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Protein

Sigma non-opioid intracellular receptor 1

Gene

Sigmar1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 (PubMed:12730355). 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:11149946, PubMed:14622179, PubMed:15571673, PubMed:15777781, PubMed:23332758, PubMed:9425306, PubMed:9603192). Necessary for proper mitochondrial axonal transport in motor neurons, in particular the retrograde movement of mitochondria (PubMed:25678561). Plays a role in protecting cells against oxidative stress-induced cell death via its interaction with RNF112 (PubMed:26792191).10 Publications

Miscellaneous

Depletion by RNAi enhances kappa-type opioid receptor-mediated analgesia and prevents the memory-improving effects of (-)- and (+)-pentazocine.
Sigma receptors are classified into two subtypes (Sigma-1 and Sigma-2) based on their different pharmacological profile.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei126Important for ligand bindingBy similarity1
Sitei172Important for ligand bindingBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionReceptor
Biological processLipid transport, Transport

Names & Taxonomyi

Protein namesi
Recommended name:
Sigma non-opioid intracellular receptor 1
Alternative name(s):
Sigma 1-type opioid receptor
Short name:
Sigma1-receptor
Short name:
Sigma1R
Gene namesi
Name:Sigmar1
Synonyms:Oprs1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:1195268 Sigmar1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 9LumenalBy similarity9
Transmembranei10 – 30HelicalBy similarityAdd BLAST21
Topological domaini31 – 223CytoplasmicBy similarityAdd BLAST193

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasmic vesicle, Endoplasmic reticulum, Lipid droplet, Membrane, Nucleus, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Disruption phenotypei

Mice display decreased hypermotility response induced by (+)SKF-10047 challenge and reduced formalin-induced pain (PubMed:14622179). Mice display motor coordination defects, muscle weakness, partial neuromuscular junction innervation, and motor neuron degeneration (PubMed:20167253, PubMed:25678561).3 Publications

Chemistry databases

ChEMBLiCHEMBL3465

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002686531 – 223Sigma non-opioid intracellular receptor 1Add BLAST223

Proteomic databases

MaxQBiO55242
PaxDbiO55242
PeptideAtlasiO55242
PRIDEiO55242

PTM databases

PhosphoSitePlusiO55242

Expressioni

Tissue specificityi

Widely expressed with higher expression in liver, brain, kidney and thymus. Expressed throughout the brain with higher expression within cerebral cortex, hippocampus and cerebellum. Within the hippocampus expressed in cornu ammonis pyramidal neurons, the granular cells of the dentate gyrus as well as interneurons. Within the cerebellum, expressed in Purkinje cell bodies (PubMed:11207432, PubMed:11476895, PubMed:11687279, PubMed:9603192). Highly expressed in the brainstem and motor neurons of the spinal cord (PubMed:20167253). Expressed by neural retina, retinal pigment epithelial cells and lens (PubMed:11207432, PubMed:11476895, PubMed:11687279, PubMed:9603192).5 Publications

Gene expression databases

BgeeiENSMUSG00000036078 Expressed in 267 organ(s), highest expression level in liver
CleanExiMM_OPRS1
ExpressionAtlasiO55242 baseline and differential
GenevisibleiO55242 MM

Interactioni

Subunit structurei

Homotrimer (By similarity). Interacts with KCNA4 (By similarity). Interacts with KCNA2; cocaine consumption leads to increased interaction (PubMed:23332758). Forms a ternary complex with ANK2 and ITPR3. The complex is disrupted by agonists (PubMed:11149946). Interacts with RNF112 in an oxidative stress-regulated manner (PubMed:26792191).By similarity3 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

IntActiO55242, 2 interactors
STRINGi10090.ENSMUSP00000056027

Structurei

3D structure databases

SMRiO55242
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 8Targeting to endoplasmic reticulum-associated lipid droplets1 Publication7
Regioni99 – 106Important for ligand-bindingBy similarity8
Regioni177 – 223C-terminal hydrophobic regionCuratedAdd BLAST47

Domaini

The C-terminal helices form a flat, hydrophobic surface that is probably tightly associated with the cytosolic surface of the endoplasmic reticulum membrane.By similarity

Sequence similaritiesi

Belongs to the ERG2 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4143 Eukaryota
ENOG410XP0Z LUCA
GeneTreeiENSGT00390000012082
HOGENOMiHOG000211245
HOVERGENiHBG058220
InParanoidiO55242
KOiK20719
OMAiWKEGTTK
OrthoDBiEOG091G0KD7
PhylomeDBiO55242
TreeFamiTF300106

Family and domain databases

InterProiView protein in InterPro
IPR006716 ERG2_sigma1_rcpt-like
PANTHERiPTHR10868 PTHR10868, 1 hit
PfamiView protein in Pfam
PF04622 ERG2_Sigma1R, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: O55242-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MPWAAGRRWA WITLILTIIA VLIQAAWLWL GTQNFVFSRE EIAQLARQYA
60 70 80 90 100
GLDHELAFSR LIVELRRLHP GHVLPDEELQ WVFVNAGGWM GAMCILHASL
110 120 130 140 150
SEYVLLFGTA LGSHGHSGRY WAEISDTIIS GTFHQWKEGT TKSEVFYPGE
160 170 180 190 200
TVVHGPGEAT ALEWGPNTWM VEYGRGVIPS TLFFALADTF FSTQDYLTLF
210 220
YTLRAYARGL RLELTTYLFG QDS
Length:223
Mass (Da):25,250
Last modified:June 1, 1998 - v1
Checksum:i54BB2F14472E3512
GO
Isoform 2 (identifier: O55242-2) [UniParc]FASTAAdd to basket
Also known as: Beta

The sequence of this isoform differs from the canonical sequence as follows:
     118-148: Missing.

Show »
Length:192
Mass (Da):21,633
Checksum:i6C75160BF446D3BC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti192S → G in AAF64281 (Ref. 3) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_021987118 – 148Missing in isoform 2. 1 PublicationAdd BLAST31

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF030198 mRNA Translation: AAC39951.1
AF030199 Genomic DNA Translation: AAB97683.1
AF004927 mRNA Translation: AAC33306.1
AF226605 mRNA Translation: AAF64281.1
AK154300 mRNA Translation: BAE32499.1
AK159886 mRNA Translation: BAE35455.1
BC002000 mRNA Translation: AAH02000.1
BC019930 mRNA Translation: AAH19930.1
CCDSiCCDS18070.1 [O55242-1]
CCDS71362.1 [O55242-2]
PIRiJC5815
RefSeqiNP_001273467.1, NM_001286538.1
NP_001273468.1, NM_001286539.1 [O55242-2]
NP_001273469.1, NM_001286540.1
NP_001273470.1, NM_001286541.1
NP_001273480.1, NM_001286551.1
NP_035144.1, NM_011014.3 [O55242-1]
XP_017175516.1, XM_017320027.1
UniGeneiMm.425181

Genome annotation databases

EnsembliENSMUST00000059354; ENSMUSP00000056027; ENSMUSG00000036078 [O55242-1]
ENSMUST00000071561; ENSMUSP00000071492; ENSMUSG00000036078 [O55242-2]
GeneIDi18391
KEGGimmu:18391
UCSCiuc008sjk.2 mouse [O55242-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF030198 mRNA Translation: AAC39951.1
AF030199 Genomic DNA Translation: AAB97683.1
AF004927 mRNA Translation: AAC33306.1
AF226605 mRNA Translation: AAF64281.1
AK154300 mRNA Translation: BAE32499.1
AK159886 mRNA Translation: BAE35455.1
BC002000 mRNA Translation: AAH02000.1
BC019930 mRNA Translation: AAH19930.1
CCDSiCCDS18070.1 [O55242-1]
CCDS71362.1 [O55242-2]
PIRiJC5815
RefSeqiNP_001273467.1, NM_001286538.1
NP_001273468.1, NM_001286539.1 [O55242-2]
NP_001273469.1, NM_001286540.1
NP_001273470.1, NM_001286541.1
NP_001273480.1, NM_001286551.1
NP_035144.1, NM_011014.3 [O55242-1]
XP_017175516.1, XM_017320027.1
UniGeneiMm.425181

3D structure databases

SMRiO55242
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO55242, 2 interactors
STRINGi10090.ENSMUSP00000056027

Chemistry databases

ChEMBLiCHEMBL3465

PTM databases

PhosphoSitePlusiO55242

Proteomic databases

MaxQBiO55242
PaxDbiO55242
PeptideAtlasiO55242
PRIDEiO55242

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000059354; ENSMUSP00000056027; ENSMUSG00000036078 [O55242-1]
ENSMUST00000071561; ENSMUSP00000071492; ENSMUSG00000036078 [O55242-2]
GeneIDi18391
KEGGimmu:18391
UCSCiuc008sjk.2 mouse [O55242-1]

Organism-specific databases

CTDi10280
MGIiMGI:1195268 Sigmar1

Phylogenomic databases

eggNOGiKOG4143 Eukaryota
ENOG410XP0Z LUCA
GeneTreeiENSGT00390000012082
HOGENOMiHOG000211245
HOVERGENiHBG058220
InParanoidiO55242
KOiK20719
OMAiWKEGTTK
OrthoDBiEOG091G0KD7
PhylomeDBiO55242
TreeFamiTF300106

Miscellaneous databases

ChiTaRSiSigmar1 mouse
PROiPR:O55242
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000036078 Expressed in 267 organ(s), highest expression level in liver
CleanExiMM_OPRS1
ExpressionAtlasiO55242 baseline and differential
GenevisibleiO55242 MM

Family and domain databases

InterProiView protein in InterPro
IPR006716 ERG2_sigma1_rcpt-like
PANTHERiPTHR10868 PTHR10868, 1 hit
PfamiView protein in Pfam
PF04622 ERG2_Sigma1R, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSGMR1_MOUSE
AccessioniPrimary (citable) accession number: O55242
Secondary accession number(s): Q9JKU9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 12, 2006
Last sequence update: June 1, 1998
Last modified: October 10, 2018
This is version 138 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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