EKS-RAN-00148

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-RAN-00148

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TK/FGFR	529.6	1.6E-159	465	741	277

Status

Reviewed

Ensembl Protein

ENSRNOP00000050988

UniProt Accession

Q498D6;

Protein Name

Fibroblast growth factor receptor 4

Protein Synonyms/Alias

FGFR-4;

Gene Name

Fgfr4

Gene Synonyms/Alias

Fgfr4;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSRNOG00000016763	ENSRNOP00000050988	ENSRNOT00000042394

Organism

Rattus norvegicus

Functional Description

Tyrosine-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 (By similarity).

Protein Length

800

Protein Sequence
(FASTA)

MWLLLALLSI FQETPAFSLE ASEEMEQEPC PAPISEQQEQ VLTVALGQPV RLCCGRTERG 60

RHWYKEGSRL ASAGRVRGWR GRLEIASFLP EDAGRYLCLA RGSMTVVHNL TLIMDDSLPS 120

INNEDPKTLS SSSSGHSYLQ QAPYWTHPQR MEKKLHAVPA GNTVKFRCPA AGNPMPTIHW 180

LKNGQAFHGE NRIGGIRLRH QHWSLVMESV VPSDRGTYTC LVENSLGSIR YSYLLDVLER 240

SPHRPILQAG LPANTTAVVG SNVELLCKVY SDAQPHIQWL KHIVINGSSF GADGFPYVQV 300

LKTTDINSSE VEVLYLRNVS AEDAGEYTCL AGNSIGLSYQ SAWLTVLPAE EEDLAWTTAT 360

SEARYTDIIL YVSGSLALVL LLLLAGVYHR QAIHGHHSRQ PVTVQKLSRF PLARQFSLES 420

RSSGKSSLSL VRGVRLSSSG PPLLTGLVSL DLPLDPLWEF PRDRLVLGKP LGEGCFGQVV 480

RAEALGMDSS RPDQTSTVAV KMLKDNASDK DLADLISEME MMKLIGRHKN IINLLGVCTQ 540

EGPLYVIVEY AAKGNLREFL RARRPPGPDL SPDGPRSSEG PLSFPALVSC AYQVARGMQY 600

LESRKCIHRD LAARNVLVTE DDVMKIADFG LARGVHHIDY YKKTSNGRLP VKWMAPEALF 660

DRVYTHQSDV WSFGILLWEI FTLGGSPYPG IPVEELFSLL REGHRMERPP NCPSELYGLM 720

RECWHAAPSQ RPTFKQLVEA LDKVLLAVSE EYLDLRLTFG PYSPNNGDAS STCSSSDSVF 780

SHDPLPLEPS PFPFPEAQTT 800

Nucleotide Sequence
(FASTA)

ATGTGGCTGC TGTTGGCTTT GTTGAGCATC TTTCAGGAGA CACCAGCCTT CTCCCTTGAG 60

GCCTCTGAGG AAATGGAACA GGAGCCCTGC CCAGCCCCAA TCTCGGAGCA GCAAGAGCAG 120

GTGTTGACTG TGGCCCTTGG GCAGCCTGTG CGGCTATGCT GTGGCCGCAC TGAGCGTGGT 180

CGTCATTGGT ACAAGGAGGG CAGCCGTTTA GCATCTGCTG GGAGAGTACG GGGCTGGAGA 240

GGCCGCCTGG AGATCGCCAG CTTCCTTCCT GAGGATGCTG GCCGGTACCT CTGCCTGGCC 300

CGTGGCTCCA TGACTGTCGT ACACAATCTT ACTTTGATTA TGGATGACTC CTTACCCTCC 360

ATCAATAACG AGGACCCCAA GACCCTCAGC AGCTCCTCGA GTGGGCACTC CTACCTGCAG 420

CAAGCACCTT ACTGGACACA CCCCCAACGC ATGGAGAAGA AACTGCACGC GGTACCTGCC 480

GGGAACACTG TCAAATTCCG CTGTCCAGCT GCAGGGAACC CCATGCCCAC CATCCACTGG 540

CTCAAGAACG GACAGGCCTT CCACGGAGAG AATCGTATCG GAGGCATTCG GCTGCGTCAC 600

CAACACTGGA GCCTCGTGAT GGAGAGCGTG GTGCCCTCAG ACCGTGGCAC GTACACGTGT 660

CTTGTGGAGA ACTCTCTGGG TAGCATTCGC TACAGCTATC TGCTGGATGT GCTGGAGCGG 720

TCCCCGCACC GGCCCATCCT GCAGGCGGGA CTCCCAGCCA ACACCACGGC TGTGGTTGGC 780

AGCAACGTGG AGCTGCTGTG CAAGGTGTAC AGTGACGCCC AGCCGCACAT CCAGTGGCTG 840

AAGCACATCG TTATCAACGG CAGCAGTTTC GGCGCTGATG GTTTCCCCTA CGTACAAGTC 900

CTGAAGACAA CAGACATCAA TAGCTCAGAG GTGGAGGTGC TGTATCTGAG GAACGTGTCG 960

GCTGAGGATG CAGGGGAGTA CACCTGCCTG GCGGGCAACT CCATCGGCCT CTCCTACCAG 1020

TCAGCGTGGC TCACAGTGCT ACCCGCAGAG GAAGAAGACC TCGCGTGGAC AACAGCAACA 1080

TCGGAGGCCA GATATACAGA TATTATCCTA TATGTATCTG GCTCACTGGC TTTGGTTTTG 1140

CTCCTGCTGC TGGCCGGGGT GTATCACCGA CAAGCAATCC ACGGCCACCA CTCTCGACAG 1200

CCTGTCACTG TACAGAAGCT GTCCCGGTTC CCTTTGGCCC GGCAGTTCTC CTTGGAGTCG 1260

AGGTCCTCTG GCAAGTCAAG TTTGTCCCTG GTGCGAGGTG TCCGGCTCTC CTCCAGTGGC 1320

CCGCCCTTGC TCACGGGCCT TGTGAGTCTA GACCTACCTC TCGATCCACT TTGGGAGTTC 1380

CCCCGGGACA GGCTGGTGCT CGGAAAGCCC CTGGGTGAGG GCTGCTTTGG GCAAGTGGTT 1440

CGTGCAGAAG CCCTTGGCAT GGATTCCTCC CGGCCAGACC AAACCAGCAC CGTGGCTGTG 1500

AAGATGCTGA AAGACAATGC CTCCGACAAG GATTTGGCAG ACCTGATCTC TGAGATGGAG 1560

ATGATGAAGC TAATCGGAAG ACACAAGAAC ATCATTAACC TGCTGGGTGT CTGCACTCAG 1620

GAAGGGCCCC TGTATGTGAT TGTGGAATAT GCGGCCAAGG GAAACCTTCG GGAATTCCTC 1680

CGTGCCCGGC GTCCCCCAGG CCCTGATCTC AGCCCTGATG GGCCTCGGAG CAGCGAAGGA 1740

CCGCTCTCCT TCCCGGCCCT GGTCTCCTGT GCCTACCAGG TGGCCCGAGG CATGCAGTAT 1800

CTGGAGTCTC GGAAGTGCAT CCACCGGGAC CTGGCTGCCC GAAACGTGCT GGTGACCGAG 1860

GATGACGTGA TGAAGATCGC TGACTTTGGT CTGGCCCGTG GTGTCCACCA CATCGACTAC 1920

TATAAGAAAA CCAGCAATGG CCGCCTGCCA GTCAAGTGGA TGGCTCCTGA GGCGTTGTTT 1980

GACCGTGTAT ACACACACCA GAGTGACGTG TGGTCCTTCG GGATCCTGCT GTGGGAAATC 2040

TTCACCCTCG GGGGCTCCCC ATACCCCGGC ATCCCAGTGG AGGAGCTGTT CTCACTGCTG 2100

CGAGAGGGGC ACAGGATGGA GCGGCCCCCA AACTGCCCCT CAGAGCTGTA TGGGCTAATG 2160

AGGGAGTGTT GGCACGCAGC TCCTTCTCAG AGGCCGACTT TTAAGCAGCT GGTGGAAGCT 2220

CTGGACAAGG TCCTGCTGGC TGTCTCTGAA GAGTACCTTG ACCTCCGCCT GACCTTTGGA 2280

CCCTATTCCC CCAACAATGG GGATGCCAGC AGCACGTGCT CCTCCAGCGA CTCGGTTTTC 2340

AGCCACGACC CTTTGCCCCT CGAGCCAAGC CCCTTCCCAT TTCCTGAGGC GCAGACCACA 2400

TGA 2403

Domain Profile

S: 1     lvlgkllGeGafGqvvkaeaigldkdkekkevtvavkmlkedatdkdladlvsemevlkl  60

         lvlgk+lGeG+fGqvv+aea+g+d +++++++tvavkmlk++a+dkdladl+seme++kl

Q: 465   LVLGKPLGEGCFGQVVRAEALGMDSSRPDQTSTVAVKMLKDNASDKDLADLISEMEMMKL  524

         79**********************************************************

S: 61    iGkhkniinllGactqeGplyviveyaakGnlreflrarrpkgeeaskdkskaseeqlte  120

         iG+hkniinllG+ctqeGplyviveyaakGnlreflrarrp+g + s d +++se  l++

Q: 525   IGRHKNIINLLGVCTQEGPLYVIVEYAAKGNLREFLRARRPPGPDLSPDGPRSSEGPLSF  584

         ************************************************************

S: 121   kdlvsfayqvarGmeylaskkcihrdlaarnvlvtednvlkiadfGlardvheidyykkt  180

           lvs+ayqvarGm+yl+s+kcihrdlaarnvlvted+v+kiadfGlar+vh+idyykkt

Q: 585   PALVSCAYQVARGMQYLESRKCIHRDLAARNVLVTEDDVMKIADFGLARGVHHIDYYKKT  644

         ************************************************************

S: 181   tnGrlpvkwmapealfdrvytsqsdvwsfGvllweiltlGgspypgiaveelfkllkeGh  240

         +nGrlpvkwmapealfdrvyt+qsdvwsfG+llwei+tlGgspypgi+veelf+ll+eGh

Q: 645   SNGRLPVKWMAPEALFDRVYTHQSDVWSFGILLWEIFTLGGSPYPGIPVEELFSLLREGH  704

         ************************************************************

S: 241   rmekpakctkelyvlmrecwhakaserptfkqlvedl  277

         rme+p +c++ely lmrecwha++s+rptfkqlve+l

Q: 705   RMERPPNCPSELYGLMRECWHAAPSQRPTFKQLVEAL  741

         **********************************986

Domain Sequence
(FASTA)

LVLGKPLGEG CFGQVVRAEA LGMDSSRPDQ TSTVAVKMLK DNASDKDLAD LISEMEMMKL 60

IGRHKNIINL LGVCTQEGPL YVIVEYAAKG NLREFLRARR PPGPDLSPDG PRSSEGPLSF 120

PALVSCAYQV ARGMQYLESR KCIHRDLAAR NVLVTEDDVM KIADFGLARG VHHIDYYKKT 180

SNGRLPVKWM APEALFDRVY THQSDVWSFG ILLWEIFTLG GSPYPGIPVE ELFSLLREGH 240

RMERPPNCPS ELYGLMRECW HAAPSQRPTF KQLVEAL 277

Keyword

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

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Equus caballus"; ?>Felis catus"; ?>Ictidomys tridecemlineatus"; ?>Loxodonta africana"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Oryctolagus cuniculus"; ?>Pan troglodytes"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Xenopus tropicalis"; ?>

Gene Ontology

GO:0005911	; C:cell-cell junction
GO:0005783	; C:endoplasmic reticulum
GO:0005768	; C:endosome
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: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

rno:25114

;

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 Date

20-Feb-2013