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| | <StructureSection load='6nf0' size='340' side='right'caption='[[6nf0]], [[Resolution|resolution]] 2.70Å' scene=''> | | <StructureSection load='6nf0' size='340' side='right'caption='[[6nf0]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6nf0]] is a 1 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=6NF0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NF0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6nf0]] is a 1 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=6NF0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NF0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</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]] 2.7Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></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>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6nf0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nf0 OCA], [https://pdbe.org/6nf0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nf0 RCSB], [https://www.ebi.ac.uk/pdbsum/6nf0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nf0 ProSAT]</span></td></tr> |
| - | <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=6nf0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nf0 OCA], [http://pdbe.org/6nf0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nf0 RCSB], [http://www.ebi.ac.uk/pdbsum/6nf0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nf0 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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Du, J]] | + | [[Category: Du J]] |
| - | [[Category: Estrella, M A]] | + | [[Category: Estrella MA]] |
| - | [[Category: Korennykh, A]] | + | [[Category: Korennykh A]] |
| - | [[Category: Circadian clock]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Metabolism]]
| + | |
| Structural highlights
Function
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).
Publication Abstract from PubMed
Nocturnin (NOCT) is a rhythmically expressed protein that regulates metabolism under the control of circadian clock. It has been proposed that NOCT deadenylates and regulates metabolic enzyme mRNAs. However, in contrast to other deadenylases, purified NOCT lacks the deadenylase activity. To identify the substrate of NOCT, we conducted a mass spectrometry screen and report that NOCT specifically and directly converts the dinucleotide NADP(+) into NAD(+) and NADPH into NADH. Further, we demonstrate that the Drosophila NOCT ortholog, Curled, has the same enzymatic activity. We obtained the 2.7 A crystal structure of the human NOCT*NADPH complex, which revealed that NOCT recognizes the chemically unique ribose-phosphate backbone of the metabolite, placing the 2'-terminal phosphate productively for removal. We provide evidence for NOCT targeting to mitochondria and propose that NADP(H) regulation, which takes place at least in part in mitochondria, establishes the molecular link between circadian clock and metabolism.
The metabolites NADP(+) and NADPH are the targets of the circadian protein Nocturnin (Curled).,Estrella MA, Du J, Chen L, Rath S, Prangley E, Chitrakar A, Aoki T, Schedl P, Rabinowitz J, Korennykh A Nat Commun. 2019 May 30;10(1):2367. doi: 10.1038/s41467-019-10125-z. PMID:31147539[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Estrella MA, Du J, Chen L, Rath S, Prangley E, Chitrakar A, Aoki T, Schedl P, Rabinowitz J, Korennykh A. The metabolites NADP(+) and NADPH are the targets of the circadian protein Nocturnin (Curled). Nat Commun. 2019 May 30;10(1):2367. doi: 10.1038/s41467-019-10125-z. PMID:31147539 doi:http://dx.doi.org/10.1038/s41467-019-10125-z
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