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4wn5

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Revision as of 07:16, 7 April 2023

Crystal 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.
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.

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4wn5"

@@ Line 3: / Line 3: @@
 <StructureSection load='4wn5' size='340' side='right'caption='[[4wn5]], [[Resolution|resolution]] 1.15&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4wn5]] 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=4WN5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/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"><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='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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HIF3A, BHLHE17, MOP7, PASD7 ([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=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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4wn5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wn5 OCA], [http://pdbe.org/4wn5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4wn5 RCSB], [http://www.ebi.ac.uk/pdbsum/4wn5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4wn5 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/HIF3A_HUMAN 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]<ref>PMID:11573933</ref> <ref>PMID:16126907</ref> <ref>PMID:19694616</ref> <ref>PMID:20416395</ref> <ref>PMID:21069422</ref>   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.<ref>PMID:11573933</ref>   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.<ref>PMID:19694616</ref> <ref>PMID:20416395</ref> <ref>PMID:21069422</ref>   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).<ref>PMID:16126907</ref> <ref>PMID:17998805</ref> <ref>PMID:19694616</ref> <ref>PMID:20416395</ref>   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.<ref>PMID:21069422</ref>
+[https://www.uniprot.org/uniprot/HIF3A_HUMAN 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]<ref>PMID:11573933</ref> <ref>PMID:16126907</ref> <ref>PMID:19694616</ref> <ref>PMID:20416395</ref> <ref>PMID:21069422</ref>   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.<ref>PMID:11573933</ref>   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.<ref>PMID:19694616</ref> <ref>PMID:20416395</ref> <ref>PMID:21069422</ref>   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).<ref>PMID:16126907</ref> <ref>PMID:17998805</ref> <ref>PMID:19694616</ref> <ref>PMID:20416395</ref>   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.<ref>PMID:21069422</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 22: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Ambrosio, A L]]
+[[Category: Ambrosio AL]]
-[[Category: Dias, S M]]
+[[Category: Dias SM]]
-[[Category: Fala, A M]]
+[[Category: Fala AM]]
-[[Category: Oliveira, J F]]
+[[Category: Oliveira JF]]
-[[Category: Fatty acid]]
-[[Category: Hif-3alpha]]
-[[Category: Lipid]]
-[[Category: Monoacylglycerol]]
-[[Category: Pas domain]]
-[[Category: Transcription]]

4wn5

From Proteopedia

Revision as of 07:16, 7 April 2023

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

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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