4bwn - Revision history

OCA at 11:59, 20 December 2023

OCA — Wed, 20 Dec 2023 11:59:29 GMT

←Older revision		Revision as of 11:59, 20 December 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4bwn]] 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=4BWN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BWN FirstGlance]. <br>		<table><tr><td colspan='2'>[[4bwn]] 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=4BWN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BWN 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=4bwn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bwn OCA], [https://pdbe.org/4bwn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bwn RCSB], [https://www.ebi.ac.uk/pdbsum/4bwn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bwn ProSAT]</span></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]] 2.27Å</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=4bwn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bwn OCA], [https://pdbe.org/4bwn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bwn RCSB], [https://www.ebi.ac.uk/pdbsum/4bwn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bwn ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==

OCA at 12:28, 1 February 2023

OCA — Wed, 01 Feb 2023 12:28:57 GMT

←Older revision		Revision as of 12:28, 1 February 2023
Line 3:		Line 3:
	<StructureSection load='4bwn' size='340' side='right'caption='[[4bwn]], [[Resolution\|resolution]] 2.27Å' scene=''>		<StructureSection load='4bwn' size='340' side='right'caption='[[4bwn]], [[Resolution\|resolution]] 2.27Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4bwn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BWN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BWN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4bwn]] 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=4BWN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BWN 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=4bwn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bwn OCA], [https://pdbe.org/4bwn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bwn RCSB], [https://www.ebi.ac.uk/pdbsum/4bwn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bwn ProSAT]</span></td></tr>		</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=4bwn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bwn OCA], [https://pdbe.org/4bwn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bwn RCSB], [https://www.ebi.ac.uk/pdbsum/4bwn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bwn ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/NEMO_HUMAN NEMO_HUMAN]] Defects in IKBKG are the cause of ectodermal dysplasia anhidrotic with immunodeficiency X-linked (EDAID) [MIM:[https://omim.org/entry/300291 300291]]; also known as hypohidrotic ectodermal dysplasia with immunodeficiency (HED-ID). Is a form of ectoderma dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Characterized by absence of sweat glands, sparse scalp hair, rare conical teeth and immunological abnormalities resulting in severe infectious diseases.<ref>PMID:14651848</ref> <ref>PMID:16547522</ref> <ref>PMID:21606507</ref> <ref>PMID:19185524</ref> <ref>PMID:11047757</ref> <ref>PMID:11242109</ref> <ref>PMID:11224521</ref> <ref>PMID:12045264</ref> <ref>PMID:15100680</ref> Defects in IKBKG are the cause of ectodermal dysplasia anhidrotic with immunodeficiency-osteopetrosis-lymphedema (OLEDAID) [MIM:[https://omim.org/entry/300301 300301]]. Defects in IKBKG are a cause of immunodeficiency NEMO-related without anhidrotic ectodermal dysplasia (NEMOID) [MIM:[https://omim.org/entry/300584 300584]]; also called immunodeficiency without anhidrotic ectodermal dysplasia, isolated immunodeficiency or pure immunodeficiency. Patients manifest immunodeficiency not associated with other abnormalities, and resulting in increased infection susceptibility. Patients suffer from multiple episodes of infectious diseases.<ref>PMID:15100680</ref> <ref>PMID:15356572</ref> Defects in IKBKG are the cause of susceptibility to X-linked familial atypical micobacteriosis type 1 (AMCBX1) [MIM:[https://omim.org/entry/300636 300636]]; also known as X-linked disseminated atypical mycobacterial infection type 1 or X-linked susceptibility to mycobacterial disease type 1. AMCBX1 is the X-linked recessive form of Mendelian susceptibility to mycobacterial disease (MSMD). MSMD is a congenital syndrome resulting in predisposition to clinical disease caused by weakly virulent mycobacterial species, such as bacillus Calmette-Guerin vaccines and non-tuberculous, environmental mycobacteria. Patients are also susceptible to the more virulent species Mycobacterium tuberculosis.<ref>PMID:19185524</ref> <ref>PMID:16818673</ref> Defects in IKBKG are the cause of recurrent isolated invasive pneumococcal disease type 2 (IPD2) [MIM:[https://omim.org/entry/300640 300640]]. Recurrent invasive pneumococcal disease (IPD) is defined as two episodes of IPD occurring at least 1 month apart, whether caused by the same or different serotypes or strains. Recurrent IPD occurs in at least 2% of patients in most series, making IPD the most important known risk factor for subsequent IPD.<ref>PMID:16950813</ref> Defects in IKBKG are the cause of incontinentia pigmenti (IP) [MIM:[https://omim.org/entry/308300 308300]]; formerly designed familial incontinentia pigmenti type II (IP2). IP is a genodermatosis usually prenatally lethal in males. In affected females, it causes abnormalities of the skin, hair, eyes, nails, teeth, skeleton, heart, and central nervous system. The prominent skin signs occur in four classic cutaneous stages: perinatal inflammatory vesicles, verrucous patches, a distinctive pattern of hyperpigmentation and dermal scarring.<ref>PMID:20010814</ref> <ref>PMID:17728323</ref> <ref>PMID:19185524</ref> <ref>PMID:16950813</ref> <ref>PMID:10839543</ref> <ref>PMID:19033441</ref> <ref>PMID:11590134</ref> <ref>PMID:15229184</ref>	+	[https://www.uniprot.org/uniprot/NEMO_HUMAN NEMO_HUMAN] Defects in IKBKG are the cause of ectodermal dysplasia anhidrotic with immunodeficiency X-linked (EDAID) [MIM:[https://omim.org/entry/300291 300291]; also known as hypohidrotic ectodermal dysplasia with immunodeficiency (HED-ID). Is a form of ectoderma dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Characterized by absence of sweat glands, sparse scalp hair, rare conical teeth and immunological abnormalities resulting in severe infectious diseases.<ref>PMID:14651848</ref> <ref>PMID:16547522</ref> <ref>PMID:21606507</ref> <ref>PMID:19185524</ref> <ref>PMID:11047757</ref> <ref>PMID:11242109</ref> <ref>PMID:11224521</ref> <ref>PMID:12045264</ref> <ref>PMID:15100680</ref> Defects in IKBKG are the cause of ectodermal dysplasia anhidrotic with immunodeficiency-osteopetrosis-lymphedema (OLEDAID) [MIM:[https://omim.org/entry/300301 300301]. Defects in IKBKG are a cause of immunodeficiency NEMO-related without anhidrotic ectodermal dysplasia (NEMOID) [MIM:[https://omim.org/entry/300584 300584]; also called immunodeficiency without anhidrotic ectodermal dysplasia, isolated immunodeficiency or pure immunodeficiency. Patients manifest immunodeficiency not associated with other abnormalities, and resulting in increased infection susceptibility. Patients suffer from multiple episodes of infectious diseases.<ref>PMID:15100680</ref> <ref>PMID:15356572</ref> Defects in IKBKG are the cause of susceptibility to X-linked familial atypical micobacteriosis type 1 (AMCBX1) [MIM:[https://omim.org/entry/300636 300636]; also known as X-linked disseminated atypical mycobacterial infection type 1 or X-linked susceptibility to mycobacterial disease type 1. AMCBX1 is the X-linked recessive form of Mendelian susceptibility to mycobacterial disease (MSMD). MSMD is a congenital syndrome resulting in predisposition to clinical disease caused by weakly virulent mycobacterial species, such as bacillus Calmette-Guerin vaccines and non-tuberculous, environmental mycobacteria. Patients are also susceptible to the more virulent species Mycobacterium tuberculosis.<ref>PMID:19185524</ref> <ref>PMID:16818673</ref> Defects in IKBKG are the cause of recurrent isolated invasive pneumococcal disease type 2 (IPD2) [MIM:[https://omim.org/entry/300640 300640]. Recurrent invasive pneumococcal disease (IPD) is defined as two episodes of IPD occurring at least 1 month apart, whether caused by the same or different serotypes or strains. Recurrent IPD occurs in at least 2% of patients in most series, making IPD the most important known risk factor for subsequent IPD.<ref>PMID:16950813</ref> Defects in IKBKG are the cause of incontinentia pigmenti (IP) [MIM:[https://omim.org/entry/308300 308300]; formerly designed familial incontinentia pigmenti type II (IP2). IP is a genodermatosis usually prenatally lethal in males. In affected females, it causes abnormalities of the skin, hair, eyes, nails, teeth, skeleton, heart, and central nervous system. The prominent skin signs occur in four classic cutaneous stages: perinatal inflammatory vesicles, verrucous patches, a distinctive pattern of hyperpigmentation and dermal scarring.<ref>PMID:20010814</ref> <ref>PMID:17728323</ref> <ref>PMID:19185524</ref> <ref>PMID:16950813</ref> <ref>PMID:10839543</ref> <ref>PMID:19033441</ref> <ref>PMID:11590134</ref> <ref>PMID:15229184</ref>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/NEMO_HUMAN NEMO_HUMAN]] Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. Its binding to scaffolding polyubiquitin seems to play a role in IKK activation by multiple signaling receptor pathways. However, the specific type of polyubiquitin recognized upon cell stimulation (either 'Lys-63'-linked or linear polyubiquitin) and its functional importance is reported conflictingly. Also considered to be a mediator for TAX activation of NF-kappa-B. Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity (By similarity). Essential for viral activation of IRF3. Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination.<ref>PMID:14695475</ref> <ref>PMID:19854139</ref> <ref>PMID:20724660</ref>	+	[https://www.uniprot.org/uniprot/NEMO_HUMAN NEMO_HUMAN] Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. Its binding to scaffolding polyubiquitin seems to play a role in IKK activation by multiple signaling receptor pathways. However, the specific type of polyubiquitin recognized upon cell stimulation (either 'Lys-63'-linked or linear polyubiquitin) and its functional importance is reported conflictingly. Also considered to be a mediator for TAX activation of NF-kappa-B. Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity (By similarity). Essential for viral activation of IRF3. Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination.<ref>PMID:14695475</ref> <ref>PMID:19854139</ref> <ref>PMID:20724660</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	NEMO is an integral part of the IkappaB kinase complex and serves as a molecular switch by which the NF-kappaB signaling pathway can be regulated. Oligomerization and polyubiquitin (poly-Ub) binding, mediated through the regulatory CC2-LZ domain, were shown to be key features governing NEMO function, but the relationship between these two activities remains unclear. In this study, we solved the structure of this domain in complex with a designed ankyrin repeat protein, which helps its crystallization. We generated several NEMO mutants in this domain, including those associated with human diseases incontinentia pigmenti and immunodeficiency with or without anhidrotic ectodermal dysplasia. Analytical ultracentrifugation and thermal denaturation experiments were used to evaluate the dimerization properties of these mutants. A fluorescence-based assay was developed, as well, to quantify the interaction to monoubiquitin and poly-Ub chains. Moreover, the effect of these mutations was investigated for the full-length protein. We show that a proper folding of the ubiquitin-binding domain, termed NOA/UBAN/NUB, into a stable coiled-coil dimer is required but not sufficient for efficient interaction with poly-Ub. In addition, we show that binding to poly-Ub and, to a lesser extent, to monoubiquitin increases the stability of the NOA coiled-coil dimer. Collectively, these data provide structural insights into how several pathological mutations within and outside of the CC2-LZ's NOA ubiquitin binding site affect IkappaB kinase activation in the NF-kappaB signaling pathway.	+
-		+
-	DARPin-assisted crystallography of the CC2-LZ domain of NEMO reveals a coupling between dimerization and ubiquitin binding.,Grubisha O, Kaminska M, Duquerroy S, Fontan E, Cordier F, Haouz A, Raynal B, Chiaravalli J, Delepierre M, Israel A, Veron M, Agou F J Mol Biol. 2010 Jan 8;395(1):89-104. Epub 2009 Oct 23. PMID:19854204<ref>PMID:19854204</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 4bwn" style="background-color:#fffaf0;"></div~~>	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Agou, F]]	+	[[Category: Agou F]]
-	[[Category: Dubosclard, V]]	+	[[Category: Dubosclard V]]
-	[[Category: Duquerroy, S]]	+	[[Category: Duquerroy S]]
-	[[Category: Fontan, E]]	+	[[Category: Fontan E]]
-	~~[[Category: Nemo - ikk gamma]]~~	+
-	~~[[Category: Nfkb pathway]]~~	+
-	~~[[Category: Signaling protein]]~~	+
-	~~[[Category: Transcription regulation]]~~	+
-	~~[[Category: Ubl conjugattion~~]]	+

OCA at 05:24, 28 April 2021

OCA — Wed, 28 Apr 2021 05:24:01 GMT

←Older revision		Revision as of 05:24, 28 April 2021
Line 3:		Line 3:
	<StructureSection load='4bwn' size='340' side='right'caption='[[4bwn]], [[Resolution\|resolution]] 2.27Å' scene=''>		<StructureSection load='4bwn' size='340' side='right'caption='[[4bwn]], [[Resolution\|resolution]] 2.27Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4bwn]] 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=4BWN OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4BWN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4bwn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BWN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BWN FirstGlance]. <br>
-	</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=4bwn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bwn OCA], [~~http~~://pdbe.org/4bwn PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4bwn RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4bwn PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4bwn ProSAT]</span></td></tr>	+	</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=4bwn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bwn OCA], [https://pdbe.org/4bwn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bwn RCSB], [https://www.ebi.ac.uk/pdbsum/4bwn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bwn ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/NEMO_HUMAN NEMO_HUMAN]] Defects in IKBKG are the cause of ectodermal dysplasia anhidrotic with immunodeficiency X-linked (EDAID) [MIM:[~~http~~://omim.org/entry/300291 300291]]; also known as hypohidrotic ectodermal dysplasia with immunodeficiency (HED-ID). Is a form of ectoderma dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Characterized by absence of sweat glands, sparse scalp hair, rare conical teeth and immunological abnormalities resulting in severe infectious diseases.<ref>PMID:14651848</ref> <ref>PMID:16547522</ref> <ref>PMID:21606507</ref> <ref>PMID:19185524</ref> <ref>PMID:11047757</ref> <ref>PMID:11242109</ref> <ref>PMID:11224521</ref> <ref>PMID:12045264</ref> <ref>PMID:15100680</ref> Defects in IKBKG are the cause of ectodermal dysplasia anhidrotic with immunodeficiency-osteopetrosis-lymphedema (OLEDAID) [MIM:[~~http~~://omim.org/entry/300301 300301]]. Defects in IKBKG are a cause of immunodeficiency NEMO-related without anhidrotic ectodermal dysplasia (NEMOID) [MIM:[~~http~~://omim.org/entry/300584 300584]]; also called immunodeficiency without anhidrotic ectodermal dysplasia, isolated immunodeficiency or pure immunodeficiency. Patients manifest immunodeficiency not associated with other abnormalities, and resulting in increased infection susceptibility. Patients suffer from multiple episodes of infectious diseases.<ref>PMID:15100680</ref> <ref>PMID:15356572</ref> Defects in IKBKG are the cause of susceptibility to X-linked familial atypical micobacteriosis type 1 (AMCBX1) [MIM:[~~http~~://omim.org/entry/300636 300636]]; also known as X-linked disseminated atypical mycobacterial infection type 1 or X-linked susceptibility to mycobacterial disease type 1. AMCBX1 is the X-linked recessive form of Mendelian susceptibility to mycobacterial disease (MSMD). MSMD is a congenital syndrome resulting in predisposition to clinical disease caused by weakly virulent mycobacterial species, such as bacillus Calmette-Guerin vaccines and non-tuberculous, environmental mycobacteria. Patients are also susceptible to the more virulent species Mycobacterium tuberculosis.<ref>PMID:19185524</ref> <ref>PMID:16818673</ref> Defects in IKBKG are the cause of recurrent isolated invasive pneumococcal disease type 2 (IPD2) [MIM:[~~http~~://omim.org/entry/300640 300640]]. Recurrent invasive pneumococcal disease (IPD) is defined as two episodes of IPD occurring at least 1 month apart, whether caused by the same or different serotypes or strains. Recurrent IPD occurs in at least 2% of patients in most series, making IPD the most important known risk factor for subsequent IPD.<ref>PMID:16950813</ref> Defects in IKBKG are the cause of incontinentia pigmenti (IP) [MIM:[~~http~~://omim.org/entry/308300 308300]]; formerly designed familial incontinentia pigmenti type II (IP2). IP is a genodermatosis usually prenatally lethal in males. In affected females, it causes abnormalities of the skin, hair, eyes, nails, teeth, skeleton, heart, and central nervous system. The prominent skin signs occur in four classic cutaneous stages: perinatal inflammatory vesicles, verrucous patches, a distinctive pattern of hyperpigmentation and dermal scarring.<ref>PMID:20010814</ref> <ref>PMID:17728323</ref> <ref>PMID:19185524</ref> <ref>PMID:16950813</ref> <ref>PMID:10839543</ref> <ref>PMID:19033441</ref> <ref>PMID:11590134</ref> <ref>PMID:15229184</ref>	+	[[https://www.uniprot.org/uniprot/NEMO_HUMAN NEMO_HUMAN]] Defects in IKBKG are the cause of ectodermal dysplasia anhidrotic with immunodeficiency X-linked (EDAID) [MIM:[https://omim.org/entry/300291 300291]]; also known as hypohidrotic ectodermal dysplasia with immunodeficiency (HED-ID). Is a form of ectoderma dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Characterized by absence of sweat glands, sparse scalp hair, rare conical teeth and immunological abnormalities resulting in severe infectious diseases.<ref>PMID:14651848</ref> <ref>PMID:16547522</ref> <ref>PMID:21606507</ref> <ref>PMID:19185524</ref> <ref>PMID:11047757</ref> <ref>PMID:11242109</ref> <ref>PMID:11224521</ref> <ref>PMID:12045264</ref> <ref>PMID:15100680</ref> Defects in IKBKG are the cause of ectodermal dysplasia anhidrotic with immunodeficiency-osteopetrosis-lymphedema (OLEDAID) [MIM:[https://omim.org/entry/300301 300301]]. Defects in IKBKG are a cause of immunodeficiency NEMO-related without anhidrotic ectodermal dysplasia (NEMOID) [MIM:[https://omim.org/entry/300584 300584]]; also called immunodeficiency without anhidrotic ectodermal dysplasia, isolated immunodeficiency or pure immunodeficiency. Patients manifest immunodeficiency not associated with other abnormalities, and resulting in increased infection susceptibility. Patients suffer from multiple episodes of infectious diseases.<ref>PMID:15100680</ref> <ref>PMID:15356572</ref> Defects in IKBKG are the cause of susceptibility to X-linked familial atypical micobacteriosis type 1 (AMCBX1) [MIM:[https://omim.org/entry/300636 300636]]; also known as X-linked disseminated atypical mycobacterial infection type 1 or X-linked susceptibility to mycobacterial disease type 1. AMCBX1 is the X-linked recessive form of Mendelian susceptibility to mycobacterial disease (MSMD). MSMD is a congenital syndrome resulting in predisposition to clinical disease caused by weakly virulent mycobacterial species, such as bacillus Calmette-Guerin vaccines and non-tuberculous, environmental mycobacteria. Patients are also susceptible to the more virulent species Mycobacterium tuberculosis.<ref>PMID:19185524</ref> <ref>PMID:16818673</ref> Defects in IKBKG are the cause of recurrent isolated invasive pneumococcal disease type 2 (IPD2) [MIM:[https://omim.org/entry/300640 300640]]. Recurrent invasive pneumococcal disease (IPD) is defined as two episodes of IPD occurring at least 1 month apart, whether caused by the same or different serotypes or strains. Recurrent IPD occurs in at least 2% of patients in most series, making IPD the most important known risk factor for subsequent IPD.<ref>PMID:16950813</ref> Defects in IKBKG are the cause of incontinentia pigmenti (IP) [MIM:[https://omim.org/entry/308300 308300]]; formerly designed familial incontinentia pigmenti type II (IP2). IP is a genodermatosis usually prenatally lethal in males. In affected females, it causes abnormalities of the skin, hair, eyes, nails, teeth, skeleton, heart, and central nervous system. The prominent skin signs occur in four classic cutaneous stages: perinatal inflammatory vesicles, verrucous patches, a distinctive pattern of hyperpigmentation and dermal scarring.<ref>PMID:20010814</ref> <ref>PMID:17728323</ref> <ref>PMID:19185524</ref> <ref>PMID:16950813</ref> <ref>PMID:10839543</ref> <ref>PMID:19033441</ref> <ref>PMID:11590134</ref> <ref>PMID:15229184</ref>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/NEMO_HUMAN NEMO_HUMAN]] Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. Its binding to scaffolding polyubiquitin seems to play a role in IKK activation by multiple signaling receptor pathways. However, the specific type of polyubiquitin recognized upon cell stimulation (either 'Lys-63'-linked or linear polyubiquitin) and its functional importance is reported conflictingly. Also considered to be a mediator for TAX activation of NF-kappa-B. Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity (By similarity). Essential for viral activation of IRF3. Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination.<ref>PMID:14695475</ref> <ref>PMID:19854139</ref> <ref>PMID:20724660</ref>	+	[[https://www.uniprot.org/uniprot/NEMO_HUMAN NEMO_HUMAN]] Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. Its binding to scaffolding polyubiquitin seems to play a role in IKK activation by multiple signaling receptor pathways. However, the specific type of polyubiquitin recognized upon cell stimulation (either 'Lys-63'-linked or linear polyubiquitin) and its functional importance is reported conflictingly. Also considered to be a mediator for TAX activation of NF-kappa-B. Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity (By similarity). Essential for viral activation of IRF3. Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination.<ref>PMID:14695475</ref> <ref>PMID:19854139</ref> <ref>PMID:20724660</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 13:47, 13 March 2019

OCA — Wed, 13 Mar 2019 13:47:11 GMT

←Older revision		Revision as of 13:47, 13 March 2019
Line 1:		Line 1:

	==NEMO CC2-LZ DOMAIN==		==NEMO CC2-LZ DOMAIN==
-	<StructureSection load='4bwn' size='340' side='right' caption='[[4bwn]], [[Resolution\|resolution]] 2.27Å' scene=''>	+	<StructureSection load='4bwn' size='340' side='right'caption='[[4bwn]], [[Resolution\|resolution]] 2.27Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4bwn]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BWN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BWN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4bwn]] 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=4BWN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BWN FirstGlance]. <br>
	</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=4bwn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bwn OCA], [http://pdbe.org/4bwn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bwn RCSB], [http://www.ebi.ac.uk/pdbsum/4bwn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bwn ProSAT]</span></td></tr>		</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=4bwn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bwn OCA], [http://pdbe.org/4bwn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bwn RCSB], [http://www.ebi.ac.uk/pdbsum/4bwn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bwn ProSAT]</span></td></tr>
	</table>		</table>
Line 23:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Agou, F]]		[[Category: Agou, F]]
	[[Category: Dubosclard, V]]		[[Category: Dubosclard, V]]

OCA at 08:46, 11 August 2016

OCA — Thu, 11 Aug 2016 08:46:08 GMT

←Older revision		Revision as of 08:46, 11 August 2016
Line 1:		Line 1:
		+
	==NEMO CC2-LZ DOMAIN==		==NEMO CC2-LZ DOMAIN==
	<StructureSection load='4bwn' size='340' side='right' caption='[[4bwn]], [[Resolution\|resolution]] 2.27Å' scene=''>		<StructureSection load='4bwn' size='340' side='right' caption='[[4bwn]], [[Resolution\|resolution]] 2.27Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4bwn]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BWN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BWN FirstGlance]. <br>		<table><tr><td colspan='2'>[[4bwn]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BWN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BWN FirstGlance]. <br>
-	</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=4bwn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bwn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bwn RCSB], [http://www.ebi.ac.uk/pdbsum/4bwn PDBsum]</span></td></tr>	+	</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=4bwn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bwn OCA], [http://pdbe.org/4bwn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bwn RCSB], [http://www.ebi.ac.uk/pdbsum/4bwn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bwn ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 17:		Line 18:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4bwn" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:00, 25 January 2015

OCA — Sun, 25 Jan 2015 10:00:02 GMT

←Older revision		Revision as of 10:00, 25 January 2015
Line 21:		Line 21:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Agou, F.]]	+	[[Category: Agou, F]]
-	[[Category: Dubosclard, V.]]	+	[[Category: Dubosclard, V]]
-	[[Category: Duquerroy, S.]]	+	[[Category: Duquerroy, S]]
-	[[Category: Fontan, E.]]	+	[[Category: Fontan, E]]
	[[Category: Nemo - ikk gamma]]		[[Category: Nemo - ikk gamma]]
	[[Category: Nfkb pathway]]		[[Category: Nfkb pathway]]

OCA at 08:57, 29 October 2014

OCA — Wed, 29 Oct 2014 08:57:16 GMT

←Older revision		Revision as of 08:57, 29 October 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4bwn]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BWN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BWN FirstGlance]. <br>		<table><tr><td colspan='2'>[[4bwn]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BWN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BWN FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4bwn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bwn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bwn RCSB], [http://www.ebi.ac.uk/pdbsum/4bwn PDBsum]</span></td></tr>	+	</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=4bwn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bwn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bwn RCSB], [http://www.ebi.ac.uk/pdbsum/4bwn PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/NEMO_HUMAN NEMO_HUMAN]] Defects in IKBKG are the cause of ectodermal dysplasia anhidrotic with immunodeficiency X-linked (EDAID) [MIM:[http://omim.org/entry/300291 300291]]; also known as hypohidrotic ectodermal dysplasia with immunodeficiency (HED-ID). Is a form of ectoderma dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Characterized by absence of sweat glands, sparse scalp hair, rare conical teeth and immunological abnormalities resulting in severe infectious diseases.<ref>PMID:14651848</ref> <ref>PMID:16547522</ref> <ref>PMID:21606507</ref> <ref>PMID:19185524</ref> <ref>PMID:11047757</ref> <ref>PMID:11242109</ref> <ref>PMID:11224521</ref> <ref>PMID:12045264</ref> <ref>PMID:15100680</ref> Defects in IKBKG are the cause of ectodermal dysplasia anhidrotic with immunodeficiency-osteopetrosis-lymphedema (OLEDAID) [MIM:[http://omim.org/entry/300301 300301]]. Defects in IKBKG are a cause of immunodeficiency NEMO-related without anhidrotic ectodermal dysplasia (NEMOID) [MIM:[http://omim.org/entry/300584 300584]]; also called immunodeficiency without anhidrotic ectodermal dysplasia, isolated immunodeficiency or pure immunodeficiency. Patients manifest immunodeficiency not associated with other abnormalities, and resulting in increased infection susceptibility. Patients suffer from multiple episodes of infectious diseases.<ref>PMID:15100680</ref> <ref>PMID:15356572</ref> Defects in IKBKG are the cause of susceptibility to X-linked familial atypical micobacteriosis type 1 (AMCBX1) [MIM:[http://omim.org/entry/300636 300636]]; also known as X-linked disseminated atypical mycobacterial infection type 1 or X-linked susceptibility to mycobacterial disease type 1. AMCBX1 is the X-linked recessive form of Mendelian susceptibility to mycobacterial disease (MSMD). MSMD is a congenital syndrome resulting in predisposition to clinical disease caused by weakly virulent mycobacterial species, such as bacillus Calmette-Guerin vaccines and non-tuberculous, environmental mycobacteria. Patients are also susceptible to the more virulent species Mycobacterium tuberculosis.<ref>PMID:19185524</ref> <ref>PMID:16818673</ref> Defects in IKBKG are the cause of recurrent isolated invasive pneumococcal disease type 2 (IPD2) [MIM:[http://omim.org/entry/300640 300640]]. Recurrent invasive pneumococcal disease (IPD) is defined as two episodes of IPD occurring at least 1 month apart, whether caused by the same or different serotypes or strains. Recurrent IPD occurs in at least 2% of patients in most series, making IPD the most important known risk factor for subsequent IPD.<ref>PMID:16950813</ref> Defects in IKBKG are the cause of incontinentia pigmenti (IP) [MIM:[http://omim.org/entry/308300 308300]]; formerly designed familial incontinentia pigmenti type II (IP2). IP is a genodermatosis usually prenatally lethal in males. In affected females, it causes abnormalities of the skin, hair, eyes, nails, teeth, skeleton, heart, and central nervous system. The prominent skin signs occur in four classic cutaneous stages: perinatal inflammatory vesicles, verrucous patches, a distinctive pattern of hyperpigmentation and dermal scarring.<ref>PMID:20010814</ref> <ref>PMID:17728323</ref> <ref>PMID:19185524</ref> <ref>PMID:16950813</ref> <ref>PMID:10839543</ref> <ref>PMID:19033441</ref> <ref>PMID:11590134</ref> <ref>PMID:15229184</ref>		[[http://www.uniprot.org/uniprot/NEMO_HUMAN NEMO_HUMAN]] Defects in IKBKG are the cause of ectodermal dysplasia anhidrotic with immunodeficiency X-linked (EDAID) [MIM:[http://omim.org/entry/300291 300291]]; also known as hypohidrotic ectodermal dysplasia with immunodeficiency (HED-ID). Is a form of ectoderma dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Characterized by absence of sweat glands, sparse scalp hair, rare conical teeth and immunological abnormalities resulting in severe infectious diseases.<ref>PMID:14651848</ref> <ref>PMID:16547522</ref> <ref>PMID:21606507</ref> <ref>PMID:19185524</ref> <ref>PMID:11047757</ref> <ref>PMID:11242109</ref> <ref>PMID:11224521</ref> <ref>PMID:12045264</ref> <ref>PMID:15100680</ref> Defects in IKBKG are the cause of ectodermal dysplasia anhidrotic with immunodeficiency-osteopetrosis-lymphedema (OLEDAID) [MIM:[http://omim.org/entry/300301 300301]]. Defects in IKBKG are a cause of immunodeficiency NEMO-related without anhidrotic ectodermal dysplasia (NEMOID) [MIM:[http://omim.org/entry/300584 300584]]; also called immunodeficiency without anhidrotic ectodermal dysplasia, isolated immunodeficiency or pure immunodeficiency. Patients manifest immunodeficiency not associated with other abnormalities, and resulting in increased infection susceptibility. Patients suffer from multiple episodes of infectious diseases.<ref>PMID:15100680</ref> <ref>PMID:15356572</ref> Defects in IKBKG are the cause of susceptibility to X-linked familial atypical micobacteriosis type 1 (AMCBX1) [MIM:[http://omim.org/entry/300636 300636]]; also known as X-linked disseminated atypical mycobacterial infection type 1 or X-linked susceptibility to mycobacterial disease type 1. AMCBX1 is the X-linked recessive form of Mendelian susceptibility to mycobacterial disease (MSMD). MSMD is a congenital syndrome resulting in predisposition to clinical disease caused by weakly virulent mycobacterial species, such as bacillus Calmette-Guerin vaccines and non-tuberculous, environmental mycobacteria. Patients are also susceptible to the more virulent species Mycobacterium tuberculosis.<ref>PMID:19185524</ref> <ref>PMID:16818673</ref> Defects in IKBKG are the cause of recurrent isolated invasive pneumococcal disease type 2 (IPD2) [MIM:[http://omim.org/entry/300640 300640]]. Recurrent invasive pneumococcal disease (IPD) is defined as two episodes of IPD occurring at least 1 month apart, whether caused by the same or different serotypes or strains. Recurrent IPD occurs in at least 2% of patients in most series, making IPD the most important known risk factor for subsequent IPD.<ref>PMID:16950813</ref> Defects in IKBKG are the cause of incontinentia pigmenti (IP) [MIM:[http://omim.org/entry/308300 308300]]; formerly designed familial incontinentia pigmenti type II (IP2). IP is a genodermatosis usually prenatally lethal in males. In affected females, it causes abnormalities of the skin, hair, eyes, nails, teeth, skeleton, heart, and central nervous system. The prominent skin signs occur in four classic cutaneous stages: perinatal inflammatory vesicles, verrucous patches, a distinctive pattern of hyperpigmentation and dermal scarring.<ref>PMID:20010814</ref> <ref>PMID:17728323</ref> <ref>PMID:19185524</ref> <ref>PMID:16950813</ref> <ref>PMID:10839543</ref> <ref>PMID:19033441</ref> <ref>PMID:11590134</ref> <ref>PMID:15229184</ref>

OCA at 07:52, 23 July 2014

OCA — Wed, 23 Jul 2014 07:52:28 GMT

←Older revision		Revision as of 07:52, 23 July 2014
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==NEMO CC2-LZ DOMAIN==
		+	<StructureSection load='4bwn' size='340' side='right' caption='[[4bwn]], [[Resolution\|resolution]] 2.27Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4bwn]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BWN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BWN FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4bwn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bwn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bwn RCSB], [http://www.ebi.ac.uk/pdbsum/4bwn PDBsum]</span></td></tr>
		+	<table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/NEMO_HUMAN NEMO_HUMAN]] Defects in IKBKG are the cause of ectodermal dysplasia anhidrotic with immunodeficiency X-linked (EDAID) [MIM:[http://omim.org/entry/300291 300291]]; also known as hypohidrotic ectodermal dysplasia with immunodeficiency (HED-ID). Is a form of ectoderma dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Characterized by absence of sweat glands, sparse scalp hair, rare conical teeth and immunological abnormalities resulting in severe infectious diseases.<ref>PMID:14651848</ref> <ref>PMID:16547522</ref> <ref>PMID:21606507</ref> <ref>PMID:19185524</ref> <ref>PMID:11047757</ref> <ref>PMID:11242109</ref> <ref>PMID:11224521</ref> <ref>PMID:12045264</ref> <ref>PMID:15100680</ref> Defects in IKBKG are the cause of ectodermal dysplasia anhidrotic with immunodeficiency-osteopetrosis-lymphedema (OLEDAID) [MIM:[http://omim.org/entry/300301 300301]]. Defects in IKBKG are a cause of immunodeficiency NEMO-related without anhidrotic ectodermal dysplasia (NEMOID) [MIM:[http://omim.org/entry/300584 300584]]; also called immunodeficiency without anhidrotic ectodermal dysplasia, isolated immunodeficiency or pure immunodeficiency. Patients manifest immunodeficiency not associated with other abnormalities, and resulting in increased infection susceptibility. Patients suffer from multiple episodes of infectious diseases.<ref>PMID:15100680</ref> <ref>PMID:15356572</ref> Defects in IKBKG are the cause of susceptibility to X-linked familial atypical micobacteriosis type 1 (AMCBX1) [MIM:[http://omim.org/entry/300636 300636]]; also known as X-linked disseminated atypical mycobacterial infection type 1 or X-linked susceptibility to mycobacterial disease type 1. AMCBX1 is the X-linked recessive form of Mendelian susceptibility to mycobacterial disease (MSMD). MSMD is a congenital syndrome resulting in predisposition to clinical disease caused by weakly virulent mycobacterial species, such as bacillus Calmette-Guerin vaccines and non-tuberculous, environmental mycobacteria. Patients are also susceptible to the more virulent species Mycobacterium tuberculosis.<ref>PMID:19185524</ref> <ref>PMID:16818673</ref> Defects in IKBKG are the cause of recurrent isolated invasive pneumococcal disease type 2 (IPD2) [MIM:[http://omim.org/entry/300640 300640]]. Recurrent invasive pneumococcal disease (IPD) is defined as two episodes of IPD occurring at least 1 month apart, whether caused by the same or different serotypes or strains. Recurrent IPD occurs in at least 2% of patients in most series, making IPD the most important known risk factor for subsequent IPD.<ref>PMID:16950813</ref> Defects in IKBKG are the cause of incontinentia pigmenti (IP) [MIM:[http://omim.org/entry/308300 308300]]; formerly designed familial incontinentia pigmenti type II (IP2). IP is a genodermatosis usually prenatally lethal in males. In affected females, it causes abnormalities of the skin, hair, eyes, nails, teeth, skeleton, heart, and central nervous system. The prominent skin signs occur in four classic cutaneous stages: perinatal inflammatory vesicles, verrucous patches, a distinctive pattern of hyperpigmentation and dermal scarring.<ref>PMID:20010814</ref> <ref>PMID:17728323</ref> <ref>PMID:19185524</ref> <ref>PMID:16950813</ref> <ref>PMID:10839543</ref> <ref>PMID:19033441</ref> <ref>PMID:11590134</ref> <ref>PMID:15229184</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/NEMO_HUMAN NEMO_HUMAN]] Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. Its binding to scaffolding polyubiquitin seems to play a role in IKK activation by multiple signaling receptor pathways. However, the specific type of polyubiquitin recognized upon cell stimulation (either 'Lys-63'-linked or linear polyubiquitin) and its functional importance is reported conflictingly. Also considered to be a mediator for TAX activation of NF-kappa-B. Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity (By similarity). Essential for viral activation of IRF3. Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination.<ref>PMID:14695475</ref> <ref>PMID:19854139</ref> <ref>PMID:20724660</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	NEMO is an integral part of the IkappaB kinase complex and serves as a molecular switch by which the NF-kappaB signaling pathway can be regulated. Oligomerization and polyubiquitin (poly-Ub) binding, mediated through the regulatory CC2-LZ domain, were shown to be key features governing NEMO function, but the relationship between these two activities remains unclear. In this study, we solved the structure of this domain in complex with a designed ankyrin repeat protein, which helps its crystallization. We generated several NEMO mutants in this domain, including those associated with human diseases incontinentia pigmenti and immunodeficiency with or without anhidrotic ectodermal dysplasia. Analytical ultracentrifugation and thermal denaturation experiments were used to evaluate the dimerization properties of these mutants. A fluorescence-based assay was developed, as well, to quantify the interaction to monoubiquitin and poly-Ub chains. Moreover, the effect of these mutations was investigated for the full-length protein. We show that a proper folding of the ubiquitin-binding domain, termed NOA/UBAN/NUB, into a stable coiled-coil dimer is required but not sufficient for efficient interaction with poly-Ub. In addition, we show that binding to poly-Ub and, to a lesser extent, to monoubiquitin increases the stability of the NOA coiled-coil dimer. Collectively, these data provide structural insights into how several pathological mutations within and outside of the CC2-LZ's NOA ubiquitin binding site affect IkappaB kinase activation in the NF-kappaB signaling pathway.

-	~~The entry 4bwn is ON HOLD until Paper Publication~~	+	DARPin-assisted crystallography of the CC2-LZ domain of NEMO reveals a coupling between dimerization and ubiquitin binding.,Grubisha O, Kaminska M, Duquerroy S, Fontan E, Cordier F, Haouz A, Raynal B, Chiaravalli J, Delepierre M, Israel A, Veron M, Agou F J Mol Biol. 2010 Jan 8;395(1):89-104. Epub 2009 Oct 23. PMID:19854204<ref>PMID:19854204</ref>

-	~~Authors~~: Dubosclard, V., Duquerroy, S., Fontan, E.~~, Agou, F.~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~NEMO CC2~~-~~LZ DOMAIN~~	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Agou, F.]]
		+	[[Category: Dubosclard, V.]]
		+	[[Category: Duquerroy, S.]]
		+	[[Category: Fontan, E.]]
		+	[[Category: Nemo - ikk gamma]]
		+	[[Category: Nfkb pathway]]
		+	[[Category: Signaling protein]]
		+	[[Category: Transcription regulation]]
		+	[[Category: Ubl conjugattion]]

OCA at 12:45, 11 December 2013

OCA — Wed, 11 Dec 2013 12:45:29 GMT

←Older revision		Revision as of 12:45, 11 December 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4bwn is ON HOLD	+	The entry 4bwn is ON HOLD until Paper Publication

	Authors: Dubosclard, V., Duquerroy, S., Fontan, E., Agou, F.		Authors: Dubosclard, V., Duquerroy, S., Fontan, E., Agou, F.

	Description: NEMO CC2-LZ DOMAIN		Description: NEMO CC2-LZ DOMAIN

OCA: Protected "4bwn" [edit=sysop:move=sysop]

OCA — Wed, 10 Jul 2013 14:46:32 GMT

Protected "4bwn" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:46, 10 July 2013