CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-011039
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Fibroblast growth factor receptor 4 
Protein Synonyms/Alias
 FGFR-4; Protein-tyrosine kinase receptor MPK-11; CD334 
Gene Name
 Fgfr4 
Gene Synonyms/Alias
 Fgfr-4; Mpk-11 
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
405RQPVTIQKLSRFPLAubiquitination[1]
468RDRLVLGKPLGEGCFubiquitination[1]
Reference
 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 
Functional Description
 Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4. Plays a role in postnatal lung development. May be involved in the development of skeletal muscle cell lineages. 
Sequence Annotation
 DOMAIN 17 115 Ig-like C2-type 1.
 DOMAIN 149 237 Ig-like C2-type 2.
 DOMAIN 246 346 Ig-like C2-type 3.
 DOMAIN 464 752 Protein kinase.
 NP_BIND 470 478 ATP (By similarity).
 ACT_SITE 609 609 Proton acceptor (By similarity).
 BINDING 500 500 ATP (By similarity).
 MOD_RES 639 639 Phosphotyrosine; by autocatalysis (By
 MOD_RES 640 640 Phosphotyrosine; by autocatalysis (By
 MOD_RES 751 751 Phosphotyrosine; by autocatalysis (By
 CARBOHYD 109 109 N-linked (GlcNAc...) (Potential).
 CARBOHYD 255 255 N-linked (GlcNAc...) (Potential).
 CARBOHYD 287 287 N-linked (GlcNAc...) (Potential).
 CARBOHYD 308 308 N-linked (GlcNAc...).
 CARBOHYD 319 319 N-linked (GlcNAc...) (Potential).
 DISULFID 54 98 By similarity.
 DISULFID 169 221 By similarity.
 DISULFID 268 330 By similarity.  
Keyword
 Alternative splicing; ATP-binding; Cell membrane; Complete proteome; Disulfide bond; Endoplasmic reticulum; Endosome; Glycoprotein; Immunoglobulin domain; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 799 AA 
Protein Sequence
MWLLLALLSI FQGTPALSLE ASEEMEQEPC LAPILEQQEQ VLTVALGQPV RLCCGRTERG 60
RHWYKEGSRL ASAGRVRGWR GRLEIASFLP EDAGRYLCLA RGSMTVVHNL TLLMDDSLTS 120
ISNDEDPKTL SSSSSGHVYP QQAPYWTHPQ RMEKKLHAVP AGNTVKFRCP AAGNPMPTIH 180
WLKDGQAFHG ENRIGGIRLR HQHWSLVMES VVPSDRGTYT CLVENSLGSI RYSYLLDVLE 240
RSPHRPILQA GLPANTTAVV GSDVELLCKV YSDAQPHIQW LKHVVINGSS FGADGFPYVQ 300
VLKTTDINSS EVEVLYLRNV SAEDAGEYTC LAGNSIGLSY QSAWLTVLPE EDLTWTTATP 360
EARYTDIILY VSGSLVLLVL LLLAGVYHRQ VIRGHYSRQP VTIQKLSRFP LARQFSLESR 420
SSGKSSLSLV RGVRLSSSGP PLLTGLVNLD LPLDPLWEFP RDRLVLGKPL GEGCFGQVVR 480
AEAFGMDPSR PDQTSTVAVK MLKDNASDKD LADLVSEMEV MKLIGRHKNI INLLGVCTQE 540
GPLYVIVECA AKGNLREFLR ARRPPGPDLS PDGPRSSEGP LSFPALVSCA YQVARGMQYL 600
ESRKCIHRDL AARNVLVTED DVMKIADFGL ARGVHHIDYY KKTSNGRLPV KWMAPEALFD 660
RVYTHQSDVW SFEILLWEIF TLGGSPYPGI PVEELFSLLR EGHRMERPPN CPSELYGLMR 720
ECWHAAPSQR PTFKQLVEAL DKVLLAVSEE YLDLRLTFGP FSPSNGDASS TCSSSDSVFS 780
HDPLPLEPSP FPFSDSQTT 799 
Gene Ontology
 GO:0005911; C:cell-cell junction; IEA:Compara.
 GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
 GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
 GO:0005887; C:integral to plasma membrane; ISS:UniProtKB.
 GO:0005634; C:nucleus; IEA:Compara.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0017134; F:fibroblast growth factor binding; ISS:UniProtKB.
 GO:0005007; F:fibroblast growth factor-activated receptor activity; ISS:UniProtKB.
 GO:0008201; F:heparin binding; ISS:UniProtKB.
 GO:0061144; P:alveolar secondary septum development; IGI:MGI.
 GO:0016477; P:cell migration; ISS:UniProtKB.
 GO:0042593; P:glucose homeostasis; IMP:UniProtKB.
 GO:0001759; P:organ induction; IMP:MGI.
 GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
 GO:0055062; P:phosphate ion homeostasis; IMP:UniProtKB.
 GO:0008284; P:positive regulation of cell proliferation; ISS:UniProtKB.
 GO:2000573; P:positive regulation of DNA biosynthetic process; ISS:UniProtKB.
 GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
 GO:0048554; P:positive regulation of metalloenzyme activity; ISS:UniProtKB.
 GO:0045862; P:positive regulation of proteolysis; ISS:UniProtKB.
 GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
 GO:0070857; P:regulation of bile acid biosynthetic process; IMP:UniProtKB.
 GO:2000188; P:regulation of cholesterol homeostasis; IMP:UniProtKB.
 GO:0010715; P:regulation of extracellular matrix disassembly; ISS:UniProtKB. 
Interpro
 IPR007110; Ig-like_dom.
 IPR013783; Ig-like_fold.
 IPR013098; Ig_I-set.
 IPR003598; Ig_sub2.
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
 IPR008266; Tyr_kinase_AS.
 IPR020635; Tyr_kinase_cat_dom.
 IPR016248; Tyr_kinase_fibroblast_GF_rcpt. 
Pfam
 PF07679; I-set
 PF07714; Pkinase_Tyr 
SMART
 SM00408; IGc2
 SM00219; TyrKc 
PROSITE
 PS50835; IG_LIKE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00109; PROTEIN_KINASE_TYR 
PRINTS
 PR00109; TYRKINASE.