O55242 (SGMR1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sigma non-opioid intracellular receptor 1

Alternative name(s):
Sigma 1-type opioid receptor
Short name=Sigma1-receptor
Short name=Sigma1R

Gene names

Name:	Sigmar1
Synonyms:	Oprs1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	223 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.1 Ref.2 Ref.9 Ref.10 Ref.12 Ref.13
Subunit structure	Interacts with KCNA4 By similarity. Forms a ternary complex with ANK2 and ITPR3. The complex is disrupted by agonists. Ref.9
Subcellular location	Nucleus inner membrane. Nucleus outer membrane. Endoplasmic reticulum membrane. Lipid droplet. Cell junction. Cell membrane. Cell projection › growth cone. Note: Targeted to lipid droplets, cholesterol and galactosylceramide-enriched domains of the endoplasmic reticulum. Enriched at cell-cell communication regions, growth cone and postsynaptic structures. Localization is modulated by ligand-binding. Ref.9 Ref.11
Tissue specificity	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. Expressed by neural retina, retinal pigment epithelial cells and lens. Ref.2 Ref.6 Ref.7 Ref.8
Disruption phenotype	Mice display decreased hypermotility response induced by (+)SKF-10047 challenge and reduced formalin-induced pain. Ref.10
Miscellaneous	Depletion by RNAi enhances kappa-type opioid receptor-mediated analgesia and prevents the memory-improving effects of (-)- and (+)-pentazocine.
Sequence similarities	Belongs to the ERG2 family.

Ontologies

Keywords
Biological process	Lipid transport Transport
Cellular component	Cell junction Cell membrane Cell projection Endoplasmic reticulum Lipid droplet Membrane Nucleus
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
Molecular function	Receptor
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ergosterol biosynthetic process Inferred from electronic annotation. Source: InterPro lipid transport Inferred from electronic annotation. Source: UniProtKB-KW nervous system development Inferred from electronic annotation. Source: Compara regulation of neuron apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell growth cone Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW lipid particle Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear inner membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear outer membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	C-8 sterol isomerase activity Inferred from electronic annotation. Source: InterPro opioid receptor activity Inferred from electronic annotation. Source: Compara receptor activity Inferred from direct assay Ref.10. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
I79_019946	G3I8R9	3	EBI-1557700,EBI-988311	From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O55242-1)

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.

Isoform 2 (identifier: O55242-2)

Also known as: Beta;

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 223	223	Sigma non-opioid intracellular receptor 1		PRO_0000268653
Regions
	Topological domain	1 – 9	9	Cytoplasmic Potential
	Transmembrane	10 – 30	21	Helical; Potential
	Topological domain	31 – 80	50	Extracellular Potential
	Transmembrane	81 – 101	21	Helical; Potential
	Topological domain	102 – 223	122	Cytoplasmic Potential
	Region	2 – 8	7	Targeting to lipid droplets
	Region	118 – 148	31	Mediates ligand-binding By similarity
Natural variations
	Alternative sequence	118 – 148	31	Missing in isoform 2.		VSP_021987
Experimental info
	Sequence conflict	192	1	S → G in AAF64281. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: 54BB2F14472E3512	FASTA	223	25,250
	10 20 30 40 50 60 MPWAAGRRWA WITLILTIIA VLIQAAWLWL GTQNFVFSRE EIAQLARQYA GLDHELAFSR 70 80 90 100 110 120 LIVELRRLHP GHVLPDEELQ WVFVNAGGWM GAMCILHASL SEYVLLFGTA LGSHGHSGRY 130 140 150 160 170 180 WAEISDTIIS GTFHQWKEGT TKSEVFYPGE TVVHGPGEAT ALEWGPNTWM VEYGRGVIPS 190 200 210 220 TLFFALADTF FSTQDYLTLF YTLRAYARGL RLELTTYLFG QDS
	Isoform 2 (Beta) [UniParc]. Checksum: 6C75160BF446D3BC	FASTA	192	21,633
	10 20 30 40 50 60 MPWAAGRRWA WITLILTIIA VLIQAAWLWL GTQNFVFSRE EIAQLARQYA GLDHELAFSR 70 80 90 100 110 120 LIVELRRLHP GHVLPDEELQ WVFVNAGGWM GAMCILHASL SEYVLLFGTA LGSHGHSGET 130 140 150 160 170 180 VVHGPGEATA LEWGPNTWMV EYGRGVIPST LFFALADTFF STQDYLTLFY TLRAYARGLR 190 LELTTYLFGQ DS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and structural analysis of the cDNA and the gene encoding the murine type 1 sigma receptor." Seth P., Leibach F.H., Ganapathy V. Biochem. Biophys. Res. Commun. 241:535-540(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), FUNCTION. Strain: 129/Sv and C57BL/6. Tissue: Kidney.
[2]	"Cloning and characterization of a mouse sigma1 receptor." Pan Y.-X., Mei J., Xu J., Wan B.-L., Zuckerman A., Pasternak G.W. J. Neurochem. 70:2279-2285(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY. Strain: C57BL/6. Tissue: Brain.
[3]	Wang L.-M., Shelness G.S., Childers S.R., Mach R.H., Wheeler K.T. Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Strain: C3H/HeJ. Tissue: Mammary gland.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: C57BL/6J and NOD. Tissue: Dendritic cell and Osteoclast.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: FVB/N. Tissue: Liver and Mammary tumor.
[6]	"Expression of the purported sigma(1) (sigma(1)) receptor in the mammalian brain and its possible relevance in deficits induced by antagonism of the NMDA receptor complex as revealed using an antisense strategy." Kitaichi K., Chabot J.-G., Moebius F.F., Flandorfer A., Glossmann H., Quirion R. J. Chem. Neuroanat. 20:375-387(2000) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"Expression pattern of the type 1 sigma receptor in the brain and identity of critical anionic amino acid residues in the ligand-binding domain of the receptor." Seth P., Ganapathy M.E., Conway S.J., Bridges C.D., Smith S.B., Casellas P., Ganapathy V. Biochim. Biophys. Acta 1540:59-67(2001) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[8]	"Expression pattern of sigma receptor 1 mRNA and protein in mammalian retina." Ola M.S., Moore P., El-Sherbeny A., Roon P., Agarwal N., Sarthy V.P., Casellas P., Ganapathy V., Smith S.B. Brain Res. Mol. Brain Res. 95:86-95(2001) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[9]	"Regulating ankyrin dynamics: roles of sigma-1 receptors." Hayashi T., Su T.-P. Proc. Natl. Acad. Sci. U.S.A. 98:491-496(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH ANK2 AND ITPR3, SUBCELLULAR LOCATION.
[10]	"Generation and phenotypic analysis of sigma receptor type I (sigma 1) knockout mice." Langa F., Codony X., Tovar V., Lavado A., Gimenez E., Cozar P., Cantero M., Dordal A., Hernandez E., Perez R., Monroy X., Zamanillo D., Guitart X., Montoliu L. Eur. J. Neurosci. 18:2188-2196(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[11]	"Sigma-1 receptors (sigma(1) binding sites) form raft-like microdomains and target lipid droplets on the endoplasmic reticulum: roles in endoplasmic reticulum lipid compartmentalization and export." Hayashi T., Su T.-P. J. Pharmacol. Exp. Ther. 306:718-725(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[12]	"Involvement of kappa-opioid receptors and sigma receptors in memory function demonstrated using an antisense strategy." Hiramatsu M., Hoshino T. Brain Res. 1030:247-255(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[13]	"Formalin-induced pain is reduced in sigma(1) receptor knockout mice." Cendan C.M., Pujalte J.M., Portillo-Salido E., Montoliu L., Baeyens J.M. Eur. J. Pharmacol. 511:73-74(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00116750. IPI00311649.
PIR	JC5815.
RefSeq	NP_035144.1. NM_011014.2.
UniGene	Mm.425181.
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	O55242. 1 interaction.
PTM databases
PhosphoSite	O55242.
Proteomic databases
PaxDb	O55242.
PRIDE	O55242.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000059354; ENSMUSP00000056027; ENSMUSG00000036078. ENSMUST00000071561; ENSMUSP00000071492; ENSMUSG00000036078.
GeneID	18391.
KEGG	mmu:18391.
Organism-specific databases
CTD	10280.
MGI	MGI:1195268. Sigmar1.
Phylogenomic databases
eggNOG	NOG296707.
GeneTree	ENSGT00390000012082.
HOGENOM	HOG000211245.
HOVERGEN	HBG058220.
InParanoid	O55242.
OMA	FYTLRAY.
OrthoDB	EOG4WWRKG.
Gene expression databases
ArrayExpress	O55242.
Bgee	O55242.
CleanEx	MM_OPRS1.
Genevestigator	O55242.
GermOnline	ENSMUSG00000036078. Mus musculus.
Family and domain databases
InterPro	IPR006716. ERG2_sigma1_rcpt-like. [Graphical view]
Pfam	PF04622. ERG2_Sigma1R. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	O55242.
ChEMBL	CHEMBL3465.
ChiTaRS	SIGMAR1. mouse.
NextBio	293992.
SOURCE	Search...

Entry information

Entry name

SGMR1_MOUSE

Accession

Primary (citable) accession number: O55242
Secondary accession number(s): Q9JKU9

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 12, 2006
Last sequence update:	June 1, 1998
Last modified:	May 1, 2013
This is version 96 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program