AIM2
entrez
9447
canonical
uniprot
O14862
canonical
ensembl
ENSG00000163568
resolver
ensp
ENSP00000357112
resolver
ensp
ENSP00000512038
resolver
ensp
ENSP00000512039
resolver
ensp
ENSP00000512040
resolver
ensp
ENSP00000520906
resolver
ensp
ENSP00000583901
resolver
enst
ENST00000368130
resolver
enst
ENST00000411768
resolver
enst
ENST00000695580
resolver
enst
ENST00000850621
resolver
enst
ENST00000913842
resolver
genesymbol
AIM2
resolver
hgnc
HGNC:357
resolver
uniprot
A8K7M7
resolver
uniprot
Q5T3V9
resolver
uniprot
Q96FG9
resolver
uniprot_entry
AIM2_HUMAN
resolver
uniprot_sec
A8K7M7
resolver
uniprot_sec
Q5T3V9
resolver
uniprot_sec
Q96FG9
resolver
activity_regulation
ACTIVITY REGULATION: Inactive in absence of double-stranded DNA (dsDNA) (PubMed:22483801, PubMed:26197926). Homooligomerizes upon binding to dsDNA, dsDNA serving as an oligomerization platform (PubMed:26197926, PubMed:33980849). AIM2 requires large dsDNA to generate a structural template that couples dsDNA ligand-binding and homooligomerization (PubMed:26197926). Homooligomerization is followed by recruitment of PYCARD/ASC to initiate speck formation (nucleation) (PubMed:22483801, PubMed:26197926, PubMed:29440442, PubMed:33980849). AIM2 and PYCARD/ASC homooligomer filaments assemble bidirectionally and the recognition between AIM2 and PYCARD/ASC oligomers occurs in a head-to-tail manner (PubMed:33980849). 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 (PubMed:19158675, PubMed:19158676). 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:16432157, PubMed:19158675, PubMed:19158676). 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) (By similarity). Activation of the AIM2 inflammasome is inhibited by isoform IFI16-beta of IFI16, which prevents the interaction between AIM2 and PYCARD/ASC (PubMed:30104205). Activation of the AIM2 inflammasome is inhibited by TRIM11, which promotes autophagy-dependent degradation of AIM2 (PubMed:27498865). {ECO:0000250|UniProtKB:Q91VJ1, ECO:0000269|PubMed:16432157, ECO:0000269|PubMed:19158675, ECO:0000269|PubMed:19158676, ECO:0000269|PubMed:22483801, ECO:0000269|PubMed:26197926, ECO:0000269|PubMed:27498865, ECO:0000269|PubMed:29440442, ECO:0000269|PubMed:30104205, ECO:0000269|PubMed:33980849}.
uniprot
proteins
amino_acid_sequence
MESKYKEILLLTGLDNITDEELDRFKFFLSDEFNIATGKLHTANRIQVATLMIQNAGAVSAVMKTIRIFQKLNYMLLAKRLQEEKEKVDKQYKSVTKPKPLSQAEMSPAASAAIRNDVAKQRAAPKVSPHVKPEQKQMVAQQESIREGFQKRCLPVMVLKAKKPFTFETQEGKQEMFHATVATEKEFFFVKVFNTLLKDKFIPKRIIIIARYYRHSGFLEVNSASRVLDAESDQKVNVPLNIIRKAGETPKINTLQTQPLGTIVNGLFVVQKVTEKKKNILFDLSDNTGKMEVLGVRNEDTMKCKEGDKVRLTFFTLSKNGEKLQLTSGVHSTIKVIKAKKKT
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:17726700, PubMed:19158675, PubMed:19158676, PubMed:19158679, PubMed:20566831, PubMed:23530044, PubMed:26197926, PubMed:26583071, PubMed:29440442, PubMed:33980849, PubMed:37364111). 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:17726700, PubMed:19158675, PubMed:19158676, PubMed:19158679, PubMed:20566831, PubMed:26197926, PubMed:29440442, PubMed:33980849). 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:17726700, PubMed:19158675, PubMed:19158676, PubMed:19158679, PubMed:20566831, PubMed:26197926, PubMed:29440442, PubMed:33980849). 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:17726700, PubMed:19158675, PubMed:19158676, PubMed:19158679, PubMed:20566831). In some cells, CASP1 activation mediates cleavage and activation of GSDMD, triggering pyroptosis without promoting cytokine secretion (PubMed:19158675, PubMed:19158676). Detects cytosolic dsDNA of viral and bacterial origin in a non-sequence-specific manner (PubMed:17726700, PubMed:19158675, PubMed:19158676, PubMed:19158679, PubMed:20566831, PubMed:26197926, PubMed:26583071, PubMed:29440442, PubMed:33980849). 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 (By similarity). Mechanistically, AIM2 senses DNA damage in the nucleus to mediate inflammasome assembly and inflammatory cell death (By similarity). 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 (By similarity). Pyroptosis mediated by the AIM2 inflammasome in response to DNA damage is dependent on GSDMD without involving IL1B and IL18 cytokine secretion (By similarity). Also acts as a mediator of pyroptosis, necroptosis and apoptosis (PANoptosis), an integral part of host defense against pathogens, in response to bacterial infection (By similarity). Can also trigger PYCARD/ASC-dependent, caspase-1-independent cell death that involves caspase-8 (CASP8) (By similarity). {ECO:0000250|UniProtKB:Q91VJ1, ECO:0000269|PubMed:17726700, ECO:0000269|PubMed:19158675, ECO:0000269|PubMed:19158676, ECO:0000269|PubMed:19158679, ECO:0000269|PubMed:20566831, ECO:0000269|PubMed:23530044, ECO:0000269|PubMed:26197926, ECO:0000269|PubMed:26583071, ECO:0000269|PubMed:29440442, ECO:0000269|PubMed:33980849, ECO:0000269|PubMed:37364111}.; FUNCTION: Also acts as a tumor suppressor independently of its role in inflammatory response (PubMed:16432157). 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 (By similarity). AIM2 suppresses cell proliferation by inhibiting phosphorylation of AKT1 at 'Ser-473', preventing AKT1 activation and AKT-mTOR signaling pathway (By similarity). Inhibits AKT1 phosphorylation both by inhibiting the activity of PRKDC/DNA-PK kinase and promoting dephosphorylation by PP2A phosphatase (By similarity). Also acts as a key regulator of regulatory T-cells (Treg) homeostasis by promoting their stability: acts by preventing AKT1 activation (By similarity). Its role in Treg homeostasis is important to restain autoimmune diseases (By similarity). {ECO:0000250|UniProtKB:Q91VJ1, ECO:0000269|PubMed:16432157}.
uniprot
proteins
mass_dalton
38954
uniprot
proteins
mutagenesis
MUTAGEN 10..11; /note="LL->AA: Impaired double-stranded DNA (dsDNA)-binding, preventing homooligomerization."; /evidence="ECO:0000269|PubMed:26197926"; MUTAGEN 11; /note="L->A: Impaired homooligomerization."; /evidence="ECO:0000269|PubMed:33980849"; MUTAGEN 14; /note="L->A: Fails to activate interleukin-1 beta production."; /evidence="ECO:0000269|PubMed:19158679"; MUTAGEN 19..23; /note="DEELD->AAALA: In Mut2; abolished interaction with PYCARD/ASC. Abolished ability to bind double-stranded DNA (dsDNA)."; /evidence="ECO:0000269|PubMed:23530044, ECO:0000269|PubMed:26197926"; MUTAGEN 21; /note="E->K: Impaired ability to nucleate with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33980849"; MUTAGEN 23; /note="D->K: Impaired homooligomerization."; /evidence="ECO:0000269|PubMed:33980849"; MUTAGEN 27..28; /note="FF->AA: In Mut1; abolished interaction with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:23530044"; MUTAGEN 27; /note="F->G: Abolished ability to homooligomerize."; /evidence="ECO:0000269|PubMed:24406744"; MUTAGEN 27; /note="F->L: Strongly impaired ability to homooligomerize."; /evidence="ECO:0000269|PubMed:24406744"; MUTAGEN 27; /note="F->W,Y: Impaired ability to homooligomerize."; /evidence="ECO:0000269|PubMed:24406744"; MUTAGEN 36; /note="A->R,D: Impaired homooligomerization."; /evidence="ECO:0000269|PubMed:33980849"; MUTAGEN 46; /note="I->D: Impaired homooligomerization."; /evidence="ECO:0000269|PubMed:33980849"; MUTAGEN 50; /note="T->A: Impaired double-stranded DNA (dsDNA)-binding, preventing homooligomerization."; /evidence="ECO:0000269|PubMed:26197926"; MUTAGEN 73; /note="N->L: Impaired ability to form AIM2 inflammasome filaments in response to double-stranded DNA (dsDNA)."; /evidence="ECO:0000269|PubMed:33980849"; MUTAGEN 75; /note="M->D: Impaired ability to nucleate with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33980849"; MUTAGEN 147; /note="E->A: Strongly reduced ability to homooligomerize upon double-stranded DNA (dsDNA)-binding."; /evidence="ECO:0000269|PubMed:26197926"; MUTAGEN 160; /note="K->A: Impairs DNA binding; when associated with A-160; A-K162; A-163; A-198; A-204. Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204; A-244; A-251; A-309; A-311; A-355 and A-337."; /evidence="ECO:0000269|PubMed:22483801"; MUTAGEN 162; /note="K->A: Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204; A-244; A-251; A-309; A-311; A-355 and A-337."; /evidence="ECO:0000269|PubMed:22483801"; MUTAGEN 163; /note="K->A: Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204; A-244; A-251; A-309; A-311; A-355 and A-337."; /evidence="ECO:0000269|PubMed:22483801"; MUTAGEN 165; /note="F->A: Impairs DNA binding."; /evidence="ECO:0000269|PubMed:19158679"; MUTAGEN 167; /note="F->A: Strongly reduced ability to homooligomerize upon double-stranded DNA (dsDNA)-binding."; /evidence="ECO:0000269|PubMed:26197926"; MUTAGEN 173; /note="K->A: Impaired double-stranded DNA (dsDNA)-binding, preventing homooligomerization."; /evidence="ECO:0000269|PubMed:26197926"; MUTAGEN 198; /note="K->A: Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204; A-244; A-251; A-309; A-311; A-355 and A-337."; /evidence="ECO:0000269|PubMed:22483801"; MUTAGEN 204; /note="K->A: Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204; A-244; A-251; A-309; A-311; A-355 and A-337."; /evidence="ECO:0000269|PubMed:22483801"; MUTAGEN 244; /note="R->A: Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204; A-244; A-251; A-309; A-311; A-355 and A-337."; /evidence="ECO:0000269|PubMed:22483801"; MUTAGEN 251; /note="K->A: Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204; A-244; A-251; A-309; A-311; A-355 and A-337."; /evidence="ECO:0000269|PubMed:22483801"; MUTAGEN 258; /note="Q->A: Impaired double-stranded DNA (dsDNA)-binding, preventing homooligomerization."; /evidence="ECO:0000269|PubMed:26197926"; MUTAGEN 272; /note="K->A: Strongly reduced ability to homooligomerize upon double-stranded DNA (dsDNA)-binding."; /evidence="ECO:0000269|PubMed:26197926"; MUTAGEN 309; /note="K->A: Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204; A-244; A-251; A-309; A-311; A-355 and A-337."; /evidence="ECO:0000269|PubMed:22483801"; MUTAGEN 311; /note="R->A: Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204; A-244; A-251; A-309; A-311; A-355 and A-337."; /evidence="ECO:0000269|PubMed:22483801"; MUTAGEN 335; /note="K->A: Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204; A-244; A-251; A-309; A-311; A-355 and A-337."; /evidence="ECO:0000269|PubMed:22483801"; MUTAGEN 337; /note="I->A: Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204; A-244; A-251; A-309; A-311; A-355 and A-337."; /evidence="ECO:0000269|PubMed:22483801
uniprot
proteins
post_translational_modification
PTM: Degraded via selective autophagy following interaction with TRIM11. {ECO:0000269|PubMed:27498865}.
uniprot
proteins
protein_family
HIN-200 family
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15582594
uniprot
proteins
pubmed
16432157
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17726700
uniprot
proteins
pubmed
19158675
uniprot
proteins
pubmed
19158676
uniprot
proteins
pubmed
19158679
uniprot
proteins
pubmed
20566831
uniprot
proteins
pubmed
22046441
uniprot
proteins
pubmed
22483801
uniprot
proteins
pubmed
22801494
uniprot
proteins
pubmed
22869553
uniprot
proteins
pubmed
23530044
uniprot
proteins
pubmed
24406744
uniprot
proteins
pubmed
24531343
uniprot
proteins
pubmed
26197926
uniprot
proteins
pubmed
26583071
uniprot
proteins
pubmed
27498865
uniprot
proteins
pubmed
29440442
uniprot
proteins
pubmed
30104205
uniprot
proteins
pubmed
33980849
uniprot
proteins
pubmed
37364111
uniprot
proteins
pubmed
8454910
uniprot
proteins
pubmed
9242382
uniprot
proteins
sequence_length
343
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19158675, ECO:0000269|PubMed:19158676, ECO:0000269|PubMed:19158679, ECO:0000269|PubMed:24531343, ECO:0000269|PubMed:8454910}. Inflammasome {ECO:0000269|PubMed:19158676, ECO:0000269|PubMed:19158679}. Nucleus {ECO:0000269|PubMed:15582594}. Note=Activated inflammasomes can aggregate in the cytosol as speck-like particles (PubMed:19158675, PubMed:19158676, 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 (By similarity). {ECO:0000250|UniProtKB:Q91VJ1, ECO:0000269|PubMed:19158675, ECO:0000269|PubMed:19158676, ECO:0000269|PubMed:19158679}.
uniprot
proteins