AIM2

 Interferon-inducible protein AIM2 also known as absent in melanoma 2 or simply AIM2 is a protein that in humans is encoded by the AIM2 gene.^[5][6] Recent research has shown that AIM2 is part of the inflammasome and contributes to the defence against bacterial and viral DNA.^[7]

AIM2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3RN2, 3RN5, 3VD8, 4O7Q
Identifiers
Aliases	AIM2, PYHIN4, absent in melanoma 2
External IDs	OMIM: 604578 MGI: 2686159 HomoloGene: 83226 GeneCards: AIM2
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1q23.1-q23.2 Start 159,062,484 bp[1] End 159,147,096 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1|1 H3 Start 173,350,879 bp[2] End 173,466,040 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • DNA binding • GO:0001948 protein binding • identical protein binding • double-stranded DNA binding Cellular component • cytoplasm • AIM2 inflammasome complex • cell nucleus • nucleoplasm • mitochondrion • cytosol Biological process • positive regulation of cysteine-type endopeptidase activity • pyroptosis • cellular response to interferon-beta • immune system process • tumor necrosis factor-mediated signaling pathway • cellular response to drug • positive regulation of NF-kappaB transcription factor activity • immune response • positive regulation of interleukin-1 beta production • positive regulation of protein oligomerization • activation of innate immune response • inflammatory response • negative regulation of NF-kappaB transcription factor activity • positive regulation of defense response to virus by host • apoptotic process • innate immune system Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	9447	383619
Ensembl	ENSG00000163568	ENSMUSG00000037860
UniProt	O14862	Q91VJ1
RefSeq (mRNA)	NM_004833 NM_001348247	NM_001013779
RefSeq (protein)	NP_004824 NP_001335176	NP_001013801
Location (UCSC)	Chr 1: 159.06 – 159.15 Mb	Chr 1: 173.35 – 173.47 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

StructureEdit

AIM2 is a 343 amino acid protein with a N-terminal DAPIN (or pyrin) domain (amino acids 1-87) and a C-terminal HIN-200 domain (amino acids 138-337), which is known to have two oligonucleotide-binding folds.^[8]

FunctionEdit

AIM2 is a member of the Ifi202/IFI16 family. It plays a putative role in tumorigenic reversion and may control cell proliferation. Interferon-gamma induces expression of AIM2.^[6]

Though there has been virtually no biochemistry performed, a model based on cell-based or in vivo experiments has led to the current model of how AIM2 triggers the inflammasome. The C-terminal HIN domain binds double stranded DNA (either viral, bacterial, or even host) and acts as a cytosolic dsDNA sensor. This leads to the oligomerization of the inflammasome complex. The N-terminal pyrin domain of AIM2 interacts with the pyrin domain of another protein ASC (or Apoptosis-associated Speck-like protein containing a caspase activation and recruitment domain). ASC also contains a CARD domain (caspase activation and recruitment domain), that recruits procaspase-1 to the complex. This leads to the autoactivation of caspase-1, an enzyme that processes proinflammatory cytokines (IL-1b and IL-18).^[7] AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity.^[9]

Clinical relevanceEdit

Elevated levels of AIM2 expression are found in skin cells from people with psoriasis.^[10] In systemic lupus erythematosus, lysosome dysfunction allows DNA to gain access to the cytosol and activate AIM2 resulting in increased type 1 interferon production.^[11]

This article uses material from the Wikipedia article  Metasyntactic variable, which is released under the  Creative Commons Attribution-ShareAlike 3.0 Unported License.