| SIGMAR1 Protein | |
|---|---|
| Gene | [SIGMAR1](/genes/sigma1) |
| UniProt ID | [Q9Y6X5](https://www.uniprot.org/uniprot/Q9Y6X5) |
| PDB Structures | 5HK1, 5IU4, 6AL7 |
| Molecular Weight | 25.3 kDa |
| Subcellular Localization | Mitochondria, Endoplasmic Reticulum, Plasma Membrane |
| Protein Family | Sigma non-opioid intracellular receptor family |
| Associated Diseases | [ALS](/diseases/amyotrophic-lateral-sclerosis), [Frontotemporal Dementia](/diseases/frontotemporal-dementia), [Parkinson's Disease](/diseases/parkinsons-disease) |
SIGMAR1 Protein is a protein encoded by the SIGMAR1 gene that sigmar1 functions as a dynamic chaperone at the mam interface, regulating calcium signaling, lipid metabolism, and mitochondrial function. key normal functions include:. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
SIGMAR1 (Sigma-1 Receptor) is a unique transmembrane protein located primarily at the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs). The protein forms a trimeric assembly with a chaperone-like structure that acts as a ligand-operated molecular chaperone [1]. The receptor binds various ligands including neurosteroids, certain antidepressants, and synthetic compounds, undergoing conformational changes that modulate its chaperone activity [2].
SIGMAR1 functions as a dynamic chaperone at the MAM interface, regulating calcium signaling, lipid metabolism, and mitochondrial function. Key normal functions include:
Mutations in SIGMAR1 cause autosomal recessive motor neuron disease characterized by juvenile-onset ALS phenotype [5]. Disease mechanisms include:
SIGMAR1 is a druggable target with several therapeutic approaches: