AIM2
GeneName
AIM2
Summary
AIM2, also known as AIM-2, is a 39 kDa protein that functions primarily as a pattern recognition receptor, playing a crucial role in the innate immune response. It is located in various cellular compartments including the cytoplasm, mitochondrion, and nucleus, and is involved in the assembly of the AIM2 inflammasome complex. AIM2 binds to double-stranded DNA, which activates signalling pathways that lead to the production of pro-inflammatory cytokines, such as interleukin-1 beta. This protein is also implicated in cellular responses to DNA damage and has a role in brain development and neuron cellular homeostasis.
Importance
AIM2 is relevant to: - The activation of the innate immune response and the assembly of the AIM2 inflammasome, which are critical for host defence against viral infections. - The regulation of inflammatory responses, influencing conditions such as autoimmune diseases and chronic inflammation. - The cellular response to interferon-beta, highlighting its role in antiviral immunity. - The modulation of NF-kappaB activity, which is important in various signalling pathways related to inflammation and immune responses.
Top Products
For researchers investigating AIM2, we highly recommend the well-cited polyclonal antibody, Anti-AIM2 antibody (ab93015). This antibody has garnered 49 citations, reflecting its reliability and trust within the scientific community. It is particularly effective for Western blotting (WB) and immunohistochemistry (IHC), making it a versatile choice for various experimental needs. Its proven performance in these applications will support your research endeavours in studying AIM2 effectively.
Abcam Product Citation Summary
The AIM2 target has been studied in various human contexts, particularly in relation to liver diseases such as chronic hepatitis B and HBV-associated glomerulonephritis. The use of Abcam antibody ab93015 in both immunohistochemistry and western blotting highlights its versatility in detecting AIM2 in different cell types and conditions, including responses to viral infections.
Abcam Product Citation Table
Domain
The pyrin domain mediates homotypic interaction with PYCARD/ASC (PubMed:19158675, PubMed:19158676).
The HIN-200 domain mediates dsDNA binding via electrostatic interactions.
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).
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).
Post-translational modifications
Degraded via selective autophagy following interaction with TRIM11.
Sequence Similarities
Belongs to the HIN-200 family.
Tissue Specificity
Expressed in spleen, small intestine, peripheral blood leukocytes, and testis.
Cellular localization
- Cytoplasm
- Inflammasome
- Nucleus
- 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).
Alternative names
Interferon-inducible protein AIM2, Absent in melanoma 2, AIM2