4wn5: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
Line 4: Line 4:
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4wn5]] 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=4WN5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WN5 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4wn5]] 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=4WN5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WN5 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MVC:MONOVACCENIN'>MVC</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</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]] 1.15&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MVC:MONOVACCENIN'>MVC</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4wn5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wn5 OCA], [https://pdbe.org/4wn5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wn5 RCSB], [https://www.ebi.ac.uk/pdbsum/4wn5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wn5 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=4wn5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wn5 OCA], [https://pdbe.org/4wn5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wn5 RCSB], [https://www.ebi.ac.uk/pdbsum/4wn5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wn5 ProSAT]</span></td></tr>
</table>
</table>
Line 18: Line 19:
</div>
</div>
<div class="pdbe-citations 4wn5" style="background-color:#fffaf0;"></div>
<div class="pdbe-citations 4wn5" style="background-color:#fffaf0;"></div>
==See Also==
*[[3D structures of hypoxia-inducible factor|3D structures of hypoxia-inducible factor]]
== References ==
== References ==
<references/>
<references/>

Latest revision as of 10:33, 27 September 2023

Crystal structure of the C-terminal Per-Arnt-Sim (PASb) of human HIF-3alpha9 bound to 18:1-1-monoacylglycerolCrystal structure of the C-terminal Per-Arnt-Sim (PASb) of human HIF-3alpha9 bound to 18:1-1-monoacylglycerol

Structural highlights

4wn5 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.15Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HIF3A_HUMAN Acts as a transcriptional regulator in adaptive response to low oxygen tension. Acts as a regulator of hypoxia-inducible gene expression (PubMed:11573933, PubMed:16126907, PubMed:19694616, PubMed:20416395, PubMed:21069422). Functions as an inhibitor of angiogenesis in hypoxic cells of the cornea. Plays a role in the development of the cardiorespiratory system. May also be involved in apoptosis (By similarity).[UniProtKB:Q0VBL6][1] [2] [3] [4] [5] Isoform 2: Attenuates the ability of transcription factor HIF1A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation. Also inhibits hypoxia-inducible ARNT-mediated gene expression.[6] Isoform 3: Attenuates the ability of transcription factor HIF1A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation.[7] [8] [9] isoform 4: Attenuates the ability of transcription factor HIF1A and EPAS1/HIF2A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation (PubMed:16126907, PubMed:17998805, PubMed:19694616, PubMed:20416395). May act as a tumor suppressor and inhibits malignant cell transformation (PubMed:17998805).[10] [11] [12] [13] Isoform 5: Attenuates the ability of transcription factor HIF1A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation.[14]

Publication Abstract from PubMed

Hypoxia-inducible transcription factors (HIF) form heterodimeric complexes that mediate cell responses to hypoxia. The oxygen-dependent stability and activity of the HIF-alpha subunits is traditionally associated to post-translational modifications such as hydroxylation, acetylation, ubiquitination, and phosphorylation. Here we report novel evidence showing that unsaturated fatty acids are naturally occurring, non-covalent structural ligands of HIF-3alpha, thus providing the initial framework for exploring its exceptional role as a lipid sensor under hypoxia.

Unsaturated fatty acids as high-affinity ligands of the C-terminal Per-ARNT-Sim domain from the Hypoxia-inducible factor 3alpha.,Fala AM, Oliveira JF, Adamoski D, Aricetti JA, Dias MM, Dias MVB, Sforca ML, Lopes-de-Oliveira PS, Rocco SA, Caldana C, Dias SMG, Ambrosio ALB Sci Rep. 2015 Aug 3;5:12698. doi: 10.1038/srep12698. PMID:26237540[15]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Hara S, Hamada J, Kobayashi C, Kondo Y, Imura N. Expression and characterization of hypoxia-inducible factor (HIF)-3alpha in human kidney: suppression of HIF-mediated gene expression by HIF-3alpha. Biochem Biophys Res Commun. 2001 Oct 5;287(4):808-13. PMID:11573933 doi:http://dx.doi.org/10.1006/bbrc.2001.5659
  2. ↑ Maynard MA, Evans AJ, Hosomi T, Hara S, Jewett MA, Ohh M. Human HIF-3alpha4 is a dominant-negative regulator of HIF-1 and is down-regulated in renal cell carcinoma. FASEB J. 2005 Sep;19(11):1396-406. PMID:16126907 doi:http://dx.doi.org/10.1096/fj.05-3788com
  3. ↑ Tanaka T, Wiesener M, Bernhardt W, Eckardt KU, Warnecke C. The human HIF (hypoxia-inducible factor)-3alpha gene is a HIF-1 target gene and may modulate hypoxic gene induction. Biochem J. 2009 Oct 23;424(1):143-51. doi: 10.1042/BJ20090120. PMID:19694616 doi:http://dx.doi.org/10.1042/BJ20090120
  4. ↑ Pasanen A, Heikkila M, Rautavuoma K, Hirsila M, Kivirikko KI, Myllyharju J. Hypoxia-inducible factor (HIF)-3alpha is subject to extensive alternative splicing in human tissues and cancer cells and is regulated by HIF-1 but not HIF-2. Int J Biochem Cell Biol. 2010 Jul;42(7):1189-200. doi:, 10.1016/j.biocel.2010.04.008. Epub 2010 Apr 21. PMID:20416395 doi:http://dx.doi.org/10.1016/j.biocel.2010.04.008
  5. ↑ Augstein A, Poitz DM, Braun-Dullaeus RC, Strasser RH, Schmeisser A. Cell-specific and hypoxia-dependent regulation of human HIF-3alpha: inhibition of the expression of HIF target genes in vascular cells. Cell Mol Life Sci. 2011 Aug;68(15):2627-42. doi: 10.1007/s00018-010-0575-4. Epub , 2010 Nov 11. PMID:21069422 doi:http://dx.doi.org/10.1007/s00018-010-0575-4
  6. ↑ Hara S, Hamada J, Kobayashi C, Kondo Y, Imura N. Expression and characterization of hypoxia-inducible factor (HIF)-3alpha in human kidney: suppression of HIF-mediated gene expression by HIF-3alpha. Biochem Biophys Res Commun. 2001 Oct 5;287(4):808-13. PMID:11573933 doi:http://dx.doi.org/10.1006/bbrc.2001.5659
  7. ↑ Tanaka T, Wiesener M, Bernhardt W, Eckardt KU, Warnecke C. The human HIF (hypoxia-inducible factor)-3alpha gene is a HIF-1 target gene and may modulate hypoxic gene induction. Biochem J. 2009 Oct 23;424(1):143-51. doi: 10.1042/BJ20090120. PMID:19694616 doi:http://dx.doi.org/10.1042/BJ20090120
  8. ↑ Pasanen A, Heikkila M, Rautavuoma K, Hirsila M, Kivirikko KI, Myllyharju J. Hypoxia-inducible factor (HIF)-3alpha is subject to extensive alternative splicing in human tissues and cancer cells and is regulated by HIF-1 but not HIF-2. Int J Biochem Cell Biol. 2010 Jul;42(7):1189-200. doi:, 10.1016/j.biocel.2010.04.008. Epub 2010 Apr 21. PMID:20416395 doi:http://dx.doi.org/10.1016/j.biocel.2010.04.008
  9. ↑ Augstein A, Poitz DM, Braun-Dullaeus RC, Strasser RH, Schmeisser A. Cell-specific and hypoxia-dependent regulation of human HIF-3alpha: inhibition of the expression of HIF target genes in vascular cells. Cell Mol Life Sci. 2011 Aug;68(15):2627-42. doi: 10.1007/s00018-010-0575-4. Epub , 2010 Nov 11. PMID:21069422 doi:http://dx.doi.org/10.1007/s00018-010-0575-4
  10. ↑ Maynard MA, Evans AJ, Hosomi T, Hara S, Jewett MA, Ohh M. Human HIF-3alpha4 is a dominant-negative regulator of HIF-1 and is down-regulated in renal cell carcinoma. FASEB J. 2005 Sep;19(11):1396-406. PMID:16126907 doi:http://dx.doi.org/10.1096/fj.05-3788com
  11. ↑ Maynard MA, Evans AJ, Shi W, Kim WY, Liu FF, Ohh M. Dominant-negative HIF-3 alpha 4 suppresses VHL-null renal cell carcinoma progression. Cell Cycle. 2007 Nov 15;6(22):2810-6. Epub 2007 Aug 29. PMID:17998805
  12. ↑ Tanaka T, Wiesener M, Bernhardt W, Eckardt KU, Warnecke C. The human HIF (hypoxia-inducible factor)-3alpha gene is a HIF-1 target gene and may modulate hypoxic gene induction. Biochem J. 2009 Oct 23;424(1):143-51. doi: 10.1042/BJ20090120. PMID:19694616 doi:http://dx.doi.org/10.1042/BJ20090120
  13. ↑ Pasanen A, Heikkila M, Rautavuoma K, Hirsila M, Kivirikko KI, Myllyharju J. Hypoxia-inducible factor (HIF)-3alpha is subject to extensive alternative splicing in human tissues and cancer cells and is regulated by HIF-1 but not HIF-2. Int J Biochem Cell Biol. 2010 Jul;42(7):1189-200. doi:, 10.1016/j.biocel.2010.04.008. Epub 2010 Apr 21. PMID:20416395 doi:http://dx.doi.org/10.1016/j.biocel.2010.04.008
  14. ↑ Augstein A, Poitz DM, Braun-Dullaeus RC, Strasser RH, Schmeisser A. Cell-specific and hypoxia-dependent regulation of human HIF-3alpha: inhibition of the expression of HIF target genes in vascular cells. Cell Mol Life Sci. 2011 Aug;68(15):2627-42. doi: 10.1007/s00018-010-0575-4. Epub , 2010 Nov 11. PMID:21069422 doi:http://dx.doi.org/10.1007/s00018-010-0575-4
  15. ↑ Fala AM, Oliveira JF, Adamoski D, Aricetti JA, Dias MM, Dias MVB, Sforca ML, Lopes-de-Oliveira PS, Rocco SA, Caldana C, Dias SMG, Ambrosio ALB. Unsaturated fatty acids as high-affinity ligands of the C-terminal Per-ARNT-Sim domain from the Hypoxia-inducible factor 3alpha. Sci Rep. 2015 Aug 3;5:12698. doi: 10.1038/srep12698. PMID:26237540 doi:http://dx.doi.org/10.1038/srep12698

4wn5, resolution 1.15Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=4wn5&oldid=3884199"