 -!- DEVELOPMENTAL STAGE: Maternally derived transcript whose level of
CC expression remains constant during early developmental stages or early
CC gastrula. At tail-bud stage, transcripts are localized primarily to the
CC neural and mesodermal tissues. {ECO:0000269|PubMed:1483392}.
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; X59380; CAA42023.1; -; mRNA.
DR PIR; A49151; A49151.
DR AlphaFoldDB; Q91285; -.
DR SMR; Q91285; -.
DR PRIDE; Q91285; -.
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; 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; 1.
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; Repeat; Signal; Transferase;
KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase;
KW Ubl conjugation.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..816
FT /note="Fibroblast growth factor receptor 1"
FT /id="PRO_0000249216"
FT TOPO_DOM 24..374
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 375..395
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 396..816
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 25..118
FT /note="Ig-like C2-type 1"
FT DOMAIN 156..244
FT /note="Ig-like C2-type 2"
FT DOMAIN 253..355
FT /note="Ig-like C2-type 3"
FT DOMAIN 474..763
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 118..152
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 776..816
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 776..790
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 619
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 480..486
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 510
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 558..560
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 564
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 623
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 637
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 459
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 581
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 649
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 650
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 726
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 762
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 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"
SQ SEQUENCE 816 AA; 91548 MW; 91A7E16EE25256A6 CRC64;
MLSWRHLVFW AMLVMATLSA ARPAPTLPEQ VSPKAKVEVE SYSAHHGDLL QLRCRLRDDV
HSINWEKDGV QLAETNRTRI TGAEVEVRDA VQEDSGLYAC MTHRPSGTET TFFAVNVSDR
IPSVEDDDDD DEKSSSEEKE AENSKPNPVA PFWAHPEKME KKLHAVPAAK TVKFRCPAGG
TPSPTLRWLK NGKEFKPDHR IGGYKVRYQT WSIIMDSVVP SDKGPYTCLV ENNYGSINHT
YQLDVVERSP HRPILQAGLP ANQTVPVGSN VDFVCKVYSD PQPHIQWLKH VTVNGSKYGS
DGLPLVQVLK AAGVNTTDKE MEVLHLRNVS FEDAWEYTCL AGNSIGISHH SAWLTVVEAI
SENPVIMTSP LYLEIIIYCT GAFLISCMLV TVIIYKMKNT TKKTDFNSQP AVHKLAKSFP
LQRQVSADSS SSMSSGVMLV RPSRLSSSGS PMLTGVSEYE LPEDPRWEFS RDRLILGKPL
GEGCFGQVVM GEAIGLDKEK PNRVTKVAVK MLKSDATEKD LSDLISEMEM MKMIGKHKNI
INLLGACTQD GPLYVIVEYA SKGNLREYLR ARRPPGMEYC YNPIHVSKDM LSFKDLVSCA
YQVARGMEYL ASKKCIHRDL AARNVLVTED SVMKIADFGL ARDIHHIDYY KKTTNGRLPV
KWMAPEALFD RIYTHQSDVW SFGVLLWEIF TLGGSPYPGV PVEELFKLLK EGHRMDKPGN
CTNELYMMMR DCWHAVPSQR PTFKQLVEDL DRIVAMTSNQ EYLDLSMPVD QYSPGFPDTR
SSTCSSGEDS VFSHDPLPDE PCLPKYQHAN GGLKKR
