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MGP003907

UniProt Annotations

Entry Information
Gene Nameabsent in melanoma 2
Protein EntryAIM2_HUMAN
UniProt IDO14862
SpeciesHuman
Comments
Comment typeDescription
DomainThe DAPIN domain mediates homotypic interaction with PYCARD (PubMed:19158676, PubMed:19158675). {ECO:0000269|PubMed:19158675, ECO:0000269|PubMed:19158676}.
DomainThe HIN-20 domain mediates dsDNA binding via electrostatic interactions. {ECO:0000269|PubMed:22483801}.
Enzyme RegulationIn absence of dsDNA DAPIN and HIN-20 domain can interact inducing a closed conformation; an autoinhibitory mechanism is proposed in which binding to dsDNA liberates the DAPIN domain for homotypic downstream signaling interactions with PYCARD. {ECO:0000269|PubMed:22483801}.
FunctionInvolved in innate immune response by recognizing cytosolic double-stranded DNA and inducing caspase-1-activating inflammasome formation in macrophages. Upon binding to DNA is thought to undergo oligomerization and to associate with PYCARD initiating the recruitment of caspase-1 precusrsor and processing of interleukin-1 beta and interleukin-18. Detects cytosolic dsDNA of viral and bacterial origin in a non-sequence-specific manner. Can also trigger PYCARD-dependent, caspase-1-independent cell death that involves caspase-8 (By similarity). Tumor suppressor which may act by repressing NF-kappa-B transcriptional activity. {ECO:0000250, ECO:0000269|PubMed:16432157, ECO:0000269|PubMed:17726700, ECO:0000269|PubMed:19158675, ECO:0000269|PubMed:19158676, ECO:0000269|PubMed:19158679, ECO:0000269|PubMed:20566831}.
InductionBy IFNG/IFN-gamma and IFNB1/IFN-beta. {ECO:0000269|PubMed:15582594, ECO:0000269|PubMed:19158679, ECO:0000269|PubMed:9242382}.
InteractionSelf; NbExp=2; IntAct=EBI-6253193, EBI-6253193; Q9ULZ3:PYCARD; NbExp=5; IntAct=EBI-6253193, EBI-751215;
MiscellaneousDefects in AIM2 may be a cause of microsatellite unstable colon cancers.
Sequence CautionSequence=AAH10940.1; Type=Frameshift; Positions=340; Evidence={ECO:0000305};
SimilarityBelongs to the HIN-200 family. {ECO:0000305}.
SimilarityContains 1 DAPIN domain. {ECO:0000255|PROSITE- ProRule:PRU00061}.
SimilarityContains 1 HIN-200 domain. {ECO:0000255|PROSITE- ProRule:PRU00106}.
Subcellular LocationNucleus. Cytoplasm. Note=Activated inflammasomes can aggregate in the cytosol as speck-like particles.
SubunitSelf-associates; forms homooligomers in response to cytosolic dsDNA and the dsDNA seems to serve as oligomerization platform. Component of the AIM2 inflammasome. Interacts with PYCARD, IFI16, EIF2AK2/PKR and MAPRE1. {ECO:0000269|PubMed:15582594, ECO:0000269|PubMed:19158675, ECO:0000269|PubMed:19158676, ECO:0000269|PubMed:19158679, ECO:0000269|PubMed:22046441, ECO:0000269|PubMed:22483801, ECO:0000269|PubMed:22801494, ECO:0000269|PubMed:22869553}.
Tissue SpecificityExpressed in spleen, small intestine, peripheral blood leukocytes, and testis. {ECO:0000269|PubMed:9242382}.
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