FGFR4_MOUSE
ID FGFR4_MOUSE Reviewed; 799 AA.
AC Q03142; Q27Q87; Q5J7D9; Q8C3V5; Q8CIB8;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 3.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Fibroblast growth factor receptor 4;
DE Short=FGFR-4;
DE EC=2.7.10.1;
DE AltName: Full=Protein-tyrosine kinase receptor MPK-11;
DE AltName: CD_antigen=CD334;
DE Flags: Precursor;
GN Name=Fgfr4; Synonyms=Fgfr-4, Mpk-11;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC STRAIN=CD-1; TISSUE=Fetal cerebellum;
RX PubMed=1723680; DOI=10.1242/dev.113.2.641;
RA Stark K.L., McMahon J., McMahon A.P.;
RT "FGFR-4, a new member of the fibroblast growth factor receptor family,
RT expressed in the definitive endoderm and skeletal muscle lineages of the
RT mouse.";
RL Development 113:641-651(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PHOSPHORYLATION,
RP GLYCOSYLATION, SUBCELLULAR LOCATION, INDUCTION, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Myoblast;
RX PubMed=18186042; DOI=10.1002/jcp.21365;
RA Kwiatkowski B.A., Kirillova I., Richard R.E., Israeli D.,
RA Yablonka-Reuveni Z.;
RT "FGFR4 and its novel splice form in myogenic cells: interplay of
RT glycosylation and tyrosine phosphorylation.";
RL J. Cell. Physiol. 215:803-817(2008).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Lung;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 611-667 (ISOFORMS 1/2).
RC STRAIN=C57BL/6J; TISSUE=Embryonic brain;
RX PubMed=1281307;
RA Gilardi-Hebenstreit P., Nieto M.A., Frain M., Mattei M.-G., Chestier A.,
RA Wilkinson D.G., Charnay P.;
RT "An Eph-related receptor protein tyrosine kinase gene segmentally expressed
RT in the developing mouse hindbrain.";
RL Oncogene 7:2499-2506(1992).
RN [6]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=9716527; DOI=10.1242/dev.125.18.3615;
RA Weinstein M., Xu X., Ohyama K., Deng C.X.;
RT "FGFR-3 and FGFR-4 function cooperatively to direct alveogenesis in the
RT murine lung.";
RL Development 125:3615-3623(1998).
RN [7]
RP DISRUPTION PHENOTYPE, AND FUNCTION IN REGULATION OF CHOLESTEROL METABOLISM
RP AND BILE ACID SYNTHESIS.
RX PubMed=10809780; DOI=10.1074/jbc.275.20.15482;
RA Yu C., Wang F., Kan M., Jin C., Jones R.B., Weinstein M., Deng C.X.,
RA McKeehan W.L.;
RT "Elevated cholesterol metabolism and bile acid synthesis in mice lacking
RT membrane tyrosine kinase receptor FGFR4.";
RL J. Biol. Chem. 275:15482-15489(2000).
RN [8]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=17664243; DOI=10.2337/db07-0648;
RA Huang X., Yang C., Luo Y., Jin C., Wang F., McKeehan W.L.;
RT "FGFR4 prevents hyperlipidemia and insulin resistance but underlies high-
RT fat diet induced fatty liver.";
RL Diabetes 56:2501-2510(2007).
RN [9]
RP INTERACTION WITH KLB.
RX PubMed=17452648; DOI=10.1073/pnas.0701600104;
RA Ogawa Y., Kurosu H., Yamamoto M., Nandi A., Rosenblatt K.P., Goetz R.,
RA Eliseenkova A.V., Mohammadi M., Kuro-o M.;
RT "BetaKlotho is required for metabolic activity of fibroblast growth factor
RT 21.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:7432-7437(2007).
RN [10]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=19237543; DOI=10.1074/jbc.m808747200;
RA Shin D.J., Osborne T.F.;
RT "FGF15/FGFR4 integrates growth factor signaling with hepatic bile acid
RT metabolism and insulin action.";
RL J. Biol. Chem. 284:11110-11120(2009).
RN [11]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-308.
RC TISSUE=Myoblast;
RX PubMed=19656770; DOI=10.1074/mcp.m900195-mcp200;
RA Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I., Bausch-Fluck D.,
RA Elliott S.T., Boheler K.R., Van Eyk J.E., Wollscheid B.;
RT "The mouse C2C12 myoblast cell surface N-linked glycoproteome:
RT identification, glycosite occupancy, and membrane orientation.";
RL Mol. Cell. Proteomics 8:2555-2569(2009).
RN [12]
RP DISRUPTION PHENOTYPE, AND FUNCTION IN VITAMIN D AND PHOSPHATE HOMEOSTASIS.
RX PubMed=21561999; DOI=10.1152/ajprenal.00740.2010;
RA Gattineni J., Twombley K., Goetz R., Mohammadi M., Baum M.;
RT "Regulation of serum 1,25(OH)2Vitamin D3 levels by fibroblast growth factor
RT 23 is mediated by FGF receptors 3 and 4.";
RL Am. J. Physiol. 301:F371-F377(2011).
RN [13]
RP MUTAGENESIS OF GLY-385.
RX PubMed=26675719; DOI=10.1038/nature16449;
RA Ulaganathan V.K., Sperl B., Rapp U.R., Ullrich A.;
RT "Germline variant FGFR4 p.G388R exposes a membrane-proximal STAT3 binding
RT site.";
RL Nature 528:570-574(2015).
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 Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and
CC its lysosomal degradation. FGFR4 signaling is down-regulated by
CC receptor internalization and degradation; MMP14 promotes
CC internalization and degradation of FGFR4. Plays a role in postnatal
CC lung development. May be involved in the development of skeletal muscle
CC cell lineages. {ECO:0000269|PubMed:10809780,
CC ECO:0000269|PubMed:17664243, ECO:0000269|PubMed:19237543,
CC ECO:0000269|PubMed:21561999, ECO:0000269|PubMed:9716527}.
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 -!- SUBUNIT: Monomer. Homodimer after ligand binding. Interacts with FGF1,
CC FGF2, FGF4, FGF6, FGF8, FGF9, FGF16, FGF17, FGF18, FGF19, FGF21 and
CC FGF23 (in vitro). Binding affinity for FGF family members is enhanced
CC by interactions between FGFs and heparan sulfate proteoglycans.
CC Interacts with KLB; this strongly increases the affinity for FGF19 and
CC FGF23. Affinity for FGF19 is strongly increased by KLB and sulfated
CC glycosaminoglycans. KLB and KL both interact with the core-glycosylated
CC FGFR4 in the endoplasmic reticulum and promote its degradation, so that
CC only FGFR4 with fully mature N-glycans is expressed at the cell
CC surface. Identified in a complex with NCAM1, CDH2, PLCG1, FRS2, SRC,
CC SHC1, GAP43 and CTTN. Interacts with MMP14 and HIP1. Interacts with
CC STAT3 (By similarity). {ECO:0000250|UniProtKB:P22455}.
CC -!- INTERACTION:
CC Q03142; O35082: Kl; NbExp=2; IntAct=EBI-15633599, EBI-1570828;
CC Q03142; Q99N32: Klb; NbExp=2; IntAct=EBI-15633599, EBI-15633521;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18186042};
CC Single-pass type I membrane protein {ECO:0000269|PubMed:18186042}.
CC Endosome {ECO:0000250}. Endoplasmic reticulum {ECO:0000250}.
CC Note=Internalized from the cell membrane to recycling endosomes, and
CC from there back to the cell membrane. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q03142-1; Sequence=Displayed;
CC Name=2; Synonyms=Fgfr4 lacking exon 16, Fgfr4(-16);
CC IsoId=Q03142-2; Sequence=VSP_017545;
CC -!- TISSUE SPECIFICITY: Isoform 1 and isoform 2 are expressed in lung and
CC proliferating myoblasts and myotubes of primary myogenic cells (at
CC protein level). Isoform 1 and isoform 2 are expressed in liver, muscle,
CC spleen, heart, lung, kidney and in primary myogenic cells.
CC {ECO:0000269|PubMed:1723680, ECO:0000269|PubMed:18186042}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the developing gut endoderm, in
CC myotomally derived skeletal muscle, the adrenal cortex, kidney and
CC condensing cartilage. {ECO:0000269|PubMed:1723680}.
CC -!- INDUCTION: Isoform 1 and isoform 2 are up-regulated by estradiol during
CC myogenic differentiation and down-regulated in fully developed
CC myotubes. {ECO:0000269|PubMed:18186042}.
CC -!- PTM: N-glycosylated. Isoform 1 and isoform 2 are glycosylated. Full
CC maturation of the glycan chains in the Golgi is essential for high
CC affinity interaction with FGF19 (By similarity). {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.
CC Isoform 1 and isoform 2 are phosphorylated on tyrosine residues (By
CC similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Mice display an elevated
CC bile acid pool and elevated excretion of bile acids, due to loss of
CC normal regulation of CYP7A1, the rate-limiting enzyme in bile acid
CC synthesis. When on a normal diet, mice are prone to develop increased
CC levels of white adipose tissue, hyperlipidemia, hypercholesterolemia,
CC glucose intolerance and insulin resistance. Mice lacking both FGFR3 and
CC FGFR4 display pronounced dwarfism, and while their lungs appear normal
CC at birth, they are completely blocked in alveogenesis and do not form
CC secondary septae to delimit alveoli. These mice also show elevated
CC serum levels of 1,25-dihydroxyvitamin D3 and reduced serum phosphorus
CC levels. {ECO:0000269|PubMed:10809780, ECO:0000269|PubMed:17664243,
CC ECO:0000269|PubMed:19237543, ECO:0000269|PubMed:21561999,
CC ECO:0000269|PubMed:9716527}.
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; X59927; CAA42551.1; -; mRNA.
DR EMBL; DQ388428; ABD43187.1; -; mRNA.
DR EMBL; AY493377; AAS72387.2; -; mRNA.
DR EMBL; AK084850; BAC39292.1; -; mRNA.
DR EMBL; BC033313; AAH33313.1; -; mRNA.
DR EMBL; X57236; CAA40512.1; -; mRNA.
DR CCDS; CCDS26540.1; -. [Q03142-1]
DR PIR; S18209; S18209.
DR RefSeq; NP_032037.2; NM_008011.2.
DR AlphaFoldDB; Q03142; -.
DR SMR; Q03142; -.
DR BioGRID; 199660; 3.
DR CORUM; Q03142; -.
DR DIP; DIP-58508N; -.
DR IntAct; Q03142; 4.
DR STRING; 10090.ENSMUSP00000005452; -.
DR BindingDB; Q03142; -.
DR ChEMBL; CHEMBL3839; -.
DR GlyGen; Q03142; 5 sites.
DR iPTMnet; Q03142; -.
DR PhosphoSitePlus; Q03142; -.
DR jPOST; Q03142; -.
DR MaxQB; Q03142; -.
DR PaxDb; Q03142; -.
DR PRIDE; Q03142; -.
DR ProteomicsDB; 266838; -. [Q03142-1]
DR ProteomicsDB; 266839; -. [Q03142-2]
DR ABCD; Q03142; 1 sequenced antibody.
DR DNASU; 14186; -.
DR GeneID; 14186; -.
DR KEGG; mmu:14186; -.
DR UCSC; uc007qqb.1; mouse. [Q03142-1]
DR UCSC; uc011yzq.1; mouse. [Q03142-2]
DR CTD; 2264; -.
DR MGI; MGI:95525; Fgfr4.
DR eggNOG; KOG0200; Eukaryota.
DR InParanoid; Q03142; -.
DR OrthoDB; 220433at2759; -.
DR PhylomeDB; Q03142; -.
DR TreeFam; TF316307; -.
DR BRENDA; 2.7.10.1; 3474.
DR Reactome; R-MMU-109704; PI3K Cascade.
DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR Reactome; R-MMU-1307965; betaKlotho-mediated ligand binding.
DR Reactome; R-MMU-190322; FGFR4 ligand binding and activation.
DR Reactome; R-MMU-5654228; Phospholipase C-mediated cascade, FGFR4.
DR Reactome; R-MMU-5654712; FRS-mediated FGFR4 signaling.
DR Reactome; R-MMU-5654719; SHC-mediated cascade:FGFR4.
DR Reactome; R-MMU-5654720; PI-3K cascade:FGFR4.
DR Reactome; R-MMU-5654733; Negative regulation of FGFR4 signaling.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR BioGRID-ORCS; 14186; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Fgfr4; mouse.
DR PRO; PR:Q03142; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q03142; protein.
DR GO; GO:0005911; C:cell-cell junction; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0030133; C:transport vesicle; ISO:MGI.
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:0061144; P:alveolar secondary septum development; IGI:MGI.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; IMP:UniProtKB.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IGI:MGI.
DR GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB.
DR GO; GO:0030324; P:lung development; IMP:MGI.
DR GO; GO:0090272; P:negative regulation of fibroblast growth factor production; IGI:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; IGI:MGI.
DR GO; GO:0001759; P:organ induction; IMP:MGI.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:0055062; P:phosphate ion homeostasis; IMP:UniProtKB.
DR GO; GO:0043085; P:positive regulation of catalytic activity; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IGI:MGI.
DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; ISS:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:2000830; P:positive regulation of parathyroid hormone secretion; IGI:MGI.
DR GO; GO:0045862; P:positive regulation of proteolysis; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0070857; P:regulation of bile acid biosynthetic process; IMP:UniProtKB.
DR GO; GO:0010715; P:regulation of extracellular matrix disassembly; ISS:UniProtKB.
DR GO; GO:0019216; P:regulation of lipid metabolic process; IMP:UniProtKB.
DR GO; GO:0010966; P:regulation of phosphate transport; IGI:MGI.
DR GO; GO:0051174; P:regulation of phosphorus metabolic process; IGI:MGI.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0070640; P:vitamin D3 metabolic process; IGI:MGI.
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; 2.
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 Alternative splicing; ATP-binding; Cell membrane; Disulfide bond;
KW Endoplasmic reticulum; Endosome; Glycoprotein; Immunoglobulin domain;
KW Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Receptor;
KW Reference proteome; Repeat; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..799
FT /note="Fibroblast growth factor receptor 4"
FT /id="PRO_0000016788"
FT TOPO_DOM 17..366
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 367..387
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 388..799
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 17..115
FT /note="Ig-like C2-type 1"
FT DOMAIN 149..237
FT /note="Ig-like C2-type 2"
FT DOMAIN 246..346
FT /note="Ig-like C2-type 3"
FT DOMAIN 464..752
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 764..799
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 764..780
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 609
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 470..478
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 500
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 570
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22455"
FT MOD_RES 639
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P22455"
FT MOD_RES 640
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P22455"
FT MOD_RES 751
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P22455"
FT CARBOHYD 109
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 255
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 287
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 308
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19656770"
FT CARBOHYD 319
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 54..98
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 169..221
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 268..330
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 670..715
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:18186042"
FT /id="VSP_017545"
FT MUTAGEN 385
FT /note="G->R: Results in increased cell proliferation.
FT Results in STAT3 phosphorylation and signaling activation."
FT /evidence="ECO:0000269|PubMed:26675719"
FT CONFLICT 172..173
FT /note="AG -> CR (in Ref. 1; CAA42551)"
FT /evidence="ECO:0000305"
FT CONFLICT 309
FT /note="S -> I (in Ref. 1; CAA42551)"
FT /evidence="ECO:0000305"
FT CONFLICT 313
FT /note="E -> Q (in Ref. 1; CAA42551)"
FT /evidence="ECO:0000305"
FT CONFLICT 474
FT /note="C -> CFGQVVRAEA (in Ref. 1; CAA42551)"
FT /evidence="ECO:0000305"
FT CONFLICT 673
FT /note="E -> G (in Ref. 2; ABD43187, 3; BAC39292 and 4;
FT AAH33313)"
FT /evidence="ECO:0000305"
FT CONFLICT 726
FT /note="A -> V (in Ref. 4; AAH33313)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 799 AA; 88661 MW; 799E17845CD4021E CRC64;
MWLLLALLSI FQGTPALSLE ASEEMEQEPC LAPILEQQEQ VLTVALGQPV RLCCGRTERG
RHWYKEGSRL ASAGRVRGWR GRLEIASFLP EDAGRYLCLA RGSMTVVHNL TLLMDDSLTS
ISNDEDPKTL SSSSSGHVYP QQAPYWTHPQ RMEKKLHAVP AGNTVKFRCP AAGNPMPTIH
WLKDGQAFHG ENRIGGIRLR HQHWSLVMES VVPSDRGTYT CLVENSLGSI RYSYLLDVLE
RSPHRPILQA GLPANTTAVV GSDVELLCKV YSDAQPHIQW LKHVVINGSS FGADGFPYVQ
VLKTTDINSS EVEVLYLRNV SAEDAGEYTC LAGNSIGLSY QSAWLTVLPE EDLTWTTATP
EARYTDIILY VSGSLVLLVL LLLAGVYHRQ VIRGHYSRQP VTIQKLSRFP LARQFSLESR
SSGKSSLSLV RGVRLSSSGP PLLTGLVNLD LPLDPLWEFP RDRLVLGKPL GEGCFGQVVR
AEAFGMDPSR PDQTSTVAVK MLKDNASDKD LADLVSEMEV MKLIGRHKNI INLLGVCTQE
GPLYVIVECA AKGNLREFLR ARRPPGPDLS PDGPRSSEGP LSFPALVSCA YQVARGMQYL
ESRKCIHRDL AARNVLVTED DVMKIADFGL ARGVHHIDYY KKTSNGRLPV KWMAPEALFD
RVYTHQSDVW SFEILLWEIF TLGGSPYPGI PVEELFSLLR EGHRMERPPN CPSELYGLMR
ECWHAAPSQR PTFKQLVEAL DKVLLAVSEE YLDLRLTFGP FSPSNGDASS TCSSSDSVFS
HDPLPLEPSP FPFSDSQTT
