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| | <StructureSection load='5sy5' size='340' side='right'caption='[[5sy5]], [[Resolution|resolution]] 3.20Å' scene=''> | | <StructureSection load='5sy5' size='340' side='right'caption='[[5sy5]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5sy5]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SY5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5SY5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5sy5]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SY5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5SY5 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Arnt ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Npas1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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]] 3.201Å</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=5sy5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5sy5 OCA], [http://pdbe.org/5sy5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5sy5 RCSB], [http://www.ebi.ac.uk/pdbsum/5sy5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5sy5 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=5sy5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5sy5 OCA], [https://pdbe.org/5sy5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5sy5 RCSB], [https://www.ebi.ac.uk/pdbsum/5sy5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5sy5 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ARNT_MOUSE ARNT_MOUSE]] Required for activity of the Ah (dioxin) receptor. This protein is required for the ligand-binding subunit to translocate from the cytosol to the nucleus after ligand binding. The complex then initiates transcription of genes involved in the activation of PAH procarcinogens. The heterodimer with HIF1A or EPAS1/HIF2A functions as a transcriptional regulator of the adaptive response to hypoxia (By similarity). [[http://www.uniprot.org/uniprot/NPAS1_MOUSE NPAS1_MOUSE]] May control regulatory pathways relevant to schizophrenia and to psychotic illness. May play a role in late central nervous system development by modulating EPO expression in response to cellular oxygen level.<ref>PMID:15347806</ref> <ref>PMID:15635607</ref> | + | [https://www.uniprot.org/uniprot/ARNT_MOUSE ARNT_MOUSE] Required for activity of the Ah (dioxin) receptor. This protein is required for the ligand-binding subunit to translocate from the cytosol to the nucleus after ligand binding. The complex then initiates transcription of genes involved in the activation of PAH procarcinogens. The heterodimer with HIF1A or EPAS1/HIF2A functions as a transcriptional regulator of the adaptive response to hypoxia (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5sy5" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5sy5" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[3D structures of hypoxia-inducible factor|3D structures of hypoxia-inducible factor]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Kim, Y]] | + | [[Category: Kim Y]] |
| - | [[Category: Potluri, N]] | + | [[Category: Potluri N]] |
| - | [[Category: Rastinejad, F]] | + | [[Category: Rastinejad F]] |
| - | [[Category: Su, X]] | + | [[Category: Su X]] |
| - | [[Category: Wu, D]] | + | [[Category: Wu D]] |
| - | [[Category: Bhlh-pas protein]]
| + | |
| - | [[Category: Heterodimeric complex]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription factor]]
| + | |
| Structural highlights
Function
ARNT_MOUSE Required for activity of the Ah (dioxin) receptor. This protein is required for the ligand-binding subunit to translocate from the cytosol to the nucleus after ligand binding. The complex then initiates transcription of genes involved in the activation of PAH procarcinogens. The heterodimer with HIF1A or EPAS1/HIF2A functions as a transcriptional regulator of the adaptive response to hypoxia (By similarity).
Publication Abstract from PubMed
The neuronal PAS domain proteins NPAS1 and NPAS3 are members of the basic helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) family, and their genetic deficiencies are linked to a variety of human psychiatric disorders including schizophrenia, autism spectrum disorders and bipolar disease. NPAS1 and NPAS3 must each heterodimerize with the aryl hydrocarbon receptor nuclear translocator (ARNT), to form functional transcription complexes capable of DNA binding and gene regulation. Here we examined the crystal structures of multi-domain NPAS1-ARNT and NPAS3-ARNT-DNA complexes, discovering each to contain four putative ligand-binding pockets. Through expanded architectural comparisons between these complexes and HIF-1alpha-ARNT, HIF-2alpha-ARNT and CLOCK-BMAL1, we show the wider mammalian bHLH-PAS family is capable of multi-ligand-binding and presents as an ideal class of transcription factors for direct targeting by small-molecule drugs.
NPAS1-ARNT and NPAS3-ARNT crystal structures implicate the bHLH-PAS family as multi-ligand binding transcription factors.,Wu D, Su X, Potluri N, Kim Y, Rastinejad F Elife. 2016 Oct 26;5. pii: e18790. doi: 10.7554/eLife.18790. PMID:27782878[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wu D, Su X, Potluri N, Kim Y, Rastinejad F. NPAS1-ARNT and NPAS3-ARNT crystal structures implicate the bHLH-PAS family as multi-ligand binding transcription factors. Elife. 2016 Oct 26;5. pii: e18790. doi: 10.7554/eLife.18790. PMID:27782878 doi:http://dx.doi.org/10.7554/eLife.18790
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