Sigma non-opioid intracellular receptor 1

Details

Name
Sigma non-opioid intracellular receptor 1
Synonyms
  • Aging-associated gene 8 protein
  • hSigmaR1
  • OPRS1
  • SIG-1R
  • Sigma 1-type opioid receptor
  • Sigma1-receptor
  • Sigma1R
  • SR-BP
  • SR31747-binding protein
  • SRBP
Gene Name
SIGMAR1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0000311|Sigma non-opioid intracellular receptor 1
MQWAVGRRWAWAALLLAVAAVLTQVVWLWLGTQSFVFQREEIAQLARQYAGLDHELAFSR
LIVELRRLHPGHVLPDEELQWVFVNAGGWMGAMCLLHASLSEYVLLFGTALGSRGHSGRY
WAEISDTIISGTFHQWREGTTKSEVFYPGETVVHGPGEATAVEWGPNTWMVEYGRGVIPS
TLAFALADTVFSTQDFLTLFYTLRSYARGLRLELTTYLFGQDP
Number of residues
223
Molecular Weight
25127.52
Theoretical pI
5.87
GO Classification
Functions
drug binding / opioid receptor activity
Processes
lipid transport / nervous system development / regulation of neuron apoptotic process
Components
cell junction / endoplasmic reticulum membrane / growth cone / integral component of membrane / integral component of plasma membrane / lipid particle / neuronal postsynaptic density / nuclear envelope / nuclear inner membrane / nuclear outer membrane
General Function
Opioid receptor activity
Specific 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 (PubMed:16472803, PubMed:9341151). Necessary for proper mitochondrial axonal transport in motor neurons, in particular the retrograde movement of mitochondria (By similarity).
Pfam Domain Function
Transmembrane Regions
10-30 81-101
Cellular Location
Nucleus inner membrane
Gene sequence
>lcl|BSEQ0009974|Sigma non-opioid intracellular receptor 1 (SIGMAR1)
ATGCAGTGGGCCGTGGGCCGGCGGTGGGCGTGGGCCGCGCTGCTCCTGGCTGTCGCAGCG
GTGCTGACCCAGGTCGTCTGGCTCTGGCTGGGTACGCAGAGCTTCGTCTTCCAGCGCGAA
GAGATAGCGCAGTTGGCGCGGCAGTACGCTGGGCTGGACCACGAGCTGGCCTTCTCTCGT
CTGATCGTGGAGCTGCGGCGGCTGCACCCAGGCCACGTGCTGCCCGACGAGGAGCTGCAG
TGGGTGTTCGTGAATGCGGGTGGCTGGATGGGCGCCATGTGCCTTCTGCACGCCTCGCTG
TCCGAGTATGTGCTGCTCTTCGGCACCGCCTTGGGCTCCCGCGGCCACTCGGGGCGCTAC
TGGGCTGAGATCTCGGATACCATCATCTCTGGCACCTTCCACCAGTGGAGAGAGGGCACC
ACCAAAAGTGAGGTCTTCTACCCAGGACCCTTGACCAGCCAGGCCTGA
Chromosome Location
9
Locus
9p13.3
External Identifiers
ResourceLink
UniProtKB IDQ99720
UniProtKB Entry NameSGMR1_HUMAN
GenBank Protein ID1783387
GenBank Gene IDU75283
GenAtlas IDOPRS1
HGNC IDHGNC:8157
General References
  1. Kekuda R, Prasad PD, Fei YJ, Leibach FH, Ganapathy V: Cloning and functional expression of the human type 1 sigma receptor (hSigmaR1). Biochem Biophys Res Commun. 1996 Dec 13;229(2):553-8. [PubMed:8954936]
  2. Jbilo O, Vidal H, Paul R, De Nys N, Bensaid M, Silve S, Carayon P, Davi D, Galiegue S, Bourrie B, Guillemot JC, Ferrara P, Loison G, Maffrand JP, Le Fur G, Casellas P: Purification and characterization of the human SR 31747A-binding protein. A nuclear membrane protein related to yeast sterol isomerase. J Biol Chem. 1997 Oct 24;272(43):27107-15. [PubMed:9341151]
  3. Prasad PD, Li HW, Fei YJ, Ganapathy ME, Fujita T, Plumley LH, Yang-Feng TL, Leibach FH, Ganapathy V: Exon-intron structure, analysis of promoter region, and chromosomal localization of the human type 1 sigma receptor gene. J Neurochem. 1998 Feb;70(2):443-51. [PubMed:9453537]
  4. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039]
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  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  7. Dussossoy D, Carayon P, Belugou S, Feraut D, Bord A, Goubet C, Roque C, Vidal H, Combes T, Loison G, Casellas P: Colocalization of sterol isomerase and sigma(1) receptor at endoplasmic reticulum and nuclear envelope level. Eur J Biochem. 1999 Jul;263(2):377-86. [PubMed:10406945]
  8. Ganapathy ME, Prasad PD, Huang W, Seth P, Leibach FH, Ganapathy V: Molecular and ligand-binding characterization of the sigma-receptor in the Jurkat human T lymphocyte cell line. J Pharmacol Exp Ther. 1999 Apr;289(1):251-60. [PubMed:10087012]
  9. Seth P, Ganapathy ME, Conway SJ, Bridges CD, Smith SB, Casellas P, Ganapathy V: 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. Biochim Biophys Acta. 2001 Jul 25;1540(1):59-67. [PubMed:11476895]
  10. Ola MS, Moore P, El-Sherbeny A, Roon P, Agarwal N, Sarthy VP, Casellas P, Ganapathy V, Smith SB: Expression pattern of sigma receptor 1 mRNA and protein in mammalian retina. Brain Res Mol Brain Res. 2001 Nov 1;95(1-2):86-95. [PubMed:11687279]
  11. Wang L, Duncan G: Silencing of sigma-1 receptor induces cell death in human lens cells. Exp Cell Res. 2006 May 1;312(8):1439-46. Epub 2006 Feb 9. [PubMed:16472803]
  12. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460]
  13. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [PubMed:24275569]
  14. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [PubMed:25944712]
  15. Satoh F, Miyatake R, Furukawa A, Suwaki H: Lack of association between sigma receptor gene variants and schizophrenia. Psychiatry Clin Neurosci. 2004 Aug;58(4):359-63. [PubMed:15298647]
  16. Al-Saif A, Al-Mohanna F, Bohlega S: A mutation in sigma-1 receptor causes juvenile amyotrophic lateral sclerosis. Ann Neurol. 2011 Dec;70(6):913-9. doi: 10.1002/ana.22534. Epub 2011 Aug 12. [PubMed:21842496]
  17. Prause J, Goswami A, Katona I, Roos A, Schnizler M, Bushuven E, Dreier A, Buchkremer S, Johann S, Beyer C, Deschauer M, Troost D, Weis J: Altered localization, abnormal modification and loss of function of Sigma receptor-1 in amyotrophic lateral sclerosis. Hum Mol Genet. 2013 Apr 15;22(8):1581-600. doi: 10.1093/hmg/ddt008. Epub 2013 Jan 11. [PubMed:23314020]
  18. Li X, Hu Z, Liu L, Xie Y, Zhan Y, Zi X, Wang J, Wu L, Xia K, Tang B, Zhang R: A SIGMAR1 splice-site mutation causes distal hereditary motor neuropathy. Neurology. 2015 Jun 16;84(24):2430-7. doi: 10.1212/WNL.0000000000001680. Epub 2015 May 15. [PubMed:26078401]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00514DextromethorphanapprovedyesagonistDetails
DB03575PhencyclidineillicitunknownDetails
DB06174Noscapineapproved, investigationalunknownDetails
DB00652Pentazocineapproved, vet_approvedyesagonistDetails
DB01488Dimethyltryptamineexperimental, illicitunknownDetails
DB00409Remoxiprideapproved, withdrawnunknownantagonistDetails
DB00321AmitriptylineapprovedunknownagonistDetails
DB01708Prasteroneapproved, investigational, nutraceuticalunknownagonistDetails
DB09014CaptodiameexperimentalyesagonistDetails
DB00907Cocaineapproved, illicitunknownDetails
DB11186Pentoxyverineapproved, investigationalyesagonistDetails
DB00540NortriptylineapprovedunknownbinderDetails
DB01104SertralineapprovedunknownantagonistDetails