SGMR1_HUMAN
ID SGMR1_HUMAN Reviewed; 223 AA.
AC Q99720; D3DRM7; O00673; O00725; Q0Z9W6; Q153Z1; Q2TSD1; Q53GN2; Q7Z653;
AC Q8N7H3; Q9NYX0;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Sigma non-opioid intracellular receptor 1;
DE AltName: Full=Aging-associated gene 8 protein;
DE AltName: Full=SR31747-binding protein;
DE Short=SR-BP;
DE AltName: Full=Sigma 1-type opioid receptor;
DE Short=SIG-1R;
DE Short=Sigma1-receptor;
DE Short=Sigma1R;
DE Short=hSigmaR1;
GN Name=SIGMAR1; Synonyms=OPRS1, SRBP; ORFNames=AAG8;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Choriocarcinoma;
RX PubMed=8954936; DOI=10.1006/bbrc.1996.1842;
RA Kekuda R., Prasad P.D., Fei Y.-J., Leibach F.H., Ganapathy V.;
RT "Cloning and functional expression of the human type 1 sigma receptor
RT (hSigmaR1).";
RL Biochem. Biophys. Res. Commun. 229:553-558(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 40-47; 48-60;
RP 61-64; 120-133 AND 212-222, FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Lymphoblast;
RX PubMed=9341151; DOI=10.1074/jbc.272.43.27107;
RA Jbilo O., Vidal H., Paul R., De Nys N., Bensaid M., Silve S., Carayon P.,
RA Davi D., Galiegue S., Bourrie B., Guillemot J.-C., Ferrara P., Loison G.,
RA Maffrand J.-P., Le Fur G., Casellas P.;
RT "Purification and characterization of the human SR 31747A-binding protein.
RT A nuclear membrane protein related to yeast sterol isomerase.";
RL J. Biol. Chem. 272:27107-27115(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9453537; DOI=10.1046/j.1471-4159.1998.70020443.x;
RA Prasad P.D., Li H.W., Fei Y.-J., Ganapathy M.E., Fujita T., Plumley L.H.,
RA Yang-Feng T.L., Leibach F.H., Ganapathy V.;
RT "Exon-intron structure, analysis of promoter region, and chromosomal
RT localization of the human type 1 sigma receptor gene.";
RL J. Neurochem. 70:443-451(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC TISSUE=Mammary gland;
RA Wang L.-M., Shelness G.S., Childers S.R., Mach R.H., Wheeler K.T.;
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kim J.W.;
RT "Identification of a human aging-associated gene.";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4).
RC TISSUE=Mammary cancer;
RA Zhang J., Aft R.L., Zhang F., Mach R.H.;
RT "A new splice variant of sigma-1 identified in human breast cancer biopsy
RT sample.";
RL Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RC TISSUE=Thyroid;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4).
RC TISSUE=Brain, and Muscle;
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 [13]
RP SUBCELLULAR LOCATION.
RX PubMed=10406945; DOI=10.1046/j.1432-1327.1999.00500.x;
RA Dussossoy D., Carayon P., Belugou S., Feraut D., Bord A., Goubet C.,
RA Roque C., Vidal H., Combes T., Loison G., Casellas P.;
RT "Colocalization of sterol isomerase and sigma(1) receptor at endoplasmic
RT reticulum and nuclear envelope level.";
RL Eur. J. Biochem. 263:377-386(1999).
RN [14]
RP CHARACTERIZATION (ISOFORM 3).
RX PubMed=10087012;
RA Ganapathy M.E., Prasad P.D., Huang W., Seth P., Leibach F.H., Ganapathy V.;
RT "Molecular and ligand-binding characterization of the sigma-receptor in the
RT Jurkat human T lymphocyte cell line.";
RL J. Pharmacol. Exp. Ther. 289:251-260(1999).
RN [15]
RP MUTAGENESIS OF GLU-123; ASP-126; GLU-138; GLU-144; GLU-150; GLU-158;
RP GLU-163; GLU-172; ASP-188; ASP-195 AND GLU-213, AND SUBCELLULAR LOCATION.
RX PubMed=11476895; DOI=10.1016/s0167-4889(01)00117-3;
RA Seth P., Ganapathy M.E., Conway S.J., Bridges C.D., Smith S.B.,
RA Casellas P., Ganapathy V.;
RT "Expression pattern of the type 1 sigma receptor in the brain and identity
RT of critical anionic amino acid residues in the ligand-binding domain of the
RT receptor.";
RL Biochim. Biophys. Acta 1540:59-67(2001).
RN [16]
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 [17]
RP FUNCTION.
RX PubMed=16472803; DOI=10.1016/j.yexcr.2006.01.004;
RA Wang L., Duncan G.;
RT "Silencing of sigma-1 receptor induces cell death in human lens cells.";
RL Exp. Cell Res. 312:1439-1446(2006).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [21]
RP STRUCTURE BY NMR OF 36-233.
RX PubMed=25647032; DOI=10.1016/j.febslet.2015.01.033;
RA Ortega-Roldan J.L., Ossa F., Amin N.T., Schnell J.R.;
RT "Solution NMR studies reveal the location of the second transmembrane
RT domain of the human sigma-1 receptor.";
RL FEBS Lett. 589:659-665(2015).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.51 ANGSTROMS), SUBUNIT, SUBCELLULAR LOCATION,
RP TOPOLOGY, AND DOMAIN.
RX PubMed=27042935; DOI=10.1038/nature17391;
RA Schmidt H.R., Zheng S., Gurpinar E., Koehl A., Manglik A., Kruse A.C.;
RT "Crystal structure of the human sigma1 receptor.";
RL Nature 532:527-530(2016).
RN [23]
RP VARIANTS PRO-2 AND GLN-211.
RX PubMed=15298647; DOI=10.1111/j.1440-1819.2004.01268.x;
RA Satoh F., Miyatake R., Furukawa A., Suwaki H.;
RT "Lack of association between sigma receptor gene variants and
RT schizophrenia.";
RL Psychiatry Clin. Neurosci. 58:359-363(2004).
RN [24]
RP INVOLVEMENT IN ALS16, VARIANT ALS16 GLN-102, AND CHARACTERIZATION OF
RP VARIANT ALS16 GLN-102.
RX PubMed=21842496; DOI=10.1002/ana.22534;
RA Al-Saif A., Al-Mohanna F., Bohlega S.;
RT "A mutation in sigma-1 receptor causes juvenile amyotrophic lateral
RT sclerosis.";
RL Ann. Neurol. 70:913-919(2011).
RN [25]
RP MISCELLANEOUS, AND REVIEW.
RX PubMed=22292588; DOI=10.1517/17425255.2012.658367;
RA Ahmed I.S., Chamberlain C., Craven R.J.;
RT "S2R(Pgrmc1): the cytochrome-related sigma-2 receptor that regulates lipid
RT and drug metabolism and hormone signaling.";
RL Expert Opin. Drug Metab. Toxicol. 8:361-370(2012).
RN [26]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=23314020; DOI=10.1093/hmg/ddt008;
RA Prause J., Goswami A., Katona I., Roos A., Schnizler M., Bushuven E.,
RA Dreier A., Buchkremer S., Johann S., Beyer C., Deschauer M., Troost D.,
RA Weis J.;
RT "Altered localization, abnormal modification and loss of function of Sigma
RT receptor-1 in amyotrophic lateral sclerosis.";
RL Hum. Mol. Genet. 22:1581-1600(2013).
RN [27]
RP INVOLVEMENT IN DSMA2.
RX PubMed=26078401; DOI=10.1212/wnl.0000000000001680;
RA Li X., Hu Z., Liu L., Xie Y., Zhan Y., Zi X., Wang J., Wu L., Xia K.,
RA Tang B., Zhang R.;
RT "A SIGMAR1 splice-site mutation causes distal hereditary motor
RT neuropathy.";
RL Neurology 84:2430-2437(2015).
RN [28]
RP VARIANT DSMA2 GLN-65.
RX PubMed=27629094; DOI=10.1212/wnl.0000000000003212;
RA Horga A., Tomaselli P.J., Gonzalez M.A., Laura M., Muntoni F., Manzur A.Y.,
RA Hanna M.G., Blake J.C., Houlden H., Zuechner S., Reilly M.M.;
RT "SIGMAR1 mutation associated with autosomal recessive Silver-like
RT syndrome.";
RL Neurology 87:1607-1612(2016).
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 (PubMed:16472803, PubMed:9341151). Necessary for
CC proper mitochondrial axonal transport in motor neurons, in particular
CC the retrograde movement of mitochondria. Plays a role in protecting
CC cells against oxidative stress-induced cell death via its interaction
CC with RNF112 (By similarity). {ECO:0000250|UniProtKB:O55242,
CC ECO:0000269|PubMed:16472803, ECO:0000269|PubMed:9341151}.
CC -!- SUBUNIT: Homotrimer (PubMed:27042935). Forms a ternary complex with
CC ANK2 and ITPR3. The complex is disrupted by agonists. Interacts with
CC KCNA4. Interacts with KCNA2; cocaine consumption leads to increased
CC interaction. Interacts with RNF112 in an oxidative stress-regulated
CC manner (By similarity). {ECO:0000250|UniProtKB:O55242,
CC ECO:0000250|UniProtKB:Q9R0C9, ECO:0000269|PubMed:27042935}.
CC -!- INTERACTION:
CC Q99720; Q92847-1: GHSR; NbExp=8; IntAct=EBI-3248663, EBI-21459171;
CC Q99720-1; Q99720-1: SIGMAR1; NbExp=5; IntAct=EBI-16203475, EBI-16203475;
CC Q99720-4; O00213-2: APBB1; NbExp=3; IntAct=EBI-25831036, EBI-13307975;
CC Q99720-4; P17612: PRKACA; NbExp=3; IntAct=EBI-25831036, EBI-476586;
CC Q99720-4; P50454: SERPINH1; NbExp=3; IntAct=EBI-25831036, EBI-350723;
CC Q99720-4; P37173: TGFBR2; NbExp=3; IntAct=EBI-25831036, EBI-296151;
CC -!- SUBCELLULAR LOCATION: Nucleus inner membrane
CC {ECO:0000269|PubMed:10406945}. Nucleus outer membrane
CC {ECO:0000269|PubMed:10406945}. Nucleus envelope
CC {ECO:0000269|PubMed:11476895, ECO:0000269|PubMed:9341151}. Cytoplasmic
CC vesicle {ECO:0000269|PubMed:10406945}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:10406945}. Membrane {ECO:0000269|PubMed:11476895,
CC ECO:0000269|PubMed:27042935, ECO:0000269|PubMed:9341151}; Single-pass
CC membrane protein {ECO:0000269|PubMed:27042935}. Lipid droplet
CC {ECO:0000250|UniProtKB:O55242}. Cell junction. Cell membrane
CC {ECO:0000269|PubMed:23314020}. Cell projection, growth cone.
CC Postsynaptic density membrane {ECO:0000269|PubMed:23314020}.
CC Note=During interphase, detected at the inner and outer nuclear
CC membrane and the endoplasmic reticulum. Detected on cytoplasmic
CC vesicles during mitosis (PubMed:10406945). Targeted to lipid droplets,
CC cholesterol and galactosylceramide-enriched domains of the endoplasmic
CC reticulum. Accumulation at the endoplasmic reticulum is prominent in
CC alpha-motor neurons of patients with amyotrophic lateral sclerosis
CC (PubMed:23314020). Enriched at cell-cell communication regions, growth
CC cone and postsynaptic structures. Localization is modulated by ligand-
CC binding. In motor neurons it is enriched at cholinergic postsynaptic
CC densities (By similarity). {ECO:0000250|UniProtKB:O55242,
CC ECO:0000269|PubMed:10406945, ECO:0000269|PubMed:23314020}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q99720-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99720-2; Sequence=VSP_021982;
CC Name=3; Synonyms=Sigma-R1A;
CC IsoId=Q99720-3; Sequence=VSP_021986;
CC Name=4;
CC IsoId=Q99720-4; Sequence=VSP_021984, VSP_021985;
CC Name=5;
CC IsoId=Q99720-5; Sequence=VSP_021981, VSP_021983;
CC -!- TISSUE SPECIFICITY: Widely expressed with higher expression in liver,
CC colon, prostate, placenta, small intestine, heart and pancreas.
CC Expressed in the retina by retinal pigment epithelial cells. Expressed
CC in alpha-motor neurons (PubMed:23314020). {ECO:0000269|PubMed:11687279,
CC ECO:0000269|PubMed:23314020, ECO:0000269|PubMed:8954936,
CC ECO:0000269|PubMed:9341151}.
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:0000269|PubMed:27042935}.
CC -!- DISEASE: Amyotrophic lateral sclerosis 16, juvenile (ALS16)
CC [MIM:614373]: A neurodegenerative disorder affecting upper motor
CC neurons in the brain and lower motor neurons in the brain stem and
CC spinal cord, resulting in fatal paralysis. Sensory abnormalities are
CC absent. The pathologic hallmarks of the disease include pallor of the
CC corticospinal tract due to loss of motor neurons, presence of
CC ubiquitin-positive inclusions within surviving motor neurons, and
CC deposition of pathologic aggregates. The etiology of amyotrophic
CC lateral sclerosis is likely to be multifactorial, involving both
CC genetic and environmental factors. The disease is inherited in 5-10% of
CC the cases. {ECO:0000269|PubMed:21842496}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Distal spinal muscular atrophy, autosomal recessive, 2 (DSMA2)
CC [MIM:605726]: An autosomal recessive neuromuscular disorder
CC characterized by onset of distal muscle weakness and wasting affecting
CC the lower and upper limbs in the first decade. There is no sensory
CC involvement. {ECO:0000269|PubMed:26078401,
CC ECO:0000269|PubMed:27629094}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Depletion by RNAi inhibits growth and survival signaling
CC cascades and induces cell death. The antagonist rimcazole produces the
CC same effect.
CC -!- MISCELLANEOUS: Sigma receptors are classified into two subtypes (Sigma-
CC 1 and Sigma-2) based on their different pharmacological profile.
CC {ECO:0000303|PubMed:22292588}.
CC -!- SIMILARITY: Belongs to the ERG2 family. {ECO:0000305}.
CC -!- CAUTION: The NMR solution structure identifies a second transmembrane
CC helix starting with Gly-91 (PubMed:25647032). The X-ray structure
CC clearly shows that this region is not helical and not in the membrane;
CC instead it is part of two beta-strands (PubMed:27042935).
CC {ECO:0000269|PubMed:25647032, ECO:0000269|PubMed:27042935}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Sigma-1 receptor entry;
CC URL="https://en.wikipedia.org/wiki/Sigma_1_Receptor";
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DR EMBL; U75283; AAB50402.1; -; mRNA.
DR EMBL; U79528; AAB51238.1; -; mRNA.
DR EMBL; AF001977; AAC04507.1; -; Genomic_DNA.
DR EMBL; AF001976; AAC04507.1; JOINED; Genomic_DNA.
DR EMBL; AF226604; AAF64280.1; -; mRNA.
DR EMBL; AY633611; AAV33304.1; -; mRNA.
DR EMBL; DQ644568; ABG29111.1; -; mRNA.
DR EMBL; DQ647702; ABG36559.1; -; mRNA.
DR EMBL; DQ656583; ABG46369.1; -; mRNA.
DR EMBL; AK098451; BAC05307.1; -; mRNA.
DR EMBL; CR457075; CAG33356.1; -; mRNA.
DR EMBL; AK222899; BAD96619.1; -; mRNA.
DR EMBL; AL450283; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471071; EAW58431.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58434.1; -; Genomic_DNA.
DR EMBL; BC004899; AAH04899.1; -; mRNA.
DR EMBL; BC007839; AAH07839.1; -; mRNA.
DR CCDS; CCDS6562.1; -. [Q99720-1]
DR CCDS; CCDS6563.1; -. [Q99720-3]
DR PIR; JC5266; JC5266.
DR RefSeq; NP_001269134.1; NM_001282205.1.
DR RefSeq; NP_001269135.1; NM_001282206.1.
DR RefSeq; NP_001269136.1; NM_001282207.1. [Q99720-2]
DR RefSeq; NP_001269137.1; NM_001282208.1.
DR RefSeq; NP_001269138.1; NM_001282209.1.
DR RefSeq; NP_005857.1; NM_005866.3. [Q99720-1]
DR RefSeq; NP_671513.1; NM_147157.2. [Q99720-3]
DR PDB; 5HK1; X-ray; 2.51 A; A/B/C=1-223.
DR PDB; 5HK2; X-ray; 3.20 A; A/B/C=1-223.
DR PDB; 6DJZ; X-ray; 3.08 A; A/B/C=1-223.
DR PDB; 6DK0; X-ray; 2.90 A; A/B/C=1-223.
DR PDB; 6DK1; X-ray; 3.12 A; A/B/C=1-223.
DR PDBsum; 5HK1; -.
DR PDBsum; 5HK2; -.
DR PDBsum; 6DJZ; -.
DR PDBsum; 6DK0; -.
DR PDBsum; 6DK1; -.
DR AlphaFoldDB; Q99720; -.
DR BMRB; Q99720; -.
DR SMR; Q99720; -.
DR BioGRID; 115569; 142.
DR CORUM; Q99720; -.
DR DIP; DIP-61974N; -.
DR ELM; Q99720; -.
DR IntAct; Q99720; 21.
DR MINT; Q99720; -.
DR STRING; 9606.ENSP00000277010; -.
DR BindingDB; Q99720; -.
DR ChEMBL; CHEMBL287; -.
DR DrugBank; DB00321; Amitriptyline.
DR DrugBank; DB09014; Captodiame.
DR DrugBank; DB00907; Cocaine.
DR DrugBank; DB00514; Dextromethorphan.
DR DrugBank; DB01488; Dimethyltryptamine.
DR DrugBank; DB00574; Fenfluramine.
DR DrugBank; DB00502; Haloperidol.
DR DrugBank; DB00956; Hydrocodone.
DR DrugBank; DB00540; Nortriptyline.
DR DrugBank; DB06174; Noscapine.
DR DrugBank; DB00652; Pentazocine.
DR DrugBank; DB11186; Pentoxyverine.
DR DrugBank; DB03575; Phencyclidine.
DR DrugBank; DB05316; Pimavanserin.
DR DrugBank; DB01708; Prasterone.
DR DrugBank; DB00409; Remoxipride.
DR DrugBank; DB01104; Sertraline.
DR DrugCentral; Q99720; -.
DR GuidetoPHARMACOLOGY; 2552; -.
DR TCDB; 8.A.63.1.1; the sigma non-opioid intracellular receptor (s1r) family.
DR iPTMnet; Q99720; -.
DR PhosphoSitePlus; Q99720; -.
DR SwissPalm; Q99720; -.
DR BioMuta; SIGMAR1; -.
DR DMDM; 74752153; -.
DR EPD; Q99720; -.
DR jPOST; Q99720; -.
DR MassIVE; Q99720; -.
DR MaxQB; Q99720; -.
DR PaxDb; Q99720; -.
DR PeptideAtlas; Q99720; -.
DR PRIDE; Q99720; -.
DR ProteomicsDB; 78435; -. [Q99720-1]
DR ProteomicsDB; 78436; -. [Q99720-2]
DR ProteomicsDB; 78437; -. [Q99720-3]
DR ProteomicsDB; 78438; -. [Q99720-4]
DR ProteomicsDB; 78439; -. [Q99720-5]
DR TopDownProteomics; Q99720-1; -. [Q99720-1]
DR TopDownProteomics; Q99720-2; -. [Q99720-2]
DR TopDownProteomics; Q99720-3; -. [Q99720-3]
DR TopDownProteomics; Q99720-4; -. [Q99720-4]
DR TopDownProteomics; Q99720-5; -. [Q99720-5]
DR Antibodypedia; 2756; 250 antibodies from 34 providers.
DR DNASU; 10280; -.
DR Ensembl; ENST00000277010.9; ENSP00000277010.4; ENSG00000147955.18. [Q99720-1]
DR Ensembl; ENST00000353468.4; ENSP00000434453.1; ENSG00000147955.18. [Q99720-4]
DR Ensembl; ENST00000477726.1; ENSP00000420022.1; ENSG00000147955.18. [Q99720-3]
DR Ensembl; ENST00000679597.1; ENSP00000505634.1; ENSG00000147955.18. [Q99720-2]
DR GeneID; 10280; -.
DR KEGG; hsa:10280; -.
DR MANE-Select; ENST00000277010.9; ENSP00000277010.4; NM_005866.4; NP_005857.1.
DR UCSC; uc003zvb.5; human. [Q99720-1]
DR CTD; 10280; -.
DR DisGeNET; 10280; -.
DR GeneCards; SIGMAR1; -.
DR GeneReviews; SIGMAR1; -.
DR HGNC; HGNC:8157; SIGMAR1.
DR HPA; ENSG00000147955; Tissue enhanced (liver).
DR MalaCards; SIGMAR1; -.
DR MIM; 601978; gene.
DR MIM; 605726; phenotype.
DR MIM; 614373; phenotype.
DR neXtProt; NX_Q99720; -.
DR OpenTargets; ENSG00000147955; -.
DR Orphanet; 139552; Distal hereditary motor neuropathy, Jerash type.
DR Orphanet; 300605; Juvenile amyotrophic lateral sclerosis.
DR PharmGKB; PA164725706; -.
DR VEuPathDB; HostDB:ENSG00000147955; -.
DR eggNOG; KOG4143; Eukaryota.
DR GeneTree; ENSGT00390000012082; -.
DR HOGENOM; CLU_147736_0_0_1; -.
DR InParanoid; Q99720; -.
DR OMA; LWATTRI; -.
DR OrthoDB; 1285317at2759; -.
DR PhylomeDB; Q99720; -.
DR TreeFam; TF300106; -.
DR PathwayCommons; Q99720; -.
DR Reactome; R-HSA-9679191; Potential therapeutics for SARS.
DR SignaLink; Q99720; -.
DR SIGNOR; Q99720; -.
DR BioGRID-ORCS; 10280; 24 hits in 1087 CRISPR screens.
DR ChiTaRS; SIGMAR1; human.
DR GeneWiki; Sigma-1_receptor; -.
DR GenomeRNAi; 10280; -.
DR Pharos; Q99720; Tclin.
DR PRO; PR:Q99720; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q99720; protein.
DR Bgee; ENSG00000147955; Expressed in right lobe of liver and 197 other tissues.
DR ExpressionAtlas; Q99720; baseline and differential.
DR Genevisible; Q99720; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0005811; C:lipid droplet; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IDA:GO_Central.
DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0098839; C:postsynaptic density membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004985; F:G protein-coupled opioid receptor activity; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
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; IEA:Ensembl.
DR GO; GO:0070207; P:protein homotrimerization; IPI:UniProtKB.
DR GO; GO:0043523; P:regulation of neuron apoptotic process; IMP: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 3D-structure; Alternative splicing; Amyotrophic lateral sclerosis;
KW Cell junction; Cell membrane; Cell projection; Cytoplasmic vesicle;
KW Direct protein sequencing; Disease variant; Endoplasmic reticulum;
KW Lipid droplet; Lipid transport; Membrane; Neurodegeneration; Nucleus;
KW Postsynaptic cell membrane; Receptor; Reference proteome; Synapse;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..223
FT /note="Sigma non-opioid intracellular receptor 1"
FT /id="PRO_0000268652"
FT TOPO_DOM 1..9
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:27042935"
FT TRANSMEM 10..30
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:27042935"
FT TOPO_DOM 31..223
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:27042935"
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:0000269|PubMed:27042935"
FT SITE 126
FT /note="Important for ligand binding"
FT /evidence="ECO:0000269|PubMed:11476895"
FT SITE 172
FT /note="Important for ligand binding"
FT /evidence="ECO:0000269|PubMed:11476895"
FT VAR_SEQ 31..52
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_021981"
FT VAR_SEQ 31..50
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.6"
FT /id="VSP_021982"
FT VAR_SEQ 63..76
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_021983"
FT VAR_SEQ 103..106
FT /note="YVLL -> ALLG (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.6"
FT /id="VSP_021984"
FT VAR_SEQ 107..223
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.6"
FT /id="VSP_021985"
FT VAR_SEQ 118..148
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.4, ECO:0000303|Ref.6"
FT /id="VSP_021986"
FT VARIANT 2
FT /note="Q -> P (in dbSNP:rs1800866)"
FT /evidence="ECO:0000269|PubMed:15298647"
FT /id="VAR_029750"
FT VARIANT 65
FT /note="L -> Q (in DSMA2; unknown pathological significance;
FT dbSNP:rs140376902)"
FT /evidence="ECO:0000269|PubMed:27629094"
FT /id="VAR_078816"
FT VARIANT 102
FT /note="E -> Q (in ALS16; the mutation decreases the
FT viability of motor neurons; the mutant protein is shifted
FT to lower density membranes and forms detergent-resistant
FT complexes; there is an almost 2-fold increase in apoptosis
FT in response to stress compared to controls;
FT dbSNP:rs387906829)"
FT /evidence="ECO:0000269|PubMed:21842496"
FT /id="VAR_067311"
FT VARIANT 211
FT /note="R -> Q (in dbSNP:rs192644838)"
FT /evidence="ECO:0000269|PubMed:15298647"
FT /id="VAR_029751"
FT MUTAGEN 123
FT /note="E->G: No effect on ligand-binding."
FT /evidence="ECO:0000269|PubMed:11476895"
FT MUTAGEN 126
FT /note="D->G: Reduces ligand-binding. No effect on
FT subcellular localization."
FT /evidence="ECO:0000269|PubMed:11476895"
FT MUTAGEN 138
FT /note="E->G: No effect on ligand-binding."
FT /evidence="ECO:0000269|PubMed:11476895"
FT MUTAGEN 144
FT /note="E->G: No effect on ligand-binding."
FT /evidence="ECO:0000269|PubMed:11476895"
FT MUTAGEN 150
FT /note="E->G: No effect on ligand-binding."
FT /evidence="ECO:0000269|PubMed:11476895"
FT MUTAGEN 158
FT /note="E->G: No effect on ligand-binding."
FT /evidence="ECO:0000269|PubMed:11476895"
FT MUTAGEN 163
FT /note="E->G: No effect on ligand-binding."
FT /evidence="ECO:0000269|PubMed:11476895"
FT MUTAGEN 172
FT /note="E->G: Reduces ligand-binding. No effect on
FT subcellular localization."
FT /evidence="ECO:0000269|PubMed:11476895"
FT MUTAGEN 188
FT /note="D->G: No effect on ligand-binding."
FT /evidence="ECO:0000269|PubMed:11476895"
FT MUTAGEN 195
FT /note="D->G: No effect on ligand-binding."
FT /evidence="ECO:0000269|PubMed:11476895"
FT MUTAGEN 213
FT /note="E->G: No effect on ligand-binding."
FT /evidence="ECO:0000269|PubMed:11476895"
FT CONFLICT 151
FT /note="T -> A (in Ref. 4; AAF64280)"
FT /evidence="ECO:0000305"
FT CONFLICT 168
FT /note="T -> A (in Ref. 6; ABG29111)"
FT /evidence="ECO:0000305"
FT CONFLICT 208
FT /note="R -> W (in Ref. 5; AAV33304)"
FT /evidence="ECO:0000305"
FT CONFLICT 218
FT /note="L -> I (in Ref. 6; ABG29111)"
FT /evidence="ECO:0000305"
FT CONFLICT 219
FT /note="F -> S (in Ref. 9; BAD96619)"
FT /evidence="ECO:0000305"
FT HELIX 1..3
FT /evidence="ECO:0007829|PDB:6DK0"
FT HELIX 9..31
FT /evidence="ECO:0007829|PDB:5HK1"
FT HELIX 39..49
FT /evidence="ECO:0007829|PDB:5HK1"
FT HELIX 54..68
FT /evidence="ECO:0007829|PDB:5HK1"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:5HK1"
FT STRAND 82..86
FT /evidence="ECO:0007829|PDB:5HK1"
FT STRAND 89..98
FT /evidence="ECO:0007829|PDB:5HK1"
FT STRAND 100..111
FT /evidence="ECO:0007829|PDB:5HK1"
FT STRAND 113..116
FT /evidence="ECO:0007829|PDB:5HK1"
FT STRAND 121..131
FT /evidence="ECO:0007829|PDB:5HK1"
FT STRAND 133..137
FT /evidence="ECO:0007829|PDB:5HK1"
FT STRAND 144..146
FT /evidence="ECO:0007829|PDB:5HK1"
FT STRAND 151..154
FT /evidence="ECO:0007829|PDB:5HK1"
FT STRAND 160..164
FT /evidence="ECO:0007829|PDB:5HK1"
FT STRAND 166..176
FT /evidence="ECO:0007829|PDB:5HK1"
FT HELIX 178..180
FT /evidence="ECO:0007829|PDB:5HK1"
FT HELIX 182..185
FT /evidence="ECO:0007829|PDB:5HK1"
FT HELIX 187..191
FT /evidence="ECO:0007829|PDB:5HK1"
FT HELIX 196..218
FT /evidence="ECO:0007829|PDB:5HK1"
SQ SEQUENCE 223 AA; 25128 MW; 0C498636BEB1C443 CRC64;
MQWAVGRRWA WAALLLAVAA VLTQVVWLWL GTQSFVFQRE EIAQLARQYA GLDHELAFSR
LIVELRRLHP GHVLPDEELQ WVFVNAGGWM GAMCLLHASL SEYVLLFGTA LGSRGHSGRY
WAEISDTIIS GTFHQWREGT TKSEVFYPGE TVVHGPGEAT AVEWGPNTWM VEYGRGVIPS
TLAFALADTV FSTQDFLTLF YTLRSYARGL RLELTTYLFG QDP
