EKS-MUM-00154

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-MUM-00154

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TK/FGFR	528.9	5.4E-159	464	740	277

Status

Reviewed

Ensembl Protein

ENSMUSP00000005452

UniProt Accession

Q03142; Q27Q87; Q5J7D9; Q8C3V5; Q8CIB8;

Protein Name

Fibroblast growth factor receptor 4

Protein Synonyms/Alias

FGFR-4; Protein-tyrosine kinase receptor MPK-11;

Gene Name

Fgfr4

Gene Synonyms/Alias

Fgfr4; Fgfr-4, Mpk-11;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSMUSG00000005320	ENSMUSP00000005452	ENSMUST00000005452

Organism

Mus musculus

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. Plays a role in postnatal lung development. May be involved in the development of skeletal muscle cell lineages.

Protein Length

799

Protein Sequence
(FASTA)

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 SFGILLWEIF TLGGSPYPGI PVEELFSLLR EGHRMERPPN CPSELYGLMR 720

ECWHAAPSQR PTFKQLVEAL DKVLLAVSEE YLDLRLTFGP FSPSNGDASS TCSSSDSVFS 780

HDPLPLEPSP FPFSDSQTT 799

Nucleotide Sequence
(FASTA)

ATGTGGCTGC TCTTGGCCCT GTTGAGCATC TTTCAGGGGA CACCAGCTTT GTCCCTTGAG 60

GCCTCTGAGG AAATGGAGCA GGAGCCCTGC CTAGCCCCAA TCCTGGAGCA GCAAGAGCAG 120

GTGTTGACGG TGGCCCTGGG GCAGCCTGTG AGGCTGTGCT GTGGGCGCAC CGAGCGTGGT 180

CGTCACTGGT ACAAAGAGGG CAGCCGCCTA GCATCTGCTG GGCGAGTACG GGGTTGGAGA 240

GGCCGCCTGG AGATCGCCAG CTTCCTTCCT GAGGATGCTG GCCGATACCT CTGCCTGGCC 300

CGTGGCTCCA TGACCGTCGT ACACAATCTT ACGTTGCTTA TGGATGACTC CTTAACCTCC 360

ATCAGTAATG ATGAAGACCC CAAGACACTC AGCAGCTCCT CGAGTGGTCA TGTCTACCCA 420

CAGCAAGCAC CCTACTGGAC ACACCCCCAA CGCATGGAGA AGAAACTGCA TGCAGTGCCT 480

GCCGGGAATA CTGTCAAATT CCGCTGTCCA GCTGCAGGGA ACCCCATGCC TACCATCCAC 540

TGGCTCAAGG ATGGACAGGC CTTCCACGGG GAGAATCGTA TTGGAGGCAT TCGGCTGCGC 600

CACCAACACT GGAGCCTGGT GATGGAAAGT GTGGTACCCT CGGACCGTGG CACATACACA 660

TGCCTTGTGG AGAACTCTCT GGGTAGCATT CGCTACAGCT ATCTCCTGGA TGTGCTGGAG 720

CGGTCCCCGC ACCGGCCCAT CCTGCAGGCG GGGCTCCCAG CCAACACCAC AGCTGTGGTT 780

GGCAGCGATG TGGAGCTACT CTGCAAGGTG TACAGCGACG CCCAGCCCCA CATACAGTGG 840

CTGAAACACG TCGTCATCAA CGGCAGCAGC TTCGGCGCCG ACGGTTTCCC CTACGTACAA 900

GTCCTGAAGA CAACAGACAT CAATAGCTCG GAGGTAGAGG TCTTGTATCT GAGGAACGTG 960

TCCGCTGAGG ATGCAGGAGA GTATACCTGT CTGGCGGGCA ACTCCATCGG CCTTTCCTAC 1020

CAGTCAGCGT GGCTCACGGT GCTGCCAGAG GAAGACCTCA CGTGGACAAC AGCAACCCCT 1080

GAGGCCAGAT ACACAGATAT CATCCTGTAT GTATCAGGCT CACTGGTTCT GCTTGTGCTC 1140

CTGCTGCTGG CCGGGGTGTA TCATCGGCAA GTCATCCGTG GCCACTACTC TCGCCAGCCT 1200

GTCACTATAC AAAAGCTGTC CCGTTTCCCT TTGGCCCGAC AGTTCTCTTT GGAGTCGAGG 1260

TCCTCTGGCA AGTCAAGTTT GTCCCTGGTG CGAGGTGTCC GTCTCTCCTC CAGCGGCCCG 1320

CCCTTGCTCA CGGGCCTTGT GAATCTAGAC CTGCCTCTCG ATCCGCTTTG GGAATTCCCC 1380

CGGGACAGGT TGGTGCTCGG AAAGCCCCTG GGTGAGGGCT GCTTTGGGCA AGTGGTTCGT 1440

GCAGAGGCCT TTGGTATGGA TCCCTCCCGG CCCGACCAAA CCAGCACCGT GGCTGTGAAG 1500

ATGCTGAAAG ACAATGCCTC CGACAAGGAT TTGGCAGACC TGGTCTCCGA GATGGAGGTG 1560

ATGAAGCTAA TCGGAAGACA CAAGAACATC ATCAACCTGC TGGGTGTCTG CACTCAGGAA 1620

GGGCCCCTGT ACGTGATTGT GGAATGTGCC GCCAAGGGAA ACCTTCGGGA ATTCCTCCGT 1680

GCCCGGCGCC CCCCAGGCCC TGATCTCAGC CCTGATGGAC CTCGGAGCAG CGAAGGACCA 1740

CTCTCCTTCC CGGCCCTAGT CTCCTGTGCC TACCAGGTGG CCCGAGGCAT GCAGTATCTG 1800

GAGTCTCGGA AGTGCATCCA CCGGGACCTG GCTGCCCGAA ATGTGCTGGT GACCGAGGAT 1860

GATGTGATGA AGATCGCTGA CTTTGGGCTG GCACGTGGTG TCCACCACAT TGACTACTAT 1920

AAGAAAACCA GCAACGGCCG CCTGCCAGTC AAATGGATGG CTCCAGAGGC ATTGTTCGAC 1980

CGCGTGTACA CACACCAGAG TGACGTGTGG TCTTTCGGGA TCCTGCTGTG GGAAATCTTC 2040

ACCCTCGGGG GCTCCCCATA CCCTGGCATT CCGGTGGAGG AGCTCTTCTC ACTGCTGCGA 2100

GAGGGGCACA GGATGGAGCG GCCCCCAAAC TGCCCCTCAG AGCTGTATGG GCTAATGAGG 2160

GAGTGCTGGC ACGCAGCCCC ATCTCAGAGG CCTACTTTTA AGCAGCTGGT GGAAGCTCTG 2220

GACAAGGTCC TGCTGGCTGT CTCTGAAGAG TACCTTGACC TCCGCCTGAC CTTTGGACCC 2280

TTTTCTCCCT CCAATGGGGA TGCCAGCAGC ACCTGCTCCT CCAGTGACTC GGTTTTCAGC 2340

CACGACCCTT TGCCCCTCGA GCCAAGCCCC TTCCCTTTCT CTGACTCGCA GACGACATGA 2400

Domain Profile

S: 1     lvlgkllGeGafGqvvkaeaigldkdkekkevtvavkmlkedatdkdladlvsemevlkl  60

         lvlgk+lGeG+fGqvv+aea+g+d +++++++tvavkmlk++a+dkdladlvsemev+kl

Q: 464   LVLGKPLGEGCFGQVVRAEAFGMDPSRPDQTSTVAVKMLKDNASDKDLADLVSEMEVMKL  523

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

S: 61    iGkhkniinllGactqeGplyviveyaakGnlreflrarrpkgeeaskdkskaseeqlte  120

         iG+hkniinllG+ctqeGplyvive+aakGnlreflrarrp+g + s d +++se  l++

Q: 524   IGRHKNIINLLGVCTQEGPLYVIVECAAKGNLREFLRARRPPGPDLSPDGPRSSEGPLSF  583

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

S: 121   kdlvsfayqvarGmeylaskkcihrdlaarnvlvtednvlkiadfGlardvheidyykkt  180

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

Q: 584   PALVSCAYQVARGMQYLESRKCIHRDLAARNVLVTEDDVMKIADFGLARGVHHIDYYKKT  643

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

S: 181   tnGrlpvkwmapealfdrvytsqsdvwsfGvllweiltlGgspypgiaveelfkllkeGh  240

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

Q: 644   SNGRLPVKWMAPEALFDRVYTHQSDVWSFGILLWEIFTLGGSPYPGIPVEELFSLLREGH  703

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

S: 241   rmekpakctkelyvlmrecwhakaserptfkqlvedl  277

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

Q: 704   RMERPPNCPSELYGLMRECWHAAPSQRPTFKQLVEAL  740

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

Domain Sequence
(FASTA)

LVLGKPLGEG CFGQVVRAEA FGMDPSRPDQ TSTVAVKMLK DNASDKDLAD LVSEMEVMKL 60

IGRHKNIINL LGVCTQEGPL YVIVECAAKG NLREFLRARR PPGPDLSPDG PRSSEGPLSF 120

PALVSCAYQV ARGMQYLESR KCIHRDLAAR NVLVTEDDVM KIADFGLARG VHHIDYYKKT 180

SNGRLPVKWM APEALFDRVY THQSDVWSFG ILLWEIFTLG GSPYPGIPVE ELFSLLREGH 240

RMERPPNCPS ELYGLMRECW HAAPSQRPTF KQLVEAL 277

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

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Equus caballus"; ?>Felis catus"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Monodelphis domestica"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Oryctolagus cuniculus"; ?>Pan troglodytes"; ?>Rattus norvegicus"; ?>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

mmu:14186

;

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