View source for 5ebz


==Crystal structure of human IKK1==
<StructureSection load='5ebz' size='340' side='right'caption='[[5ebz]], [[Resolution|resolution]] 4.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ebz]] is a 12 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=5EBZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EBZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 4.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5LS:[(2~{R},3~{S},4~{S},5~{R},6~{S})-2-(HYDROXYMETHYL)-4,6-BIS(OXIDANYL)-5-SULFOOXY-OXAN-3-YL]+HYDROGEN+SULFATE'>5LS</scene>, <scene name='pdbligand=5TH:[(2~{S},3~{R},4~{S},5~{S},6~{R})-6-(HYDROXYMETHYL)-2,4-BIS(OXIDANYL)-5-OXIDANYLSULFANYLOXY-OXAN-3-YL]+HYDROGEN+SULFATE'>5TH</scene>, <scene name='pdbligand=5TJ:[(2~{R},3~{R},4~{R},5~{R},6~{S})-2-(HYDROXYMETHYL)-5,6-BIS(OXIDANYL)-3-OXIDANYLSULFANYLOXY-OXAN-4-YL]+HYDROGEN+SULFATE'>5TJ</scene>, <scene name='pdbligand=5TK:(2~{S},3~{R},4~{R},5~{S},6~{R})-6-(HYDROXYMETHYL)-5-OXIDANYLSULFANYLOXY-OXANE-2,3,4-TRIOL'>5TK</scene>, <scene name='pdbligand=5TL:2-AZANYL-5-PHENYL-3-(4-SULFAMOYLPHENYL)BENZAMIDE'>5TL</scene>, <scene name='pdbligand=5TM:[(2~{S},3~{R},4~{S},5~{R},6~{R})-6-(HYDROXYMETHYL)-2,5-BIS(OXIDANYL)-4-OXIDANYLSULFANYLOXY-OXAN-3-YL]+HYDROGEN+SULFATE'>5TM</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=PDX:2,3-DI-O-SULFO-ALPHA-D-GLUCOPYRANOSE'>PDX</scene>, <scene name='pdbligand=Z4K:2-O-SULFO-ALPHA-D-GLUCOPYRANOSE'>Z4K</scene></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=5ebz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ebz OCA], [https://pdbe.org/5ebz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ebz RCSB], [https://www.ebi.ac.uk/pdbsum/5ebz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ebz ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/IKKA_HUMAN IKKA_HUMAN] The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/IKKA_HUMAN IKKA_HUMAN] Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Negatively regulates the pathway by phosphorylating the scaffold protein TAXBP1 and thus promoting the assembly of the A20/TNFAIP3 ubiquitin-editing complex (composed of A20/TNFAIP3, TAX1BP1, and the E3 ligases ITCH and RNF11). Therefore, CHUK plays a key role in the negative feedback of NF-kappa-B canonical signaling to limit inflammatory gene activation. As part of the non-canonical pathway of NF-kappa-B activation, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. In turn, these complexes regulate genes encoding molecules involved in B-cell survival and lymphoid organogenesis. Participates also in the negative feedback of the non-canonical NF-kappa-B signaling pathway by phosphorylating and destabilizing MAP3K14/NIK. Within the nucleus, phosphorylates CREBBP and consequently increases both its transcriptional and histone acetyltransferase activities. Modulates chromatin accessibility at NF-kappa-B-responsive promoters by phosphorylating histones H3 at 'Ser-10' that are subsequently acetylated at 'Lys-14' by CREBBP. Additionally, phosphorylates the CREBBP-interacting protein NCOA3. Also phosphorylates FOXO3 and may regulate this pro-apoptotic transcription factor (PubMed:15084260).<ref>PMID:12789342</ref> <ref>PMID:15084260</ref> <ref>PMID:17434128</ref> <ref>PMID:20434986</ref> <ref>PMID:20501937</ref> <ref>PMID:21765415</ref> 
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Biswas T]]
[[Category: Ghosh G]]
[[Category: Huang D]]
[[Category: Lyumkis D]]
[[Category: Passos D]]
[[Category: Polley S]]
[[Category: Verma I]]