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2kup

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{{STRUCTURE_2kup| PDB=2kup | SCENE= }}
 
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===Solution structure of the complex of the PTB domain of SNT-2 and 19-residue peptide (aa 1571-1589) of HALK===
 
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{{ABSTRACT_PUBMED_20454865}}
 
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==Disease==
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==Solution structure of the complex of the PTB domain of SNT-2 and 19-residue peptide (aa 1571-1589) of HALK==
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[[http://www.uniprot.org/uniprot/ALK_HUMAN ALK_HUMAN]] Note=A chromosomal aberration involving ALK is found in a form of non-Hodgkin lymphoma. Translocation t(2;5)(p23;q35) with NPM1. The resulting chimeric NPM1-ALK protein homodimerize and the kinase becomes constitutively activated. The constitutively active fusion proteins are responsible for 5-10% of non-Hodgkin lymphomas. Note=A chromosomal aberration involving ALK is associated with inflammatory myofibroblastic tumors (IMTs). Translocation t(2;11)(p23;p15) with CARS; translocation t(2;4)(p23;q21) with SEC31A. Note=A chromosomal aberration involving ALK is associated with anaplastic large-cell lymphoma (ALCL). Translocation t(2;17)(p23;q25) with ALO17. Defects in ALK are the cause of susceptibility to neuroblastoma type 3 (NBLST3) [MIM:[http://omim.org/entry/613014 613014]]. Neuroblastoma is a common neoplasm of early childhood arising from embryonic cells that form the primitive neural crest and give rise to the adrenal medulla and the sympathetic nervous system.<ref>PMID:18724359</ref><ref>PMID:18923523</ref><ref>PMID:18923525</ref> Note=The ALK signaling pathway plays an important role in glioblastoma, the most common malignant brain tumor of adults and one of the most lethal cancers. It regulates both glioblastoma migration and growth.
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<StructureSection load='2kup' size='340' side='right'caption='[[2kup]]' scene=''>
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== Structural highlights ==
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==Function==
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<table><tr><td colspan='2'>[[2kup]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KUP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KUP FirstGlance]. <br>
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[[http://www.uniprot.org/uniprot/FRS3_HUMAN FRS3_HUMAN]] Adapter protein that links FGF and NGF receptors to downstream signaling pathways. Involved in the activation of MAP kinases. Down-regulates ERK2 signaling by interfering with the phosphorylation and nuclear translocation of ERK2.<ref>PMID:15094036</ref> [[http://www.uniprot.org/uniprot/ALK_HUMAN ALK_HUMAN]] Neuronal orphan receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system. Transduces signals from ligands at the cell surface, through specific activation of the mitogen-activated protein kinase (MAPK) pathway. Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif. Following activation by ligand, ALK induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Acts as a receptor for ligands pleiotrophin (PTN), a secreted growth factor, and midkine (MDK), a PTN-related factor, thus participating in PTN and MDK signal transduction. PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation. MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction. Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase. Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK.<ref>PMID:11387242</ref><ref>PMID:11121404</ref><ref>PMID:11278720</ref><ref>PMID:11809760</ref><ref>PMID:12107166</ref><ref>PMID:12122009</ref><ref>PMID:15226403</ref><ref>PMID:15908427</ref><ref>PMID:16317043</ref><ref>PMID:17274988</ref><ref>PMID:16878150</ref>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2kup FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kup OCA], [https://pdbe.org/2kup PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kup RCSB], [https://www.ebi.ac.uk/pdbsum/2kup PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kup ProSAT]</span></td></tr>
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==About this Structure==
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</table>
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[[2kup]] is a 2 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=2KUP OCA].
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== Function ==
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[https://www.uniprot.org/uniprot/FRS3_HUMAN FRS3_HUMAN] Adapter protein that links FGF and NGF receptors to downstream signaling pathways. Involved in the activation of MAP kinases. Down-regulates ERK2 signaling by interfering with the phosphorylation and nuclear translocation of ERK2.<ref>PMID:15094036</ref>
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==Reference==
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== Evolutionary Conservation ==
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<ref group="xtra">PMID:020454865</ref><references group="xtra"/><references/>
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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/ku/2kup_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/main_output.php?pdb_ID=2kup ConSurf].
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<div style="clear:both"></div>
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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]]
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[[Category: Inoue, M.]]
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[[Category: Large Structures]]
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[[Category: Kigawa, T.]]
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[[Category: Inoue M]]
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[[Category: Koshiba, S.]]
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[[Category: Kigawa T]]
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[[Category: Li, H.]]
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[[Category: Koshiba S]]
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[[Category: Yokoyama, S.]]
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[[Category: Li H]]
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[[Category: Complex]]
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[[Category: Yokoyama S]]
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[[Category: Halk]]
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[[Category: National project on protein structural and functional analyse]]
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[[Category: Nppsfa]]
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[[Category: Ptb domain]]
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[[Category: Riken structural genomics/proteomics initiative]]
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[[Category: Rsgi]]
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[[Category: Signaling protein]]
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[[Category: Signaling protein-oncoprotein complex]]
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[[Category: Snt-2]]
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[[Category: Structural genomic]]
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Current revision

Solution structure of the complex of the PTB domain of SNT-2 and 19-residue peptide (aa 1571-1589) of HALK

PDB ID 2kup

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