ID FGFR4_DANRE Reviewed; 922 AA.
AC Q90413;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 27-MAR-2024, entry version 156.
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 Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8589434; DOI=10.1002/aja.1002030309;
RA Thisse B., Thisse C., Weston J.A.;
RT "Novel FGF receptor (Z-FGFR4) is dynamically expressed in mesoderm and
RT neurectoderm during early zebrafish embryogenesis.";
RL Dev. Dyn. 203:377-391(1995).
CC -!- FUNCTION: Tyrosine-protein kinase that acts as a 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 -!- INTERACTION:
CC Q90413; Q7SX76: fgfrl1; NbExp=2; IntAct=EBI-1579413, EBI-1579511;
CC Q90413; Q5K373: fgfrl1b beta; NbExp=2; IntAct=EBI-1579413, EBI-42470198;
CC Q90413; Q8UVD6: wu:fa16d03; NbExp=2; IntAct=EBI-1579413, EBI-2268159;
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; U23839; AAA96816.1; -; mRNA.
DR RefSeq; NP_571505.1; NM_131430.1.
DR AlphaFoldDB; Q90413; -.
DR SMR; Q90413; -.
DR IntAct; Q90413; 5.
DR STRING; 7955.ENSDARP00000143805; -.
DR GlyCosmos; Q90413; 9 sites, No reported glycans.
DR PaxDb; 7955-ENSDARP00000091059; -.
DR GeneID; 100000160; -.
DR KEGG; dre:100000160; -.
DR AGR; ZFIN:ZDB-GENE-980526-488; -.
DR CTD; 2264; -.
DR ZFIN; ZDB-GENE-980526-488; fgfr4.
DR eggNOG; KOG0200; Eukaryota.
DR InParanoid; Q90413; -.
DR OrthoDB; 1614410at2759; -.
DR PhylomeDB; Q90413; -.
DR Reactome; R-DRE-109704; PI3K Cascade.
DR Reactome; R-DRE-1257604; PIP3 activates AKT signaling.
DR Reactome; R-DRE-1307965; betaKlotho-mediated ligand binding.
DR Reactome; R-DRE-190322; FGFR4 ligand binding and activation.
DR Reactome; R-DRE-5654228; Phospholipase C-mediated cascade, FGFR4.
DR Reactome; R-DRE-5654712; FRS-mediated FGFR4 signaling.
DR Reactome; R-DRE-5654719; SHC-mediated cascade:FGFR4.
DR Reactome; R-DRE-5654720; PI-3K cascade:FGFR4.
DR Reactome; R-DRE-5654733; Negative regulation of FGFR4 signaling.
DR Reactome; R-DRE-5673001; RAF/MAP kinase cascade.
DR Reactome; R-DRE-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR SignaLink; Q90413; -.
DR PRO; PR:Q90413; -.
DR Proteomes; UP000000437; Chromosome 21.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
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; IBA:GO_Central.
DR GO; GO:0005007; F:fibroblast growth factor receptor activity; ISS:ZFIN.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; ISS:ZFIN.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IBA:GO_Central.
DR GO; GO:0070857; P:regulation of bile acid biosynthetic process; IBA:GO_Central.
DR GO; GO:1902036; P:regulation of hematopoietic stem cell differentiation; IMP:ZFIN.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd05857; IgI_2_FGFR; 1.
DR CDD; cd05099; PTKc_FGFR4; 1.
DR Gene3D; 6.10.250.1740; -; 1.
DR Gene3D; 2.60.40.10; Immunoglobulins; 4.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
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 PANTHER; PTHR24416:SF343; FIBROBLAST GROWTH FACTOR RECEPTOR 4; 1.
DR PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1.
DR Pfam; PF07679; I-set; 2.
DR Pfam; PF00047; ig; 2.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PIRSF; PIRSF000615; TyrPK_CSF1-R; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00409; IG; 4.
DR SMART; SM00408; IGc2; 4.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; Immunoglobulin; 4.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR PROSITE; PS50835; IG_LIKE; 4.
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 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..19
FT /evidence="ECO:0000255"
FT CHAIN 20..922
FT /note="Fibroblast growth factor receptor 4"
FT /id="PRO_0000249208"
FT TOPO_DOM 20..480
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 481..501
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 502..922
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 27..134
FT /note="Ig-like C2-type 1"
FT DOMAIN 143..223
FT /note="Ig-like C2-type 2"
FT DOMAIN 258..351
FT /note="Ig-like C2-type 3"
FT DOMAIN 360..460
FT /note="Ig-like C2-type 4"
FT DOMAIN 578..866
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 723
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 584..592
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 614
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 753
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 754
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 865
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 46
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 96
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 107
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 219
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 332
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 369
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 401
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 422
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 433
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 59..118
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 163..208
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 283..335
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 382..444
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 922 AA; 103465 MW; 9560EFBEDFEBDCF5 CRC64;
MLSILKVFIA ICFMELVCSR SITSGEPRAK DIRVSRHILT PGYPENATVL VGGHVKLVCK
LHQPASTRLQ WFKKDSNRLG PDGSPVLTAL TPLLENLSKV NIFPLVNISL EDAGEYVCKA
ENSAGQATRS AWVEVLSEVS EEPTEEPSEH LLLELGDVLK LRCDTNRPGA VQWFKSGVRV
QHNARIQIRA AVMEIADVTY EDSGVYVCML RGTKEALRNF TITVADAVGS GDDDDEDNGL
DDIGPETEND QVYISRAPYW THTQRMEKKL YAVPAGNTVK FRCPATGSPL PTIRWLKNGR
EFRGEHRIGG IKLRHQHWSL VMESVVPSDR GNYSCVVENK YGSIAHTYLL DVLERSPHRP
ILQAGLPKNT TAIVGGDAQF LCKVYSDAQP HIQWLKHIEM NGSRYGPDGI PYVKIVKTGS
LNMSEVEVLY LTNISMEDAG EYSCLAGNSI GFSHQSAWLT VLSEEDVAKE VDLMEAKYTD
IIIYASGFLA LVMAIVIVVL CRMQVHPSRE PFDTLPVQKL SKFPLRRQYS VESNSSGKSS
ASLMRVARLS SSCSPMLAGV MEFELPYDPD WEFPRENLTL GKPLGEGCFG QVVRAEAYGI
NKENQDHMAT VAVKMLKDDA TDKDLADLIS EMELMKVMDK HKNIINLLGV CTQDGPLYVL
VEYASKGSLR EYLRARRPPG MDYTFDVTKV PEEQLTFKDL VSCAYQVARG MEYLASKRCI
HRDLAARNVL VTEDNVMKIA DFGLARGVHQ IDYYKKTTNG RMPVKWMAPE ALFDRVYTHQ
SDVWSFGVLM WEIFTLGGSP YPGIPVEELF KLLKEGHRMD KPSNCTHELY MKMRECWHAV
PTQRPTFKQL VEELDRVLVS ISDEYLDLST PFEQYSPSCE DTSSSCSSDN DSVFTHDALS
TEPCLLGYHD VHSRMDLKTT MR
//
