Property Summary

NCBI Gene PubMed Count 81
PubMed Score 177.50
PubTator Score 84.16

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (5)

Disease log2 FC p
medulloblastoma, large-cell 1.300 2.5e-03
pancreatic ductal adenocarcinoma liver m... -2.013 3.8e-04
lung cancer 2.200 1.1e-04
colon cancer 1.600 3.0e-03
ovarian cancer 1.400 3.9e-06

MLP Assay (2)

AID Type Active / Inconclusive / Inactive Description
1788 other 0 / 0 / 0 Discovery of novel allosteric modulators of the M1 muscarinic receptor: Agonist Ancillary Activity
1921 other 2 / 0 / 0 Discovery of a Highly Selective in vitro and in vivo M4 Positive Allosteric Modulator: Ancillary Activity

Gene RIF (72)

PMID Text
27042935 crystal structures of the human sigma1 receptor in complex with two chemically divergent ligands, PD144418 and 4-IBP
26792723 Collectively, these studies define Sig1R as a key mediator of TRAIL induction of cancer-specific killing.
26078401 Homozygous c.151+1G>T mutation in SIGMAR1 caused a novel form of autosomal recessive distal hereditary motor neuropathy (dHMN) in a Chinese consanguineous family; endoplasmic reticulum stress may have a role in the pathogenesis of dHMN
25902777 Central and peripheral pharmacological blockade of Sig-1R could be an effective option to treat inflammatory pain--{REVIEW}
25704016 Expression of mutant Sig-1R protein reduces mitochondrial ATP production, inhibits proteasome activity and causes mitochondrial injury, aggravating ER stress-induced neuronal death.
25704015 mutations of the SIGMAR1 gene worsen outcome in Alzheimer's disease and myotrophic lateral sclerosis supporting a role of Sig-1R in neurodegenerative disease.
25704014 overview of the biological mechanisms frequently associated with neurodegeneration, and discuss how sigma-1 receptors may alter these mechanisms to preserve or restore neuronal function.
25704013 Removal of the S1R gene in the Superoxide Dismutase-1 (SOD-1) mouse model of ALS exacerbated the neurodegenerative condition and resulted in a significantly reduced longevity.
25704011 Recent studies indicate that sigma-1 receptors, partly in sake of its unique subcellular localization, regulate the mitochondria function that involves bioenergetics and free radical generation.
25569182 Inhibition of sigma receptor or VEGFR causes a significant decrease in HIV-1 Tat- and cocaine-induced H2O2 generation in human pulmonary arterial smooth muscle cells
25510962 Data suggest that SIGMAR1 occurs in vivo (here, as recombinant fusion proteins expressed in COS-7 cells) in multiple monomeric/dimeric/oligomeric forms and that SIGMAR1 ligands alter distribution of SIGMAR1 in such structures/aggregates.
25449906 Results suggest that the ubiquitin-proteasome pathway is implicated in nuclear inclusion formation, and that SIGMAR1 degrades aberrant proteins in the nucleus via the endoplasmic reticulum-related degradation machinery
25344871 Patients with hilar cholangiocarcinoma overexpressed Sig1R and had an earlier recurrence and worse overall survival than those not overexpressing Sig1R.
25266722 sigma-1 receptor may bind to hERG in the endoplasmic reticulum, aiding its assembly and trafficking to the plasma membrane
25261976 examined blood samples from 3081 ischemic stroke (IS) patients and 1595 control subjects regarding 10 single nucleotide polymorphisms (SNPs) in the APOD and SIGMAR1 genes to find possible associations with IS risk, IS severity and recovery after IS
24922074 results support the notion that loss of SigR1 function contributes to ALS pathology by causing abnormal ER morphology, lipid raft destabilization and defective endolysosomal pathways.
24726897 SIGMAR1 is an alternative upstream STAT3 activator in addition to IL6/JAK signalling pathway.
24684794 Causative mutation in the SIGMAR1 gene is rare in Korean patients with either familial or sporadic ALS.
24634165 Combination of AAG8 antagonist and very low concentration of a MEK inhibitor synergistically restricts the growth of drug-resistant cells.
24616099 The non-opioid sigma-1 receptor (S1R) was identified as a novel effector of GAP activity of ELMOD1-3 proteins as its direct binding to either ELMOD1 or ELMOD2 resulted in loss of GAP activity.
24592734 the possible pathways by which the sigma-1 receptor may reduce the excitability of motoneurons and thereby play a protective function during the progression of ALS.
24409324 Inhibition of sigma receptor or VEGFR causes a significant decrease in HIV-1 Tat- and cocaine-induced H2O2 generation in human pulmonary arterial smooth muscle cells
24313828 SIGMAR1 might shuttle between the nucleus and the cytoplasm
24227730 Sigma-1 receptor binds to the GluN1/GluN2A NMDA receptor specifically via the GluN1 subunit.
24204710 Data indicate that the mitochondrion-associated ER membrane (MAM) regulates cellular survival via an MAM-residing ER chaperone the sigma-1 receptor (Sig-1R).
24085347 SIGMAR1 is reported to be associated with juvenile amyotrophic sclerosis. A homozygous missense mutation, E102Q, in SIGMAR1 gene was identified in autosomal recessive FALS from Saudi Arabia.
24006496 unfolded protein response (UPR)and autophagy are engaged as primary and secondary cytoprotective responses, respectively, to Sigma1 ligand-induced disruption of cancer cell protein homeostasis.
23988449 OPRS1 mediates IL-24-induced cancer-specific apoptosis.
23906352 It is probably due to double nature of Sig1R action - in certain conditions it could act pro- or antiapoptotic. This action might depend on Sig1R activity resulting from its expression level.
23760505 the chaperone domain of S1R interacts with full-length BiP.
23536676 Sigma-1 receptor regulates early steps of hepatitis C viral RNA replication at the onset of infection.
23121507 Data using recombinant proteins expressed in vascular endothelial cells suggest that SigmaR1 is not involved in regulation of calcium signaling via TRPC5/TRPM3 channels (transient receptor potential cation channels C5/M3).
23041531 Sigma 1 receptor stimulation protects against oxidative damage through suppression of the ER stress responses in the human lens
22952230 Each set of six transmembrane regions in Nav1.5 likely constitutes a Sig1R binding site, suggesting that the Sig1R interacts with the transmembrane regions of its binding partners.
22818711 This study demonistrated that association between the SIGMAR1 Gln2Pro polymorphism and schizophrenia in our Japanese population.
22739338 coding and noncoding variants located in the 3'-UTR region of the SIGMAR1 gene are not the cause of FTLD-MND in our cohort, and more than half of this targeted cohort is genetically explained by C9ORF72 repeat expansions.
22561649 Our data demonstrates an association between the SIGMAR1 TT-P variant and the risk for developing Alzheimer's diseasE
22511599 sigma1R may serve as a potential predictive factor for pTNM classification and tumor development in esophageal squamous cell carcinoma.
22433979 Sigma1R likely interacts with different domains of Kv ion channel family proteins resulting in distinct modulation of different channels.
22322890 The sigma-1 receptor plays an important role in modifying the function of transmembrane proteases.
22079628 These results indicate that Sig-1Rs are transcriptionally upregulated via the PERK/eIF2alpha/ATF4 pathway and ameliolate cell death signaling.
21842496 This study demonistrated that A mutation in sigma-1 receptor(E102Q ) causes juvenile amyotrophic lateral sclerosis
21744858 Data indicate that fluorescent sigma(2) ligands show their potential in clarifying the mechanisms of action of sigma(2) receptors.
21680736 Sig1R protein regulates hERG channel expression through a post-translational mechanism in leukemic cells.
21605063 SIGMAR1 and APOE interact to influence Alzheimer's disease severity across ethnic populations.
21549171 gives evidence Pro carriers more common among pts with schizophrenia, have validly lower activation right PFC comp to pts with Gln/Gln genotype. data imply SIGMAR1 SNP associated w/ increased risk of schz & differential activation of Prefrontal cortex
21486275 Sigma-1 receptor antagonists, but not agonists, show GTP- and suramin-sensitive high-affinity binding.
21211548 Suppression of NMDA responses of rat retinal ganglion cells caused by the activation of zeta receptor-1 may be mediated by a distinct intracellular divalent calcium ion-dependent signaling pathway.
21031579 SIGMAR1 is a causative gene for a familial form of FTLD-MND.
20468064 Observational study of gene-disease association. (HuGE Navigator)
20178807 rs1800866 in SIGMAR1 may play a role in the pathophysiology of major depressive disorder (MDD) in the Japanese population. Also, SIGMAR1 does not play a role in the therapeutic response to SSRI in Japanese MDD patients.
20178807 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20053954 Detergent-resistant microdomains determine the localization of sigma-1 receptors to the endoplasmic reticulum-mitochondria junction.
19439245 From this imaging genetics study implicated that the association between Sig-1R gene polymorphism (Gln2Pro) and prefrontal cortical function in schizophrenia.
19279232 Na(+) channels represent a new addition to the large number of voltage-gated ion channels modulated by sigma-receptors
19204726 Observational study of gene-disease association. (HuGE Navigator)
18583979 Meta-analysis of gene-disease association. (HuGE Navigator)
18539593 sigma-1R overexpression drives sigma agonist-independent dissociation of ANK 220 from IP3R-3, resulting in activation
17961544 Developed an unambiguous assay system for measuring the affinity of ligands to the cloned human sigma(1) receptor.
17457031 Observational study of gene-disease association. (HuGE Navigator)
17457031 No significant differences were observed for the SIGMAR1 allele, genotype, haplotype, and diplotype distributions between a group of Polish patients with late-onset AD, patients with mild cognitive impairment, and a control group.
17419803 These results suggest that HP may irreversibly inactivate sigma(1) receptors in guinea pig and human cells, probably after metabolism to reduced HP.
16954606 These results suggest that the effect of cocaine on sigma(1) receptor gene expression in the brain might be indirect and mediated through dopamine-1 receptors.
16945406 the present review details the evidences showing that the sigma(1) receptor is a target for neurosteroids in physiological conditions--{REVIEW}
16472803 This study establishes a central role for Sig-1R in cell survival and death.
16388898 sigma1 receptor plays a role in proliferation and adhesion of breast cancer cells
16319298 Observational study of gene-disease association. (HuGE Navigator)
16319298 a variant of SIGMAR1 gene is a protective factor for Alzheimer's disease
15542696 Observational study of gene-disease association. (HuGE Navigator)
15298647 Observational study of gene-disease association. (HuGE Navigator)
14706429 Observational study of gene-disease association. (HuGE Navigator)
14567761 Observational study and meta-analysis of gene-disease association. (HuGE Navigator)

AA Sequence

MQWAVGRRWAWAALLLAVAAVLTQVVWLWLGTQSFVFQREEIAQLARQYAGLDHELAFSRLIVELRRLHP      1 - 70
GHVLPDEELQWVFVNAGGWMGAMCLLHASLSEYVLLFGTALGSRGHSGRYWAEISDTIISGTFHQWREGT     71 - 140
TKSEVFYPGETVVHGPGEATAVEWGPNTWMVEYGRGVIPSTLAFALADTVFSTQDFLTLFYTLRSYARGL    141 - 210
RLELTTYLFGQDP                                                             211 - 223
//

Text Mined References (85)

PMID Year Title
27042935 2016 Crystal structure of the human ?1 receptor.
26792723 2016 Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) activates caspases in human prostate cancer cells through sigma 1 receptor.
26078401 2015 A SIGMAR1 splice-site mutation causes distal hereditary motor neuropathy.
25944712 2015 N-terminome analysis of the human mitochondrial proteome.
25902777 2015 Sigma-1 receptor and inflammatory pain.
25704016 2015 The role of SIGMAR1 gene mutation and mitochondrial dysfunction in amyotrophic lateral sclerosis.
25704015 2015 The involvement of the sigma-1 receptor in neurodegeneration and neurorestoration.
25704014 2015 Role of sigma-1 receptors in neurodegenerative diseases.
25704013 2015 Role of the Sigma-1 receptor in Amyotrophic Lateral Sclerosis (ALS).
25704011 2015 Sigma-1 receptor: the novel intracellular target of neuropsychotherapeutic drugs.
25647032 2015 Solution NMR studies reveal the location of the second transmembrane domain of the human sigma-1 receptor.
25510962 2015 The sigma-1 receptors are present in monomeric and oligomeric forms in living cells in the presence and absence of ligands.
25449906 2015 Sigma-1 receptor is involved in degradation of intranuclear inclusions in a cellular model of Huntington's disease.
25344871 2014 Overexpression of Sig1R is closely associated with tumor progression and poor outcome in patients with hilar cholangiocarcinoma.
25266722 2014 A direct interaction between the sigma-1 receptor and the hERG voltage-gated K+ channel revealed by atomic force microscopy and homogeneous time-resolved fluorescence (HTRF®).
25261976 2014 Variations in apolipoprotein D and sigma non-opioid intracellular receptor 1 genes with relation to risk, severity and outcome of ischemic stroke.
24922074 2014 Loss of function of the ALS protein SigR1 leads to ER pathology associated with defective autophagy and lipid raft disturbances.
24726897 2014 AAG8 promotes carcinogenesis by activating STAT3.
24684794 2014 Mutations in UBQLN2 and SIGMAR1 genes are rare in Korean patients with amyotrophic lateral sclerosis.
24634165 2014 Modeling tandem AAG8-MEK inhibition in melanoma cells.
24616099 2014 Characterization of recombinant ELMOD (cell engulfment and motility domain) proteins as GTPase-activating proteins (GAPs) for ARF family GTPases.
24592734 2013 [Protective function of sigma-1 receptor in spinal cord motor neurons].
24313828 2014 Accumulation of the sigma-1 receptor is common to neuronal nuclear inclusions in various neurodegenerative diseases.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24227730 2013 The ?-1 receptor interacts directly with GluN1 but not GluN2A in the GluN1/GluN2A NMDA receptor.
24204710 2013 Sigma-1 receptor chaperone at the ER-mitochondrion interface mediates the mitochondrion-ER-nucleus signaling for cellular survival.
24085347 2013 Amyotrophic lateral sclerosis: an update on recent genetic insights.
24006496 2013 Sequential cytoprotective responses to Sigma1 ligand-induced endoplasmic reticulum stress.
23988449 2013 Sigma 1 Receptor plays a prominent role in IL-24-induced cancer-specific apoptosis.
23906352 2013 Altered expression level of Sigma1 receptor gene in human colorectal cancer.
23760505 2013 Characterization of the human sigma-1 receptor chaperone domain structure and binding immunoglobulin protein (BiP) interactions.
23536676 2013 Sigma-1 receptor regulates early steps of viral RNA replication at the onset of hepatitis C virus infection.
23314020 2013 Altered localization, abnormal modification and loss of function of Sigma receptor-1 in amyotrophic lateral sclerosis.
23121507 2013 Inhibition of endothelial cell Ca²? entry and transient receptor potential channels by Sigma-1 receptor ligands.
23041531 Sigma 1 receptor stimulation protects against oxidative damage through suppression of the ER stress responses in the human lens.
22952230 2012 The sigma-1 receptor binds to the Nav1.5 voltage-gated Na+ channel with 4-fold symmetry.
22818711 2012 Supportive evidence for the association between the Gln2Pro polymorphism in the SIGMAR1 gene and schizophrenia in the Japanese population: a case-control study and an updated meta-analysis.
22739338 2013 Genetic analysis of SIGMAR1 as a cause of familial ALS with dementia.
22561649 2012 Association between a variant of the sigma-1 receptor gene and Alzheimer's disease.
22511599 2012 Overexpression of sigma1 receptor and its positive associations with pathologic TNM classification in esophageal squamous cell carcinoma.
22433979 2012 Sigma-1 receptor alters the kinetics of Kv1.3 voltage gated potassium channels but not the sensitivity to receptor ligands.
22322890 2012 Overexpression of sigma-1 receptor inhibits ADAM10 and ADAM17 mediated shedding in vitro.
22079628 2011 Sigma-1Rs are upregulated via PERK/eIF2?/ATF4 pathway and execute protective function in ER stress.
21842496 2011 A mutation in sigma-1 receptor causes juvenile amyotrophic lateral sclerosis.
21744858 2011 Fluorescent derivatives of ? receptor ligand 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28) as a tool for uptake and cellular localization studies in pancreatic tumor cells.
21680736 2011 Sig1R protein regulates hERG channel expression through a post-translational mechanism in leukemic cells.
21605063 2011 Genetic polymorphisms in sigma-1 receptor and apolipoprotein E interact to influence the severity of Alzheimer's disease.
21549171 2011 The SIGMAR1 gene is associated with a risk of schizophrenia and activation of the prefrontal cortex.
21486275 2011 Antagonists show GTP-sensitive high-affinity binding to the sigma-1 receptor.
21269460 2011 Initial characterization of the human central proteome.
21211548 2011 Activation of the ? receptor 1 suppresses NMDA responses in rat retinal ganglion cells.
21031579 2010 Sigma nonopioid intracellular receptor 1 mutations cause frontotemporal lobar degeneration-motor neuron disease.
20468064 2010 Association study of 182 candidate genes in anorexia nervosa.
20178807 2010 Association analysis of SIGMAR1 with major depressive disorder and SSRI response.
20053954 2010 Detergent-resistant microdomains determine the localization of sigma-1 receptors to the endoplasmic reticulum-mitochondria junction.
19439245 2009 Association between sigma-1 receptor gene polymorphism and prefrontal hemodynamic response induced by cognitive activation in schizophrenia.
19279232 2009 Voltage-gated sodium channel modulation by sigma-receptors in cardiac myocytes and heterologous systems.
19204726 2009 Transcriptomic and genetic studies identify IL-33 as a candidate gene for Alzheimer's disease.
18583979 2008 Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database.
18539593 2008 Role of sigma-1 receptor C-terminal segment in inositol 1,4,5-trisphosphate receptor activation: constitutive enhancement of calcium signaling in MCF-7 tumor cells.
17961544 2008 An unambiguous assay for the cloned human sigma1 receptor reveals high affinity interactions with dopamine D4 receptor selective compounds and a distinct structure-affinity relationship for butyrophenones.
17457031 2007 Sigma receptor type 1 gene variation in a group of Polish patients with Alzheimer's disease and mild cognitive impairment.
17419803 2007 Irreversible blockade of sigma-1 receptors by haloperidol and its metabolites in guinea pig brain and SH-SY5Y human neuroblastoma cells.
16954606 2006 Dopamine-1 receptor agonist, but not cocaine, modulates sigma(1) gene expression in SVG cells.
16945406 2006 Neuro(active)steroids actions at the neuromodulatory sigma1 (sigma1) receptor: biochemical and physiological evidences, consequences in neuroprotection.
16472803 2006 Silencing of sigma-1 receptor induces cell death in human lens cells.
16388898 2006 The expression and functional characterization of sigma (sigma) 1 receptors in breast cancer cell lines.
16319298 2005 A variant of the sigma receptor type-1 gene is a protective factor for Alzheimer disease.
15542696 2004 No association found between the type 1 sigma receptor gene polymorphisms and methamphetamine abuse in the Japanese population: a collaborative study by the Japanese Genetics Initiative for Drug Abuse.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15298647 2004 Lack of association between sigma receptor gene variants and schizophrenia.
15164053 2004 DNA sequence and analysis of human chromosome 9.
14706429 2004 Functional polymorphisms in the sigma1 receptor gene associated with alcoholism.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14567761 2003 No association between the sigma receptor type 1 gene and schizophrenia: results of analysis and meta-analysis of case-control studies.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11687279 2001 Expression pattern of sigma receptor 1 mRNA and protein in mammalian retina.
11476895 2001 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.
11149946 2001 Regulating ankyrin dynamics: Roles of sigma-1 receptors.
10406945 1999 Colocalization of sterol isomerase and sigma(1) receptor at endoplasmic reticulum and nuclear envelope level.
10087012 1999 Molecular and ligand-binding characterization of the sigma-receptor in the Jurkat human T lymphocyte cell line.
9453537 1998 Exon-intron structure, analysis of promoter region, and chromosomal localization of the human type 1 sigma receptor gene.
9341151 1997 Purification and characterization of the human SR 31747A-binding protein. A nuclear membrane protein related to yeast sterol isomerase.
8954936 1996 Cloning and functional expression of the human type 1 sigma receptor (hSigmaR1).
8125298 1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.