1rja

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{{STRUCTURE_1rja| PDB=1rja | SCENE= }}
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==Solution Structure and Backbone Dynamics of the Nonreceptor Tyrosine Kinase PTK6/Brk SH2 Domain==
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===Solution Structure and Backbone Dynamics of the Nonreceptor Tyrosine Kinase PTK6/Brk SH2 Domain===
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<StructureSection load='1rja' size='340' side='right' caption='[[1rja]], [[NMR_Ensembles_of_Models | 21 NMR models]]' scene=''>
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{{ABSTRACT_PUBMED_15056653}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1rja]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RJA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1RJA FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] </span></td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1rja FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rja OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1rja RCSB], [http://www.ebi.ac.uk/pdbsum/1rja PDBsum]</span></td></tr>
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<table>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rj/1rja_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Human protein-tyrosine kinase-6 (PTK6, also known as breast tumor kinase (Brk)) is a member of the non-receptor protein-tyrosine kinase family and is expressed in two-thirds of all breast tumors. To understand the structural basis of PTK6 function, we have determined the solution structure and backbone dynamics of the PTK6-Src homology 2 (SH2) domain using multidimensional NMR spectroscopy. The solution structure clearly indicates that the SH2 domain of human PTK6 contains a consensus alpha/beta-fold and a Tyr(P) peptide binding surface, which are common to other SH2 domains. However, two of the alpha-helices (alphaA and alphaB) are located on opposite faces of the central beta-sheet. In addition, the topological arrangement of a central four-stranded antiparallel beta-sheet (strands betaA, betaB, betaC, and betaD) differs from that of other Src family members. Backbone dynamics and Tyr(P) peptide titration experiments revealed that the putative ligand binding sites of the PTK6-SH2 domain undergo distinctive internal motions when compared with other regions of the protein. Surface plasmon resonance analysis showed that the Tyr(P) peptide had a dissociation constant of about 60 microm, which is substantially weaker binding than previously reported for Src family members. The solution structure together with data from the ligand binding mode of PTK6-SH2 provides insight into the molecular basis of the autoinhibitory role of PTK6.
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==Function==
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Solution structure and backbone dynamics of the non-receptor protein-tyrosine kinase-6 Src homology 2 domain.,Hong E, Shin J, Kim HI, Lee ST, Lee W J Biol Chem. 2004 Jul 9;279(28):29700-8. Epub 2004 Mar 31. PMID:15056653<ref>PMID:15056653</ref>
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[[http://www.uniprot.org/uniprot/PTK6_HUMAN PTK6_HUMAN]] Non-receptor tyrosine-protein kinase implicated in the regulation 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.<ref>PMID:10980601</ref> <ref>PMID:15471878</ref> <ref>PMID:15572663</ref> <ref>PMID:15539407</ref> <ref>PMID:16179349</ref> <ref>PMID:16568091</ref> <ref>PMID:17997837</ref> <ref>PMID:18829532</ref> <ref>PMID:21479203</ref> Isoform 2 inhibits PTK6 phosphorylation and PTK6 association with other tyrosine-phosphorylated proteins.<ref>PMID:10980601</ref> <ref>PMID:15471878</ref> <ref>PMID:15572663</ref> <ref>PMID:15539407</ref> <ref>PMID:16179349</ref> <ref>PMID:16568091</ref> <ref>PMID:17997837</ref> <ref>PMID:18829532</ref> <ref>PMID:21479203</ref>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[1rja]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RJA OCA].
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</div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:015056653</ref><references group="xtra"/><references/>
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*[[Tyrosine kinase|Tyrosine kinase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Transferase]]
[[Category: Transferase]]

Revision as of 11:17, 3 October 2014

Solution Structure and Backbone Dynamics of the Nonreceptor Tyrosine Kinase PTK6/Brk SH2 Domain

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