SIGMAR1

This gene encodes a receptor protein that interacts with a variety of psychotomimetic drugs, including cocaine and amphetamines. The receptor is believed to play an important role in the cellular functions of various tissues associated with the endocrine, immune, and nervous systems. As indicated by its previous name, opioid receptor sigma 1 (OPRS1), the product of this gene was erroneously thought to function as an opioid receptor; it is now thought to be a non-opioid receptor. Mutations in this gene has been associated with juvenile amyotrophic lateral sclerosis 16. Alternative splicing of this gene results in transcript variants encoding distinct isoforms. [provided by RefSeq, Aug 2013]

Sigma Non-Opioid Intracellular Receptor 1

Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane. Involved in the regulation of different receptors it plays a role in BDNF signaling and EGF signaling. Also regulates ion channels like the potassium channel and could modulate neurotransmitter release. Plays a role in calcium signaling through modulation together with ANK2 of the ITP3R-dependent calcium efflux at the endoplasmic reticulum. Plays a role in several other cell functions including proliferation, survival and death. Originally identified for its ability to bind various psychoactive drugs it is involved in learning processes, memory and mood alteration (PubMed:16472803, PubMed:9341151).
Necessary for proper mitochondrial axonal transport in motor neurons, in particular the retrograde movement of mitochondria. Plays a role in protecting cells against oxidative stress-induced cell death via its interaction with RNF112 (By similarity).

Biological Process cell death in response to hydrogen peroxideISS:UniProtKB
Biological Process lipid transportIEA:UniProtKB-KW
Biological Process nervous system developmentIEA:Ensembl
Biological Process protein homotrimerizationManual Assertion Based On ExperimentIPI:UniProtKB
Biological Process regulation of neuron apoptotic processManual Assertion Based On ExperimentIMP:UniProtKB

Nucleus inner membrane
Nucleus outer membrane
Nucleus envelope
Cytoplasmic vesicle
Endoplasmic reticulum membrane
Membrane
Lipid droplet
Cell junction
Cell membrane
Cell projection, growth cone
Postsynaptic density membrane
During interphase, detected at the inner and outer nuclear membrane and the endoplasmic reticulum. Detected on cytoplasmic vesicles during mitosis (PubMed:10406945).
Targeted to lipid droplets, cholesterol and galactosylceramide-enriched domains of the endoplasmic reticulum. Accumulation at the endoplasmic reticulum is prominent in alpha-motor neurons of patients with amyotrophic lateral sclerosis (PubMed:23314020).
Enriched at cell-cell communication regions, growth cone and postsynaptic structures. Localization is modulated by ligand-binding. In motor neurons it is enriched at cholinergic postsynaptic densities (By similarity).

Amyotrophic lateral sclerosis 16, juvenile (ALS16):
A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.
Distal spinal muscular atrophy, autosomal recessive, 2 (DSMA2):
An autosomal recessive neuromuscular disorder characterized by onset of distal muscle weakness and wasting affecting the lower and upper limbs in the first decade. There is no sensory involvement.

Lumenal: 1-9
Helical: 10-30
Cytoplasmic: 31-223