1h2k
From Proteopedia
(Difference between revisions)
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<StructureSection load='1h2k' size='340' side='right'caption='[[1h2k]], [[Resolution|resolution]] 2.15Å' scene=''> | <StructureSection load='1h2k' size='340' side='right'caption='[[1h2k]], [[Resolution|resolution]] 2.15Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[1h2k]] is a 2 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[1h2k]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H2K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H2K FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</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=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1d7g|1d7g]], [[1h2l|1h2l]], [[1h2m|1h2m]], [[1h2n|1h2n]], [[1l8c|1l8c]], [[1lm8|1lm8]], [[1lqb|1lqb]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1d7g|1d7g]], [[1h2l|1h2l]], [[1h2m|1h2m]], [[1h2n|1h2n]], [[1l8c|1l8c]], [[1lm8|1lm8]], [[1lqb|1lqb]]</div></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1h2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h2k OCA], [https://pdbe.org/1h2k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h2k RCSB], [https://www.ebi.ac.uk/pdbsum/1h2k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h2k ProSAT]</span></td></tr> |
</table> | </table> | ||
== Function == | == Function == | ||
| - | [[ | + | [[https://www.uniprot.org/uniprot/HIF1N_HUMAN HIF1N_HUMAN]] Hydroxylates HIF-1 alpha at 'Asp-803' in the C-terminal transactivation domain (CAD). Functions as an oxygen sensor and, under normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300-interacting transactivator. Involved in transcriptional repression through interaction with HIF1A, VHL and histone deacetylases. Hydroxylates specific Asn residues within ankyrin repeat domains (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A and several other ARD-containing proteins. Also hydroxylates Asp and His residues within ARDs of ANK1 and TNKS2, respectively. Negatively regulates NOTCH1 activity, accelerating myogenic differentiation. Positively regulates ASB4 activity, promoting vascular differentiation.<ref>PMID:12080085</ref> <ref>PMID:12042299</ref> <ref>PMID:17003112</ref> <ref>PMID:18299578</ref> <ref>PMID:19245366</ref> <ref>PMID:17573339</ref> <ref>PMID:21251231</ref> <ref>PMID:21177872</ref> [[https://www.uniprot.org/uniprot/HIF1A_HUMAN HIF1A_HUMAN]] Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBPB and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia.<ref>PMID:9887100</ref> <ref>PMID:11566883</ref> <ref>PMID:11292861</ref> <ref>PMID:15465032</ref> <ref>PMID:16543236</ref> <ref>PMID:16973622</ref> <ref>PMID:17610843</ref> <ref>PMID:19528298</ref> <ref>PMID:20624928</ref> |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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==See Also== | ==See Also== | ||
*[[Factor inhibiting HIF|Factor inhibiting HIF]] | *[[Factor inhibiting HIF|Factor inhibiting HIF]] | ||
| + | *[[Hypoxia-Inducible factor 1 alpha inhibitor|Hypoxia-Inducible factor 1 alpha inhibitor]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 09:17, 8 September 2021
Factor Inhibiting HIF-1 alpha in complex with HIF-1 alpha fragment peptide
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