Mu-type opioid receptor

Details

Name
Mu-type opioid receptor
Synonyms
  • hMOP
  • M-OR-1
  • MOP
  • MOR1
  • Mu opiate receptor
  • Mu opioid receptor
Gene Name
OPRM1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0001536|Mu-type opioid receptor
MDSSAAPTNASNCTDALAYSSCSPAPSPGSWVNLSHLDGNLSDPCGPNRTDLGGRDSLCP
PTGSPSMITAITIMALYSIVCVVGLFGNFLVMYVIVRYTKMKTATNIYIFNLALADALAT
STLPFQSVNYLMGTWPFGTILCKIVISIDYYNMFTSIFTLCTMSVDRYIAVCHPVKALDF
RTPRNAKIINVCNWILSSAIGLPVMFMATTKYRQGSIDCTLTFSHPTWYWENLLKICVFI
FAFIMPVLIITVCYGLMILRLKSVRMLSGSKEKDRNLRRITRMVLVVVAVFIVCWTPIHI
YVIIKALVTIPETTFQTVSWHFCIALGYTNSCLNPVLYAFLDENFKRCFREFCIPTSSNI
EQQNSTRIRQNTRDHPSTANTVDRTNHQLENLEAETAPLP
Number of residues
400
Molecular Weight
44778.855
Theoretical pI
8.29
GO Classification
Functions
beta-endorphin receptor activity / G-protein alpha-subunit binding / G-protein beta-subunit binding / G-protein coupled receptor activity / morphine receptor activity / neuropeptide binding / voltage-gated calcium channel activity
Processes
adenylate cyclase-activating dopamine receptor signaling pathway / adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway / behavioral response to ethanol / calcium ion transmembrane transport / cellular response to morphine / cellular response to stress / G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / locomotory behavior / negative regulation of adenylate cyclase activity / negative regulation of cAMP-mediated signaling / negative regulation of cell proliferation / negative regulation of cytosolic calcium ion concentration / negative regulation of nitric oxide biosynthetic process / negative regulation of Wnt protein secretion / neuropeptide signaling pathway / opioid receptor signaling pathway / phospholipase C-activating G-protein coupled receptor signaling pathway / positive regulation of cAMP-mediated signaling / positive regulation of cytosolic calcium ion concentration / positive regulation of ERK1 and ERK2 cascade / positive regulation of neurogenesis / positive regulation of nitric oxide biosynthetic process / regulation of N-methyl-D-aspartate selective glutamate receptor activity / sensory perception / sensory perception of pain / synaptic transmission
Components
cytosol / endoplasmic reticulum / Golgi apparatus / integral component of plasma membrane / neuron projection / plasma membrane
General Function
Voltage-gated calcium channel activity
Specific Function
Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors. The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extend to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15. They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B. Also couples to adenylate cyclase stimulatory G alpha proteins. The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4. Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization. Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction. The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins. The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation. Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling. Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling. Endogenous ligands induce rapid desensitization, endocytosis and recycling whereas morphine induces only low desensitization and endocytosis. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis. Isoform 12 couples to GNAS and is proposed to be involved in excitatory effects. Isoform 16 and isoform 17 do not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity.
Pfam Domain Function
Transmembrane Regions
69-93 107-131 143-165 186-207 231-255 284-307 315-338
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0021649|Mu-type opioid receptor (OPRM1)
ATGGACAGCAGCGCTGCCCCCACGAACGCCAGCAATTGCACTGATGCCTTGGCGTACTCA
AGTTGCTCCCCAGCACCCAGCCCCGGTTCCTGGGTCAACTTGTCCCACTTAGATGGCAAC
CTGTCCGACCCATGCGGTCCGAACCGCACCGACCTGGGCGGGAGAGACAGCCTGTGCCCT
CCGACCGGCAGTCCCTCCATGATCACGGCCATCACGATCATGGCCCTCTACTCCATCGTG
TGCGTGGTGGGGCTCTTCGGAAACTTCCTGGTCATGTATGTGATTGTCAGATACACCAAG
ATGAAGACTGCCACCAACATCTACATTTTCAACCTTGCTCTGGCAGATGCCTTAGCCACC
AGTACCCTGCCCTTCCAGAGTGTGAATTACCTAATGGGAACATGGCCATTTGGAACCATC
CTTTGCAAGATAGTGATCTCCATAGATTACTATAACATGTTCACCAGCATATTCACCCTC
TGCACCATGAGTGTTGATCGATACATTGCAGTCTGCCACCCTGTCAAGGCCTTAGATTTC
CGTACTCCCCGAAATGCCAAAATTATCAATGTCTGCAACTGGATCCTCTCTTCAGCCATT
GGTCTTCCTGTAATGTTCATGGCTACAACAAAATACAGGCAAGGTTCCATAGATTGTACA
CTAACATTCTCTCATCCAACCTGGTACTGGGAAAACCTGCTGAAGATCTGTGTTTTCATC
TTCGCCTTCATTATGCCAGTGCTCATCATTACCGTGTGCTATGGACTGATGATCTTGCGC
CTCAAGAGTGTCCGCATGCTCTCTGGCTCCAAAGAAAAGGACAGGAATCTTCGAAGGATC
ACCAGGATGGTGCTGGTGGTGGTGGCTGTGTTCATCGTCTGCTGGACTCCCATTCACATT
TACGTCATCATTAAAGCCTTGGTTACAATCCCAGAAACTACGTTCCAGACTGTTTCTTGG
CACTTCTGCATTGCTCTAGGTTACACAAACAGCTGCCTCAACCCAGTCCTTTATGCATTT
CTGGATGAAAACTTCAAACGATGCTTCAGAGAGTTCTGTATCCCAACCTCTTCCAACATT
GAGCAACAAAACTCCACTCGAATTCGTCAGAACACTAGAGACCACCCCTCCACGGCCAAT
ACAGTGGATAGAACTAATCATCAGCTAGAAAATCTGGAAGCAGAAACTGCTCCGTTGCCC
TAA
Chromosome Location
6
Locus
6q24-q25
External Identifiers
ResourceLink
UniProtKB IDP35372
UniProtKB Entry NameOPRM_HUMAN
GenBank Protein ID452073
GenBank Gene IDL25119
GenAtlas IDOPRM1
HGNC IDHGNC:8156
General References
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  4. Pan YX, Xu J, Mahurter L, Xu M, Gilbert AK, Pasternak GW: Identification and characterization of two new human mu opioid receptor splice variants, hMOR-1O and hMOR-1X. Biochem Biophys Res Commun. 2003 Feb 21;301(4):1057-61. [Article]
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  6. Pan L, Xu J, Yu R, Xu MM, Pan YX, Pasternak GW: Identification and characterization of six new alternatively spliced variants of the human mu opioid receptor gene, Oprm. Neuroscience. 2005;133(1):209-20. [Article]
  7. Xu J, Xu M, Hurd YL, Pasternak GW, Pan YX: Isolation and characterization of new exon 11-associated N-terminal splice variants of the human mu opioid receptor gene. J Neurochem. 2009 Feb;108(4):962-72. doi: 10.1111/j.1471-4159.2008.05833.x. Epub 2008 Dec 10. [Article]
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  11. 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. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00193Tramadolapproved, investigationalyesagonistDetails
DB00295Morphineapproved, investigationalyesagonistregulatorDetails
DB00318Codeineapproved, illicityesagonistregulatorDetails
DB00327Hydromorphoneapproved, illicityesagonistDetails
DB00504Levallorphanapprovedyespartial agonistDetails
DB00647Dextropropoxypheneapproved, illicit, investigational, withdrawnyesagonistDetails
DB00652Pentazocineapproved, vet_approvedyesantagonistDetails
DB00704Naltrexoneapproved, investigational, vet_approvedyesantagonistDetails
DB00708Sufentanilapproved, investigationalyesagonistDetails
DB00802Alfentanilapproved, illicityesagonistDetails
DB00813Fentanylapproved, illicit, investigational, vet_approvedyesagonistDetails
DB00854LevorphanolapprovedyesagonistDetails
DB00899RemifentanilapprovedyesagonistDetails
DB00913Anileridineapproved, illicityesagonistDetails
DB00956Hydrocodoneapproved, illicit, investigationalyesagonistDetails
DB01081Diphenoxylateapproved, illicityesagonistDetails
DB01183Naloxoneapproved, vet_approvedyesantagonistDetails
DB01192Oxymorphoneapproved, investigational, vet_approvedyesagonistDetails
DB01209Dezocineapproved, investigationalyesagonistDetails
DB01227Levacetylmethadolapproved, investigational, withdrawnyesagonistDetails
DB00333MethadoneapprovedyesagonistDetails
DB00611Butorphanolapproved, illicit, vet_approvedyesantagonistDetails
DB00836LoperamideapprovedyesagonistDetails
DB00844NalbuphineapprovedyesantagonistDetails
DB00921Buprenorphineapproved, illicit, investigational, vet_approvedyespartial agonistDetails
DB01497Etorphineillicit, vet_approvedyesagonistDetails
DB01535Carfentanilillicit, investigational, vet_approvedyesagonistDetails
DB014393-Methylthiofentanylexperimental, illicityesagonistDetails
DB01444Dimethylthiambuteneexperimental, illicityesagonistDetails
DB01452Diamorphineapproved, illicit, investigationalyesagonistDetails
DB015713-MethylfentanylillicityesagonistDetails
DB05046V1003investigationalunknownDetails
DB01433Methadyl acetateexperimental, illicityesagonistDetails
DB00497Oxycodoneapproved, illicit, investigationalyesagonistDetails
DB05492Epicept NP-1investigationalunknownDetails
DB05509LI-301investigationalunknownDetails
DB06204TapentadolapprovedyesagonistDetails
DB06230Nalmefeneapproved, investigational, withdrawnyesantagonistDetails
DB06409Morphine glucuronideinvestigationalunknownDetails
DB06274Alvimopanapproved, investigationalyesantagonistDetails
DB01466Ethylmorphineexperimental, illicityesagonistDetails
DB01565Dihydromorphineexperimental, illicityesagonistDetails
DB01548Diprenorphineillicit, vet_approvedyesantagonistDetails
DB00904Ondansetronapproved, withdrawnunknownother/unknownDetails
DB06800MethylnaltrexoneapprovedyesantagonistDetails
DB06738KetobemidoneinvestigationalyesagonistDetails
DB00514DextromethorphanapprovedunknownagonistregulatorDetails
DB00454MeperidineapprovedunknownagonistDetails
DB00321AmitriptylineapprovedunknownbinderDetails
DB01221Ketamineapproved, vet_approvedunknownbinderDetails
DB09049NaloxegolapprovedyesantagonistDetails
DB09272Eluxadolineapproved, investigationalyesagonistDetails
DB09089TrimebutineapprovedyesagonistDetails
DB11691Naldemedineapproved, investigationalyesantagonistDetails
DB09061Cannabidiolapproved, investigationalunknownDetails
DB09209Pholcodineapproved, illicityesantagonistDetails
DB11130Opiumapproved, illicityesagonistDetails
DB14011NabiximolsinvestigationalunknownDetails
DB14009Medical Cannabisexperimental, investigationalunknownDetails
DB11186Pentoxyverineapproved, investigational, withdrawnunknownantagonistDetails
DB09289TianeptineinvestigationalyesagonistDetails
DB14146LoxicodegolinvestigationalyesagonistDetails
DB09173ButyrfentanylillicityesagonistDetails
DB01238Aripiprazoleapproved, investigationalunknownligandDetails
DB12668MetenkefalininvestigationalunknownagonistDetails
DB14881Oliceridineapproved, investigationalyesagonistDetails
DB06288Amisulprideapproved, investigationalnoagonistDetails
DB12543Samidorphanapproved, investigationalyesantagonistDetails