Q9R0C9 (SGMR1_RAT) 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

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [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 › Rattus

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.7 Ref.10 Ref.11 Ref.12
Subunit structure	Forms a ternary complex with ANK2 and ITPR3. The complex is disrupted by agonists. Interacts with KCNA4. Ref.6 Ref.7
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.4 Ref.6 Ref.7 Ref.10
Tissue specificity	Expressed in ependymocytes and neurons throughout the CNS from the olfactory bulb to the spinal cord. Expressed by progenitor, mature and satellite oligodendrocytes and by Schwann cells (at protein level). Expressed in liver, intestine, kidney, brain, lung and heart. Expressed by retinal cells. Ref.1 Ref.4 Ref.5 Ref.8 Ref.9
Miscellaneous	Depletion by RNAi alters oligodendrocyte differentiation and enhances opioid analgesia.
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 direct assay PubMed 12438547. Source: RGD 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 Traceable author statement PubMed 12438547. Source: RGD 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 direct assay PubMed 12438547. Source: RGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Hspa5	P06761	3	EBI-1557826,EBI-916036

Alternative products

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

Isoform 1 (identifier: Q9R0C9-1)

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: Q9R0C9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     103-106: YVLL → TILG
     107-223: 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_0000268655
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 By similarity
	Region	118 – 148	31	Mediates ligand-binding By similarity
Natural variations
	Alternative sequence	103 – 106	4	YVLL → TILG in isoform 2.		VSP_021988
	Alternative sequence	107 – 223	117	Missing in isoform 2.		VSP_021989
Experimental info
	Sequence conflict	161	1	A → D in AAD01198. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: B125A0388F1FFC6E	FASTA	223	25,270
	10 20 30 40 50 60 MPWAVGRRWA WITLFLTIVA VLIQAVWLWL GTQSFVFQRE EIAQLARQYA GLDHELAFSR 70 80 90 100 110 120 LIVELRRLHP GHVLPDEELQ WVFVNAGGWM GAMCLLHASL SEYVLLFGTA LGSHGHSGRY 130 140 150 160 170 180 WAEISDTIIS GTFHQWREGT TKSEVYYPGE TVVHGPGEAT AVEWGPNTWM VEYGRGVIPS 190 200 210 220 TLAFALSDTI FSTQDFLTLF YTLRAYARGL RLELTTYLFG QDP
	Isoform 2 [UniParc]. Checksum: 8BA4159B6A9E2A0F	FASTA	106	12,153
	10 20 30 40 50 60 MPWAVGRRWA WITLFLTIVA VLIQAVWLWL GTQSFVFQRE EIAQLARQYA GLDHELAFSR 70 80 90 100 LIVELRRLHP GHVLPDEELQ WVFVNAGGWM GAMCLLHASL SETILG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and functional characterization of a sigma receptor from rat brain." Seth P., Fei Y.-J., Li H.W., Huang W., Leibach F.H., Ganapathy V. J. Neurochem. 70:922-931(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY. Strain: Sprague-Dawley. Tissue: Brain.
[2]	"Sigma1 receptor modulation of opioid analgesia in the mouse." Mei J., Pasternak G.W. J. Pharmacol. Exp. Ther. 300:1070-1074(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION. Tissue: Brain.
[3]	"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). Tissue: Prostate.
[4]	"Immunocytochemical localization of the sigma(1) receptor in the adult rat central nervous system." Alonso G., Phan V.-L., Guillemain I., Saunier M., Legrand A., Anoal M., Maurice T. Neuroscience 97:155-170(2000) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[5]	"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.
[6]	"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: INTERACTION WITH ANK2 AND ITPR3, SUBCELLULAR LOCATION.
[7]	"The sigma receptor as a ligand-regulated auxiliary potassium channel subunit." Aydar E., Palmer C.P., Klyachko V.A., Jackson M.B. Neuron 34:399-410(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TOPOLOGY, SUBCELLULAR LOCATION, INTERACTION WITH KCNA4.
[8]	"Immunohistochemical localization of the sigma1-receptor in oligodendrocytes in the rat central nervous system." Palacios G., Muro A., Vela J.M., Molina-Holgado E., Guitart X., Ovalle S., Zamanillo D. Brain Res. 961:92-99(2003) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[9]	"Immunohistochemical localization of the sigma1 receptor in Schwann cells of rat sciatic nerve." Palacios G., Muro A., Verdu E., Pumarola M., Vela J.M. Brain Res. 1007:65-70(2004) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[10]	"Sigma-1 receptors at galactosylceramide-enriched lipid microdomains regulate oligodendrocyte differentiation." Hayashi T., Su T.-P. Proc. Natl. Acad. Sci. U.S.A. 101:14949-14954(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[11]	"Sigma-1 receptors potentiate epidermal growth factor signaling towards neuritogenesis in PC12 cells: potential relation to lipid raft reconstitution." Takebayashi M., Hayashi T., Su T.-P. Synapse 53:90-103(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"Chronic antidepressants potentiate via sigma-1 receptors the brain-derived neurotrophic factor-induced signaling for glutamate release." Yagasaki Y., Numakawa T., Kumamaru E., Hayashi T., Su T.-P., Kunugi H. J. Biol. Chem. 281:12941-12949(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF004218 mRNA. Translation: AAD01198.1. AF067769 mRNA. Translation: AAF08342.1. AF087827 mRNA. Translation: AAD49439.1. BC061978 mRNA. Translation: AAH61978.1.
IPI	IPI00202168. IPI00210327.
RefSeq	NP_112258.1. NM_030996.1.
UniGene	Rn.1129.
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9R0C9. 2 interactions.
Proteomic databases
PaxDb	Q9R0C9.
PRIDE	Q9R0C9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000019795; ENSRNOP00000019795; ENSRNOG00000014604.
GeneID	29336.
KEGG	rno:29336.
UCSC	RGD:68364. rat.
Organism-specific databases
CTD	10280.
RGD	68364. Sigmar1.
Phylogenomic databases
eggNOG	NOG296707.
GeneTree	ENSGT00390000012082.
HOVERGEN	HBG058220.
InParanoid	Q9R0C9.
OMA	FYTLRAY.
OrthoDB	EOG4WWRKG.
Gene expression databases
ArrayExpress	Q9R0C9.
Genevestigator	Q9R0C9.
GermOnline	ENSRNOG00000014604. Rattus norvegicus.
Family and domain databases
InterPro	IPR006716. ERG2_sigma1_rcpt-like. [Graphical view]
Pfam	PF04622. ERG2_Sigma1R. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q9R0C9.
ChEMBL	CHEMBL3602.
NextBio	608816.

Entry information

Entry name

SGMR1_RAT

Accession

Primary (citable) accession number: Q9R0C9
Secondary accession number(s): Q9R1J7, Q9Z2W2

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 12, 2006
Last sequence update:	May 1, 2000
Last modified:	April 3, 2013
This is version 68 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program