AIM2
AIM2 (absent in melanoma 2, also known as PYHIN4) is an interferon-inducible protein of the HIN-200 family. It localises to the cytoplasm, nucleus and inflammasome, and acts as a tumour suppressor and regulator of regulatory T-cell homeostasis. Browse Assay Genie's current range of AIM2 research reagents below, or read on for the biology behind the target.
AIM2 is best known as a component of the inflammasome, and UniProt annotates it as acting as a tumour suppressor independently of its role in the inflammatory response. In enterocytes it suppresses overt cell proliferation and restricts stem cell proliferation in the intestinal mucosa in an inflammasome-independent manner, which contributes to a lower likelihood of colorectal cancer development.
Mechanistically, AIM2 suppresses proliferation by inhibiting phosphorylation of AKT1 at Ser-473, which prevents AKT1 activation and dampens signalling through the AKT-mTOR pathway. It does this in two ways: by inhibiting the activity of the PRKDC/DNA-PK kinase and by promoting dephosphorylation by PP2A phosphatase. By preventing AKT1 activation, AIM2 also promotes the stability of regulatory T-cells (Treg), and this role in Treg homeostasis is important for restraining autoimmune disease.
The AIM2 gene encodes a protein that belongs to the HIN-200 family. HGNC places it in the pyrin domain containing group and the pyrin and HIN domain family, and NCBI Gene describes it as a member of the IFI20X/IFI16 family. Its name reflects its original description as absent in melanoma. NCBI Gene notes a putative role in tumorigenic reversion and a possible role in controlling cell proliferation, and records that interferon-gamma induces AIM2 expression. The mouse ortholog is Aim2, which allows the pathway to be studied in murine models.
AIM2 is found in the inflammasome compartment, making it a focus for studies of innate immune complexes and inflammatory signalling.
AIM2 restricts intestinal stem cell proliferation in the mucosa, lowering the likelihood of colorectal cancer development in an inflammasome-independent manner.
AIM2 inhibits AKT1 Ser-473 phosphorylation through PRKDC/DNA-PK inhibition and PP2A-mediated dephosphorylation, preventing AKT-mTOR pathway activation.
AIM2 promotes regulatory T-cell stability by preventing AKT1 activation, a role important for restraining autoimmune disease.
AIM2 acts as a tumour suppressor independently of inflammation. It inhibits AKT1 phosphorylation at Ser-473, limiting AKT-mTOR signalling and cell proliferation, including in intestinal enterocytes. It also promotes regulatory T-cell stability by preventing AKT1 activation, which helps restrain autoimmune disease.
The HGNC name is absent in melanoma 2, and the UniProt protein name is interferon-inducible protein AIM2. PYHIN4 is a recorded alias. The gene sits in the pyrin domain containing group and the pyrin and HIN domain family, and the protein belongs to the HIN-200 family.
A mouse ortholog, Aim2, exists. UniProt links AIM2 to suppression of colorectal cancer development and to restraint of autoimmune disease through Treg homeostasis. NCBI Gene notes a putative role in tumorigenic reversion. Check the datasheet of any product for its validated reactivity.
Other proteins with related names or roles in inflammasome, interferon and proliferation research, with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt O14862; product specifications from Assay Genie datasheets.