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| | ==Structure of the human Nocturnin catalytic domain with bound sulfate anion== | | ==Structure of the human Nocturnin catalytic domain with bound sulfate anion== |
| - | <StructureSection load='6bt2' size='340' side='right' caption='[[6bt2]], [[Resolution|resolution]] 2.41Å' scene=''> | + | <StructureSection load='6bt2' size='340' side='right'caption='[[6bt2]], [[Resolution|resolution]] 2.41Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6bt2]] 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=6BT2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BT2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6bt2]] 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=6BT2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BT2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.411Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6bt1|6bt1]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NOCT, CCR4, CCRN4L, NOC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6bt2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bt2 OCA], [https://pdbe.org/6bt2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bt2 RCSB], [https://www.ebi.ac.uk/pdbsum/6bt2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bt2 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Poly(A)-specific_ribonuclease Poly(A)-specific ribonuclease], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.13.4 3.1.13.4] </span></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=6bt2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bt2 OCA], [http://pdbe.org/6bt2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bt2 RCSB], [http://www.ebi.ac.uk/pdbsum/6bt2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bt2 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NOCT_HUMAN NOCT_HUMAN]] Circadian deadenylase which plays an important role in post-transcriptional regulation of metabolic genes under circadian control. Degrades poly(A) tails of specific target mRNAs leading to their degradation and suppression of translation. Exerts a rhythmic post-transcriptional control of genes necessary for metabolic functions including nutrient absorption, glucose/insulin sensitivity, lipid metabolism, adipogenesis, inflammation and osteogenesis. Plays an important role in favoring adipogenesis over osteoblastogenesis and acts as a key regulator of the adipogenesis/osteogenesis balance. Promotes adipogenesis by activating PPARG transcriptional activity in a deadenylase-independent manner by facilitating its nuclear translocation. Regulates circadian expression of NOS2 in the liver and negatively regulates the circadian expression of IGF1 in the bone. Critical for proper development of early embryos (By similarity). | + | [https://www.uniprot.org/uniprot/NOCT_HUMAN NOCT_HUMAN] Circadian deadenylase which plays an important role in post-transcriptional regulation of metabolic genes under circadian control. Degrades poly(A) tails of specific target mRNAs leading to their degradation and suppression of translation. Exerts a rhythmic post-transcriptional control of genes necessary for metabolic functions including nutrient absorption, glucose/insulin sensitivity, lipid metabolism, adipogenesis, inflammation and osteogenesis. Plays an important role in favoring adipogenesis over osteoblastogenesis and acts as a key regulator of the adipogenesis/osteogenesis balance. Promotes adipogenesis by activating PPARG transcriptional activity in a deadenylase-independent manner by facilitating its nuclear translocation. Regulates circadian expression of NOS2 in the liver and negatively regulates the circadian expression of IGF1 in the bone. Critical for proper development of early embryos (By similarity). |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | The circadian protein Nocturnin (NOCT) belongs to the exonuclease, endonuclease and phosphatase superfamily and is most similar to the CCR4-class of deadenylases that degrade the poly-adenosine tails of mRNAs. NOCT-deficient mice are resistant to high-fat diet induced weight gain, and exhibit dysregulation of bone formation. However, the mechanisms by which NOCT regulates these processes remain to be determined. Here, we describe a pair of high-resolution crystal structures of the human NOCT catalytic domain. The active site of NOCT is highly conserved with other exoribonucleases, and when directed to a transcript in cells, NOCT can reduce translation and abundance of that mRNA in a manner dependent on key active site residues. In contrast to the related deadenylase CNOT6L, purified recombinant NOCT lacks in vitro ribonuclease activity, suggesting that unidentified factors are necessary for enzymatic activity. We also find the ability of NOCT to repress reporter mRNAs in cells depends upon the 3' end of the mRNA, as reporters terminating with a 3' MALAT1 structure cannot be repressed by NOCT. Together, these data demonstrate that NOCT is an exoribonuclease that can degrade mRNAs to inhibit protein expression, suggesting a molecular mechanism for its regulatory role in lipid metabolism and bone development.
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| - | The structure of human Nocturnin reveals a conserved ribonuclease domain that represses target transcript translation and abundance in cells.,T Abshire E, Chasseur J, Bohn JA, Del Rizzo PA, Freddolino PL, Goldstrohm AC, Trievel RC Nucleic Acids Res. 2018 Jun 1. pii: 5026266. doi: 10.1093/nar/gky412. PMID:29860338<ref>PMID:29860338</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 6bt2" style="background-color:#fffaf0;"></div>
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| - | == References ==
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| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Abshire, E T]] | + | [[Category: Large Structures]] |
| - | [[Category: Chasseur, J]] | + | [[Category: Abshire ET]] |
| - | [[Category: Rizzo, P Del]] | + | [[Category: Chasseur J]] |
| - | [[Category: Trievel, R]] | + | [[Category: Del Rizzo P]] |
| - | [[Category: Eep superfamily]]
| + | [[Category: Trievel R]] |
| - | [[Category: Hydrolase]]
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| - | [[Category: Rna binding protein]]
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