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| | <StructureSection load='5fu7' size='340' side='right'caption='[[5fu7]], [[Resolution|resolution]] 3.10Å' scene=''> | | <StructureSection load='5fu7' size='340' side='right'caption='[[5fu7]], [[Resolution|resolution]] 3.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5fu7]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Drome Drome] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FU7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5FU7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5fu7]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FU7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FU7 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5fu6|5fu6]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.1Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5fu7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fu7 OCA], [http://pdbe.org/5fu7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fu7 RCSB], [http://www.ebi.ac.uk/pdbsum/5fu7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fu7 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5fu7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fu7 OCA], [https://pdbe.org/5fu7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fu7 RCSB], [https://www.ebi.ac.uk/pdbsum/5fu7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fu7 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/CNOT3_HUMAN CNOT3_HUMAN]] Precursor T-cell acute lymphoblastic leukemia. | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CNOT1_HUMAN CNOT1_HUMAN]] Belongs to the CCR4-NOT complex that functions as general transcription regulation complex. Acts as a transcriptional repressor. Represses the ligand-dependent transcriptional activation by nuclear receptors.<ref>PMID:10637334</ref> <ref>PMID:16778766</ref> [[http://www.uniprot.org/uniprot/CNOT3_HUMAN CNOT3_HUMAN]] Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. May be involved in metabolic regulation; may be involved in recruitment of the CCR4-NOT complex to deadenylation target mRNAs involved in energy metabolism. Involved in mitotic progression and regulation of the spindle assembly checkpoint by regulating the stability of MAD1L1 mRNA. Can repress transcription and may link the CCR4-NOT complex to transcriptional regulation; the repressive function may involve histone deacetylases. Involved in the maintenance of emryonic stem (ES) cell identity.<ref>PMID:14707134</ref> <ref>PMID:22342980</ref> <ref>PMID:22367759</ref> [[http://www.uniprot.org/uniprot/CNOT2_HUMAN CNOT2_HUMAN]] Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Required for the CCR4-NOT complex structural integrity. Can repress transcription and may link the CCR4-NOT complex to transcriptional regulation; the repressive function may specificly involve the N-Cor repressor complex containing HDAC3, NCOR1 and NCOR2. Involved in the maintenance of emryonic stem (ES) cell identity.<ref>PMID:14707134</ref> <ref>PMID:16712523</ref> <ref>PMID:21299754</ref> <ref>PMID:22367759</ref> | + | [https://www.uniprot.org/uniprot/CNOT1_HUMAN CNOT1_HUMAN] Belongs to the CCR4-NOT complex that functions as general transcription regulation complex. Acts as a transcriptional repressor. Represses the ligand-dependent transcriptional activation by nuclear receptors.<ref>PMID:10637334</ref> <ref>PMID:16778766</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> |
| - | [[Category: Drome]] | + | [[Category: Drosophila melanogaster]] |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bhandari, D]] | + | [[Category: Bhandari D]] |
| - | [[Category: Helms, S]] | + | [[Category: Helms S]] |
| - | [[Category: Izaurralde, E]] | + | [[Category: Izaurralde E]] |
| - | [[Category: Raisch, T]] | + | [[Category: Raisch T]] |
| - | [[Category: Sabath, K]] | + | [[Category: Sabath K]] |
| - | [[Category: Valkov, E]] | + | [[Category: Valkov E]] |
| - | [[Category: Weichenrieder, O]] | + | [[Category: Weichenrieder O]] |
| - | [[Category: Ccr4-not]]
| + | |
| - | [[Category: Deadenylation]]
| + | |
| - | [[Category: Gene regulation]]
| + | |
| - | [[Category: Mrna decay]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Translational repression]]
| + | |
| Structural highlights
Function
CNOT1_HUMAN Belongs to the CCR4-NOT complex that functions as general transcription regulation complex. Acts as a transcriptional repressor. Represses the ligand-dependent transcriptional activation by nuclear receptors.[1] [2]
Publication Abstract from PubMed
Nanos proteins repress the expression of target mRNAs by recruiting effector complexes through non-conserved N-terminal regions. In vertebrates, Nanos proteins interact with the NOT1 subunit of the CCR4-NOT effector complex through a NOT1 interacting motif (NIM), which is absent in Nanos orthologs from several invertebrate species. Therefore, it has remained unclear whether the Nanos repressive mechanism is conserved and whether it also involves direct interactions with the CCR4-NOT deadenylase complex in invertebrates. Here, we identify an effector domain (NED) that is necessary for the Drosophila melanogaster (Dm) Nanos to repress mRNA targets. The NED recruits the CCR4-NOT complex through multiple and redundant binding sites, including a central region that interacts with the NOT module, which comprises the C-terminal domains of NOT1-3. The crystal structure of the NED central region bound to the NOT module reveals an unanticipated bipartite binding interface that contacts NOT1 and NOT3 and is distinct from the NIM of vertebrate Nanos. Thus, despite the absence of sequence conservation, the N-terminal regions of Nanos proteins recruit CCR4-NOT to assemble analogous repressive complexes.
Distinct modes of recruitment of the CCR4-NOT complex by Drosophila and vertebrate Nanos.,Raisch T, Bhandari D, Sabath K, Helms S, Valkov E, Weichenrieder O, Izaurralde E EMBO J. 2016 May 2;35(9):974-90. doi: 10.15252/embj.201593634. Epub 2016 Mar 11. PMID:26968986[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Albert TK, Lemaire M, van Berkum NL, Gentz R, Collart MA, Timmers HT. Isolation and characterization of human orthologs of yeast CCR4-NOT complex subunits. Nucleic Acids Res. 2000 Feb 1;28(3):809-17. PMID:10637334
- ↑ Winkler GS, Mulder KW, Bardwell VJ, Kalkhoven E, Timmers HT. Human Ccr4-Not complex is a ligand-dependent repressor of nuclear receptor-mediated transcription. EMBO J. 2006 Jul 12;25(13):3089-99. Epub 2006 Jun 15. PMID:16778766 doi:7601194
- ↑ Raisch T, Bhandari D, Sabath K, Helms S, Valkov E, Weichenrieder O, Izaurralde E. Distinct modes of recruitment of the CCR4-NOT complex by Drosophila and vertebrate Nanos. EMBO J. 2016 May 2;35(9):974-90. doi: 10.15252/embj.201593634. Epub 2016 Mar 11. PMID:26968986 doi:http://dx.doi.org/10.15252/embj.201593634
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