FGFR4_PLEWA
ID FGFR4_PLEWA Reviewed; 822 AA.
AC Q91288;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Fibroblast growth factor receptor 4;
DE Short=FGFR-4;
DE EC=2.7.10.1;
DE AltName: Full=PFR4;
DE Flags: Precursor;
GN Name=FGFR4;
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.
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 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 -!- DEVELOPMENTAL STAGE: First expressed at the late blastula stage,
CC predominantly localized to the presumptive ectoderm. Most abundantly
CC expressed in neural tissue with more transcripts in lateral plate
CC mesoderm than in the somites. {ECO:0000269|PubMed:1483392}.
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; X65059; CAA46192.1; -; mRNA.
DR PIR; B49151; B49151.
DR PIR; S19947; S19947.
DR AlphaFoldDB; Q91288; -.
DR SMR; Q91288; -.
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; 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; Disulfide bond; Endoplasmic reticulum;
KW Endosome; Glycoprotein; Immunoglobulin domain; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Receptor; Repeat; Signal; Transferase;
KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase;
KW Ubl conjugation.
FT SIGNAL 1..35
FT /evidence="ECO:0000255"
FT CHAIN 36..822
FT /note="Fibroblast growth factor receptor 4"
FT /id="PRO_0000249219"
FT TOPO_DOM 36..388
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 389..409
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 410..822
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 39..129
FT /note="Ig-like C2-type 1"
FT DOMAIN 157..259
FT /note="Ig-like C2-type 2"
FT DOMAIN 268..368
FT /note="Ig-like C2-type 3"
FT DOMAIN 486..774
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 136..166
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 631
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 492..500
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 522
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 661
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 662
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 773
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 13
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 72
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 125
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 240
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 277
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 309
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 330
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 341
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 69..114
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 191..243
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 290..352
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 822 AA; 92069 MW; 3EC4BA4BBC9AB81A CRC64;
MGVQKDSRDI RWNRTTRPLA LLLCGLLAFS ALSCARTLPE GRKANLAELV SEEEEHFLLD
PGNALRLFCD TNQTTIVNWY TESTRLQHGG RIRLTDTVLE IADVTYEDSG LYLCVVPGTG
HILRNFTISV VDSLASGDDD DEDHGREDSA GDMGEDPPYS TSYRAPFWSQ PQRMDKKLYA
VPAGNTVKFR CPSAGNPTPG IRWLKNGREF GGEHRIGGIR LRHQHWSLVM ESVVPSDRGN
YTCLVENKFG SISYSYLLDV LERSPHRPIL QAGLPANTTA MLGSDVQFFC KVYSDAQPHI
QWLKHIEVNG SRYGPDGVPF VQVLKTADIN SSEVEVLYLH NVSFEDAGEY TCLAGNSIGL
SYQSAWLTVL PEEDFAKEAE GPETRYTDII IYTSGSLALL MAAVIVVLCR MQLPPTKTHL
EPATVHKLSR FPLMRQFSLE SSSSGKSSTS LVRVTRLSSS CTPMLPGVLE FDLPLDSKWE
FPRERLVLGK PLGEGCFGQV VRAEAYGINK DQPDKAITVA IKIVKDKGTD KELSDLISEM
ELMKLMGKHK NIINLLGVCT QDGPLYMIVE YASKGNLREF LRARRPPSPD YTFDMTKVPE
EQLSFQDLVS CSYQVARGMA YLESKRCIHR DLAARNVLVT GENVMKIADF GLARGVHDID
YYKKTSNGRL PVKWMAPEAL FDRVYTHQSD VWSFGVLTWE IFTLGGSPYP GIPVEELFKL
LREGHRMDKP SNCTHELYML MRECWHAAPS QRPTFKQLVE TLDRILATVA EEYLDLSMPF
EQYSPACEDT TSTCSSDDSV FTHEPDVPSL FTHHTTTSMV GT
