EKS-HOS-00155
Eukaryotic Protein Kinase & Protein Phosphatase Database
TagContent
EKPD IDEKS-HOS-00155
Classification
Group/FamilyScoreE-ValueStartEndDomain Length
TK/FGFR527.52.8E-158399675277
StatusReviewed
Ensembl ProteinENSP00000377259
UniProt AccessionP22455; O43785; Q14309; Q71TW8; Q8TDA0;
Protein NameFibroblast growth factor receptor 4
Protein Synonyms/Alias FGFR-4;
Gene NameFGFR4
Gene Synonyms/Alias FGFR4; JTK2, TKF;
Ensembl Information
Ensembl Gene IDEnsembl Protein IDEnsembl Transcript ID
ENSG00000160867ENSP00000395164ENST00000430285
ENSG00000160867ENSP00000377259ENST00000393648
ENSG00000160867ENSP00000424905ENST00000503708
ENSG00000160867ENSP00000292410ENST00000292410
ENSG00000160867ENSP00000424960ENST00000502906
ENSG00000160867ENSP00000377254ENST00000393637
ENSG00000160867ENSP00000427222ENST00000510911
ENSG00000160867ENSP00000426492ENST00000514472
ENSG00000160867ENSP00000292408ENST00000292408
ENSG00000160867ENSP00000422889ENST00000513166
ENSG00000160867ENSP00000424670ENST00000511076
OrganismHomo sapiens
Functional DescriptionTyrosine-protein kinase that acts as cell-surfacereceptor 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. Mutations that lead to constitutive kinase activation or impair normal FGFR4 inactivation lead to aberrant signaling.
Protein Length734
Protein Sequence
(FASTA)
MRLLLALLGV LLSVPGPPVL SLEASEEVEL EPCLAPSLEQ QEQELTVALG QPVRLCCGRA 60
ERGGHWYKEG SRLAPAGRVR GWRGRLEIAS FLPEDAGRYL CLARGSMIVL QNLTLITGDS 120
LTSSNDDEDP KSHRDPSNRH SYPQQAPYWT HPQRMEKKLH AVPAGNTVKF RCPAAGNPTP 180
TIRWLKDGQA FHGENRIGGI RLRHQHWSLV MESVVPSDRG TYTCLVENAV GSIRYNYLLD 240
VLERSPHRPI LQAGLPANTT AVVGSDVELL CKVYSDAQPH IQWLKHIVIN GSSFGADGFP 300
YVQVLKTADI NSSEVEVLYL RNVSAEDAGE YTCLAGNSIG LSYQSAWLTV LPEEDPTWTA 360
AAPEASSPWS QALPASQAHP WYEACVSPPA APPCSPASLV LGKPLGEGCF GQVVRAEAFG 420
MDPARPDQAS TVAVKMLKDN ASDKDLADLV SEMEVMKLIG RHKNIINLLG VCTQEGPLYV 480
IVECAAKGNL REFLRARRPP GPDLSPDGPR SSEGPLSFPV LVSCAYQVAR GMQYLESRKC 540
IHRDLAARNV LVTEDNVMKI ADFGLARGVH HIDYYKKTSN GRLPVKWMAP EALFDRVYTH 600
QSDVWSFGIL LWEIFTLGGS PYPGIPVEEL FSLLREGHRM DRPPHCPPEL YGLMRECWHA 660
APSQRPTFKQ LVEALDKVLL AVSEEYLDLR LTFGPYSPSG GDASSTCSSS DSVFSHDPLP 720
LGSSSFPFGS GVQT 734
Nucleotide Sequence
(FASTA)
ATGCGGCTGC TGCTGGCCCT GTTGGGGGTC CTGCTGAGTG TGCCTGGGCC TCCAGTCTTG 60
TCCCTGGAGG CCTCTGAGGA AGTGGAGCTT GAGCCCTGCC TGGCTCCCAG CCTGGAGCAG 120
CAAGAGCAGG AGCTGACAGT AGCCCTTGGG CAGCCTGTGC GTCTGTGCTG TGGGCGGGCT 180
GAGCGTGGTG GCCACTGGTA CAAGGAGGGC AGTCGCCTGG CACCTGCTGG CCGTGTACGG 240
GGCTGGAGGG GCCGCCTAGA GATTGCCAGC TTCCTACCTG AGGATGCTGG CCGCTACCTC 300
TGCCTGGCAC GAGGCTCCAT GATCGTCCTG CAGAATCTCA CCTTGATTAC AGGTGACTCC 360
TTGACCTCCA GCAACGATGA TGAGGACCCC AAGTCCCATA GGGACCCCTC GAATAGGCAC 420
AGTTACCCCC AGCAAGCACC CTACTGGACA CACCCCCAGC GCATGGAGAA GAAACTGCAT 480
GCAGTACCTG CGGGGAACAC CGTCAAGTTC CGCTGTCCAG CTGCAGGCAA CCCCACGCCC 540
ACCATCCGCT GGCTTAAGGA TGGACAGGCC TTTCATGGGG AGAACCGCAT TGGAGGCATT 600
CGGCTGCGCC ATCAGCACTG GAGTCTCGTG ATGGAGAGCG TGGTGCCCTC GGACCGCGGC 660
ACATACACCT GCCTGGTAGA GAACGCTGTG GGCAGCATCC GCTATAACTA CCTGCTAGAT 720
GTGCTGGAGC GGTCCCCGCA CCGGCCCATC CTGCAGGCCG GGCTCCCGGC CAACACCACA 780
GCCGTGGTGG GCAGCGACGT GGAGCTGCTG TGCAAGGTGT ACAGCGATGC CCAGCCCCAC 840
ATCCAGTGGC TGAAGCACAT CGTCATCAAC GGCAGCAGCT TCGGAGCCGA CGGTTTCCCC 900
TATGTGCAAG TCCTAAAGAC TGCAGACATC AATAGCTCAG AGGTGGAGGT CCTGTACCTG 960
CGGAACGTGT CAGCCGAGGA CGCAGGCGAG TACACCTGCC TCGCAGGCAA TTCCATCGGC 1020
CTCTCCTACC AGTCTGCCTG GCTCACGGTG CTGCCAGAGG AGGACCCCAC ATGGACCGCA 1080
GCAGCGCCCG AGGCCAGTTC TCCCTGGAGT CAGGCTCTTC CGGCAAGTCA AGCTCATCCC 1140
TGGTACGAGG CGTGCGTCTC TCCTCCAGCG GCCCCGCCTT GCTCGCCGGC CTCGCTGGTG 1200
CTTGGGAAGC CCCTAGGCGA GGGCTGCTTT GGCCAGGTAG TACGTGCAGA GGCCTTTGGC 1260
ATGGACCCTG CCCGGCCTGA CCAAGCCAGC ACTGTGGCCG TCAAGATGCT CAAAGACAAC 1320
GCCTCTGACA AGGACCTGGC CGACCTGGTC TCGGAGATGG AGGTGATGAA GCTGATCGGC 1380
CGACACAAGA ACATCATCAA CCTGCTTGGT GTCTGCACCC AGGAAGGGCC CCTGTACGTG 1440
ATCGTGGAGT GCGCCGCCAA GGGAAACCTG CGGGAGTTCC TGCGGGCCCG GCGCCCCCCA 1500
GGCCCCGACC TCAGCCCCGA CGGTCCTCGG AGCAGTGAGG GGCCGCTCTC CTTCCCAGTC 1560
CTGGTCTCCT GCGCCTACCA GGTGGCCCGA GGCATGCAGT ATCTGGAGTC CCGGAAGTGT 1620
ATCCACCGGG ACCTGGCTGC CCGCAATGTG CTGGTGACTG AGGACAATGT GATGAAGATT 1680
GCTGACTTTG GGCTGGCCCG CGGCGTCCAC CACATTGACT ACTATAAGAA AACCAGCAAC 1740
GGCCGCCTGC CTGTGAAGTG GATGGCGCCC GAGGCCTTGT TTGACCGGGT GTACACACAC 1800
CAGAGTGACG TGTGGTCTTT TGGGATCCTG CTATGGGAGA TCTTCACCCT CGGGGGCTCC 1860
CCGTATCCTG GCATCCCGGT GGAGGAGCTG TTCTCGCTGC TGCGGGAGGG ACATCGGATG 1920
GACCGACCCC CACACTGCCC CCCAGAGCTG TACGGGCTGA TGCGTGAGTG CTGGCACGCA 1980
GCGCCCTCCC AGAGGCCTAC CTTCAAGCAG CTGGTGGAGG CGCTGGACAA GGTCCTGCTG 2040
GCCGTCTCTG AGGAGTACCT CGACCTCCGC CTGACCTTCG GACCCTATTC CCCCTCTGGT 2100
GGGGACGCCA GCAGCACCTG CTCCTCCAGC GATTCTGTCT TCAGCCACGA CCCCCTGCCA 2160
TTGGGATCCA GCTCCTTCCC CTTCGGGTCT GGGGTGCAGA CATGA 2205
Domain Profile
S: 1     lvlgkllGeGafGqvvkaeaigldkdkekkevtvavkmlkedatdkdladlvsemevlkl  60
         lvlgk+lGeG+fGqvv+aea+g+d  ++++++tvavkmlk++a+dkdladlvsemev+kl
Q: 399   LVLGKPLGEGCFGQVVRAEAFGMDPARPDQASTVAVKMLKDNASDKDLADLVSEMEVMKL  458
         79**********************************************************
S: 61    iGkhkniinllGactqeGplyviveyaakGnlreflrarrpkgeeaskdkskaseeqlte  120
         iG+hkniinllG+ctqeGplyvive+aakGnlreflrarrp+g + s d +++se  l++
Q: 459   IGRHKNIINLLGVCTQEGPLYVIVECAAKGNLREFLRARRPPGPDLSPDGPRSSEGPLSF  518
         ************************************************************
S: 121   kdlvsfayqvarGmeylaskkcihrdlaarnvlvtednvlkiadfGlardvheidyykkt  180
           lvs+ayqvarGm+yl+s+kcihrdlaarnvlvtednv+kiadfGlar+vh+idyykkt
Q: 519   PVLVSCAYQVARGMQYLESRKCIHRDLAARNVLVTEDNVMKIADFGLARGVHHIDYYKKT  578
         ************************************************************
S: 181   tnGrlpvkwmapealfdrvytsqsdvwsfGvllweiltlGgspypgiaveelfkllkeGh  240
         +nGrlpvkwmapealfdrvyt+qsdvwsfG+llwei+tlGgspypgi+veelf+ll+eGh
Q: 579   SNGRLPVKWMAPEALFDRVYTHQSDVWSFGILLWEIFTLGGSPYPGIPVEELFSLLREGH  638
         ************************************************************
S: 241   rmekpakctkelyvlmrecwhakaserptfkqlvedl  277
         rm++p +c+ ely lmrecwha++s+rptfkqlve+l
Q: 639   RMDRPPHCPPELYGLMRECWHAAPSQRPTFKQLVEAL  675
         **********************************986
Domain Sequence
(FASTA)
LVLGKPLGEG CFGQVVRAEA FGMDPARPDQ ASTVAVKMLK DNASDKDLAD LVSEMEVMKL 60
IGRHKNIINL LGVCTQEGPL YVIVECAAKG NLREFLRARR PPGPDLSPDG PRSSEGPLSF 120
PVLVSCAYQV ARGMQYLESR KCIHRDLAAR NVLVTEDNVM KIADFGLARG VHHIDYYKKT 180
SNGRLPVKWM APEALFDRVY THQSDVWSFG ILLWEIFTLG GSPYPGIPVE ELFSLLREGH 240
RMDRPPHCPP ELYGLMRECW HAAPSQRPTF KQLVEAL 277
Keyword3D-structure; Alternative splicing; ATP-binding; Cell membrane; Complete proteome; Direct protein sequencing; Disulfide bond; Endoplasmic reticulum; Endosome; Glycoprotein; Immunoglobulin domain; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; Receptor; Reference proteome; Repeat; Secreted; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation.
Sequence SourceEnsembl
Orthology
Ortholog group
Gorilla gorilla"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pteropus vampyrus"; ?>
EKS-GOG-00149
EKS-OTG-00155
EKS-PAT-00140
EKS-PTV-00140
Gene Ontology
GO:0005783; C:endoplasmic reticulum
GO:0005768; C:endosome
GO:0005576; C:extracellular region
GO:0005887; C:integral to plasma membrane
GO:0005634; C:nucleus
GO:0005524; F:ATP binding
GO:0017134; F:fibroblast growth factor binding
GO:0005007; F:fibroblast growth factor-activated receptor activity
GO:0008201; F:heparin binding
GO:0061144; P:alveolar secondary septum development
GO:0016477; P:cell migration
GO:0042593; P:glucose homeostasis
GO:0008286; P:insulin receptor signaling pathway
GO:0001759; P:organ induction
GO:0018108; P:peptidyl-tyrosine phosphorylation
GO:0055062; P:phosphate ion homeostasis
GO:0008284; P:positive regulation of cell proliferation
GO:2000573; P:positive regulation of DNA biosynthetic process
GO:0070374; P:positive regulation of ERK1 and ERK2 cascade
GO:0048554; P:positive regulation of metalloenzyme activity
GO:0045862; P:positive regulation of proteolysis
GO:0046777; P:protein autophosphorylation
GO:0070857; P:regulation of bile acid biosynthetic process
GO:2000188; P:regulation of cholesterol homeostasis
GO:0010715; P:regulation of extracellular matrix disassembly
KEGG
hsa:2264;
InterPros
IPR007110; Ig-like.
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; 2.
PF07714; Pkinase_Tyr; 1.
SMARTs
SM00408; IGc2; 3.
SM00219; TyrKc; 1.
Prosites
PS50835; IG_LIKE; 2.
PS00107; PROTEIN_KINASE_ATP; 1.
PS50011; PROTEIN_KINASE_DOM; 1.
PS00109; PROTEIN_KINASE_TYR; 1.
Prints
PR00109; TYRKINASE.
Created Date20-Feb-2013