5wch: Difference between revisions

Revision as of 08:15, 20 March 2019

Crystal structure of the catalytic domain of human USP9X

Structural highlights

5wch is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	UNX, ZN
Gene:	USP9X, DFFRX, FAM, USP9 (HUMAN)
Activity:	Ubiquitinyl hydrolase 1, with EC number 3.4.19.12
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[USP9X_HUMAN] X-linked non-syndromic intellectual disability. The disease is caused by mutations affecting the gene represented in this entry.

Function

[USP9X_HUMAN] Deubiquitinase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins. May therefore play an important regulatory role at the level of protein turnover by preventing degradation of proteins through the removal of conjugated ubiquitin. Specifically hydrolyzes 'Lys-48'-, 'Lys-29'- and 'Lys-33'-linked polyubiquitins chains. Essential component of TGF-beta/BMP signaling cascade. Specifically deubiquitinates monoubiquitinated SMAD4, opposing the activity of E3 ubiquitin-protein ligase TRIM33. Deubiquitinates alkylation repair enzyme ALKBH3. OTUD4 recruits USP7 and USP9X to stabilize ALKBH3, thereby promoting the repair of alkylated DNA lesions (PubMed:25944111). Regulates chromosome alignment and segregation in mitosis by regulating the localization of BIRC5/survivin to mitotic centromeres. Involved in axonal growth and neuronal cell migration (PubMed:16322459, PubMed:18254724, PubMed:19135894, PubMed:24607389).^[1] ^[2] ^[3] ^[4] ^[5]

References

↑ Vong QP, Cao K, Li HY, Iglesias PA, Zheng Y. Chromosome alignment and segregation regulated by ubiquitination of survivin. Science. 2005 Dec 2;310(5753):1499-504. PMID:16322459 doi:10.1126/science.1120160
↑ Al-Hakim AK, Zagorska A, Chapman L, Deak M, Peggie M, Alessi DR. Control of AMPK-related kinases by USP9X and atypical Lys(29)/Lys(33)-linked polyubiquitin chains. Biochem J. 2008 Apr 15;411(2):249-60. doi: 10.1042/BJ20080067. PMID:18254724 doi:https://dx.doi.org/10.1042/BJ20080067
↑ Dupont S, Mamidi A, Cordenonsi M, Montagner M, Zacchigna L, Adorno M, Martello G, Stinchfield MJ, Soligo S, Morsut L, Inui M, Moro S, Modena N, Argenton F, Newfeld SJ, Piccolo S. FAM/USP9x, a deubiquitinating enzyme essential for TGFbeta signaling, controls Smad4 monoubiquitination. Cell. 2009 Jan 9;136(1):123-35. doi: 10.1016/j.cell.2008.10.051. PMID:19135894 doi:https://dx.doi.org/10.1016/j.cell.2008.10.051
↑ Homan CC, Kumar R, Nguyen LS, Haan E, Raymond FL, Abidi F, Raynaud M, Schwartz CE, Wood SA, Gecz J, Jolly LA. Mutations in USP9X are associated with X-linked intellectual disability and disrupt neuronal cell migration and growth. Am J Hum Genet. 2014 Mar 6;94(3):470-8. doi: 10.1016/j.ajhg.2014.02.004. PMID:24607389 doi:https://dx.doi.org/10.1016/j.ajhg.2014.02.004
↑ Zhao Y, Majid MC, Soll JM, Brickner JR, Dango S, Mosammaparast N. Noncanonical regulation of alkylation damage resistance by the OTUD4 deubiquitinase. EMBO J. 2015 Jun 12;34(12):1687-703. doi: 10.15252/embj.201490497. Epub 2015 May , 5. PMID:25944111 doi:https://dx.doi.org/10.15252/embj.201490497

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OCA

[1] Vong QP, Cao K, Li HY, Iglesias PA, Zheng Y. Chromosome alignment and segregation regulated by ubiquitination of survivin. Science. 2005 Dec 2;310(5753):1499-504. PMID:16322459 doi:10.1126/science.1120160

[2] Al-Hakim AK, Zagorska A, Chapman L, Deak M, Peggie M, Alessi DR. Control of AMPK-related kinases by USP9X and atypical Lys(29)/Lys(33)-linked polyubiquitin chains. Biochem J. 2008 Apr 15;411(2):249-60. doi: 10.1042/BJ20080067. PMID:18254724 doi:https://dx.doi.org/10.1042/BJ20080067

[3] Dupont S, Mamidi A, Cordenonsi M, Montagner M, Zacchigna L, Adorno M, Martello G, Stinchfield MJ, Soligo S, Morsut L, Inui M, Moro S, Modena N, Argenton F, Newfeld SJ, Piccolo S. FAM/USP9x, a deubiquitinating enzyme essential for TGFbeta signaling, controls Smad4 monoubiquitination. Cell. 2009 Jan 9;136(1):123-35. doi: 10.1016/j.cell.2008.10.051. PMID:19135894 doi:https://dx.doi.org/10.1016/j.cell.2008.10.051

[4] Homan CC, Kumar R, Nguyen LS, Haan E, Raymond FL, Abidi F, Raynaud M, Schwartz CE, Wood SA, Gecz J, Jolly LA. Mutations in USP9X are associated with X-linked intellectual disability and disrupt neuronal cell migration and growth. Am J Hum Genet. 2014 Mar 6;94(3):470-8. doi: 10.1016/j.ajhg.2014.02.004. PMID:24607389 doi:https://dx.doi.org/10.1016/j.ajhg.2014.02.004

[5] Zhao Y, Majid MC, Soll JM, Brickner JR, Dango S, Mosammaparast N. Noncanonical regulation of alkylation damage resistance by the OTUD4 deubiquitinase. EMBO J. 2015 Jun 12;34(12):1687-703. doi: 10.15252/embj.201490497. Epub 2015 May , 5. PMID:25944111 doi:https://dx.doi.org/10.15252/embj.201490497

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@@ Line 1: / Line 1: @@
-==Crystal structure of a peptidase==
+==Crystal structure of the catalytic domain of human USP9X==
-<StructureSection load='5wch' size='340' side='right' caption='[[5wch]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+<StructureSection load='5wch' size='340' side='right'caption='[[5wch]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5wch]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WCH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WCH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5wch]] is a 4 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=5WCH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WCH FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">USP9X, DFFRX, FAM, USP9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.19.12 3.4.19.12] </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=5wch FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wch OCA], [http://pdbe.org/5wch PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wch RCSB], [http://www.ebi.ac.uk/pdbsum/5wch PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wch ProSAT]</span></td></tr>
@@ Line 16: / Line 17: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Ubiquitinyl hydrolase 1]]
 [[Category: Arrowsmith, C H]]

5wch: Difference between revisions

Revision as of 08:15, 20 March 2019

Crystal structure of the catalytic domain of human USP9X

Structural highlights

Disease

Function

References

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