Recombinant Human Sigma non-opioid intracellular receptor 1 (SIGMAR1), partial

1. Disruption of the association of Sig-1R with TRPV1 by synthetic or natural antagonists leads to degradation of TRPV1 protein and to decreased levels of the ion channel protein as well as to a decrease in TRPV1-associated pain. PMID: 29378958
2. Findings indicate that sigma1R is decreased in hepatocellular carcinoma and is closely correlated with histological differentiation. PMID: 29399701
3. mutation in Sigma receptor-1 leads to ER stress-mediated defects in protein homeostasis and dysregulation of RNA-binding proteins PMID: 28622300
4. These findings indicate that a loss of Sig1R function is causative for juvenile amyotrophic lateral sclerosis (ALS16), and collapse of the mitochondria-associated membrane is a common pathomechanism in both Sig1R- and SOD1-linked ALS. PMID: 27821430
5. Analyses of tissue microarray from colorectal cancer patients showed higher SigmaR1 expression levels in cancer samples and a correlation with tumor grade. Moreover, the exploration of a cohort of 4937 breast cancer patients indicated that high expression of SigmaR1 and Orai1 channels was significantly correlated to a lower overall survival. PMID: 28114279
6. our data show that Sigma1 modulators can be used to suppress AR/ARV-driven prostate cancer cells via regulation of pharmacologically responsive Sigma1-AR/ARV interactions, both in vitro and in vivo PMID: 28235766
7. Genetic variant within the encoding gene SIGMAR1 (rs1800866A>C) associated with Major Depressive Disorder and Bipolar Disorder. PMID: 28144920
8. Data demonstrate the involvement of SIGMAR1 in motor neuron maintenance and survival by correlating mutations in this gene to distal motor dysfunction and highlight the chaperone activity of sigma-1R as a critical aspect in distal hereditary motor neuropathy pathology. PMID: 27402882
9. Changes of Sig1R and SOD2 expression point to mitochondria as main organelle responsible for survival of tumor cells exposed to hypoxia or oxidative stress. Studied proteins are involved in intracellular response to stress related with different concentrations of oxygen. PMID: 27829319
10. the sigma-1 receptor and the nNav1.5 channel formed a physical, functional complex PMID: 27160185
11. Collectively, these studies define Sig1R as a key mediator of TRAIL induction of cancer-specific killing. PMID: 26792723
12. crystal structures of the human sigma1 receptor in complex with two chemically divergent ligands, PD144418 and 4-IBP PMID: 27042935
13. Expression of mutant Sig-1R protein reduces mitochondrial ATP production, inhibits proteasome activity and causes mitochondrial injury, aggravating ER stress-induced neuronal death. PMID: 25704016
14. 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. PMID: 25704011
15. 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. PMID: 25704013
16. 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. PMID: 25704014
17. mutations of the SIGMAR1 gene worsen outcome in Alzheimer's disease and myotrophic lateral sclerosis supporting a role of Sig-1R in neurodegenerative disease. PMID: 25704015
18. 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 PMID: 25261976
19. Central and peripheral pharmacological blockade of Sig-1R could be an effective option to treat inflammatory pain--{REVIEW} PMID: 25902777
20. 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 PMID: 25449906
21. 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 PMID: 26078401
22. Patients with hilar cholangiocarcinoma overexpressed Sig1R and had an earlier recurrence and worse overall survival than those not overexpressing Sig1R. PMID: 25344871
23. 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. PMID: 25510962
24. SIGMAR1 is an alternative upstream STAT3 activator in addition to IL6/JAK signalling pathway. PMID: 24726897
25. Combination of AAG8 antagonist and very low concentration of a MEK inhibitor synergistically restricts the growth of drug-resistant cells. PMID: 24634165
26. 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. PMID: 24922074
27. sigma-1 receptor may bind to hERG in the endoplasmic reticulum, aiding its assembly and trafficking to the plasma membrane PMID: 25266722
28. Causative mutation in the SIGMAR1 gene is rare in Korean patients with either familial or sporadic ALS. PMID: 24684794
29. SIGMAR1 might shuttle between the nucleus and the cytoplasm PMID: 24313828
30. Data indicate that the mitochondrion-associated ER membrane (MAM) regulates cellular survival via an MAM-residing ER chaperone the sigma-1 receptor (Sig-1R). PMID: 24204710
31. 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. PMID: 24085347
32. 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. PMID: 24616099
33. 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. PMID: 23906352
34. 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. PMID: 24592734
35. Sigma-1 receptor binds to the GluN1/GluN2A NMDA receptor specifically via the GluN1 subunit. PMID: 24227730
36. 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. PMID: 24006496
37. OPRS1 mediates IL-24-induced cancer-specific apoptosis. PMID: 23988449
38. the chaperone domain of S1R interacts with full-length BiP. PMID: 23760505
39. 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). PMID: 23121507
40. Sigma-1 receptor regulates early steps of hepatitis C viral RNA replication at the onset of infection. PMID: 23536676
41. 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. PMID: 22739338
42. Sigma 1 receptor stimulation protects against oxidative damage through suppression of the ER stress responses in the human lens PMID: 23041531
43. This study demonistrated that association between the SIGMAR1 Gln2Pro polymorphism and schizophrenia in our Japanese population. PMID: 22818711
44. 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. PMID: 22952230
45. Sigma1R likely interacts with different domains of Kv ion channel family proteins resulting in distinct modulation of different channels. PMID: 22433979
46. Our data demonstrates an association between the SIGMAR1 TT-P variant and the risk for developing Alzheimer's diseasE PMID: 22561649
47. sigma1R may serve as a potential predictive factor for pTNM classification and tumor development in esophageal squamous cell carcinoma. PMID: 22511599
48. The sigma-1 receptor plays an important role in modifying the function of transmembrane proteases. PMID: 22322890
49. Sig1R protein regulates hERG channel expression through a post-translational mechanism in leukemic cells. PMID: 21680736
50. SIGMAR1 and APOE interact to influence Alzheimer's disease severity across ethnic populations. PMID: 21605063

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HGNC: 8157

OMIM: 601978

KEGG: hsa:10280

STRING: 9606.ENSP00000277010

UniGene: Hs.522087