EKS-MUM-00407
Eukaryotic Protein Kinase & Protein Phosphatase Database
TagContent
EKPD IDEKS-MUM-00407
Classification
Group/FamilyScoreE-ValueStartEndDomain Length
TK/Src386.21.5E-115192441250
StatusReviewed
Ensembl ProteinENSMUSP00000016511
UniProt AccessionQ64434;
Protein NameProtein-tyrosine kinase 6
Protein Synonyms/Alias SRC-related intestinal kinase;
Gene NamePtk6
Gene Synonyms/Alias Ptk6; Sik;
Ensembl Information
Ensembl Gene IDEnsembl Protein IDEnsembl Transcript ID
ENSMUSG00000038751ENSMUSP00000016511ENSMUST00000016511
OrganismMus musculus
Functional DescriptionNon-receptor tyrosine-protein kinase implicated in theregulation of a variety of signaling pathways that control the differentiation and maintenance of normal epithelia, as well as tumor growth. Function seems to be context dependent and differ depending on cell type, as well as its intracellular localization. A number of potential nuclear and cytoplasmic substrates have been identified. These include the RNA-binding proteins: KHDRBS1/SAM68, KHDRBS2/SLM1, KHDRBS3/SLM2 and SFPQ/PSF; transcription factors: STAT3 and STAT5A/B and a variety of signaling molecules: ARHGAP35/p190RhoGAP, PXN/paxillin, BTK/ATK, STAP2/BKS. Associates also with a variety of proteins that are likely upstream of PTK6 in various signaling pathways, or for which PTK6 may play an adapter-like role. These proteins include ADAM15, EGFR, ERBB2, ERBB3 and IRS4. In normal or non-tumorigenic tissues, PTK6 promotes cellular differentiation and apoptosis. In tumors PTK6 contributes to cancer progression by sensitizing cells to mitogenic signals and enhancing proliferation, anchorage- independent survival and migration/invasion. Association with EGFR, ERBB2, ERBB3 may contribute to mammary tumor development and growth through enhancement of EGF-induced signaling via BTK/AKT and PI3 kinase. Contributes to migration and proliferation by contributing to EGF-mediated phosphorylation of ARHGAP35/p190RhoGAP, which promotes association with RASA1/p120RasGAP, inactivating RhoA while activating RAS. EGF stimulation resulted in phosphorylation of PNX/Paxillin by PTK6 and activation of RAC1 via CRK/CrKII, thereby promoting migration and invasion. PTK6 activates STAT3 and STAT5B to promote proliferation. Nuclear PTK6 may be important for regulating growth in normal epithelia, while cytoplasmic PTK6 might activate oncogenic signaling pathways.
Protein Length451
Protein Sequence
(FASTA)
MVSWDKAHLG PKYVGLWDFK ARTDEELSFQ AGDLLHVTKK EELWWWATLL DAEGKALAEG 60
YVPHNYLAEK ETVESEPWFF GCISRSEAMH RLQAEDNSKG AFLIRVSQKP GADYVLSVRD 120
AQAVRHYRIW KNNEGRLHLN EAVSFSNLSE LVDYHKTQSL SHGLQLSMPC WKHKTEPLPH 180
WDDWERPREE FTLCKKLGAG YFGEVFEALW KGQVHVAVKV ISRDNLLHQH TFQAEIQAMK 240
KLRHKHILSL YAVATAGDPV YIITELMPKG NLLQLLRDSD EKALPILELV DFASQVAEGM 300
CYLESQNYIH RDLAARNVLV TENNLCKVGD FGLARLVKED IYLSHEHNVP YKWTAPEALS 360
RGHYSIKSDV WSFGVLLHEI FSRGQMPYPG MSNHETFLRV DAGYRMPCPL ECPPNIHKLM 420
LSCWSRDPKQ RPCFKDLCEK LTGITRYENL V 451
Nucleotide Sequence
(FASTA)
ATGGTGTCTT GGGACAAGGC TCACCTGGGT CCTAAGTATG TGGGCCTCTG GGACTTCAAG 60
GCACGGACAG ATGAGGAGCT GAGCTTTCAG GCAGGAGACC TCCTCCATGT TACCAAGAAG 120
GAGGAACTGT GGTGGTGGGC CACCCTGCTG GATGCAGAAG GCAAGGCCTT GGCTGAGGGC 180
TATGTGCCTC ACAACTACCT GGCTGAGAAG GAAACTGTGG AGTCTGAACC GTGGTTCTTT 240
GGTTGCATCT CCCGCTCAGA GGCCATGCAC AGGCTGCAGG CTGAGGACAA CTCGAAGGGT 300
GCCTTCCTGA TCAGAGTCAG CCAGAAGCCA GGAGCAGACT ATGTCCTCTC TGTCCGGGAT 360
GCTCAGGCCG TGCGACATTA CAGGATCTGG AAGAACAACG AGGGCCGGCT GCACCTGAAT 420
GAGGCGGTAT CCTTCTCCAA TCTGTCTGAG CTTGTGGACT ACCATAAGAC CCAGAGCCTG 480
TCTCATGGCC TACAGCTGTC CATGCCCTGC TGGAAGCACA AAACTGAGCC CTTGCCCCAC 540
TGGGATGACT GGGAGAGGCC GAGGGAGGAG TTCACACTCT GTAAGAAGCT GGGGGCCGGC 600
TACTTTGGGG AGGTCTTTGA AGCGCTCTGG AAAGGCCAGG TCCATGTGGC TGTGAAGGTG 660
ATCTCTAGAG ACAATCTCCT GCACCAGCAC ACCTTCCAGG CTGAGATTCA GGCCATGAAG 720
AAGCTGCGGC ACAAGCACAT CCTGTCACTG TACGCTGTGG CGACTGCAGG GGACCCGGTC 780
TACATCATCA CGGAGCTCAT GCCCAAGGGG AACCTGCTGC AGCTACTGCG TGACTCTGAT 840
GAGAAAGCCC TGCCTATTTT GGAGCTGGTG GACTTTGCAT CACAGGTTGC TGAGGGCATG 900
TGCTACCTGG AATCTCAGAA TTACATCCAC CGTGACCTGG CTGCAAGGAA CGTTCTTGTT 960
ACAGAGAACA ATCTCTGCAA AGTGGGGGAC TTTGGGCTTG CCAGGCTTGT CAAGGAGGAC 1020
ATCTACCTTT CCCATGAGCA CAATGTCCCC TACAAATGGA CAGCACCTGA GGCACTTTCC 1080
CGAGGGCATT ACTCCATCAA GTCTGATGTC TGGTCTTTTG GAGTTCTTCT TCATGAAATT 1140
TTCAGCAGGG GGCAGATGCC CTACCCAGGC ATGTCCAATC ATGAAACCTT CCTGAGGGTG 1200
GATGCCGGCT ACCGCATGCC CTGCCCTCTG GAGTGCCCAC CCAACATACA CAAGCTGATG 1260
CTCAGCTGCT GGAGCAGAGA CCCCAAGCAG AGACCTTGCT TCAAAGACCT GTGTGAGAAA 1320
CTCACAGGTA TCACCAGGTA TGAGAACCTG GTCTGA 1356
Domain Profile
S: 2     klvkklGeGqfGevwlgkwkgsvkvavktlkegt.lspeafleeaqilkklrheklvkly  60
         +l+kklG+G+fGev++++wkg+v+vavk++++++ l++++f++e+q++kklrh+++++ly
Q: 192   TLCKKLGAGYFGEVFEALWKGQVHVAVKVISRDNlLHQHTFQAEIQAMKKLRHKHILSLY  251
         799******************************98999**********************
S: 61    avvseeePiyivtelmakGslldflkeeegkklklpklvdlaaqvaeGmayleeknlihr  120
         av+++++P+yi+telm kG+ll++l+++++k+l++ +lvd+a+qvaeGm+yle++n+ihr
Q: 252   AVATAGDPVYIITELMPKGNLLQLLRDSDEKALPILELVDFASQVAEGMCYLESQNYIHR  311
         ************************************************************
S: 121   dlaarnvlvgeslvvkvadfGlarlieddeytakegaklPikWtaPeaiklgkftiksdv  180
         dlaarnvlv+e++++kv+dfGlarl+++d+y ++e +++P+kWtaPea++ g+++iksdv
Q: 312   DLAARNVLVTENNLCKVGDFGLARLVKEDIYLSHE-HNVPYKWTAPEALSRGHYSIKSDV  370
         ********************************987.99**********************
S: 181   WsfGillteivtkGkvPypGmtneevleqvergyrlprpeecpeelyelllecwkkdpee  240
         WsfG+ll+ei+++G++PypGm+n+e++ +v++gyr+p+p ecp ++++l+l+cw++dp++
Q: 371   WSFGVLLHEIFSRGQMPYPGMSNHETFLRVDAGYRMPCPLECPPNIHKLMLSCWSRDPKQ  430
         ************************************************************
S: 241   rPtfetlqevl  251
         rP+f+ l+e+l
Q: 431   RPCFKDLCEKL  441
         ******99875
Domain Sequence
(FASTA)
TLCKKLGAGY FGEVFEALWK GQVHVAVKVI SRDNLLHQHT FQAEIQAMKK LRHKHILSLY 60
AVATAGDPVY IITELMPKGN LLQLLRDSDE KALPILELVD FASQVAEGMC YLESQNYIHR 120
DLAARNVLVT ENNLCKVGDF GLARLVKEDI YLSHEHNVPY KWTAPEALSR GHYSIKSDVW 180
SFGVLLHEIF SRGQMPYPGM SNHETFLRVD AGYRMPCPLE CPPNIHKLML SCWSRDPKQR 240
PCFKDLCEKL 250
KeywordATP-binding; Cell projection; Complete proteome; Cytoplasm; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; SH2 domain; SH3 domain; Transferase; Tyrosine-protein kinase.
Sequence SourceEnsembl
Orthology
Ortholog group
Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Callithrix jacchus"; ?>Cavia porcellus"; ?>Danio rerio"; ?>Equus caballus"; ?>Erinaceus europaeus"; ?>Felis catus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Homo sapiens"; ?>Ictidomys tridecemlineatus"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Macropus eugenii"; ?>Monodelphis domestica"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Ornithorhynchus anatinus"; ?>Oryzias latipes"; ?>Pelodiscus sinensis"; ?>Pongo abelii"; ?>Procavia capensis"; ?>Pteropus vampyrus"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Tetraodon nigroviridis"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>
EKS-AIM-00349
EKS-ANC-00363
EKS-BOT-00375
EKS-CAJ-00379
EKS-CAP-00407
EKS-DAR-00754
EKS-EQC-00366
EKS-ERE-00055
EKS-FEC-00362
EKS-GAA-00458
EKS-GOG-00364
EKS-HOS-00381
EKS-ICT-00355
EKS-LOA-00382
EKS-MAM-00374
EKS-MAE-00042
EKS-MOD-00364
EKS-MUP-00369
EKS-MYL-00371
EKS-NOL-00342
EKS-ORA-00325
EKS-ORL-00444
EKS-PES-00332
EKS-POA-00364
EKS-PRC-00072
EKS-PTV-00096
EKS-RAN-00389
EKS-SAH-00345
EKS-TEN-00473
EKS-XET-00506
EKS-XIM-00472
Gene Ontology
GO:0005737; C:cytoplasm
GO:0005634; C:nucleus
GO:0005886; C:plasma membrane
GO:0001726; C:ruffle
GO:0005524; F:ATP binding
GO:0004715; F:non-membrane spanning protein tyrosine kinase activity
GO:0004674; F:protein serine/threonine kinase activity
GO:0016477; P:cell migration
GO:0071300; P:cellular response to retinoic acid
GO:0060575; P:intestinal epithelial cell differentiation
GO:0045926; P:negative regulation of growth
GO:0061099; P:negative regulation of protein tyrosine kinase activity
GO:0010976; P:positive regulation of neuron projection development
GO:0046777; P:protein autophosphorylation
GO:0042503; P:tyrosine phosphorylation of Stat3 protein
GO:0042506; P:tyrosine phosphorylation of Stat5 protein
KEGG
mmu:20459;
InterPros
IPR011009; Kinase-like_dom.
IPR000719; Prot_kinase_cat_dom.
IPR017441; Protein_kinase_ATP_BS.
IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
IPR000980; SH2.
IPR001452; SH3_domain.
IPR008266; Tyr_kinase_AS.
IPR020635; Tyr_kinase_cat_dom.
Pfam
PF07714; Pkinase_Tyr; 1.
PF00017; SH2; 1.
PF00018; SH3_1; 1.
SMARTs
SM00252; SH2; 1.
SM00326; SH3; 1.
SM00219; TyrKc; 1.
Prosites
PS00107; PROTEIN_KINASE_ATP; 1.
PS50011; PROTEIN_KINASE_DOM; 1.
PS00109; PROTEIN_KINASE_TYR; 1.
PS50001; SH2; 1.
PS50002; SH3; 1.
Prints
PR00401; SH2DOMAIN.
PR00452; SH3DOMAIN.
PR00109; TYRKINASE.
Created Date20-Feb-2013