OCA at 19:40, 29 May 2024

2024-05-29T19:40:17Z

← Older revision		Revision as of 19:40, 29 May 2024
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	====		==Cryo-EM structure of human HUWE1 in complex with DDIT4==
	<StructureSection load='7mop' size='340' side='right'caption='[[7mop]]' scene=''>		<StructureSection load='7mop' size='340' side='right'caption='[[7mop]], [[Resolution\|resolution]] 3.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>		<table><tr><td colspan='2'>[[7mop]] 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=7MOP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MOP FirstGlance]. <br>
	</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=7mop FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mop OCA], [https://pdbe.org/7mop PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mop RCSB], [https://www.ebi.ac.uk/pdbsum/7mop PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mop ProSAT]</span></td></tr>		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 3.3Å</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=7mop FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mop OCA], [https://pdbe.org/7mop PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mop RCSB], [https://www.ebi.ac.uk/pdbsum/7mop PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mop ProSAT]</span></td></tr>
	</table>		</table>
			== Disease ==
			[https://www.uniprot.org/uniprot/HUWE1_HUMAN HUWE1_HUMAN] Defects in HUWE1 are the cause of mental retardation syndromic X-linked Turner type (MRXST) [MIM:[https://omim.org/entry/300706 300706]; also known as mental retardation and macrocephaly syndrome. MRXST shows clinical variability. Associated phenotypes include macrocephaly and variable contractures. A chromosomal microduplication involving HUWE1 and HSD17B10 is the cause of mental retardation X-linked type 17 (MRX17) [MIM:[https://omim.org/entry/300705 300705]; also known as mental retardation X-linked type 31 (MRX31). Mental retardation is characterized by significantly sub-average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. In contrast to syndromic or specific X-linked mental retardation which also present with associated physical, neurological and/or psychiatric manifestations, intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation.<ref>PMID:18252223</ref>
			== Function ==
			[https://www.uniprot.org/uniprot/HUWE1_HUMAN HUWE1_HUMAN] E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins. Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1. Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair. Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4. Binds to an upstream initiator-like sequence in the preprodynorphin gene. Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN. May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation.<ref>PMID:15989956</ref> <ref>PMID:15989957</ref> <ref>PMID:15767685</ref> <ref>PMID:15567145</ref> <ref>PMID:17567951</ref> <ref>PMID:18488021</ref> <ref>PMID:19713937</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			HECT ubiquitin ligases play essential roles in metazoan development and physiology. The HECT ligase HUWE1 is central to the cellular stress response by mediating degradation of key death or survival factors, including Mcl1, p53, DDIT4, and Myc. Although mutations in HUWE1 and related HECT ligases are widely implicated in human disease, our molecular understanding remains limited. Here we present a comprehensive investigation of full-length HUWE1, deepening our understanding of this class of enzymes. The N-terminal approximately 3,900 amino acids of HUWE1 are indispensable for proper ligase function, and our cryo-EM structures of HUWE1 offer a complete molecular picture of this large HECT ubiquitin ligase. HUWE1 forms an alpha solenoid-shaped assembly with a central pore decorated with protein interaction modules. Structures of HUWE1 variants linked to neurodevelopmental disorders as well as of HUWE1 bound to a model substrate link the functions of this essential enzyme to its three-dimensional organization.

			Solenoid architecture of HUWE1 contributes to ligase activity and substrate recognition.,Hunkeler M, Jin CY, Ma MW, Monda JK, Overwijn D, Bennett EJ, Fischer ES Mol Cell. 2021 Jul 16. pii: S1097-2765(21)00543-8. doi:, 10.1016/j.molcel.2021.06.032. PMID:34314700<ref>PMID:34314700</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 7mop" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Ubiquitin protein ligase 3D structures\|Ubiquitin protein ligase 3D structures]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: ~~Z-disk~~]]		[[Category: Fischer ES]]
			[[Category: Hunkeler M]]

OCA at 10:35, 28 July 2021

2021-07-28T10:35:02Z

← Older revision		Revision as of 10:35, 28 July 2021
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	~~'''Unreleased structure'''~~

	~~The entry~~ 7mop is ~~ON HOLD until Paper Publication~~		====
			<StructureSection load='7mop' size='340' side='right'caption='[[7mop]]' scene=''>
	~~Authors:~~		== Structural highlights ==
			<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
	~~Description~~:		</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=7mop FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mop OCA], [https://pdbe.org/7mop PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mop RCSB], [https://www.ebi.ac.uk/pdbsum/7mop PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mop ProSAT]</span></td></tr>
	[[Category: ~~Unreleased Structures~~]]		</table>
			__TOC__
			</StructureSection>
			[[Category: Large Structures]]
			[[Category: Z-disk]]

OCA at 11:04, 9 June 2021

2021-06-09T11:04:39Z

← Older revision		Revision as of 11:04, 9 June 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 7mop is ON HOLD		The entry 7mop is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7mop" [edit=sysop:move=sysop]

2021-05-12T08:13:45Z

Protected "7mop" [edit=sysop:move=sysop]

← Older revision	Revision as of 08:13, 12 May 2021
(No difference)

OCA: New page: '''Unreleased structure''' The entry 7mop is ON HOLD Authors: Description: Category: Unreleased Structures

2021-05-12T08:13:44Z

New page: '''Unreleased structure''' The entry 7mop is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7mop is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

7mop - Revision history

OCA at 19:40, 29 May 2024

OCA at 10:35, 28 July 2021

OCA at 11:04, 9 June 2021

OCA: Protected "7mop" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7mop is ON HOLD Authors: Description: Category: Unreleased Structures