| Tag | Content |
|---|
| EKPD ID | EKS-HOS-00381 |
| Classification | | Group/Family | Score | E-Value | Start | End | Domain Length |
|---|
| TK/Src | 387.9 | 9.9E-116 | 91 | 339 | 249 |
|
| Status | Reviewed |
| Ensembl Protein | ENSP00000442460 |
| UniProt Accession | Q13882; B2RCR3; B4DW46; Q58F01; |
| Protein Name | Protein-tyrosine kinase 6 |
| Protein Synonyms/Alias | Breast tumor kinase; Tyrosine-protein kinase BRK; |
| Gene Name | PTK6 |
| Gene Synonyms/Alias | PTK6; BRK; |
| Ensembl Information | |
| Organism | Homo sapiens |
| Functional Description | Non-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. Isoform 2 inhibits PTK6 phosphorylation and PTK6association with other tyrosine-phosphorylated proteins. |
| Protein Length | 350 |
Protein Sequence
(FASTA) | | MCPTTTWPRG RRWSRNLRDT QAVRHYKIWR RAGGRLHLNE AVSFLSLPEL VNYHRAQSLS 60 | | HGLRLAAPCR KHEPEPLPHW DDWERPREEF TLCRKLGSGY FGEVFEGLWK DRVQVAIKVI 120 | | SRDNLLHQQM LQSEIQAMKK LRHKHILALY AVVSVGDPVY IITELMAKGS LLELLRDSDE 180 | | KVLPVSELLD IAWQVAEGMC YLESQNYIHR DLAARNILVG ENTLCKVGDF GLARLIKEDV 240 | | YLSHDHNIPY KWTAPEALSR GHYSTKSDVW SFGILLHEMF SRGQVPYPGM SNHEAFLRVD 300 | | AGYRMPCPLE CPPSVHKLML TCWCRDPEQR PCFKALRERL SSFTSYENPT 350 |
|
Nucleotide Sequence
(FASTA) | | ATGTGCCCCA CAACTACCTG GCCGAGAGGG AGACGGTGGA GTCGGAACCT GCGGGACACG 60 | | CAGGCTGTGC GGCACTACAA GATCTGGCGG CGTGCCGGGG GCCGGCTGCA CCTGAACGAG 120 | | GCGGTGTCCT TCCTCAGCCT GCCCGAGCTT GTGAACTACC ACAGGGCCCA GAGCCTGTCC 180 | | CACGGCCTGC GGCTGGCCGC GCCCTGCCGG AAGCACGAGC CTGAGCCCCT GCCCCATTGG 240 | | GATGACTGGG AGAGGCCGAG GGAGGAGTTC ACGCTCTGCA GGAAGCTGGG GTCCGGCTAC 300 | | TTTGGGGAGG TCTTCGAGGG GCTCTGGAAA GACCGGGTCC AGGTGGCCAT TAAGGTGATT 360 | | TCTCGAGACA ACCTCCTGCA CCAGCAGATG CTGCAGTCGG AGATCCAGGC CATGAAGAAG 420 | | CTGCGGCACA AACACATCCT GGCGCTGTAC GCCGTGGTGT CCGTGGGGGA CCCCGTGTAC 480 | | ATCATCACGG AGCTCATGGC CAAGGGCAGC CTGCTGGAGC TGCTCCGCGA CTCTGATGAG 540 | | AAAGTCCTGC CCGTTTCGGA GCTGCTGGAC ATCGCCTGGC AGGTGGCTGA GGGCATGTGT 600 | | TACCTGGAGT CGCAGAATTA CATCCACCGG GACCTGGCCG CCAGGAACAT CCTCGTCGGG 660 | | GAAAACACCC TCTGCAAAGT TGGGGACTTC GGGTTAGCCA GGCTTATCAA GGAGGACGTC 720 | | TACCTCTCCC ATGACCACAA TATCCCCTAC AAGTGGACGG CCCCTGAAGC GCTCTCCCGA 780 | | GGCCATTACT CCACCAAATC CGACGTCTGG TCCTTTGGGA TTCTCCTGCA TGAGATGTTC 840 | | AGCAGGGGTC AGGTGCCCTA CCCAGGCATG TCCAACCATG AGGCCTTCCT GAGGGTGGAC 900 | | GCCGGCTACC GCATGCCCTG CCCTCTGGAG TGCCCGCCCA GCGTGCACAA GCTGATGCTG 960 | | ACATGCTGGT GCAGGGACCC CGAGCAGAGA CCCTGCTTCA AGGCCCTGCG GGAGAGGCTC 1020 | | TCCAGCTTCA CCAGCTACGA GAACCCGACC TGA 1053 |
|
| Domain Profile | S: 2 klvkklGeGqfGevwlgkwkgsvkvavktlkegt.lspeafleeaqilkklrheklvkly 60 | +l++klG+G+fGev++g+wk++v+va+k++++++ l+++++++e+q++kklrh+++++ly | Q: 91 TLCRKLGSGYFGEVFEGLWKDRVQVAIKVISRDNlLHQQMLQSEIQAMKKLRHKHILALY 150 | 799******************************9778888999***************** |
| S: 61 avvseeePiyivtelmakGslldflkeeegkklklpklvdlaaqvaeGmayleeknlihr 120 | avvs ++P+yi+telmakGsll++l+++++k l++++l+d+a+qvaeGm+yle++n+ihr | Q: 151 AVVSVGDPVYIITELMAKGSLLELLRDSDEKVLPVSELLDIAWQVAEGMCYLESQNYIHR 210 | ************************************************************ |
| S: 121 dlaarnvlvgeslvvkvadfGlarlieddeytakegaklPikWtaPeaiklgkftiksdv 180 | dlaarn+lvge++++kv+dfGlarli++d y +++ +++P+kWtaPea++ g++++ksdv | Q: 211 DLAARNILVGENTLCKVGDFGLARLIKEDVYLSHD-HNIPYKWTAPEALSRGHYSTKSDV 269 | *******************************9876.99********************** |
| S: 181 WsfGillteivtkGkvPypGmtneevleqvergyrlprpeecpeelyelllecwkkdpee 240 | WsfGill+e++++G+vPypGm+n+e++ +v++gyr+p+p ecp ++++l+l+cw +dpe+ | Q: 270 WSFGILLHEMFSRGQVPYPGMSNHEAFLRVDAGYRMPCPLECPPSVHKLMLTCWCRDPEQ 329 | ************************************************************ |
| S: 241 rPtfetlqev 250 | rP+f++l+e | Q: 330 RPCFKALRER 339 | *******986 |
|
Domain Sequence
(FASTA) | | TLCRKLGSGY FGEVFEGLWK DRVQVAIKVI SRDNLLHQQM LQSEIQAMKK LRHKHILALY 60 | | AVVSVGDPVY IITELMAKGS LLELLRDSDE KVLPVSELLD IAWQVAEGMC YLESQNYIHR 120 | | DLAARNILVG ENTLCKVGDF GLARLIKEDV YLSHDHNIPY KWTAPEALSR GHYSTKSDVW 180 | | SFGILLHEMF SRGQVPYPGM SNHEAFLRVD AGYRMPCPLE CPPSVHKLML TCWCRDPEQR 240 | | PCFKALRER 249 |
|
| Keyword | 3D-structure; Alternative splicing; ATP-binding; Cell projection; Complete proteome; Cytoplasm; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; SH2 domain; SH3 domain; Transferase; Tyrosine-protein kinase. |
| Sequence Source | Ensembl |
| Orthology | |
| Gene Ontology | |
| KEGG | |
| InterPros | |
| Pfam | |
| SMARTs | |
| Prosites | |
| Prints | |
| Created Date | 20-Feb-2013 |