2n5k: Difference between revisions

<StructureSection load='2n5k' size='340' side='right' caption='[[2n5k]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>

<table><tr><td colspan='2'>[[2n5k]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N5K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2N5K FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2n5j|2n5j]], [[2n5l|2n5l]]</td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Zc3h12a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=2n5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n5k OCA], [http://pdbe.org/2n5k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2n5k RCSB], [http://www.ebi.ac.uk/pdbsum/2n5k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2n5k ProSAT]</span></td></tr>

[[http://www.uniprot.org/uniprot/ZC12A_MOUSE ZC12A_MOUSE]] Increased expression of ZC3H12A is associated with ischemic heart disease (PubMed:16574901).<ref>PMID:16574901</ref>   

[[http://www.uniprot.org/uniprot/ZC12A_MOUSE ZC12A_MOUSE]] Bifunctional enzyme with both endoribonuclease and deubiquitinase activities involved in various biological functions such as cellular inflammatory response and immune homeostasis, glial differentiation of neuroprogenitor cells, cell death of cardiomyocytes, adipogenesis and angiogenesis. Functions as an endoribonuclease involved in mRNA decay (PubMed:26000482). Modulates the inflammatory response by promoting the degradation of a set of translationally active cytokine-induced inflammation-related mRNAs, such as IL6 and IL12B, during the early phase of inflammation (PubMed:19322177, PubMed:21115689, PubMed:23185455, PubMed:26000482). Prevents aberrant T-cell-mediated immune reaction by degradation of multiple mRNAs controlling T-cell activation, such as those encoding cytokines (IL6 and IL2), cell surface receptors (ICOS, TNFRSF4 and TNFR2) and transcription factor (REL) (PubMed:23706741). Self regulates by destabilizing its own mRNA (PubMed:22037600). Cleaves mRNA harboring a stem-loop (SL), often located in their 3'-UTRs, during the early phase of inflammation in a helicase UPF1-dependent manner (PubMed:19322177, PubMed:23185455, PubMed:23706741, PubMed:26000482, PubMed:26134560). Plays a role in the inhibition of microRNAs (miRNAs) biogenesis (By similarity). Cleaves the terminal loop of a set of precursor miRNAs (pre-miRNAs) important for the regulation of the inflammatory response leading to their degradation, and thus preventing the biosynthesis of mature miRNAs (By similarity). Plays also a role in promoting angiogenesis in response to inflammatory cytokines by inhibiting the production of antiangiogenic microRNAs via its anti-dicer RNase activity (By similarity). Functions as a deubiquitinase that affects the overall ubiquitination of cellular proteins (PubMed:21115689). Possesses deubiquitinase activity that specifically cleaves 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains on TNF receptor-associated factors (TRAFs), preventing JNK and NF-kappa-B signaling pathway activation, and hence negatively regulates macrophage-mediated inflammatory response and immune homeostasis (PubMed:21115689). Deubiquitinates also the transcription factor HIF1A, probably leading to its stabilization and nuclear import, thereby positively regulating the expression of proangiogenic HIF1A-targeted genes (By similarity). Prevents stress granules (SGs) formation and promotes macrophage apoptosis under stress conditions, including arsenite-induced oxidative stress, heat shock, and energy deprivation, which may be dependent on its deubiquitinase activity (PubMed:21971051). Plays a role in the regulation of macrophage polarization; promotes IL4-induced polarization of macrophages M1 into anti-inflammatory M2 state, depending on both endoribonuclease and deubiquitinase activities (PubMed:25934862). May also act as a transcription factor that regulates the expression of multiple genes involved in inflammatory response, angiogenesis, adipogenesis and apoptosis (PubMed:18178554, PubMed:19666473, PubMed:22739135). Functions as a positive regulator of glial differentiation of neuroprogenitor cells through an amyloid precursor protein (APP)-dependent signaling pathway (By similarity). Attenuates septic myocardial contractile dysfunction in response to lipopolysaccharide (LPS) by reducing I-kappa-B-kinase (IKK)-mediated NF-kappa-B activation, and hence myocardial proinflammatory cytokine production (PubMed:21616078).[UniProtKB:Q5D1E8]<ref>PMID:18178554</ref> <ref>PMID:19322177</ref> <ref>PMID:19666473</ref> <ref>PMID:21115689</ref> <ref>PMID:21616078</ref> <ref>PMID:21971051</ref> <ref>PMID:22037600</ref> <ref>PMID:22739135</ref> <ref>PMID:23185455</ref> <ref>PMID:23706741</ref> <ref>PMID:25934862</ref> <ref>PMID:26000482</ref> <ref>PMID:26134560</ref>