The reference OMIM entry for this protein is 601978

Sigma nonopioid intracellular receptor 1; sigmar1
Sigma receptor, type 1
Sr31747a-binding protein; srbp

DESCRIPTION

The SIGMAR1 gene encodes an endoplasmic reticulum (ER) chaperone that binds a wide variety of ligands, including neurosteroids, psychostimulants, and dextrobenzomorphans. It is ubiquitously expressed, and is enriched in motor neurons of the brain and spinal cord (summary by Al-Saif et al., 2011). SIGMAR1 has the ability to translocate from the ER to the plasma membrane or to mitochondrial-associated membranes (MAMs), and plays an important role in the regulation of ion channels (summary by Mavlyutov et al., 2010).

CLONING

Sigma receptors are defined as nonopiate and nonphencyclidine sites that bind certain benzomorphan opioids with high affinity. Kekuda et al. (1996) cloned a functional sigma receptor type 1 cDNA from a human placental choriocarcinoma cell (JAR) library using a guinea pig-specific mRNA RT-PCR product (Hanner et al., 1996). The human cDNA predicts a protein of 223 amino acids with a single putative transmembrane domain. It shares 93% identity with the guinea pig sigma receptor. The amino acid sequence motif MQWAVGRR, which is thought to be an endoplasmic reticulum retention signal, is present at the N terminus of both proteins. When functionally expressed in HeLa cells, the cDNA enhanced the binding of tritiated haloperidol, a sigma receptor ligand, to HeLa cell membranes. Several human tissues, including placenta, liver, pancreas, and brain, and several human intestinal and JAR cell lines express the sigma receptor type 1 to a variable degree. The sigma receptor ligand SR31747A is an immunosuppressive agent that blocks lymphocyte proliferation. It also blocks yeast proliferation by inhibiting Erg2, a sterol isomerase. Jbilo et al. (1997) purified an SR31747A-binding protein from membrane preparations of a human T leukemia cell line, and using primers based on peptide fragments, followed by 5-prime RACE and screening a Burkitt lymphoma cell line cDNA library, Jbilo et al. (1997) cloned SIGMAR1, which they called SRBP. The deduced 223-amino acid protein has a calculated molecular mass of 24.8 kD. SIGMAR1 has 2 hydrophobic stretches, one of which is a conserved central domain similar to that of yeast Erg2. SIGMAR1 shares 93% identity with guinea pig Sigmar1 and 29.9% identity with yeast Erg2. Northern blot analysis detected a 2.0-kb SIGMAR1 transcript in all tissues examined, with highest expression in liver and lowest expression in brain. RNA dot blot analysis confirmed ubiquitous expression and highest expression in adult and fetal liver. Immunohistochemical analysis and confocal microscopy showed SIGMAR1 associated with the nuclear envelope in several human cell types. SDS-PAGE and Western blot analysis showed that SIGMAR1 has an apparent molecular mass of 28 kD. In mouse tissue, Mavlyutov et al. (2010) found that Sigmar1 was localized primarily in motoneurons in the brainstem and spinal cord. Expression was restricted to large cholinergic postsynaptic densities on the soma of motoneurons, and colocalized with the Kv2.1 potassium channel (KCNB1; 600397) and the muscarinic type 2 cholinergic receptor (CHRM2; 118493). Ultrastructural studies showed that Sigmar1 was located close to, but separate from, the plasma membrane, possibly in cisternae formed from the ER.

GENE FUNCTION

The sigma-1 receptor pharmacophore includes an alkylamine core, also found in the endogenous compound N,N-dimethyltryptamine (DMT), which also acts as a hallucinogen. Fontanilla et al. (2009) demonstrated ... More on the omim web site

Subscribe to this protein entry history

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 601978 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).