View source for 9y4l


==CryoEM Structure of human MDA5 in complex with dsRNA (two protein subunits on dsRNA)==
<StructureSection load='9y4l' size='340' side='right'caption='[[9y4l]], [[Resolution|resolution]] 2.96&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9y4l]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/In_vitro_transcription_vector_pT7-Fluc(deltai) In vitro transcription vector pT7-Fluc(deltai)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9Y4L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9Y4L FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.96&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</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=9y4l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9y4l OCA], [https://pdbe.org/9y4l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9y4l RCSB], [https://www.ebi.ac.uk/pdbsum/9y4l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9y4l ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/IFIH1_HUMAN IFIH1_HUMAN] Genetic variation in IFIH1 is associated with diabetes mellitus insulin-dependent type 19 (IDDM19) [MIM:[https://omim.org/entry/610155 610155]. A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.<ref>PMID:16699517</ref>   Note=IFIH1 is the CADM-140 autoantigen, involved in clinically amyopathic dermatomyositis (CADM). This is a chronic inflammatory disorder that shows typical skin manifestations of dermatomyositis but has no or little evidence of clinical myositis. Anti-CADM-140 antibodies appear to be specific to dermatomyositis, especially CADM. Patients with anti-CADM-140 antibodies frequently develop life-threatening acute progressive interstitial lung disease (ILD).<ref>PMID:19565506</ref> <ref>PMID:20015976</ref> 
== Function ==
[https://www.uniprot.org/uniprot/IFIH1_HUMAN IFIH1_HUMAN] Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and proinflammatory cytokines. Its ligands include mRNA lacking 2'-O-methylation at their 5' cap and long-dsRNA (>1 kb in length). Upon ligand binding it associates with mitochondria antiviral signaling protein (MAVS/IPS1) which activates the IKK-related kinases: TBK1 and IKBKE which phosphorylate interferon regulatory factors: IRF3 and IRF7 which in turn activate transcription of antiviral immunological genes, including interferons (IFNs); IFN-alpha and IFN-beta. Responsible for detecting the Picornaviridae family members such as encephalomyocarditis virus (EMCV) and mengo encephalomyocarditis virus (ENMG). Can also detect other viruses such as dengue virus (DENV), west Nile virus (WNV), and reovirus. Also involved in antiviral signaling in response to viruses containing a dsDNA genome, such as vaccinia virus. Plays an important role in amplifying innate immune signaling through recognition of RNA metabolites that are produced during virus infection by ribonuclease L (RNase L). May play an important role in enhancing natural killer cell function and may be involved in growth inhibition and apoptosis in several tumor cell lines.<ref>PMID:14645903</ref> <ref>PMID:19211564</ref> <ref>PMID:19656871</ref> <ref>PMID:21742966</ref> <ref>PMID:21217758</ref> 
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chung K]]
[[Category: Pyle A]]
[[Category: Xu L]]