6ms4

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==Crystal structure of the DENR-MCT-1 complex==
==Crystal structure of the DENR-MCT-1 complex==
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<StructureSection load='6ms4' size='340' side='right' caption='[[6ms4]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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<StructureSection load='6ms4' size='340' side='right'caption='[[6ms4]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6ms4]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MS4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MS4 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6ms4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MS4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MS4 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.001&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MCTS1, MCT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), DENR, DRP1, H14 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ms4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ms4 OCA], [http://pdbe.org/6ms4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ms4 RCSB], [http://www.ebi.ac.uk/pdbsum/6ms4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ms4 ProSAT]</span></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=6ms4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ms4 OCA], [https://pdbe.org/6ms4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ms4 RCSB], [https://www.ebi.ac.uk/pdbsum/6ms4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ms4 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/MCTS1_HUMAN MCTS1_HUMAN]] Anti-oncogene that play a role in cell cycle regulation; decreases cell doubling time and anchorage-dependent growth; shortens the duration of G1 transit time and G1/S transition. When constituvely expressed, increases CDK4 and CDK6 kinases activity and CCND1/cyclin D1 protein level, as well as G1 cyclin/CDK complex formation. Plays a role as translation enhancer; Recruits the density-regulated protein/DENR and binds to the cap complex of the 5'-terminus of mRNAs, subsequently altering the mRNA translation profile; Up-regulates protein levels of BCL2L2, TFDP1, MRE11A, CCND1 and E2F1, while mRNA levels remains constant. Hyperactivates DNA damage signaling pathway; increased gamma-irradiation-induced phosphorylation of histone H2AX, and induces damage foci formation. Increases the overall number of chromosomal abnormalities such as larger chromosomes formation and multiples chromosomal fusions when overexpressed in gamma-irradiated cells. May play a role in promoting lymphoid tumor development: lymphoid cell lines overexpressing MCTS1 exhibit increased growth rates and display increased protection against apoptosis. May contribute to the pathogenesis and progression of breast cancer via promotion of angiogenesis through the decline of inhibitory THBS1/thrombospondin-1, and inhibition of apoptosis. Involved in the process of proteasome degradation to down-regulate Tumor suppressor p53/TP53 in breast cancer cell; Positively regulates phosphorylation of MAPK1 and MAPK3.<ref>PMID:9766643</ref> <ref>PMID:10440924</ref> <ref>PMID:11709712</ref> <ref>PMID:12637315</ref> <ref>PMID:16322206</ref> <ref>PMID:15897892</ref> <ref>PMID:16982740</ref> <ref>PMID:17416211</ref> <ref>PMID:17016429</ref> [[http://www.uniprot.org/uniprot/DENR_HUMAN DENR_HUMAN]] May be involved in the translation of target mRNAs by scanning and recognition of the initiation codon. Involved in translation initiation; promotes recruitmnet of aminoacetyled initiator tRNA to P site of 40S ribosomes. Can promote release of deacylated tRNA and mRNA from recycled 40S subunits following ABCE1-mediated dissociation of post-termination ribosomal complexes into subunits. Plays a role in the modulation of the translational profile of a subset of cancer-related mRNAs when recruited to the translational initiation complex by the oncogene MCTS1.<ref>PMID:16982740</ref> <ref>PMID:17878526</ref> <ref>PMID:20713520</ref>
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[https://www.uniprot.org/uniprot/MCTS1_HUMAN MCTS1_HUMAN] Anti-oncogene that play a role in cell cycle regulation; decreases cell doubling time and anchorage-dependent growth; shortens the duration of G1 transit time and G1/S transition. When constituvely expressed, increases CDK4 and CDK6 kinases activity and CCND1/cyclin D1 protein level, as well as G1 cyclin/CDK complex formation. Plays a role as translation enhancer; Recruits the density-regulated protein/DENR and binds to the cap complex of the 5'-terminus of mRNAs, subsequently altering the mRNA translation profile; Up-regulates protein levels of BCL2L2, TFDP1, MRE11A, CCND1 and E2F1, while mRNA levels remains constant. Hyperactivates DNA damage signaling pathway; increased gamma-irradiation-induced phosphorylation of histone H2AX, and induces damage foci formation. Increases the overall number of chromosomal abnormalities such as larger chromosomes formation and multiples chromosomal fusions when overexpressed in gamma-irradiated cells. May play a role in promoting lymphoid tumor development: lymphoid cell lines overexpressing MCTS1 exhibit increased growth rates and display increased protection against apoptosis. May contribute to the pathogenesis and progression of breast cancer via promotion of angiogenesis through the decline of inhibitory THBS1/thrombospondin-1, and inhibition of apoptosis. Involved in the process of proteasome degradation to down-regulate Tumor suppressor p53/TP53 in breast cancer cell; Positively regulates phosphorylation of MAPK1 and MAPK3.<ref>PMID:9766643</ref> <ref>PMID:10440924</ref> <ref>PMID:11709712</ref> <ref>PMID:12637315</ref> <ref>PMID:16322206</ref> <ref>PMID:15897892</ref> <ref>PMID:16982740</ref> <ref>PMID:17416211</ref> <ref>PMID:17016429</ref>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
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[[Category: Dmitriev, S E]]
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[[Category: Large Structures]]
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[[Category: Lomakin, I B]]
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[[Category: Dmitriev SE]]
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[[Category: Steitz, T A]]
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[[Category: Lomakin IB]]
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[[Category: Reinitiation]]
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[[Category: Steitz TA]]
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[[Category: Ribosome]]
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[[Category: Translation]]
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[[Category: Trna binding]]
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[[Category: Zinc binding]]
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Current revision

Crystal structure of the DENR-MCT-1 complex

PDB ID 6ms4

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