SGMR1_RAT
ID SGMR1_RAT Reviewed; 223 AA.
AC Q9R0C9; Q9R1J7; Q9Z2W2;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Sigma non-opioid intracellular receptor 1;
DE AltName: Full=Sigma 1-type opioid receptor;
DE Short=Sigma1-receptor;
DE Short=Sigma1R;
GN Name=Sigmar1; Synonyms=Oprs1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=9489711; DOI=10.1046/j.1471-4159.1998.70030922.x;
RA Seth P., Fei Y.-J., Li H.W., Huang W., Leibach F.H., Ganapathy V.;
RT "Cloning and functional characterization of a sigma receptor from rat
RT brain.";
RL J. Neurochem. 70:922-931(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND FUNCTION.
RC TISSUE=Brain;
RX PubMed=11861817; DOI=10.1124/jpet.300.3.1070;
RA Mei J., Pasternak G.W.;
RT "Sigma1 receptor modulation of opioid analgesia in the mouse.";
RL J. Pharmacol. Exp. Ther. 300:1070-1074(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=10771347; DOI=10.1016/s0306-4522(00)00014-2;
RA Alonso G., Phan V.-L., Guillemain I., Saunier M., Legrand A., Anoal M.,
RA Maurice T.;
RT "Immunocytochemical localization of the sigma(1) receptor in the adult rat
RT central nervous system.";
RL Neuroscience 97:155-170(2000).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=11687279; DOI=10.1016/s0169-328x(01)00249-2;
RA Ola M.S., Moore P., El-Sherbeny A., Roon P., Agarwal N., Sarthy V.P.,
RA Casellas P., Ganapathy V., Smith S.B.;
RT "Expression pattern of sigma receptor 1 mRNA and protein in mammalian
RT retina.";
RL Brain Res. Mol. Brain Res. 95:86-95(2001).
RN [6]
RP INTERACTION WITH ANK2 AND ITPR3, AND SUBCELLULAR LOCATION.
RX PubMed=11149946; DOI=10.1073/pnas.98.2.491;
RA Hayashi T., Su T.-P.;
RT "Regulating ankyrin dynamics: roles of sigma-1 receptors.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:491-496(2001).
RN [7]
RP FUNCTION, TOPOLOGY, SUBCELLULAR LOCATION, AND INTERACTION WITH KCNA4.
RX PubMed=11988171; DOI=10.1016/s0896-6273(02)00677-3;
RA Aydar E., Palmer C.P., Klyachko V.A., Jackson M.B.;
RT "The sigma receptor as a ligand-regulated auxiliary potassium channel
RT subunit.";
RL Neuron 34:399-410(2002).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=12535781; DOI=10.1016/s0006-8993(02)03892-1;
RA Palacios G., Muro A., Vela J.M., Molina-Holgado E., Guitart X., Ovalle S.,
RA Zamanillo D.;
RT "Immunohistochemical localization of the sigma1-receptor in
RT oligodendrocytes in the rat central nervous system.";
RL Brain Res. 961:92-99(2003).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=15064136; DOI=10.1016/j.brainres.2004.02.013;
RA Palacios G., Muro A., Verdu E., Pumarola M., Vela J.M.;
RT "Immunohistochemical localization of the sigma1 receptor in Schwann cells
RT of rat sciatic nerve.";
RL Brain Res. 1007:65-70(2004).
RN [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15466698; DOI=10.1073/pnas.0402890101;
RA Hayashi T., Su T.-P.;
RT "Sigma-1 receptors at galactosylceramide-enriched lipid microdomains
RT regulate oligodendrocyte differentiation.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:14949-14954(2004).
RN [11]
RP FUNCTION.
RX PubMed=15170821; DOI=10.1002/syn.20041;
RA Takebayashi M., Hayashi T., Su T.-P.;
RT "Sigma-1 receptors potentiate epidermal growth factor signaling towards
RT neuritogenesis in PC12 cells: potential relation to lipid raft
RT reconstitution.";
RL Synapse 53:90-103(2004).
RN [12]
RP FUNCTION.
RX PubMed=16522641; DOI=10.1074/jbc.m508157200;
RA Yagasaki Y., Numakawa T., Kumamaru E., Hayashi T., Su T.-P., Kunugi H.;
RT "Chronic antidepressants potentiate via sigma-1 receptors the brain-derived
RT neurotrophic factor-induced signaling for glutamate release.";
RL J. Biol. Chem. 281:12941-12949(2006).
CC -!- FUNCTION: Functions in lipid transport from the endoplasmic reticulum
CC and is involved in a wide array of cellular functions probably through
CC regulation of the biogenesis of lipid microdomains at the plasma
CC membrane. Involved in the regulation of different receptors it plays a
CC role in BDNF signaling and EGF signaling. Also regulates ion channels
CC like the potassium channel and could modulate neurotransmitter release.
CC Plays a role in calcium signaling through modulation together with ANK2
CC of the ITP3R-dependent calcium efflux at the endoplasmic reticulum.
CC Plays a role in several other cell functions including proliferation,
CC survival and death. Originally identified for its ability to bind
CC various psychoactive drugs it is involved in learning processes, memory
CC and mood alteration. Necessary for proper mitochondrial axonal
CC transport in motor neurons, in particular the retrograde movement of
CC mitochondria. Plays a role in protecting cells against oxidative
CC stress-induced cell death via its interaction with RNF112 (By
CC similarity). {ECO:0000250|UniProtKB:O55242,
CC ECO:0000269|PubMed:11861817, ECO:0000269|PubMed:11988171,
CC ECO:0000269|PubMed:15170821, ECO:0000269|PubMed:15466698,
CC ECO:0000269|PubMed:16522641, ECO:0000269|PubMed:9489711}.
CC -!- SUBUNIT: Homotrimer (By similarity). Interacts with KCNA2; cocaine
CC consumption leads to increased interaction (By similarity). Forms a
CC ternary complex with ANK2 and ITPR3. The complex is disrupted by
CC agonists (PubMed:11149946). Interacts with KCNA4 (PubMed:11988171).
CC Interacts with RNF112 in an oxidative stress-regulated manner (By
CC similarity). {ECO:0000250|UniProtKB:O55242,
CC ECO:0000250|UniProtKB:Q99720, ECO:0000269|PubMed:11149946,
CC ECO:0000269|PubMed:11988171}.
CC -!- INTERACTION:
CC Q9R0C9; P06761: Hspa5; NbExp=3; IntAct=EBI-1557826, EBI-916036;
CC Q9R0C9; P63141: Kcna2; Xeno; NbExp=3; IntAct=EBI-1557826, EBI-644033;
CC -!- SUBCELLULAR LOCATION: Nucleus inner membrane
CC {ECO:0000250|UniProtKB:Q99720}. Nucleus outer membrane
CC {ECO:0000250|UniProtKB:Q99720}. Nucleus envelope
CC {ECO:0000250|UniProtKB:Q99720}. Cytoplasmic vesicle
CC {ECO:0000250|UniProtKB:Q99720}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:15466698}. Membrane {ECO:0000250|UniProtKB:Q99720};
CC Single-pass membrane protein {ECO:0000250|UniProtKB:Q99720}. Lipid
CC droplet {ECO:0000269|PubMed:15466698}. Cell junction
CC {ECO:0000250|UniProtKB:Q99720}. Cell membrane
CC {ECO:0000250|UniProtKB:Q99720}. Cell projection, growth cone
CC {ECO:0000250|UniProtKB:Q99720}. Postsynaptic density membrane
CC {ECO:0000250|UniProtKB:Q99720}. Note=During interphase, detected at the
CC inner and outer nuclear membrane and the endoplasmic reticulum.
CC Detected on cytoplasmic vesicles during mitosis (By similarity).
CC Targeted to lipid droplets, cholesterol and galactosylceramide-enriched
CC domains of the endoplasmic reticulum (PubMed:15466698). Enriched at
CC cell-cell communication regions, growth cone and postsynaptic
CC structures. Localization is modulated by ligand-binding. In motor
CC neurons it is enriched at cholinergic postsynaptic densities (By
CC similarity). {ECO:0000250|UniProtKB:O55242,
CC ECO:0000250|UniProtKB:Q99720, ECO:0000269|PubMed:15466698}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9R0C9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9R0C9-2; Sequence=VSP_021988, VSP_021989;
CC -!- TISSUE SPECIFICITY: Expressed in ependymocytes and neurons throughout
CC the CNS from the olfactory bulb to the spinal cord. Expressed by
CC progenitor, mature and satellite oligodendrocytes and by Schwann cells
CC (at protein level). Expressed in liver, intestine, kidney, brain, lung
CC and heart. Expressed by retinal cells. {ECO:0000269|PubMed:10771347,
CC ECO:0000269|PubMed:11687279, ECO:0000269|PubMed:12535781,
CC ECO:0000269|PubMed:15064136, ECO:0000269|PubMed:9489711}.
CC -!- DOMAIN: The C-terminal helices form a flat, hydrophobic surface that is
CC probably tightly associated with the cytosolic surface of the
CC endoplasmic reticulum membrane. {ECO:0000250|UniProtKB:Q99720}.
CC -!- MISCELLANEOUS: Depletion by RNAi alters oligodendrocyte differentiation
CC and enhances opioid analgesia.
CC -!- MISCELLANEOUS: Sigma receptors are classified into two subtypes (Sigma-
CC 1 and Sigma-2) based on their different pharmacological profile.
CC {ECO:0000250|UniProtKB:Q5BJF2}.
CC -!- SIMILARITY: Belongs to the ERG2 family. {ECO:0000305}.
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DR EMBL; AF004218; AAD01198.1; -; mRNA.
DR EMBL; AF067769; AAF08342.1; -; mRNA.
DR EMBL; AF087827; AAD49439.1; -; mRNA.
DR EMBL; BC061978; AAH61978.1; -; mRNA.
DR RefSeq; NP_112258.1; NM_030996.1. [Q9R0C9-1]
DR AlphaFoldDB; Q9R0C9; -.
DR SMR; Q9R0C9; -.
DR BioGRID; 247995; 1.
DR IntAct; Q9R0C9; 4.
DR STRING; 10116.ENSRNOP00000019795; -.
DR BindingDB; Q9R0C9; -.
DR ChEMBL; CHEMBL3602; -.
DR DrugCentral; Q9R0C9; -.
DR GuidetoPHARMACOLOGY; 2552; -.
DR PhosphoSitePlus; Q9R0C9; -.
DR PaxDb; Q9R0C9; -.
DR PeptideAtlas; Q9R0C9; -.
DR PRIDE; Q9R0C9; -.
DR Ensembl; ENSRNOT00000019795; ENSRNOP00000019795; ENSRNOG00000014604. [Q9R0C9-1]
DR GeneID; 29336; -.
DR KEGG; rno:29336; -.
DR UCSC; RGD:68364; rat. [Q9R0C9-1]
DR CTD; 10280; -.
DR RGD; 68364; Sigmar1.
DR eggNOG; KOG4143; Eukaryota.
DR GeneTree; ENSGT00390000012082; -.
DR HOGENOM; CLU_085469_0_0_1; -.
DR InParanoid; Q9R0C9; -.
DR OMA; LWATTRI; -.
DR OrthoDB; 1285317at2759; -.
DR PhylomeDB; Q9R0C9; -.
DR TreeFam; TF300106; -.
DR PRO; PR:Q9R0C9; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Bgee; ENSRNOG00000014604; Expressed in liver and 20 other tissues.
DR Genevisible; Q9R0C9; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030426; C:growth cone; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005811; C:lipid droplet; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0005635; C:nuclear envelope; ISO:RGD.
DR GO; GO:0005637; C:nuclear inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005640; C:nuclear outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0014069; C:postsynaptic density; ISO:RGD.
DR GO; GO:0098839; C:postsynaptic density membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004985; F:G protein-coupled opioid receptor activity; IDA:RGD.
DR GO; GO:0038023; F:signaling receptor activity; ISO:RGD.
DR GO; GO:0036474; P:cell death in response to hydrogen peroxide; ISS:UniProtKB.
DR GO; GO:0006869; P:lipid transport; IEA:UniProtKB-KW.
DR GO; GO:0007399; P:nervous system development; IDA:RGD.
DR GO; GO:0070207; P:protein homotrimerization; ISO:RGD.
DR GO; GO:0043523; P:regulation of neuron apoptotic process; ISS:UniProtKB.
DR InterPro; IPR006716; ERG2_sigma1_rcpt-like.
DR PANTHER; PTHR10868; PTHR10868; 1.
DR Pfam; PF04622; ERG2_Sigma1R; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell junction; Cell membrane; Cell projection;
KW Cytoplasmic vesicle; Endoplasmic reticulum; Lipid droplet; Lipid transport;
KW Membrane; Nucleus; Postsynaptic cell membrane; Receptor;
KW Reference proteome; Synapse; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..223
FT /note="Sigma non-opioid intracellular receptor 1"
FT /id="PRO_0000268655"
FT TOPO_DOM 1..9
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q99720"
FT TRANSMEM 10..30
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q99720"
FT TOPO_DOM 31..223
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q99720"
FT REGION 2..8
FT /note="Targeting to endoplasmic reticulum-associated lipid
FT droplets"
FT /evidence="ECO:0000250|UniProtKB:O55242"
FT REGION 99..106
FT /note="Important for ligand-binding"
FT /evidence="ECO:0000250|UniProtKB:Q60492"
FT REGION 177..223
FT /note="C-terminal hydrophobic region"
FT /evidence="ECO:0000305"
FT SITE 126
FT /note="Important for ligand binding"
FT /evidence="ECO:0000250|UniProtKB:Q99720"
FT SITE 172
FT /note="Important for ligand binding"
FT /evidence="ECO:0000250|UniProtKB:Q99720"
FT VAR_SEQ 103..106
FT /note="YVLL -> TILG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11861817"
FT /id="VSP_021988"
FT VAR_SEQ 107..223
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11861817"
FT /id="VSP_021989"
FT CONFLICT 161
FT /note="A -> D (in Ref. 1; AAD01198)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 223 AA; 25270 MW; B125A0388F1FFC6E CRC64;
MPWAVGRRWA WITLFLTIVA VLIQAVWLWL GTQSFVFQRE EIAQLARQYA GLDHELAFSR
LIVELRRLHP GHVLPDEELQ WVFVNAGGWM GAMCLLHASL SEYVLLFGTA LGSHGHSGRY
WAEISDTIIS GTFHQWREGT TKSEVYYPGE TVVHGPGEAT AVEWGPNTWM VEYGRGVIPS
TLAFALSDTI FSTQDFLTLF YTLRAYARGL RLELTTYLFG QDP
