SGMR1_CAVPO
ID SGMR1_CAVPO Reviewed; 223 AA.
AC Q60492;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Sigma non-opioid intracellular receptor 1;
DE AltName: Full=Sigma 1-type opioid receptor;
DE Short=Sigma1-receptor;
DE Short=Sigma1R;
DE AltName: Full=Sterol isomerase-like protein;
GN Name=SIGMAR1; Synonyms=OPRS1;
OS Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 120-130; 143-165; 176-180
RP AND 209-217, AND TISSUE SPECIFICITY.
RC STRAIN=Pirbright white; TISSUE=Liver;
RX PubMed=8755605; DOI=10.1073/pnas.93.15.8072;
RA Hanner M., Moebius F.F., Flandorfer A., Knaus H.-G., Striessnig J.,
RA Kempner E., Glossmann H.;
RT "Purification, molecular cloning, and expression of the mammalian sigma1-
RT binding site.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:8072-8077(1996).
RN [2]
RP MUTAGENESIS OF SER-99; TYR-103 AND 105-LEU--LEU-106.
RX PubMed=10069366; DOI=10.1016/s0014-5793(99)00084-8;
RA Yamamoto H., Miura R., Yamamoto T., Shinohara K., Watanabe M., Okuyama S.,
RA Nakazato A., Nukada T.;
RT "Amino acid residues in the transmembrane domain of the type 1 sigma
RT receptor critical for ligand binding.";
RL FEBS Lett. 445:19-22(1999).
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 (By similarity). Necessary for proper mitochondrial
CC axonal transport in motor neurons, in particular the retrograde
CC movement of mitochondria. Plays a role in protecting cells against
CC oxidative stress-induced cell death via its interaction with RNF112 (By
CC similarity). {ECO:0000250|UniProtKB:O55242,
CC ECO:0000250|UniProtKB:Q99720}.
CC -!- SUBUNIT: Homotrimer. Forms a ternary complex with ANK2 and ITPR3. The
CC complex is disrupted by agonists. Interacts with KCNA4. Interacts with
CC KCNA2; cocaine consumption leads to increased interaction. Interacts
CC with RNF112 in an oxidative stress-regulated manner.
CC {ECO:0000250|UniProtKB:O55242, ECO:0000250|UniProtKB:Q99720,
CC ECO:0000250|UniProtKB:Q9R0C9}.
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:0000250|UniProtKB:Q99720}. Membrane
CC {ECO:0000250|UniProtKB:Q99720}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:Q99720}. Lipid droplet
CC {ECO:0000250|UniProtKB:O55242}. 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. Targeted to lipid
CC droplets, cholesterol and galactosylceramide-enriched domains of the
CC endoplasmic reticulum (By similarity). Enriched at cell-cell
CC communication regions, growth cone and postsynaptic structures.
CC Localization is modulated by ligand-binding. In motor neurons it is
CC enriched at cholinergic postsynaptic densities (By similarity).
CC {ECO:0000250|UniProtKB:O55242, ECO:0000250|UniProtKB:Q99720}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with higher expression in
CC liver, kidney and steroid-producing tissues such as placenta, ovary and
CC adrenal gland. {ECO:0000269|PubMed:8755605}.
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: 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; Z66537; CAA91441.1; -; mRNA.
DR RefSeq; NP_001166463.1; NM_001172992.1.
DR AlphaFoldDB; Q60492; -.
DR SMR; Q60492; -.
DR STRING; 10141.ENSCPOP00000019032; -.
DR BindingDB; Q60492; -.
DR ChEMBL; CHEMBL4153; -.
DR DrugCentral; Q60492; -.
DR GeneID; 100135589; -.
DR KEGG; cpoc:100135589; -.
DR CTD; 10280; -.
DR eggNOG; KOG4143; Eukaryota.
DR InParanoid; Q60492; -.
DR OrthoDB; 1285317at2759; -.
DR PRO; PR:Q60492; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
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: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; ISS:UniProtKB.
DR GO; GO:0098839; C:postsynaptic density membrane; IEA:UniProtKB-SubCell.
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: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 Cell junction; Cell membrane; Cell projection; Cytoplasmic vesicle;
KW Direct protein sequencing; Endoplasmic reticulum; Lipid droplet;
KW Lipid transport; 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_0000268651"
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:0000269|PubMed:10069366"
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 MUTAGEN 99
FT /note="S->A: Alters pentazocine and NE-100-binding. No
FT effect on pentazocine-binding and same effect on NE-100-
FT binding; when associated with 105-AA-106."
FT /evidence="ECO:0000269|PubMed:10069366"
FT MUTAGEN 103
FT /note="Y->F: Alters pentazocine and NE-100-binding."
FT /evidence="ECO:0000269|PubMed:10069366"
FT MUTAGEN 105..106
FT /note="LL->AA: Alters pentazocine and NE-100-binding. No
FT effect on pentazocine-binding and same effect on NE-100-
FT binding; when associated with A-99."
FT /evidence="ECO:0000269|PubMed:10069366"
SQ SEQUENCE 223 AA; 25311 MW; 4115E51096D548F8 CRC64;
MQWAVGRRWL WVALFLAAVA VLTQIVWLWL GTQNFVFQRE EIAQLARQYA GLDHELAFSK
LIVELRRLHP VHVLPDEELQ WVFVNAGGWM GAMCLLHASL SEYVLLFGTA LGSPRHSGRY
WAEISDTIIS GTFHQWREGT TKSEVFYPGE TVVHGPGEAT AVEWGPNTWM VEYGRGVIPS
TLGFALADTV FSTQDFLTLF YTLRVYARAL QLELTTYLFG QDP
