AIM2


Interferon-inducible protein AIM2 also known as absent in melanoma 2 or simply AIM2 is a protein that in humans is encoded by the AIM2 gene. Recent research has shown that AIM2 is part of the inflammasome and contributes to the defence against bacterial and viral DNA.

Structure

AIM2 is a 343 amino acid protein with a N-terminal DAPIN domain and a C-terminal HIN-200 domain, which is known to have two oligonucleotide-binding folds.

Function

AIM2 is a member of the Ifi202/IFI16 family. It plays a putative role in tumorigenic reversion and may control cell proliferation. Interferon-gamma induces expression of AIM2.
Though there has been virtually no biochemistry performed, a model based on cell-based or in vivo experiments has led to the current model of how AIM2 triggers the inflammasome. The C-terminal HIN domain binds double stranded DNA and acts as a cytosolic dsDNA sensor. This leads to the oligomerization of the inflammasome complex. The N-terminal pyrin domain of AIM2 interacts with the pyrin domain of another protein ASC. ASC also contains a CARD domain, that recruits procaspase-1 to the complex. This leads to the autoactivation of caspase-1, an enzyme that processes proinflammatory cytokines.
AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity.

Clinical relevance

Elevated levels of AIM2 expression are found in skin cells from people with psoriasis. In systemic lupus erythematosus, lysosome dysfunction allows DNA to gain access to the cytosol and activate AIM2 resulting in increased type 1 interferon production.