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| | <StructureSection load='4zp4' size='340' side='right'caption='[[4zp4]], [[Resolution|resolution]] 2.35Å' scene=''> | | <StructureSection load='4zp4' size='340' side='right'caption='[[4zp4]], [[Resolution|resolution]] 2.35Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4zp4]] is a 4 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=4ZP4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZP4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4zp4]] is a 4 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=4ZP4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZP4 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4zph|4zph]], [[4zpk|4zpk]], [[4zpr|4zpr]]</td></tr> | + | </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=4zp4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zp4 OCA], [https://pdbe.org/4zp4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zp4 RCSB], [https://www.ebi.ac.uk/pdbsum/4zp4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zp4 ProSAT]</span></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]), Epas1, Hif2a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=4zp4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zp4 OCA], [http://pdbe.org/4zp4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zp4 RCSB], [http://www.ebi.ac.uk/pdbsum/4zp4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zp4 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/EPAS1_MOUSE EPAS1_MOUSE]] Transcription factor involved in the induction of oxygen regulated genes. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Regulates the vascular endothelial growth factor (VEGF) expression and seems to be implicated in the development of blood vessels and the tubular system of lung. May also play a role in the formation of the endothelium that gives rise to the blood brain barrier. Potent activator of the Tie-2 tyrosine kinase expression. Activation requires recruitment of transcriptional coactivators such as CREBPB and probably EP300. Interaction with redox regulatory protein APEX seems to activate CTAD (By similarity). | + | [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 4zp4" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4zp4" 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: Lu, J]] | + | [[Category: Lu J]] |
| - | [[Category: Potluri, N]] | + | [[Category: Potluri N]] |
| - | [[Category: Rastinejad, F]] | + | [[Category: Rastinejad F]] |
| - | [[Category: Wu, D]] | + | [[Category: Wu D]] |
| - | [[Category: Arnt]]
| + | |
| - | [[Category: Bhlh-pa]]
| + | |
| - | [[Category: Hif-2a complex]]
| + | |
| - | [[Category: Protein transport-transcription complex]]
| + | |
| 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 hypoxia-inducible factors (HIFs) coordinate cellular adaptations to low oxygen stress by regulating transcriptional programs in erythropoiesis, angiogenesis and metabolism. These programs promote the growth and progression of many tumours, making HIFs attractive anticancer targets. Transcriptionally active HIFs consist of HIF-alpha and ARNT (also called HIF-1beta) subunits. Here we describe crystal structures for each of mouse HIF-2alpha-ARNT and HIF-1alpha-ARNT heterodimers in states that include bound small molecules and their hypoxia response element. A highly integrated quaternary architecture is shared by HIF-2alpha-ARNT and HIF-1alpha-ARNT, wherein ARNT spirals around the outside of each HIF-alpha subunit. Five distinct pockets are observed that permit small-molecule binding, including PAS domain encapsulated sites and an interfacial cavity formed through subunit heterodimerization. The DNA-reading head rotates, extends and cooperates with a distal PAS domain to bind hypoxia response elements. HIF-alpha mutations linked to human cancers map to sensitive sites that establish DNA binding and the stability of PAS domains and pockets.
Structural integration in hypoxia-inducible factors.,Wu D, Potluri N, Lu J, Kim Y, Rastinejad F Nature. 2015 Aug 5. doi: 10.1038/nature14883. PMID:26245371[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wu D, Potluri N, Lu J, Kim Y, Rastinejad F. Structural integration in hypoxia-inducible factors. Nature. 2015 Aug 5. doi: 10.1038/nature14883. PMID:26245371 doi:http://dx.doi.org/10.1038/nature14883
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