Property Summary

NCBI Gene PubMed Count 87
PubMed Score 289.80
PubTator Score 692.59

Knowledge Summary

Patent (7,765)

Expression

  Differential Expression (9)

Disease log2 FC p
astrocytic glioma -2.600 3.9e-03
ependymoma -2.900 4.5e-03
oligodendroglioma -2.400 8.7e-03
glioblastoma -2.700 1.0e-04
medulloblastoma -2.800 3.7e-09
atypical teratoid / rhabdoid tumor -2.100 1.8e-04
medulloblastoma, large-cell -2.700 3.7e-05
pediatric high grade glioma -2.200 4.9e-05
pilocytic astrocytoma -2.500 4.6e-09

MLP Assay (32)

AID Type Active / Inconclusive / Inactive Description
1777 confirmatory 51 / 0 / 284169 uHTS identification of small molecule agonists of the kappa opioid receptor via a luminescent beta-arrestin assay
1778 confirmatory 265 / 0 / 290244 uHTS identification of small molecule antagonists of the kappa opioid receptor via a luminescent beta-arrestin assay
1785 summary 2 / 0 / 0 Summary of small molecule antagonists of the kappa opioid receptor
1786 summary 2 / 0 / 0 Summary of small molecule agonists of the kappa opioid receptor
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
2133 confirmatory 24 / 0 / 13 HTS Image-Based Screen for Selective Agonists of the KOR Receptor
2136 confirmatory 44 / 0 / 166 HTS Image-Based Screen for Selective Antagonists of the KOR Receptor
2284 confirmatory 15 / 0 / 15 SAR analysis of small molecule agonists of the kappa opioid receptor via a luminescent beta-arrestin assay
2285 confirmatory 12 / 0 / 20 SAR analysis of small molecule antagonists of the kappa opioid receptor via a luminescent beta-arrestin assay
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Gene RIF (76)

PMID Text
26692286 data provide evidence for genetic modulation of opioid withdrawal severity.
26372966 The structure of the dynorphin (1-13) peptide (dynorphin) bound to the human kappa opioid receptor (KOR) has been determined by liquid-state NMR spectroscopy.
26300544 OPRK1 promoter hypermethylation might increase the risk of AD through its regulation on the gene expression of OPRK1.
26233486 findings suggest that SNPs in opioid receptors and the PNOC genes are associated with NAS severity.
25866368 OX1R and KOR heterodimerize, and this heterodimer associates with Galphas, leading to increased protein kinase A (PKA) signaling pathway activity, including upregulation of intracellular cAMP levels.
25293321 Here we describe three experimental procedures we used to evaluate the interaction between hKOPR and 14-3-3zeta: co-immunoprecipitation, pull-down assay and immunofluorescence microscopy.
25289860 RGS2 and RGS4 are new interacting partners that play key roles in G protein coupling to negatively regulate kappa-OmicronR signaling.
25241033 Low OPRK1 expression is associated with liver metastases of small bowel neuroendocrine tumors.
25229257 Results suggest that Kappa receptor availability in an amygdala-cingulate cortex-striatal circuit mediates the phenotypic expression of trauma-related loss (ie, dysphoria) symptoms.
25177835 Studied differential DNA-protein interactions of PDYN and OPRK1 SNPs significantly associated with alcohol dependence.
25133923 Data indicate that replacement of the 3-hydroxyl substituent of the 4-(3-hydroxyphenyl) group of JDTic with a H, F, or Cl substituent leads to potent and selective kappa opioid receptor (KOR) antagonists.
24651466 Data show that the crystallographic structures of the mouse mu-opioid receptor (MOPr) and human kappa-opioid receptor (KOPr) indicate putative interfacial interactions.
24616919 Data suggest that dynorphin A (DynA) is ligand for opioid receptor kappa (KOR); upon DynA binding, only small chemical shifts observed in second extracellular loop of KOR; chemical shift changes of DynA show conclusively that DynA interacts with KOR.
24603327 Suggest that methamphetamine induced early autophagic response is a survival mechanism for apoptotic endothelial cells and is mediated through the kappa opioid receptor.
24525640 findings suggest that genetic polymorphisms in OPRK1 were associated with the body weight, alcohol use, and opioid withdrawal symptoms in MMT patients.
24405578 Neurocognitive and neuroinflammatory correlates of OPRK1 mRNA expression in the anterior cingulate in postmortem brain of HIV-infected subjects.
24274990 In heroin-dependent patients, no difference was evidenced between responders and non-reponders to buprenorphine therapy in the frequency of OPRK1 SNP.
24121503 crystal structure provides fundamental insights into the activation mechanism of the kappa-opioid receptor and suggest that "functional" residues may be directly involved in transduction of the agonist binding event
23995774 This study indicates that a patient's OPRK1 genotype could be used to identify a subset of individuals for whom vaccine treatment may be an effective pharmacotherapy for cocaine dependence.
23962922 OPRK1 rs6989250 C>G is associated with stress-induced craving and cortisol, hyperactive hypothalamus/thalamus-midbrain-cerebellum responses, and also associated with greater subsequent cocaine relapse risk.
23574786 Kappa Opioid receptor in the nucleus is a novel prognostic factor of esophageal squamous cell carcinoma.
23392455 OPRK1 and PDYN polymorphisms may alter severity of HIV infection and response to treatment.
23277131 This study supports a role for NTRK2 and OPRK1 signaling in the pathophysiology of mood disorder.
23086943 hKOR activates p38 MAPK through a phosphorylation and arrestin-dependent mechanism; however, activation differs between hKOR and rKOR for some ligands
22989890 Data indicate that 14-3-3zeta interaction with kappa-opioid receptor (hKOPR) C-tail promotes export of hKOPR.
22764240 A role is estsablished for dynorphin kappa-opioid receptor signaling in fear extinction.
22752269 delta and mu-opioid receptors, but not kappa-opioid receptors, are functional in the neuronally stimulated longitudinal human vas deferens
22730276 Pairwise tag single nucleotide polymorphisms (SNPs) in DREAM, PDYN and OPRK1 were genotyped in a United Kingdom population-based discovery cohort in whom pain was assessed.
22437504 crystal structure of the human kappa-OR in complex with the selective antagonist JDTic, arranged in parallel dimers, at 2.9 A resolution
22200678 Human apelin forms a heterodimer with the kappa opioid receptor and leads to increased protein kinase C and decreased protein kinase A.
22138325 In summary, this study provides evidence that gene-gene interaction between KOR and OPRM1 can influence the risk of addiction to narcotics and alcohol.
21666232 These findings provide evidence that previously demonstrated KOR-mediated reduction in intraocular pressure could be caused, in part, by NO production in both the ciliary body and the trabecular meshwork.
21483469 Morphine treatment in the presence of Tat significantly increases intracellular expression of opioid receptors (mu, delta, and kappa) and prevents morphine-induced cell surface opioid receptor down-regulation in microglia
21447649 This is the first report detailing the initiation of a KOR-induced JAK2/STAT3 and IRF2 signaling cascade, and these pathways result in substantial down-regulation of CXCR4 expression.
21388957 because of its stronger binding for hKOPR, GEC1 is able to be recruited by hKOPR sufficiently without membrane association via its C-terminal modification; however, du GABARAP appears to require C-terminal modifications to enhance KOPR expression.
20734064 Observational study of gene-disease association. (HuGE Navigator)
20468064 Observational study of gene-disease association. (HuGE Navigator)
19874574 Observational study of gene-disease association. (HuGE Navigator)
19804796 Review. kappa-Opioid receptor signaling and brain reward function.
19086053 Observational study of gene-disease association. (HuGE Navigator)
19058789 Observational study of gene-disease association. (HuGE Navigator)
19032295 Neither pressure pain threshold nor tolerance between major and minor alleles of other SNPs of the OPRM1, OPRK1, and OPRD1 genes were significantly different suggesting an association between the IVS2+31G>A SNP of OPRM1 gene and pressure pain sensitivity.
19032295 Observational study of gene-disease association. (HuGE Navigator)
18767415 the coexpression of KOR-SA35443 (kappa opioid receptor) and NG2(chondroitin sulfate proteoglycan) in result of karyotype abnormal changes may predict a poor prognosis in Pro-B acute lymphoblastic leukemia
18537939 response to nalmefene did not vary with genotype
18537939 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
18518925 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
18353307 Show that LPK-26 is a novel selective kappa-opioid receptor agonist with highly potent antinociception effects and low physical dependence potential.
18338799 Morphine treatment in the presence of Tat significantly increases intracellular expression of opioid receptors (mu, delta, and kappa) and prevents morphine-induced cell surface opioid receptor down-regulation in microglia
18319328 Family-based association analyses detected evidence of association of an insertion in the ORK1 gene with alcoholism.
18319328 Observational study of gene-disease association. (HuGE Navigator)
18213616 genes encoding the mu-, delta-, and kappa-opioid receptors may contribute to variation in personality traits
18213616 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
17711303 Thus, N-glycosylation of the hKOR plays important roles in stability and trafficking along the biosynthesis pathway of the receptor protein as well as agonist-induced receptor regulation.
17702750 long duration KOR antagonists disrupt KOR signaling by activating JNK
17622222 There is a positive haplotypic association between OPRK1 variants and alcohol dependence in European Americans.
17622222 Observational study of gene-disease association. (HuGE Navigator)
17538007 activation of KORs alters functional properties of neural precursor cells that are relevant to human brain development and repair.
17374034 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
17373729 Observational study of gene-disease association. (HuGE Navigator)
17373729 frequency of KOR 36G > T SNP was significantly higher among heroin-dependent individuals compared with control subjects
17373729 The kappa opioid receptor (KOR) system seems to play a role in stress responsivity, opiate withdrawal and responses to psycho-stimulants, inhibiting mesolimbic dopamine.
17121830 Helical orientation of helix 2 are critical for the selectivity of salvinorin A binding to KOR and provide a structurally novel basis for ligand selectivity.
16924269 Observational study of gene-disease association. (HuGE Navigator)
16924269 Family-based analyses demonstrated associations between alcohol dependence and multiple SNPs in intron 2 of OPRK1.
16431922 GEC1 interacts with the kappa opioid receptor and enhances expression of the receptor
16331961 Results describe the residues of the transmembrane helices 7 of delta and kappa opioid receptors that are on the water-accessible surface of the binding-site crevices.
16053916 investigation of the ability of different opioid receptors to regulate the phosphorylation and degradation of tuberin
15952771 The diterpenoid salvinorin A utilizes unique residues within a commonly shared binding pocket to selectively activate KORs.
15608558 Observational study of gene-disease association. (HuGE Navigator)
15608558 OPKR1 structure and association of haplotypes with opiate addiction was found to have empirical significance.
15070904 binding of the KOR to NHERF-1/EBP50 facilitates oligomerization of NHERF-1/EBP50, leading to stimulation of NHE3.
14745298 Observational study of gene-disease association. (HuGE Navigator)
12815037 phosphorylation of serine 369 mediates KOR desensitization and internalization
12413885 These results suggest that oligomerization of chemokine receptor CCR5 and opioid receptors mu, delta and kappa on the cell membrane of human or monkey lymphocytes may modulate receptor functions.
11931835 Morphine treatment in the presence of Tat significantly increases intracellular expression of opioid receptors (mu, delta, and kappa) and prevents morphine-induced cell surface opioid receptor down-regulation in microglia

AA Sequence

MDSPIQIFRGEPGPTCAPSACLPPNSSAWFPGWAEPDSNGSAGSEDAQLEPAHISPAIPVIITAVYSVVF      1 - 70
VVGLVGNSLVMFVIIRYTKMKTATNIYIFNLALADALVTTTMPFQSTVYLMNSWPFGDVLCKIVISIDYY     71 - 140
NMFTSIFTLTMMSVDRYIAVCHPVKALDFRTPLKAKIINICIWLLSSSVGISAIVLGGTKVREDVDVIEC    141 - 210
SLQFPDDDYSWWDLFMKICVFIFAFVIPVLIIIVCYTLMILRLKSVRLLSGSREKDRNLRRITRLVLVVV    211 - 280
AVFVVCWTPIHIFILVEALGSTSHSTAALSSYYFCIALGYTNSSLNPILYAFLDENFKRCFRDFCFPLKM    281 - 350
RMERQSTSRVRNTVQDPAYLRDIDGMNKPV                                            351 - 380
//

Text Mined References (90)

PMID Year Title
26692286 2016 Searching for evidence of genetic mediation of opioid withdrawal by opioid receptor gene polymorphisms.
26372966 2015 NMR structure and dynamics of the agonist dynorphin peptide bound to the human kappa opioid receptor.
26300544 2015 OPRK1 promoter hypermethylation increases the risk of Alzheimer's disease.
26233486 2015 Variations in opioid receptor genes in neonatal abstinence syndrome.
25866368 2015 Heterodimerization of human orexin receptor 1 and kappa opioid receptor promotes protein kinase A/cAMP-response element binding protein signaling via a G?s-mediated mechanism.
25293321 2015 Identification and verification of proteins interacting with the kappa opioid receptor (KOPR).
25289860 2015 RGS2 and RGS4 proteins: New modulators of the ?-opioid receptor signaling.
25241033 2014 Gene expression accurately distinguishes liver metastases of small bowel and pancreas neuroendocrine tumors.
25229257 2014 Association of in vivo ?-opioid receptor availability and the transdiagnostic dimensional expression of trauma-related psychopathology.
25177835 2014 A molecular prospective provides new insights into implication of PDYN and OPRK1 genes in alcohol dependence.
25133923 2014 Design, synthesis, and biological evaluation of (3R)-1,2,3,4-tetrahydro-7-hydroxy-N-[(1S)-1-[[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl]-2-methylpropyl]-3-isoquinolinecarboxamide (JDTic) analogues: in vitro pharmacology and ADME profile.
25013167 2014 Evidence of efficient stop codon readthrough in four mammalian genes.
24651466 2014 Differential stability of the crystallographic interfaces of mu- and kappa-opioid receptors.
24616919 2014 Direct detection of neuropeptide dynorphin A binding to the second extracellular loop of the ? opioid receptor using a soluble protein scaffold.
24603327 2014 Methamphetamine induces autophagy as a pro-survival response against apoptotic endothelial cell death through the Kappa opioid receptor.
24525640 2014 The association of genetic polymorphisms in the ?-opioid receptor 1 gene with body weight, alcohol use, and withdrawal symptoms in patients with methadone maintenance.
24405578 2014 Neurocognitive and neuroinflammatory correlates of PDYN and OPRK1 mRNA expression in the anterior cingulate in postmortem brain of HIV-infected subjects.
24274990 2014 Association between gene variants and response to buprenorphine maintenance treatment.
24121503 2013 Chemotype-selective modes of action of ?-opioid receptor agonists.
23995774 2013 The ?-opioid receptor gene as a predictor of response in a cocaine vaccine clinical trial.
23967269 2013 A genome-wide association study of total serum and mite-specific IgEs in asthma patients.
23962922 2013 A variant on the kappa opioid receptor gene (OPRK1) is associated with stress response and related drug craving, limbic brain activation and cocaine relapse risk.
23574786 2013 ?-Opioid receptor in the nucleus is a novel prognostic factor of esophageal squamous cell carcinoma.
23392455 2013 Polymorphisms of the kappa opioid receptor and prodynorphin genes: HIV risk and HIV natural history.
23277131 2013 A large-scale candidate gene analysis of mood disorders: evidence of neurotrophic tyrosine kinase receptor and opioid receptor signaling dysfunction.
23086943 2012 Ligand directed signaling differences between rodent and human ?-opioid receptors.
22989890 2012 14-3-3? Protein regulates anterograde transport of the human ?-opioid receptor (hKOPR).
22764240 2012 Dynorphins regulate fear memory: from mice to men.
22752269 2012 Opioid receptor characterisation of neuronally stimulated isolated human vas deferens.
22730276 2013 Investigating the role of pain-modulating pathway genes in musculoskeletal pain.
22437504 2012 Structure of the human ?-opioid receptor in complex with JDTic.
22200678 2012 Heterodimerization of human apelin and kappa opioid receptors: roles in signal transduction.
22138325 2012 Epistatic effects between variants of kappa-opioid receptor gene and A118G of mu-opioid receptor gene increase susceptibility to addiction in Indian population.
21666232 2011 Kappa opioid receptor localization and coupling to nitric oxide production in cells of the anterior chamber.
21447649 2011 Transcriptional regulation of the major HIV-1 coreceptor, CXCR4, by the kappa opioid receptor.
21388957 2011 Effects of C-terminal modifications of GEC1 protein and gamma-aminobutyric acid type A (GABA(A)) receptor-associated protein (GABARAP), two microtubule-associated proteins, on kappa opioid receptor expression.
20734064 2010 A large-scale candidate gene association study of age at menarche and age at natural menopause.
20729876 2010 The role of kappa-opioid receptor activation in mediating antinociception and addiction.
20468064 2010 Association study of 182 candidate genes in anorexia nervosa.
20401607 2010 Kinase cascades and ligand-directed signaling at the kappa opioid receptor.
19874574 2009 Genetical genomic determinants of alcohol consumption in rats and humans.
19804796 2009 kappa-Opioid receptor signaling and brain reward function.
19086053 2009 Identification of new putative susceptibility genes for several psychiatric disorders by association analysis of regulatory and non-synonymous SNPs of 306 genes involved in neurotransmission and neurodevelopment.
19058789 2009 A common variant in DRD3 receptor is associated with autism spectrum disorder.
19032295 2008 Association between human opioid receptor genes polymorphisms and pressure pain sensitivity in females*.
18767415 2007 Cryptic genomic abnormalities associated with coexpression of KOR-SA3544 and NG.2 in proB acute lymphoblastic leukemia.
18577758 2008 Dissociation of heterotrimeric g proteins in cells.
18537939 2008 Effects of opioid receptor gene variation on targeted nalmefene treatment in heavy drinkers.
18518925 2008 Genetic susceptibility to heroin addiction: a candidate gene association study.
18353307 2008 LPK-26, a novel kappa-opioid receptor agonist with potent antinociceptive effects and low dependence potential.
18319328 2008 A regulatory variation in OPRK1, the gene encoding the kappa-opioid receptor, is associated with alcohol dependence.
18240029 2008 Reviews in molecular biology and biotechnology: transmembrane signaling by G protein-coupled receptors.
18213616 2008 Multiple OPR genes influence personality traits in substance dependent and healthy subjects in two American populations.
17711303 2007 N-Glycosylation of the human kappa opioid receptor enhances its stability but slows its trafficking along the biosynthesis pathway.
17702750 2007 Long-acting kappa opioid antagonists disrupt receptor signaling and produce noncompetitive effects by activating c-Jun N-terminal kinase.
17622222 2008 The OPRD1 and OPRK1 loci in alcohol or drug dependence: OPRD1 variation modulates substance dependence risk.
17538007 2007 Human neural precursor cells express functional kappa-opioid receptors.
17374034 2007 Opioid receptor gene (OPRM1, OPRK1, and OPRD1) variants and response to naltrexone treatment for alcohol dependence: results from the VA Cooperative Study.
17373729 2007 Human kappa opioid receptor gene (OPRK1) polymorphism is associated with opiate addiction.
17121830 2007 Differential helical orientations among related G protein-coupled receptors provide a novel mechanism for selectivity. Studies with salvinorin A and the kappa-opioid receptor.
16924269 2006 Association of the kappa-opioid system with alcohol dependence.
16431922 2006 GEC1 interacts with the kappa opioid receptor and enhances expression of the receptor.
16421571 2006 DNA sequence and analysis of human chromosome 8.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16331961 2005 The seventh transmembrane domains of the delta and kappa opioid receptors have different accessibility patterns and interhelical interactions.
16053916 2005 Activation of delta-, kappa-, and mu-opioid receptors induces phosphorylation of tuberin in transfected HEK 293 cells and native cells.
15952771 2005 Identification of the molecular mechanisms by which the diterpenoid salvinorin A binds to kappa-opioid receptors.
15608558 2004 Redefinition of the human kappa opioid receptor gene (OPRK1) structure and association of haplotypes with opiate addiction.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15086532 2004 Identification of a novel family of G protein-coupled receptor associated sorting proteins.
15070904 2004 kappa Opioid receptor interacts with Na(+)/H(+)-exchanger regulatory factor-1/Ezrin-radixin-moesin-binding phosphoprotein-50 (NHERF-1/EBP50) to stimulate Na(+)/H(+) exchange independent of G(i)/G(o) proteins.
14745298 2004 Endogenous opioid receptor genes and alcohol dependence among Taiwanese Han.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12815037 2003 Phosphorylation of a carboxyl-terminal serine within the kappa-opioid receptor produces desensitization and internalization.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12413885 2002 Interactions of opioid and chemokine receptors: oligomerization of mu, kappa, and delta with CCR5 on immune cells.
12004055 2002 Ezrin-radixin-moesin-binding phosphoprotein-50/Na+/H+ exchanger regulatory factor (EBP50/NHERF) blocks U50,488H-induced down-regulation of the human kappa opioid receptor by enhancing its recycling rate.
11726686 2001 Misreading of termination codons in eukaryotes by natural nonsense suppressor tRNAs.
11316510 2001 Regulations of opioid dependence by opioid receptor types.
11223000 2001 Mu-, delta- and kappa-opioid receptor populations are differentially altered in distinct areas of postmortem brains of Alzheimer's disease patients.
11069979 2000 Heterodimerization of mu and delta opioid receptors: A role in opiate synergy.
10959409 2000 Somatostatin and opioid receptors in mammary tissue. Role in cancer cell growth.
10871647 2000 Kappa opioids and TGFbeta1 interact in human endometrial cells.
9572309 1998 Differential coupling of mu-, delta-, and kappa-opioid receptors to G alpha16-mediated stimulation of phospholipase C.
8755601 1996 kappa opioid receptors in human microglia downregulate human immunodeficiency virus 1 expression.
8188308 1994 Localization of the kappa opioid receptor gene to human chromosome band 8q11.2.
8060324 1994 Isolation of a human kappa opioid receptor cDNA from placenta.
7929306 1994 Human kappa opiate receptor second extracellular loop elevates dynorphin's affinity for human mu/kappa chimeras.
7869844 1995 Cloning of a human kappa opioid receptor from the brain.
7624359 1995 kappa-Opioid receptor in humans: cDNA and genomic cloning, chromosomal assignment, functional expression, pharmacology, and expression pattern in the central nervous system.