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Sigma-1 receptor (Sig-1R, σ1R, also referred to as sigma receptor 1, SigR1) is an endoplasmic reticulum (ER) protein that is specifically located at the mitochondria-associated ER membrane (MAM), which interfaces between the ER and mitochondria. At the level of MAM, Sig-1R functions as a molecular chaperone that ensures proper calcium (Ca2+) transfer from the ER to the mitochondria and participates in the ER stress response to accumulation of unfolded proteins. On activation by agonists or in the setting of cell stress, Sig-1R translocates from the MAM to the plasma membrane, where it interacts with a variety of receptors and ion channels, or to the nuclear envelope, where it contributes to regulation of gene transcription.
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