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Gene and Protein Information | ||||||
class A G protein-coupled receptor | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 7 | 380 | 8q11.23 | OPRK1 | opioid receptor kappa 1 | 65,103,135 |
Mouse | 7 | 380 | 1 1.89 cM | Oprk1 | opioid receptor, kappa 1 | 8,47,61,77,128 |
Rat | 7 | 380 | 5q12 | Oprk1 | opioid receptor, kappa 1 | 16,59,67-68,76 |
Previous and Unofficial Names |
KOR-1 | Kappa receptor | OP2 | KOP | KOPr |
Database Links | |
Specialist databases | |
GPCRdb | oprk_human (Hs), oprk_mouse (Mm), oprk_rat (Rn) |
Other databases | |
Alphafold | P41145 (Hs), P33534 (Mm), P34975 (Rn) |
ChEMBL Target | CHEMBL237 (Hs), CHEMBL4329 (Mm), CHEMBL3614 (Rn) |
DrugBank Target | P41145 (Hs) |
Ensembl Gene | ENSG00000082556 (Hs), ENSMUSG00000025905 (Mm), ENSRNOG00000007647 (Rn) |
Entrez Gene | 4986 (Hs), 18387 (Mm), 29335 (Rn) |
Human Protein Atlas | ENSG00000082556 (Hs) |
KEGG Gene | hsa:4986 (Hs), mmu:18387 (Mm), rno:29335 (Rn) |
OMIM | 165196 (Hs) |
Pharos | P41145 (Hs) |
RefSeq Nucleotide | NM_000912 (Hs), NM_011011 (Mm), NM_017167 (Rn) |
RefSeq Protein | NP_000903 (Hs), NP_035141 (Mm), NP_058863 (Rn) |
SynPHARM |
83653 (in complex with JDTic) 83652 (in complex with JDTic) |
UniProtKB | P41145 (Hs), P33534 (Mm), P34975 (Rn) |
Wikipedia | OPRK1 (Hs) |
Selected 3D Structures | |||||||||||||
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Natural/Endogenous Ligands |
big dynorphin {Sp: Human, Mouse, Rat} |
dynorphin A-(1-13) {Sp: Human, Mouse, Rat} |
dynorphin A {Sp: Human, Mouse, Rat} |
dynorphin A-(1-8) {Sp: Human, Mouse, Rat} |
dynorphin B {Sp: Human, Mouse, Rat} |
β-endorphin {Sp: Human} , β-endorphin {Sp: Mouse} , β-endorphin {Sp: Rat} |
[Leu]enkephalin {Sp: Human, Mouse, Rat} |
[Met]enkephalin {Sp: Human, Mouse, Rat} |
α-neoendorphin {Sp: Human, Mouse, Rat} |
β-neoendorphin {Sp: Human, Mouse, Rat} |
Comments: Dynorphin A and big dynorphin are the highest potency endogenous ligands |
Principal endogenous agonists (Human) |
big dynorphin (PDYN, P01213), dynorphin A (PDYN, P01213) |
Download all structure-activity data for this target as a CSV file
Agonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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View species-specific agonist tables | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Ki values were determined in the absence of Na+ and GDP, except TRK820. Discrimination of full or partial agonism is very dependent on the level of receptor expression and on the assay used to monitor agonist effects. Many agents may behave as full agonists or potent partial agonists in cell lines expressing cloned receptors in high concentration, but in other environments they may show only weak agonist activity. The identification of agonist activity in the table is largely based on the ability to stimulate GTPγS binding in cell lines expressing cloned human kappa receptors. Agents giving 85% or greater stimulation than that given by U69593 have been characterized as Full Agonists [116]. κ opioid receptors have been divided into several different subtypes, mainly on the basis of [3H]agonist binding assays. Generally 2 subtypes are recognised: κ1 and κ2. The benzeneacetamides and peptides are considered κ1 agonists and the benzomorphans bind to κ1 and κ2. However, there is only one gene product and the subtypes are considered putative. Selective κ agonists are of several structural types. All have high affinity for the κ receptor and are full agonists. We have tagged the μ receptor as the primary drug target for hydrocodone based on this drug having the highest affinity at this receptor compared to the κ and δ receptors [75]. Similarly, we have tagged the μ receptor as the primary target of the drug hydromorphone [125]. |
Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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View species-specific antagonist tables |
Allosteric Modulator Comments | ||
Although no small molecules are considered direct allosteric regulators of κ opioid receptors, a number of proteins such as G protein-coupled receptor kinases, β-arrestins and G proteins clearly regulate receptor affinities and function. Furthermore, sodium and guanine nucleotides can modify the functional κ receptor complex and G protein interaction. Also, other G protein-coupled receptors appear to be able to form heterodimers with κ receptors, potentially modifying κ opioid receptor activity. |
Other Binding Ligands | |||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Primary Transduction Mechanisms | |
Transducer | Effector/Response |
Gi/Go family |
Adenylyl cyclase inhibition Potassium channel Calcium channel |
References: 6,31,34,46,53,69,98,111 |
Secondary Transduction Mechanisms | |
Transducer | Effector/Response |
Gi/Go family G12/G13 family |
Adenylyl cyclase inhibition Phospholipase C stimulation Other - See Comments |
Comments:
Activation of κ opioid receptors stimulates p42/p44 MAP kinase via βγ subunits of Gi/o proteins [10]. κ opioid receptors interact with NHERF-1/EBP50 to stimulate Na+/H+ exchange independent of Gi/o proteins [39]. |
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References: 10,39,52,58,72,119 |
Tissue Distribution | ||||||||
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Tissue Distribution Comments | ||||||||
κ opioid receptors show a fairly widespread distribution although quantitatively they represent only a small percentage of the total opioid receptors in the brain. This contrasts with the guinea-pig brain, where κ opioid receptor expression is far more abundant. In all species, the early receptor autoradiography was carried out with low selectivity ligands such as [3H]ethylketocycazocine and [3H]bremazocine and their cross labelling of μ and δ receptors was supressed by the use of excess cold ligands to displace their binding to μ and δ opioid sites. Since the late 1980s highly selective κ opioid receptor ligands such as [3H]U69,593 and [3H]CI-977 have been used and the distribution is more restrictive when these ligands are employed. For a review of κ opioid receptor expression in the rat see [63]. |
Expression Datasets | |
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Physiological Consequences of Altering Gene Expression | ||||||||||
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Phenotypes, Alleles and Disease Models | Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Biologically Significant Variant Comments |
κ1 and κ2 receptor subtypes have been proposed based on in vivo pharmacology showing lack of cross-tolerance between U69,593 and bremazocine and differential antagonism by quadazocine and (-)UPHIT [36-38]. Receptor binding studies have led to suggestions of κ1, κ2 and κ3 subtypes [20,95]. However, only one κ receptor cDNA clone has been reported and no κ receptor variants have been characterised. Interaction between κ and δ receptors in transfected cells has been reported and suggested to result in κ2 subtype pharmacology [43]. Multiple active conformations of the κ receptor are likely to exist. κ receptor subtypes are likely due to interaction of receptor with other proteins or receptors at the level of neuronal circuitry, but not mRNA variants. |
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