FGFR4_XENLA
ID FGFR4_XENLA Reviewed; 828 AA.
AC Q91743;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Fibroblast growth factor receptor 4;
DE Short=FGFR-4;
DE EC=2.7.10.1;
DE Flags: Precursor;
GN Name=fgfr4;
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=8573131; DOI=10.1006/bbrc.1996.0035;
RA Riou J.F., Clavilier L., Boucaut J.-C.;
RT "Early regionalized expression of a novel Xenopus fibroblast growth factor
RT receptor in neuroepithlium.";
RL Biochem. Biophys. Res. Commun. 218:198-204(1996).
CC -!- FUNCTION: Tyrosine-protein kinase that acts as cell-surface receptor
CC for fibroblast growth factors and plays a role in the regulation of
CC cell proliferation, differentiation and migration, and in regulation of
CC lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D
CC metabolism and phosphate homeostasis. Required for normal down-
CC regulation of the expression of CYP7A1, the rate-limiting enzyme in
CC bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and
CC FRS2. 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 (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 -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}. Endosome {ECO:0000250}. Endoplasmic
CC reticulum {ECO:0000250}. Note=Internalized from the cell membrane to
CC recycling endosomes, and from there back to the cell membrane.
CC {ECO:0000250}.
CC -!- PTM: Ubiquitinated. Subject to proteasomal degradation when not fully
CC glycosylated (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 (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; X89807; CAA61930.1; -; mRNA.
DR PIR; JC4583; JC4583.
DR AlphaFoldDB; Q91743; -.
DR SMR; Q91743; -.
DR PRIDE; Q91743; -.
DR Proteomes; UP000186698; Genome assembly.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; 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: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 ATP-binding; Cell membrane; Disulfide bond; Endoplasmic reticulum;
KW Endosome; Glycoprotein; 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..31
FT /evidence="ECO:0000255"
FT CHAIN 32..828
FT /note="Fibroblast growth factor receptor 4"
FT /id="PRO_0000249209"
FT TOPO_DOM 32..392
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 393..413
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 414..828
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 33..127
FT /note="Ig-like C2-type 1"
FT DOMAIN 169..259
FT /note="Ig-like C2-type 2"
FT DOMAIN 272..372
FT /note="Ig-like C2-type 3"
FT DOMAIN 490..777
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 132..156
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 133..151
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 635
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 496..504
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 526
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 665
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 666
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 776
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 244
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 281
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 345
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 67..112
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 194..247
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 294..356
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 828 AA; 93417 MW; 089EB0D887603524 CRC64;
MSGSIRRSYT AMQNFPRFLL GVLFVATLSS CRPRLSEDEA NWKGQTETSE VEEHLLLDPG
NALRLFCDTN QSSSINWYRE QERLLSGGKI RMVGTVLEVS DVTYEDSGLY ICVVRGTGKI
LRRFSISVVD SLASGDEEEE EEDDDDEDGR REDTTADINE EPVYFFQAPY WTQPSRMDKK
LHAVPAGNTV KFRCPAGGSP LPTIRWSLKN GREFRGEHRI GGIQIRHQHW SLVMESVVPS
DRGNYTCVVE NRVGSLTYTY FLDVLERSSH RPILQAGLPA NTTARVGSDV EFYCKVYSDA
QPHIQWLKHI EVNGSHFGPD DFPYVQVLKT ADINPSDVEV LHLRNITMED AGEYTCLAGN
SIGLSHQSAW LTVLPNEDFL EQAEPAESRY MDIIIYTSGF LAVAMAIMIV ILCRMQTPHS
KQTLQTPTVH KLAKFPLIRQ FSLESSSSGK SSAPLIRITR LSSSCAPMLP GVMEVELPLD
AKWEFPRDRL VLGKPLGEGC FGQVVRAEGY GIEKDRPEKP VTVAVKMLKD NGTDKDLSDL
ISEMELMKVI GKHKNIINLL GVCTQEGPLF VIVEYASKGN LREFLRARRP PTPEDAFDIT
KVPEELLSFK DLVSCAYQVA RGMEYLESKR CIHRDLAARN VLVAEDNVMK IADFGLARGV
HDIDYYKKTS NGRLPVKWMA PEALFDRVYT HQSDIWSFGV LTWEIFTLGG SPYPVIPYEE
LFKLLREGHR MDKPSNCTHE LYMLMRECWH AVPTQRPTFK QLEHLDRILT AVSEEYLDLS
MPFEQYSPSC EDSASTCSSS DDSVFAPDPV PSSPCVFNYH NIHSQLGT
