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| | <StructureSection load='3f89' size='340' side='right'caption='[[3f89]], [[Resolution|resolution]] 2.80Å' scene=''> | | <StructureSection load='3f89' size='340' side='right'caption='[[3f89]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3f89]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F89 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3F89 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3f89]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F89 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3F89 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2zvn|2zvn]], [[2zvo|2zvo]]</div></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]] 2.8Å</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=3f89 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f89 OCA], [https://pdbe.org/3f89 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3f89 RCSB], [https://www.ebi.ac.uk/pdbsum/3f89 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3f89 ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3f89 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f89 OCA], [https://pdbe.org/3f89 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3f89 RCSB], [https://www.ebi.ac.uk/pdbsum/3f89 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3f89 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/NEMO_MOUSE NEMO_MOUSE]] 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. 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. Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination (By similarity).<ref>PMID:9927690</ref>
| + | [https://www.uniprot.org/uniprot/NEMO_MOUSE NEMO_MOUSE] 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. 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. Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination (By similarity).<ref>PMID:9927690</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Akutsu, M]] | + | [[Category: Akutsu M]] |
| - | [[Category: Bloor, S]] | + | [[Category: Bloor S]] |
| - | [[Category: Dikic, I]] | + | [[Category: Dikic I]] |
| - | [[Category: Ikeda, F]] | + | [[Category: Ikeda F]] |
| - | [[Category: Kato, R]] | + | [[Category: Kato R]] |
| - | [[Category: Kawasaki, M]] | + | [[Category: Kawasaki M]] |
| - | [[Category: Kensche, T]] | + | [[Category: Kensche T]] |
| - | [[Category: Komander, D]] | + | [[Category: Komander D]] |
| - | [[Category: Rahighi, S]] | + | [[Category: Rahighi S]] |
| - | [[Category: Randow, F]] | + | [[Category: Randow F]] |
| - | [[Category: Suzuki, N]] | + | [[Category: Suzuki N]] |
| - | [[Category: Uejima, T]] | + | [[Category: Uejima T]] |
| - | [[Category: Wakatsuki, S]] | + | [[Category: Wakatsuki S]] |
| - | [[Category: Coiled coil]]
| + | |
| - | [[Category: Cytoplasm]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Nf-kb signaling]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription regulation]]
| + | |
| - | [[Category: Ubiquitin binding]]
| + | |
| - | [[Category: Ubl conjugation]]
| + | |
| - | [[Category: Zinc]]
| + | |
| - | [[Category: Zinc-finger]]
| + | |
| Structural highlights
Function
NEMO_MOUSE 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. 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. Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination (By similarity).[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Activation of nuclear factor-kappaB (NF-kappaB), a key mediator of inducible transcription in immunity, requires binding of NF-kappaB essential modulator (NEMO) to ubiquitinated substrates. Here, we report that the UBAN (ubiquitin binding in ABIN and NEMO) motif of NEMO selectively binds linear (head-to-tail) ubiquitin chains. Crystal structures of the UBAN motif revealed a parallel coiled-coil dimer that formed a heterotetrameric complex with two linear diubiquitin molecules. The UBAN dimer contacted all four ubiquitin moieties, and the integrity of each binding site was required for efficient NF-kappaB activation. Binding occurred via a surface on the proximal ubiquitin moiety and the canonical Ile44 surface on the distal one, thereby providing specificity for linear chain recognition. Residues of NEMO involved in binding linear ubiquitin chains are required for NF-kappaB activation by TNF-alpha and other agonists, providing an explanation for the detrimental effect of NEMO mutations in patients suffering from X-linked ectodermal dysplasia and immunodeficiency.
Specific recognition of linear ubiquitin chains by NEMO is important for NF-kappaB activation.,Rahighi S, Ikeda F, Kawasaki M, Akutsu M, Suzuki N, Kato R, Kensche T, Uejima T, Bloor S, Komander D, Randow F, Wakatsuki S, Dikic I Cell. 2009 Mar 20;136(6):1098-109. PMID:19303852[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Li Y, Kang J, Friedman J, Tarassishin L, Ye J, Kovalenko A, Wallach D, Horwitz MS. Identification of a cell protein (FIP-3) as a modulator of NF-kappaB activity and as a target of an adenovirus inhibitor of tumor necrosis factor alpha-induced apoptosis. Proc Natl Acad Sci U S A. 1999 Feb 2;96(3):1042-7. PMID:9927690
- ↑ Rahighi S, Ikeda F, Kawasaki M, Akutsu M, Suzuki N, Kato R, Kensche T, Uejima T, Bloor S, Komander D, Randow F, Wakatsuki S, Dikic I. Specific recognition of linear ubiquitin chains by NEMO is important for NF-kappaB activation. Cell. 2009 Mar 20;136(6):1098-109. PMID:19303852 doi:10.1016/j.cell.2009.03.007
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