Aim2
entrez
383619
canonical
uniprot
Q91VJ1
canonical
ensembl
ENSMUSG00000037860
resolver
ensp
ENSMUSP00000119465
resolver
ensp
ENSMUSP00000132253
resolver
enst
ENSMUST00000147604
resolver
enst
ENSMUST00000166137
resolver
genesymbol
Aim2
resolver
genesymbol_syn
Gm1313
resolver
genesymbol_syn
Ifi210
resolver
uniprot_entry
AIM2_MOUSE
resolver
activity_regulation
ACTIVITY REGULATION: Inactive in absence of double-stranded DNA (dsDNA) (By similarity). Homooligomerizes upon binding to dsDNA, dsDNA serving as an oligomerization platform (By similarity). AIM2 requires large dsDNA to generate a structural template that couples dsDNA ligand-binding and homooligomerization (By similarity). Homooligomerization is followed by recruitment of PYCARD/ASC to initiate speck formation (nucleation) (By similarity). AIM2 and PYCARD/ASC homooligomer filaments assemble bidirectionally and the recognition between AIM2 and PYCARD/ASC oligomers occurs in a head-to-tail manner (By similarity). Clustered PYCARD/ASC nucleates the formation of CASP1 filaments through the interaction of their respective CARD domains, acting as a platform for CASP1 polymerization and activation (By similarity). Active CASP1 then specifically processes protein precursors, such as gasdermin-D (GSDMD), IL1B and IL18, leading to the release of mature cytokines in the extracellular milieu or pyroptosis, depending on cell type (PubMed:27846608, PubMed:32350463). AIM2 can be activated in response to events that cause genomic DNA (HIV protease inhibitor nelfinavir) or mitochondrial DNA release in the cytoplasm (such as Perfluoroalkyl substance pollutants or cholesterol overload) (PubMed:27462105, PubMed:29033131, PubMed:34006824). Activation of the AIM2 inflammasome is inhibited by IFI202 (PubMed:19131592, PubMed:23850291). Activation of the AIM2 inflammasome is inhibited by TRIM11, which promotes autophagy-dependent degradation of AIM2 (By similarity). {ECO:0000250|UniProtKB:O14862, ECO:0000269|PubMed:19131592, ECO:0000269|PubMed:23850291, ECO:0000269|PubMed:27462105, ECO:0000269|PubMed:27846608, ECO:0000269|PubMed:29033131, ECO:0000269|PubMed:32350463, ECO:0000269|PubMed:34006824}.
uniprot
proteins
amino_acid_sequence
MESEYREMLLLTGLDHITEEELKRFKYFALTEFQIARSTLDVADRTELADHLIQSAGAASAVTKAINIFQKLNYMHIANALEEKKKEAERKLMTNTKKRGTQKVENRSQAENCSAASATRSDNDFKEQAATEVCPQAKPQKKQMVAEQEAIREDLQKDPLVVTVLKAINPFECETQEGRQEIFHATVATETDFFFVKVLNAQFKDKFIPKRTIKISNYLWHSNFMEVTSSSVVVDVESNHEVPNNVVKRARETPRISKLKIQPCGTIVNGLFKVQKITEEKDRVLYGIHDKTGTMEVLVLGNPSKTKCEEGDKIRLTFFEVSKNGVKIQLKSGPCSFFKVIKAAKPKTDMKSVE
uniprot
proteins
function
FUNCTION: Sensor component of the AIM2 inflammasome, which mediates inflammasome activation in response to the presence of double-stranded DNA (dsDNA) in the cytosol, leading to subsequent pyroptosis (PubMed:19131592, PubMed:19158675, PubMed:19158676, PubMed:19158679, PubMed:20351692, PubMed:20351693, PubMed:20417169, PubMed:20457908, PubMed:21902795, PubMed:23567559, PubMed:32350463, PubMed:34006824). Inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens and other damage-associated signals and play critical roles in innate immunity and inflammation (PubMed:19131592, PubMed:19158675, PubMed:19158676, PubMed:20351692, PubMed:20351693, PubMed:20417169, PubMed:20457908, PubMed:21902795, PubMed:23567559, PubMed:32350463). Acts as a recognition receptor (PRR): specifically recognizes and binds dsDNA in the cytosol, and mediates the formation of the inflammasome polymeric complex composed of AIM2, CASP1 and PYCARD/ASC (PubMed:19131592, PubMed:19158675, PubMed:19158676, PubMed:20351692, PubMed:20351693, PubMed:20417169, PubMed:20457908, PubMed:21902795, PubMed:23567559). Recruitment of pro-caspase-1 (proCASP1) to the AIM2 inflammasome promotes caspase-1 (CASP1) activation, which subsequently cleaves and activates inflammatory cytokines IL1B and IL18 and gasdermin-D (GSDMD), promoting cytokine secretion (PubMed:19158676). In some cells, CASP1 activation mediates cleavage and activation of GSDMD, triggering pyroptosis without promoting cytokine secretion (PubMed:27846608, PubMed:32350463). Detects cytosolic dsDNA of viral and bacterial origin in a non-sequence-specific manner (PubMed:19131592, PubMed:19158675, PubMed:20351692, PubMed:23567559). Involved in the DNA damage response caused by acute ionizing radiation by mediating pyroptosis of intestinal epithelial cells and bone marrow cells in response to double-strand DNA breaks (PubMed:27846608). Mechanistically, AIM2 senses DNA damage in the nucleus to mediate inflammasome assembly and inflammatory cell death (PubMed:27846608). Also acts as a regulator of neurodevelopment via its role in the DNA damage response: acts by promoting neural cell death in response to DNA damage in the developing brain, thereby purging genetically compromised cells of the central nervous system (PubMed:32350463). Pyroptosis mediated by the AIM2 inflammasome in response to DNA damage is dependent on GSDMD without involving IL1B and IL18 cytokine secretion (PubMed:27846608, PubMed:32350463). Also acts as a mediator of pyroptosis, necroptosis and apoptosis (PANoptosis), an integral part of host defense against pathogens, in response to bacterial infection (PubMed:34471287). Can also trigger PYCARD/ASC-dependent, caspase-1-independent cell death that involves caspase-8 (CASP8) (PubMed:22555457). {ECO:0000269|PubMed:19131592, ECO:0000269|PubMed:19158675, ECO:0000269|PubMed:19158676, ECO:0000269|PubMed:19158679, ECO:0000269|PubMed:20351692, ECO:0000269|PubMed:20351693, ECO:0000269|PubMed:20417169, ECO:0000269|PubMed:20457908, ECO:0000269|PubMed:21902795, ECO:0000269|PubMed:22555457, ECO:0000269|PubMed:23567559, ECO:0000269|PubMed:27846608, ECO:0000269|PubMed:32350463, ECO:0000269|PubMed:34006824, ECO:0000269|PubMed:34471287}.; FUNCTION: Also acts as a tumor suppressor independently of its role in inflammatory response (PubMed:26095253). Able to suppress overt cell proliferation in enterocytes: restricts stem cell proliferation in the intestinal mucosa in an inflammasome-independent manner, contributing to a decrease in the likelihood of colorectal cancer development (PubMed:26095253, PubMed:26107252). AIM2 suppresses cell proliferation by inhibiting phosphorylation of AKT1 at 'Ser-473', preventing AKT1 activation and AKT-mTOR signaling pathway (PubMed:26095253, PubMed:26107252). Inhibits AKT1 phosphorylation both by inhibiting the activity of PRKDC/DNA-PK kinase and promoting dephosphorylation by PP2A phosphatase (PubMed:26107252, PubMed:33505023). Also acts as a key regulator of regulatory T-cells (Treg) homeostasis by promoting their stability: acts by preventing AKT1 activation (PubMed:33505023). Its role in Treg homeostasis is important to restain autoimmune diseases (PubMed:33505023). {ECO:0000269|PubMed:26095253, ECO:0000269|PubMed:26107252, ECO:0000269|PubMed:33505023}.
uniprot
proteins
mass_dalton
40155
uniprot
proteins
post_translational_modification
PTM: Degraded via selective autophagy following interaction with TRIM11. {ECO:0000250|UniProtKB:O14862}.
uniprot
proteins
protein_family
HIN-200 family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15896773
uniprot
proteins
pubmed
19131592
uniprot
proteins
pubmed
19158675
uniprot
proteins
pubmed
19158676
uniprot
proteins
pubmed
19158679
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
20351692
uniprot
proteins
pubmed
20351693
uniprot
proteins
pubmed
20417169
uniprot
proteins
pubmed
20457908
uniprot
proteins
pubmed
21902795
uniprot
proteins
pubmed
22555457
uniprot
proteins
pubmed
23567559
uniprot
proteins
pubmed
23850291
uniprot
proteins
pubmed
25888795
uniprot
proteins
pubmed
26095253
uniprot
proteins
pubmed
26107252
uniprot
proteins
pubmed
27462105
uniprot
proteins
pubmed
27561456
uniprot
proteins
pubmed
27846608
uniprot
proteins
pubmed
29033131
uniprot
proteins
pubmed
32350463
uniprot
proteins
pubmed
33505023
uniprot
proteins
pubmed
34006824
uniprot
proteins
pubmed
34471287
uniprot
proteins
sequence_length
354
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19158679, ECO:0000269|PubMed:22555457}. Inflammasome {ECO:0000269|PubMed:19158679, ECO:0000269|PubMed:27846608}. Nucleus {ECO:0000269|PubMed:27846608}. Note=Activated inflammasomes can aggregate in the cytosol as speck-like particles (PubMed:19158679). Activated inflammasomes can also aggregate in the nucleus in response to DNA damage: AIM2 is recruited to double-strand DNA breaks and mediates activation of the AIM2 inflammasome (PubMed:27846608). {ECO:0000269|PubMed:19158679, ECO:0000269|PubMed:27846608}.
uniprot
proteins