Androgen-inducible gene 1 increases the ER Ca2 + content and cell death susceptibility against oxidative stress

•Androgen-induced gene 1 (AIG1) is expressed mainly in the liver, lung and heart.•AIG1 has three splice isoforms with a tissue-specific expression.•AIG1 has five transmembrane domains with a luminal N- and cytosolic C-terminus.•AIG1 over-expression slightly increases susceptibility to oxidative stress.•AIG1 over-expression increases the ER Ca2 + concentration.

Androgen-induced gene 1 (AIG1) is a transmembrane protein implicated with survival (its expression level was shown to correlate with the survival of patients suffering from hepatocellular carcinoma) and Ca2 + signaling (over-expression of AIG1 increased transcription mediated by the Ca2 +-dependent nuclear factor of activated T cells). We aimed to shed light on this less-studied protein and investigated its tissue expression, genomic organization, intracellular localization and membrane topology as well as its effects on cell death susceptibility and the Ca2 + content of the endoplasmic reticulum. Immunoblotting of mouse tissues demonstrated highest expression of AIG1 in the liver, lung and heart. AIG1 has a complex genomic organization and expresses several splice variants in a tissue-dependent manner. Analyzing the topology of AIG1 in the ER membrane using a protease-protection assay suggested that AIG has five transmembrane domains with a luminal N- and cytosolic C-terminus and a hydrophobic stretch between the third and fourth membrane domain that does not cross the membrane. AIG1 over-expression slightly increased susceptibility to oxidative stress, which correlated with an increased ER Ca2 + concentration in two different cell lines. Together, these results indicate that AIG1 plays a role in the control of the intracellular Ca2 + concentration and cell death susceptibility.