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| | ==Solution structure of the CUL7-CPH domain from Homo Sapiens; Northeast Structural Genomics Consortium target HT1.== | | ==Solution structure of the CUL7-CPH domain from Homo Sapiens; Northeast Structural Genomics Consortium target HT1.== |
| - | <StructureSection load='2jng' size='340' side='right' caption='[[2jng]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2jng' size='340' side='right'caption='[[2jng]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2jng]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JNG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2JNG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2jng]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JNG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JNG FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CUL7, KIAA0076 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2jng FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jng OCA], [http://pdbe.org/2jng PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2jng RCSB], [http://www.ebi.ac.uk/pdbsum/2jng PDBsum], [http://www.topsan.org/Proteins/NESGC/2jng TOPSAN]</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=2jng FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jng OCA], [https://pdbe.org/2jng PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jng RCSB], [https://www.ebi.ac.uk/pdbsum/2jng PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jng ProSAT], [https://www.topsan.org/Proteins/NESGC/2jng TOPSAN]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/CUL7_HUMAN CUL7_HUMAN]] Defects in CUL7 are the cause of 3M syndrome type 1 (3M1) [MIM:[http://omim.org/entry/273750 273750]]. An autosomal recessive disorder characterized by severe pre- and postnatal growth retardation, facial dysmorphism, large head circumference, and normal intelligence and endocrine function. Skeletal changes include long slender tubular bones and tall vertebral bodies.<ref>PMID:16142236</ref> | + | [https://www.uniprot.org/uniprot/CUL7_HUMAN CUL7_HUMAN] Defects in CUL7 are the cause of 3M syndrome type 1 (3M1) [MIM:[https://omim.org/entry/273750 273750]. An autosomal recessive disorder characterized by severe pre- and postnatal growth retardation, facial dysmorphism, large head circumference, and normal intelligence and endocrine function. Skeletal changes include long slender tubular bones and tall vertebral bodies.<ref>PMID:16142236</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CUL7_HUMAN CUL7_HUMAN]] Component of a probable SCF-like E3 ubiquitin-protein ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Probably plays a role in the degradation of proteins involved in endothelial proliferation and/or differentiation (By similarity). Seems not to promote polyubiquitination and proteasomal degradation of TP53. In vitro, complexes of CUL7 with either CUL9 or FBXW8 or TP53 contain E3 ubiquitin-protein ligase activity.<ref>PMID:16547496</ref> <ref>PMID:17332328</ref> | + | [https://www.uniprot.org/uniprot/CUL7_HUMAN CUL7_HUMAN] Component of a probable SCF-like E3 ubiquitin-protein ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Probably plays a role in the degradation of proteins involved in endothelial proliferation and/or differentiation (By similarity). Seems not to promote polyubiquitination and proteasomal degradation of TP53. In vitro, complexes of CUL7 with either CUL9 or FBXW8 or TP53 contain E3 ubiquitin-protein ligase activity.<ref>PMID:16547496</ref> <ref>PMID:17332328</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jn/2jng_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jn/2jng_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| - | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2jng ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | ==See Also== | | ==See Also== |
| - | *[[Cullin|Cullin]] | + | *[[Cullin 3D structures|Cullin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Arrowsmith, C H]] | + | [[Category: Large Structures]] |
| - | [[Category: Duan, S]] | + | [[Category: Arrowsmith CH]] |
| - | [[Category: Kaustov, L]] | + | [[Category: Duan S]] |
| - | [[Category: Lemak, A]] | + | [[Category: Kaustov L]] |
| - | [[Category: Lukin, J]] | + | [[Category: Lemak A]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Lukin J]] |
| - | [[Category: Gene regulation]]
| + | |
| - | [[Category: Nesg]]
| + | |
| - | [[Category: P53 binding domain]]
| + | |
| - | [[Category: PSI, Protein structure initiative]]
| + | |
| Structural highlights
Disease
CUL7_HUMAN Defects in CUL7 are the cause of 3M syndrome type 1 (3M1) [MIM:273750. An autosomal recessive disorder characterized by severe pre- and postnatal growth retardation, facial dysmorphism, large head circumference, and normal intelligence and endocrine function. Skeletal changes include long slender tubular bones and tall vertebral bodies.[1]
Function
CUL7_HUMAN Component of a probable SCF-like E3 ubiquitin-protein ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Probably plays a role in the degradation of proteins involved in endothelial proliferation and/or differentiation (By similarity). Seems not to promote polyubiquitination and proteasomal degradation of TP53. In vitro, complexes of CUL7 with either CUL9 or FBXW8 or TP53 contain E3 ubiquitin-protein ligase activity.[2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Cul7 is a member of the Cullin Ring Ligase (CRL) family and is required for normal mouse development and cellular proliferation. Recently, a region of Cul7 that is highly conserved in the p53-associated, Parkin-like cytoplasmic protein PARC, was shown to bind p53 directly. Here we identify the CPH domains (conserved domain within Cul7, PARC, and HERC2 proteins) of both Cul7 and PARC as p53 interaction domains using size exclusion chromatography and NMR spectroscopy. We present the first structure of the evolutionarily conserved CPH domain and provide novel insight into the Cul7-p53 interaction. The NMR structure of the Cul7-CPH domain reveals a fold similar to peptide interaction modules such as the SH3, Tudor, and KOW domains. The p53 interaction surface of both Cul7 and PARC CPH domains was mapped to a conserved surface distinct from the analogous peptide-binding regions of SH3, KOW, and Tudor domains, suggesting a novel mode of interaction. The CPH domain interaction surface of p53 resides in the tetramerization domain and is formed by residues contributed by at least two subunits.
The conserved CPH domains of Cul7 and PARC are protein-protein interaction modules that bind the tetramerization domain of p53.,Kaustov L, Lukin J, Lemak A, Duan S, Ho M, Doherty R, Penn LZ, Arrowsmith CH J Biol Chem. 2007 Apr 13;282(15):11300-7. Epub 2007 Feb 12. PMID:17298945[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Huber C, Dias-Santagata D, Glaser A, O'Sullivan J, Brauner R, Wu K, Xu X, Pearce K, Wang R, Uzielli ML, Dagoneau N, Chemaitilly W, Superti-Furga A, Dos Santos H, Megarbane A, Morin G, Gillessen-Kaesbach G, Hennekam R, Van der Burgt I, Black GC, Clayton PE, Read A, Le Merrer M, Scambler PJ, Munnich A, Pan ZQ, Winter R, Cormier-Daire V. Identification of mutations in CUL7 in 3-M syndrome. Nat Genet. 2005 Oct;37(10):1119-24. Epub 2005 Sep 4. PMID:16142236 doi:ng1628
- ↑ Andrews P, He YJ, Xiong Y. Cytoplasmic localized ubiquitin ligase cullin 7 binds to p53 and promotes cell growth by antagonizing p53 function. Oncogene. 2006 Aug 3;25(33):4534-48. Epub 2006 Mar 20. PMID:16547496 doi:1209490
- ↑ Skaar JR, Florens L, Tsutsumi T, Arai T, Tron A, Swanson SK, Washburn MP, DeCaprio JA. PARC and CUL7 form atypical cullin RING ligase complexes. Cancer Res. 2007 Mar 1;67(5):2006-14. PMID:17332328 doi:67/5/2006
- ↑ Kaustov L, Lukin J, Lemak A, Duan S, Ho M, Doherty R, Penn LZ, Arrowsmith CH. The conserved CPH domains of Cul7 and PARC are protein-protein interaction modules that bind the tetramerization domain of p53. J Biol Chem. 2007 Apr 13;282(15):11300-7. Epub 2007 Feb 12. PMID:17298945 doi:10.1074/jbc.M611297200
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