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| | <StructureSection load='6hon' size='340' side='right'caption='[[6hon]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='6hon' size='340' side='right'caption='[[6hon]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6hon]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HON OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HON FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6hon]] is a 4 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=6HON OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HON FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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]] 2.2Å</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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=6hon FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hon OCA], [https://pdbe.org/6hon PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hon RCSB], [https://www.ebi.ac.uk/pdbsum/6hon PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hon 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=6hon FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hon OCA], [https://pdbe.org/6hon PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hon RCSB], [https://www.ebi.ac.uk/pdbsum/6hon PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hon ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/CNOT9_HUMAN CNOT9_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. Involved in down-regulation of MYB- and JUN-dependent transcription. May play a role in cell differentiation (By similarity). Can bind oligonucleotides, such as poly-G, poly-C or poly-T (in vitro), but the physiological relevance of this is not certain. Does not bind poly-A. Enhances ligand-dependent transcriptional activity of nuclear hormone receptors, including RARA, expect ESR1-mediated transcription that is not only slightly increased, if at all.<ref>PMID:17189474</ref> <ref>PMID:18180299</ref>
| + | [https://www.uniprot.org/uniprot/CNOT9_HUMAN CNOT9_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. Involved in down-regulation of MYB- and JUN-dependent transcription. May play a role in cell differentiation (By similarity). Can bind oligonucleotides, such as poly-G, poly-C or poly-T (in vitro), but the physiological relevance of this is not certain. Does not bind poly-A. Enhances ligand-dependent transcriptional activity of nuclear hormone receptors, including RARA, expect ESR1-mediated transcription that is not only slightly increased, if at all.<ref>PMID:17189474</ref> <ref>PMID:18180299</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: Drosophila melanogaster]] |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Izaurralde, E]] | + | [[Category: Izaurralde E]] |
| - | [[Category: Raisch, T]] | + | [[Category: Raisch T]] |
| - | [[Category: Weichenrieder, O]] | + | [[Category: Weichenrieder O]] |
| - | [[Category: Ccr4-not]]
| + | |
| - | [[Category: Deadenylation]]
| + | |
| - | [[Category: Gene regulation]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Mrna decay]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Ubiquitination]]
| + | |
| Structural highlights
Function
CNOT9_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. Involved in down-regulation of MYB- and JUN-dependent transcription. May play a role in cell differentiation (By similarity). Can bind oligonucleotides, such as poly-G, poly-C or poly-T (in vitro), but the physiological relevance of this is not certain. Does not bind poly-A. Enhances ligand-dependent transcriptional activity of nuclear hormone receptors, including RARA, expect ESR1-mediated transcription that is not only slightly increased, if at all.[1] [2]
Publication Abstract from PubMed
The multisubunit CCR4-NOT mRNA deadenylase complex plays important roles in the posttranscriptional regulation of gene expression. The NOT4 E3 ubiquitin ligase is a stable component of the CCR4-NOT complex in yeast but does not copurify with the human or Drosophila melanogaster complex. Here we show that the C-terminal regions of human and D. melanogaster NOT4 contain a conserved sequence motif that directly binds the CAF40 subunit of the CCR4-NOT complex (CAF40-binding motif [CBM]). In addition, nonconserved sequences flanking the CBM also contact other subunits of the complex. Crystal structures of the CBM-CAF40 complex reveal a mutually exclusive binding surface for NOT4 and Roquin or Bag of marbles mRNA regulatory proteins. Furthermore, CAF40 depletion or structure-guided mutagenesis to disrupt the NOT4-CAF40 interaction impairs the ability of NOT4 to elicit decay of tethered reporter mRNAs in cells. Together with additional sequence analyses, our results reveal the molecular basis for the association of metazoan NOT4 with the CCR4-NOT complex and show that it deviates substantially from yeast. They mark the NOT4 ubiquitin ligase as an ancient but nonconstitutive cofactor of the CCR4-NOT deadenylase with potential recruitment and/or effector functions.
A conserved CAF40-binding motif in metazoan NOT4 mediates association with the CCR4-NOT complex.,Keskeny C, Raisch T, Sgromo A, Igreja C, Bhandari D, Weichenrieder O, Izaurralde E Genes Dev. 2019 Feb 1;33(3-4):236-252. doi: 10.1101/gad.320952.118. Epub 2019 Jan, 28. PMID:30692204[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Garces RG, Gillon W, Pai EF. Atomic model of human Rcd-1 reveals an armadillo-like-repeat protein with in vitro nucleic acid binding properties. Protein Sci. 2007 Feb;16(2):176-88. Epub 2006 Dec 22. PMID:17189474 doi:10.1110/ps.062600507
- ↑ Garapaty S, Mahajan MA, Samuels HH. Components of the CCR4-NOT complex function as nuclear hormone receptor coactivators via association with the NRC-interacting Factor NIF-1. J Biol Chem. 2008 Mar 14;283(11):6806-16. doi: 10.1074/jbc.M706986200. Epub 2008 , Jan 7. PMID:18180299 doi:http://dx.doi.org/10.1074/jbc.M706986200
- ↑ Keskeny C, Raisch T, Sgromo A, Igreja C, Bhandari D, Weichenrieder O, Izaurralde E. A conserved CAF40-binding motif in metazoan NOT4 mediates association with the CCR4-NOT complex. Genes Dev. 2019 Feb 1;33(3-4):236-252. doi: 10.1101/gad.320952.118. Epub 2019 Jan, 28. PMID:30692204 doi:http://dx.doi.org/10.1101/gad.320952.118
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