5eoa - Revision history

OCA at 09:11, 20 March 2024

OCA — Wed, 20 Mar 2024 09:11:16 GMT

←Older revision		Revision as of 09:11, 20 March 2024
Line 11:		Line 11:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/OPTN_HUMAN OPTN_HUMAN] Plays an important role in the maintenance of the Golgi complex, in membrane trafficking, in exocytosis, through its interaction with myosin VI and Rab8. Links myosin VI to the Golgi complex and plays an important role in Golgi ribbon formation. Negatively regulates the induction of IFNB in response to RNA virus infection. Plays a neuroprotective role in the eye and optic nerve. Probably part of the TNF-alpha signaling pathway that can shift the equilibrium toward induction of cell death. May act by regulating membrane trafficking and cellular morphogenesis via a complex that contains Rab8 and hungtingtin (HD). May constitute a cellular target for adenovirus E3 14.7, an inhibitor of TNF-alpha functions, thereby affecting cell death.<ref>PMID:11834836</ref> <ref>PMID:15837803</ref> <ref>PMID:20174559</ref>		[https://www.uniprot.org/uniprot/OPTN_HUMAN OPTN_HUMAN] Plays an important role in the maintenance of the Golgi complex, in membrane trafficking, in exocytosis, through its interaction with myosin VI and Rab8. Links myosin VI to the Golgi complex and plays an important role in Golgi ribbon formation. Negatively regulates the induction of IFNB in response to RNA virus infection. Plays a neuroprotective role in the eye and optic nerve. Probably part of the TNF-alpha signaling pathway that can shift the equilibrium toward induction of cell death. May act by regulating membrane trafficking and cellular morphogenesis via a complex that contains Rab8 and hungtingtin (HD). May constitute a cellular target for adenovirus E3 14.7, an inhibitor of TNF-alpha functions, thereby affecting cell death.<ref>PMID:11834836</ref> <ref>PMID:15837803</ref> <ref>PMID:20174559</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Optineurin is an important autophagy receptor involved in several selective autophagy processes, during which its function is regulated by TBK1. Mutations of optineurin and TBK1 are both associated with neurodegenerative diseases. However, the mechanistic basis underlying the specific interaction between optineurin and TBK1 is still elusive. Here we determine the crystal structures of optineurin/TBK1 complex and the related NAP1/TBK1 complex, uncovering the detailed molecular mechanism governing the optineurin and TBK1 interaction, and revealing a general binding mode between TBK1 and its associated adaptor proteins. In addition, we demonstrate that the glaucoma-associated optineurin E50K mutation not only enhances the interaction between optineurin and TBK1 but also alters the oligomeric state of optineurin, and the ALS-related TBK1 E696K mutation specifically disrupts the optineurin/TBK1 complex formation but has little effect on the NAP1/TBK1 complex. Thus, our study provides mechanistic insights into those currently known disease-causing optineurin and TBK1 mutations found in patients.
-
-	Structural insights into the interaction and disease mechanism of neurodegenerative disease-associated optineurin and TBK1 proteins.,Li F, Xie X, Wang Y, Liu J, Cheng X, Guo Y, Gong Y, Hu S, Pan L Nat Commun. 2016 Sep 13;7:12708. doi: 10.1038/ncomms12708. PMID:27620379<ref>PMID:27620379</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 5eoa" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 08:10, 12 July 2023

OCA — Wed, 12 Jul 2023 08:10:56 GMT

←Older revision		Revision as of 08:10, 12 July 2023
Line 3:		Line 3:
	<StructureSection load='5eoa' size='340' side='right'caption='[[5eoa]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='5eoa' size='340' side='right'caption='[[5eoa]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5eoa]] 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=5EOA OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5EOA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5eoa]] is a 4 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=5EOA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EOA FirstGlance]. <br>
-	</td></tr><tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~>[[5eof\|5eof]]</td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.503Å</td></tr>
-	~~<tr~~ id~~='gene'><td class~~="~~sblockLbl~~">~~<b>~~[[~~Gene~~\|~~Gene:~~]]~~</b></td><td class="sblockDat">OPTN, FIP2, GLC1E, HIP7, HYPL, NRP ([http://www~~.~~ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info~~&~~srchmode=5&id=9606 HUMAN]), TBK1, NAK ([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'>[https://proteopedia.org/fgij/fg.htm?mol=5eoa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eoa OCA], [https://pdbe.org/5eoa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5eoa RCSB], [https://www.ebi.ac.uk/pdbsum/5eoa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5eoa ProSAT]</span></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>	+
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5eoa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eoa OCA], [~~http~~://pdbe.org/5eoa PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5eoa RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5eoa PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5eoa ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/OPTN_HUMAN OPTN_HUMAN]] Amyotrophic lateral sclerosis;Congenital glaucoma. Primary open angle glaucoma 1E (GLC1E) [MIM:[~~http~~://omim.org/entry/137760 137760]]: A form of primary open angle glaucoma (POAG). POAG is characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. The disease is asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:11834836</ref> <ref>PMID:12939304</ref> <ref>PMID:14597044</ref> <ref>PMID:15326130</ref> <ref>PMID:15557444</ref> <ref>PMID:15226658</ref> Normal pressure glaucoma (NPG) [MIM:[~~http~~://omim.org/entry/606657 606657]]: A primary glaucoma characterized by intraocular pression consistently within the statistically normal population range. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.<ref>PMID:15370540</ref> Amyotrophic lateral sclerosis 12 (ALS12) [MIM:[~~http~~://omim.org/entry/613435 613435]]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:20428114</ref>	+	[https://www.uniprot.org/uniprot/OPTN_HUMAN OPTN_HUMAN] Amyotrophic lateral sclerosis;Congenital glaucoma. Primary open angle glaucoma 1E (GLC1E) [MIM:[https://omim.org/entry/137760 137760]: A form of primary open angle glaucoma (POAG). POAG is characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. The disease is asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:11834836</ref> <ref>PMID:12939304</ref> <ref>PMID:14597044</ref> <ref>PMID:15326130</ref> <ref>PMID:15557444</ref> <ref>PMID:15226658</ref> Normal pressure glaucoma (NPG) [MIM:[https://omim.org/entry/606657 606657]: A primary glaucoma characterized by intraocular pression consistently within the statistically normal population range. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.<ref>PMID:15370540</ref> Amyotrophic lateral sclerosis 12 (ALS12) [MIM:[https://omim.org/entry/613435 613435]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:20428114</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/OPTN_HUMAN OPTN_HUMAN]] Plays an important role in the maintenance of the Golgi complex, in membrane trafficking, in exocytosis, through its interaction with myosin VI and Rab8. Links myosin VI to the Golgi complex and plays an important role in Golgi ribbon formation. Negatively regulates the induction of IFNB in response to RNA virus infection. Plays a neuroprotective role in the eye and optic nerve. Probably part of the TNF-alpha signaling pathway that can shift the equilibrium toward induction of cell death. May act by regulating membrane trafficking and cellular morphogenesis via a complex that contains Rab8 and hungtingtin (HD). May constitute a cellular target for adenovirus E3 14.7, an inhibitor of TNF-alpha functions, thereby affecting cell death.<ref>PMID:11834836</ref> <ref>PMID:15837803</ref> <ref>PMID:20174559</ref> [[http://www.uniprot.org/uniprot/TBK1_HUMAN TBK1_HUMAN]] Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents. Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRFs leading to transcriptional activation of pro-inflammatory and antiviral genes including IFN-alpha and IFN-beta. In order to establish such an antiviral state, TBK1 form several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including FADD, TRADD, MAVS or SINTBAD can be recruited to the TBK1-containing-complexes. Under particular conditions, functions as a NF-kappa-B effector by phosphorylating NF-kappa-B inhibitor alpha/NFKBIA, IKBKB or RELA to translocate NF-Kappa-B to the nucleus. Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser-177', thus enhancing LC3 binding affinity and antibacterial autophagy. Attenuates retroviral budding by phosphorylating the endosomal sorting complex required for transport-I (ESCRT-I) subunit VPS37C. Phosphorylates and activates AKT1. Phosphorylates Borna disease virus (BDV) P protein.<ref>PMID:10581243</ref> <ref>PMID:10783893</ref> <ref>PMID:11839743</ref> <ref>PMID:12692549</ref> <ref>PMID:12702806</ref> <ref>PMID:14703513</ref> <ref>PMID:15485837</ref> <ref>PMID:15489227</ref> <ref>PMID:15367631</ref> <ref>PMID:18583960</ref> <ref>PMID:21270402</ref> <ref>PMID:21464307</ref> <ref>PMID:21617041</ref> <ref>PMID:21138416</ref>	+	[https://www.uniprot.org/uniprot/OPTN_HUMAN OPTN_HUMAN] Plays an important role in the maintenance of the Golgi complex, in membrane trafficking, in exocytosis, through its interaction with myosin VI and Rab8. Links myosin VI to the Golgi complex and plays an important role in Golgi ribbon formation. Negatively regulates the induction of IFNB in response to RNA virus infection. Plays a neuroprotective role in the eye and optic nerve. Probably part of the TNF-alpha signaling pathway that can shift the equilibrium toward induction of cell death. May act by regulating membrane trafficking and cellular morphogenesis via a complex that contains Rab8 and hungtingtin (HD). May constitute a cellular target for adenovirus E3 14.7, an inhibitor of TNF-alpha functions, thereby affecting cell death.<ref>PMID:11834836</ref> <ref>PMID:15837803</ref> <ref>PMID:20174559</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 29:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Li F]]
-	[[Category: Li, F]]	+	[[Category: Liu J]]
-	[[Category: Liu, J]]	+	[[Category: Pan L]]
-	[[Category: Pan, L]]	+	[[Category: Xie X]]
-	[[Category: Xie, X]]	+
-	~~[[Category: Al]]~~	+
-	~~[[Category: Optineurin]]~~	+
-	~~[[Category: Poag]]~~	+
-	~~[[Category: Protein binding-transferase complex]]~~	+
-	~~[[Category: Tbk1~~]]	+

OCA at 07:07, 22 April 2020

OCA — Wed, 22 Apr 2020 07:07:19 GMT

←Older revision		Revision as of 07:07, 22 April 2020
Line 1:		Line 1:

	==Crystal structure of OPTN E50K mutant and TBK1 complex==		==Crystal structure of OPTN E50K mutant and TBK1 complex==
-	<StructureSection load='5eoa' size='340' side='right' caption='[[5eoa]], [[Resolution\|resolution]] 2.50Å' scene=''>	+	<StructureSection load='5eoa' size='340' side='right'caption='[[5eoa]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5eoa]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EOA OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5EOA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5eoa]] 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=5EOA OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5EOA FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5eof\|5eof]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5eof\|5eof]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">OPTN, FIP2, GLC1E, HIP7, HYPL, NRP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TBK1, NAK ([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/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=5eoa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eoa OCA], [http://pdbe.org/5eoa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5eoa RCSB], [http://www.ebi.ac.uk/pdbsum/5eoa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5eoa ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5eoa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eoa OCA], [http://pdbe.org/5eoa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5eoa RCSB], [http://www.ebi.ac.uk/pdbsum/5eoa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5eoa ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 5eoa" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5eoa" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Li, F]]		[[Category: Li, F]]

OCA at 16:41, 3 October 2016

OCA — Mon, 03 Oct 2016 16:41:22 GMT

←Older revision		Revision as of 16:41, 3 October 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	The entry ~~5eoa~~ is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of OPTN E50K mutant and TBK1 complex==
		+	<StructureSection load='5eoa' size='340' side='right' caption='[[5eoa]], [[Resolution\|resolution]] 2.50Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5eoa]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EOA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EOA FirstGlance]. <br>
		+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5eof\|5eof]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=5eoa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eoa OCA], [http://pdbe.org/5eoa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5eoa RCSB], [http://www.ebi.ac.uk/pdbsum/5eoa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5eoa ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/OPTN_HUMAN OPTN_HUMAN]] Amyotrophic lateral sclerosis;Congenital glaucoma. Primary open angle glaucoma 1E (GLC1E) [MIM:[http://omim.org/entry/137760 137760]]: A form of primary open angle glaucoma (POAG). POAG is characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. The disease is asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:11834836</ref> <ref>PMID:12939304</ref> <ref>PMID:14597044</ref> <ref>PMID:15326130</ref> <ref>PMID:15557444</ref> <ref>PMID:15226658</ref> Normal pressure glaucoma (NPG) [MIM:[http://omim.org/entry/606657 606657]]: A primary glaucoma characterized by intraocular pression consistently within the statistically normal population range. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.<ref>PMID:15370540</ref> Amyotrophic lateral sclerosis 12 (ALS12) [MIM:[http://omim.org/entry/613435 613435]]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:20428114</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/OPTN_HUMAN OPTN_HUMAN]] Plays an important role in the maintenance of the Golgi complex, in membrane trafficking, in exocytosis, through its interaction with myosin VI and Rab8. Links myosin VI to the Golgi complex and plays an important role in Golgi ribbon formation. Negatively regulates the induction of IFNB in response to RNA virus infection. Plays a neuroprotective role in the eye and optic nerve. Probably part of the TNF-alpha signaling pathway that can shift the equilibrium toward induction of cell death. May act by regulating membrane trafficking and cellular morphogenesis via a complex that contains Rab8 and hungtingtin (HD). May constitute a cellular target for adenovirus E3 14.7, an inhibitor of TNF-alpha functions, thereby affecting cell death.<ref>PMID:11834836</ref> <ref>PMID:15837803</ref> <ref>PMID:20174559</ref> [[http://www.uniprot.org/uniprot/TBK1_HUMAN TBK1_HUMAN]] Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents. Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRFs leading to transcriptional activation of pro-inflammatory and antiviral genes including IFN-alpha and IFN-beta. In order to establish such an antiviral state, TBK1 form several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including FADD, TRADD, MAVS or SINTBAD can be recruited to the TBK1-containing-complexes. Under particular conditions, functions as a NF-kappa-B effector by phosphorylating NF-kappa-B inhibitor alpha/NFKBIA, IKBKB or RELA to translocate NF-Kappa-B to the nucleus. Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser-177', thus enhancing LC3 binding affinity and antibacterial autophagy. Attenuates retroviral budding by phosphorylating the endosomal sorting complex required for transport-I (ESCRT-I) subunit VPS37C. Phosphorylates and activates AKT1. Phosphorylates Borna disease virus (BDV) P protein.<ref>PMID:10581243</ref> <ref>PMID:10783893</ref> <ref>PMID:11839743</ref> <ref>PMID:12692549</ref> <ref>PMID:12702806</ref> <ref>PMID:14703513</ref> <ref>PMID:15485837</ref> <ref>PMID:15489227</ref> <ref>PMID:15367631</ref> <ref>PMID:18583960</ref> <ref>PMID:21270402</ref> <ref>PMID:21464307</ref> <ref>PMID:21617041</ref> <ref>PMID:21138416</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Optineurin is an important autophagy receptor involved in several selective autophagy processes, during which its function is regulated by TBK1. Mutations of optineurin and TBK1 are both associated with neurodegenerative diseases. However, the mechanistic basis underlying the specific interaction between optineurin and TBK1 is still elusive. Here we determine the crystal structures of optineurin/TBK1 complex and the related NAP1/TBK1 complex, uncovering the detailed molecular mechanism governing the optineurin and TBK1 interaction, and revealing a general binding mode between TBK1 and its associated adaptor proteins. In addition, we demonstrate that the glaucoma-associated optineurin E50K mutation not only enhances the interaction between optineurin and TBK1 but also alters the oligomeric state of optineurin, and the ALS-related TBK1 E696K mutation specifically disrupts the optineurin/TBK1 complex formation but has little effect on the NAP1/TBK1 complex. Thus, our study provides mechanistic insights into those currently known disease-causing optineurin and TBK1 mutations found in patients.

-	~~Authors~~:	+	Structural insights into the interaction and disease mechanism of neurodegenerative disease-associated optineurin and TBK1 proteins.,Li F, Xie X, Wang Y, Liu J, Cheng X, Guo Y, Gong Y, Hu S, Pan L Nat Commun. 2016 Sep 13;7:12708. doi: 10.1038/ncomms12708. PMID:27620379<ref>PMID:27620379</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5eoa" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific serine/threonine protein kinase]]
		+	[[Category: Li, F]]
		+	[[Category: Liu, J]]
		+	[[Category: Pan, L]]
		+	[[Category: Xie, X]]
		+	[[Category: Al]]
		+	[[Category: Optineurin]]
		+	[[Category: Poag]]
		+	[[Category: Protein binding-transferase complex]]
		+	[[Category: Tbk1]]

OCA at 12:30, 15 May 2016

OCA — Sun, 15 May 2016 12:30:07 GMT

←Older revision		Revision as of 12:30, 15 May 2016
Line 3:		Line 3:
	The entry 5eoa is ON HOLD until Paper Publication		The entry 5eoa is ON HOLD until Paper Publication

-	Authors: ~~Li, F., Xie, X., Liu, J., Pan, L.~~	+	Authors:

	Description:		Description:
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Xie, X]]
-	[[Category: Pan, L]]
-	[[Category: Li, F]]
-	[[Category: Liu, J]]

OCA at 14:51, 2 December 2015

OCA — Wed, 02 Dec 2015 14:51:25 GMT

←Older revision		Revision as of 14:51, 2 December 2015
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5eoa is ON HOLD	+	The entry 5eoa is ON HOLD until Paper Publication

	Authors: Li, F., Xie, X., Liu, J., Pan, L.		Authors: Li, F., Xie, X., Liu, J., Pan, L.

OCA: Protected "5eoa" [edit=sysop:move=sysop]

OCA — Tue, 01 Dec 2015 03:07:27 GMT

Protected "5eoa" [edit=sysop:move=sysop]

←Older revision

Revision as of 03:07, 1 December 2015

OCA: New page: '''Unreleased structure''' The entry 5eoa is ON HOLD Authors: Li, F., Xie, X., Liu, J., Pan, L. Description: Category: Unreleased Structures Category: Xie, X [[Category: Pan, ...

OCA — Tue, 01 Dec 2015 03:07:25 GMT

New page: '''Unreleased structure''' The entry 5eoa is ON HOLD Authors: Li, F., Xie, X., Liu, J., Pan, L. Description: Category: Unreleased Structures Category: Xie, X [[Category: Pan, ...

New page

'''Unreleased structure'''

The entry 5eoa is ON HOLD

Authors: Li, F., Xie, X., Liu, J., Pan, L.

Description:
[[Category: Unreleased Structures]]
[[Category: Xie, X]]
[[Category: Pan, L]]
[[Category: Li, F]]
[[Category: Liu, J]]