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| | <StructureSection load='4oo7' size='340' side='right'caption='[[4oo7]], [[Resolution|resolution]] 1.65Å' scene=''> | | <StructureSection load='4oo7' size='340' side='right'caption='[[4oo7]], [[Resolution|resolution]] 1.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4oo7]] 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=4OO7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OO7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4oo7]] 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=4OO7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OO7 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3fnv|3fnv]], [[4ooa|4ooa]]</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=4oo7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oo7 OCA], [https://pdbe.org/4oo7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4oo7 RCSB], [https://www.ebi.ac.uk/pdbsum/4oo7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4oo7 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CISD2, CDGSH2, ERIS, ZCD2 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4oo7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oo7 OCA], [http://pdbe.org/4oo7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4oo7 RCSB], [http://www.ebi.ac.uk/pdbsum/4oo7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4oo7 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/CISD2_HUMAN CISD2_HUMAN]] Defects in CISD2 are the cause of Wolfram syndrome type 2 (WFS2) [MIM:[http://omim.org/entry/604928 604928]]. A rare disorder characterized by juvenile-onset insulin-dependent diabetes mellitus with optic atrophy. Other manifestations include diabetes insipidus, sensorineural deafness, dementia, psychiatric illnesses. WFS2 patients additionally show a strong bleeding tendency and gastrointestinal ulceration. Diabetes insipidus may be absent.<ref>PMID:17846994</ref> | + | [https://www.uniprot.org/uniprot/CISD2_HUMAN CISD2_HUMAN] Defects in CISD2 are the cause of Wolfram syndrome type 2 (WFS2) [MIM:[https://omim.org/entry/604928 604928]. A rare disorder characterized by juvenile-onset insulin-dependent diabetes mellitus with optic atrophy. Other manifestations include diabetes insipidus, sensorineural deafness, dementia, psychiatric illnesses. WFS2 patients additionally show a strong bleeding tendency and gastrointestinal ulceration. Diabetes insipidus may be absent.<ref>PMID:17846994</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CISD2_HUMAN CISD2_HUMAN]] Regulator of autophagy that contributes to antagonize BECN1-mediated cellular autophagy at the endoplasmic reticulum. Participates in the interaction of BCL2 with BECN1 and is required for BCL2-mediated depression of endoplasmic reticulum Ca(2+) stores during autophagy. Contributes to BIK-initiated autophagy, while it is not involved in BIK-dependent activation of caspases. Involved in life span control, probably via its function as regulator of autophagy.<ref>PMID:17846994</ref> <ref>PMID:20010695</ref> | + | [https://www.uniprot.org/uniprot/CISD2_HUMAN CISD2_HUMAN] Regulator of autophagy that contributes to antagonize BECN1-mediated cellular autophagy at the endoplasmic reticulum. Participates in the interaction of BCL2 with BECN1 and is required for BCL2-mediated depression of endoplasmic reticulum Ca(2+) stores during autophagy. Contributes to BIK-initiated autophagy, while it is not involved in BIK-dependent activation of caspases. Involved in life span control, probably via its function as regulator of autophagy.<ref>PMID:17846994</ref> <ref>PMID:20010695</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Colman, A R]] | + | [[Category: Colman AR]] |
| - | [[Category: Eisenberg-Domovich, Y]] | + | [[Category: Eisenberg-Domovich Y]] |
| - | [[Category: Jenning, P A]] | + | [[Category: Jenning PA]] |
| - | [[Category: Lipper, C H]] | + | [[Category: Lipper CH]] |
| - | [[Category: Livnah, O]] | + | [[Category: Livnah O]] |
| - | [[Category: Nechushtai, R]] | + | [[Category: Nechushtai R]] |
| - | [[Category: Paddock, M L]] | + | [[Category: Paddock ML]] |
| - | [[Category: Stofleth, J T]] | + | [[Category: Stofleth JT]] |
| - | [[Category: Tamir, S]] | + | [[Category: Tamir S]] |
| - | [[Category: Membrane bound]]
| + | |
| - | [[Category: Metal binding protein]]
| + | |
| - | [[Category: Oxidative stress]]
| + | |
| - | [[Category: Thiazolidinedione]]
| + | |
| Structural highlights
Disease
CISD2_HUMAN Defects in CISD2 are the cause of Wolfram syndrome type 2 (WFS2) [MIM:604928. A rare disorder characterized by juvenile-onset insulin-dependent diabetes mellitus with optic atrophy. Other manifestations include diabetes insipidus, sensorineural deafness, dementia, psychiatric illnesses. WFS2 patients additionally show a strong bleeding tendency and gastrointestinal ulceration. Diabetes insipidus may be absent.[1]
Function
CISD2_HUMAN Regulator of autophagy that contributes to antagonize BECN1-mediated cellular autophagy at the endoplasmic reticulum. Participates in the interaction of BCL2 with BECN1 and is required for BCL2-mediated depression of endoplasmic reticulum Ca(2+) stores during autophagy. Contributes to BIK-initiated autophagy, while it is not involved in BIK-dependent activation of caspases. Involved in life span control, probably via its function as regulator of autophagy.[2] [3]
Publication Abstract from PubMed
NAF-1 is an important [2Fe-2S] NEET protein associated with human health and disease. A mis-splicing mutation in NAF-1 results in Wolfram Syndrome type 2, a lethal childhood disease. Upregulation of NAF-1 is found in epithelial breast cancer cells, and suppression of NAF-1 expression by knockdown significantly suppresses tumor growth. Key to NAF-1 function is the NEET fold with its [2Fe-2S] cluster. In this work, the high-resolution structure of native NAF-1 was determined to 1.65 A resolution (R factor = 13.5%) together with that of a mutant in which the single His ligand of its [2Fe-2S] cluster, His114, was replaced by Cys. The NAF-1 H114C mutant structure was determined to 1.58 A resolution (R factor = 16.0%). All structural differences were localized to the cluster binding site. Compared with native NAF-1, the [2Fe-2S] clusters of the H114C mutant were found to (i) be 25-fold more stable, (ii) have a redox potential that is 300 mV more negative and (iii) have their cluster donation/transfer function abolished. Because no global structural differences were found between the mutant and the native (wild-type) NAF-1 proteins, yet significant functional differences exist between them, the NAF-1 H114C mutant is an excellent tool to decipher the underlying biological importance of the [2Fe-2S] cluster of NAF-1 in vivo.
A point mutation in the [2Fe-2S] cluster binding region of the NAF-1 protein (H114C) dramatically hinders the cluster donor properties.,Tamir S, Eisenberg-Domovich Y, Conlan AR, Stofleth JT, Lipper CH, Paddock ML, Mittler R, Jennings PA, Livnah O, Nechushtai R Acta Crystallogr D Biol Crystallogr. 2014 Jun;70(Pt 6):1572-8. doi:, 10.1107/S1399004714005458. Epub 2014 May 23. PMID:24914968[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Amr S, Heisey C, Zhang M, Xia XJ, Shows KH, Ajlouni K, Pandya A, Satin LS, El-Shanti H, Shiang R. A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. Am J Hum Genet. 2007 Oct;81(4):673-83. Epub 2007 Aug 20. PMID:17846994 doi:10.1086/520961
- ↑ Amr S, Heisey C, Zhang M, Xia XJ, Shows KH, Ajlouni K, Pandya A, Satin LS, El-Shanti H, Shiang R. A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. Am J Hum Genet. 2007 Oct;81(4):673-83. Epub 2007 Aug 20. PMID:17846994 doi:10.1086/520961
- ↑ Chang NC, Nguyen M, Germain M, Shore GC. Antagonism of Beclin 1-dependent autophagy by BCL-2 at the endoplasmic reticulum requires NAF-1. EMBO J. 2010 Feb 3;29(3):606-18. doi: 10.1038/emboj.2009.369. Epub 2009 Dec 10. PMID:20010695 doi:10.1038/emboj.2009.369
- ↑ Tamir S, Eisenberg-Domovich Y, Conlan AR, Stofleth JT, Lipper CH, Paddock ML, Mittler R, Jennings PA, Livnah O, Nechushtai R. A point mutation in the [2Fe-2S] cluster binding region of the NAF-1 protein (H114C) dramatically hinders the cluster donor properties. Acta Crystallogr D Biol Crystallogr. 2014 Jun;70(Pt 6):1572-8. doi:, 10.1107/S1399004714005458. Epub 2014 May 23. PMID:24914968 doi:http://dx.doi.org/10.1107/S1399004714005458
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