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FLASH GENE

Symbol

SIGMAR1

contributors: mct - updated : 14-12-2013

HGNC name	sigma non-opioid intracellular receptor 1
HGNC id	8157

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	ALS16 amyotrophic lateral sclerosis 16, juvenile
Location	9p13.3      Physical location : 34.634.719 - 34.637.768
Genatlas name	type I sigma receptor
Synonym name	opioid receptor, sigma 1
	SR31747 binding protein 1
	aging-associated gene 8 protein
Synonym symbol(s)	ALS16, SR-BP1, OPRS1, FLJ25585, SRBP1, SIG-1R, SR-BP, SR-BP1, SRBP, hSigmaR1, sigma1R, S1R

DNA

TYPE	functioning gene
STRUCTURE	3.08 kb     4 Exon(s)

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005866 4 - 1655 NP_005857 25.1 223 - 2013 23760505 OPRS1 variant 1 NM_147157 3 - 1580 NP_671513 21.5 192 - 2013 23760505 OPRS1 variant 2 OPRS1 variant 3 - - 1547 - 187 - 2013 23760505 OPRS1 variant 4 - - 1626 - 106 - 2013 23760505 OPRS1 variant 5 - - 1706 - 67 - 2013 23760505 NM_001282205 - - 1510 NP_001269134 17.5 155 - 2013 23760505 NM_001282206 - - 1681 NP_001269135 13.6 123 - 2013 23760505 NM_001282207 - - 1668 NP_001269136 22.5 203 - 2013 23760505 NM_001282208 - - 1751 NP_001269137 - 159 - 2013 23760505 NM_001282209 - - 1588 NP_001269138 12.5 110 - 2013 23760505 SIGMAR1 short form - - 321 12 109 . localizes primarily in the ER at perinuclear regions and forms a complex with SIGMAR1 but not with IP3R in the mitochondrion-associated ER membrane 2012 22619170 SIGMAR1 short isoform, SIGMA1SR, truncated isoform of the sigma1R two transmembrane domains (TM1, amino acids 11–29; TM2, amino acids 91–109), an extracellular loop, and intracellular N and C termini with the C-terminal region including a large soluble domain has a detrimental effect on mitochondrial energy production and cell survival enhances autophagosome formation following ER stress

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol blood / hematopoietic spleen         Digestive liver         Nervous brain diencephalon hypothalamus   highly Homo sapiens   brain hindbrain cerebellum   highly Homo sapiens Reproductive female system ovary       Visual eye retina       Rattus norvegicus

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier/lining retinal pigment epithelium (RPE)     Epithelial sensory visual outer nuclear layer

cells

System Cell Pubmed Species Stage Rna symbol Nervous oligodendrocyte Rattus norvegicus Nervous Purkinje cell Visual ganglion cell Rattus norvegicus

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a single putative transmembrane domain
	a MQWAVGRR motif, which is thought to be an endoplasmic reticulum retention signal
	a chaperone domain, containing a helix at the N terminus followed by a largely dynamic region and a structured, helical C-terminal region that encompasses a membrane associated domain containing four helices

HOMOLOGY

Homologene

FAMILY

CATEGORY

chaperone/stress , receptor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,nuclear envelope,int
	intracellular,nuclear envelope,ext

basic FUNCTION	playing an important role in the cellular functions of various tissues associated with the endocrine, immune, and nervous systems
	its activation can regulate calcium homeostasis and signaling in retinal ganglion cells, likely by directly influencing the activity of L-type voltage-gated calcium channels
	may have neuromodulatory and neuroprotective roles in the retina
	amplify dopamine DRD1 signaling at presynaptic sites in the prelimbic cortex
	molecular chaperone protein highly enriched in the brain
	plays an important role in modifying the function of transmembrane proteases
	protects against cellular oxidative stress and activates antioxidant response elements
	ligand-regulated membrane protein chaperone involved in the ER stress response

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

alcohol

signaling

ergosterol biosynthesis

a component

INTERACTION

DNA

RNA

small molecule	other,
	interacts with a variety of psychotomimetic drugs, including cocaine and amphetamines

protein	SIGMAR1 amplify dopamine DRD1 signaling at presynaptic sites in the prelimbic cortex
	in retinal neurons, binds HSPA5 under stressful conditions
	its overexpression diminished ADAM17- and ADAM10-dependent shedding
	regulate the HSPA5 and the inositol triphosphate receptor calcium channel through a C-terminal domain
	is a key initial mediator of IL24 induction of cancer-specific killing

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

ALS16

Susceptibility

to schizophrenia and differential activation of the prefrontal cortex (PFC)

Variant & Polymorphism other

polymorphism is associated with an increased risk of schizophrenia and differential activation of the prefrontal cortex (PFC)

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	axonal disruption in the optic nerve head of Sigmar1-/- mice as early as 6 months of age
	motoneurons of mice lacking S1r exhibit increased excitability