OPRM_MOUSE
ID OPRM_MOUSE Reviewed; 398 AA.
AC P42866; A1XGX3; A1XGX4; A1YAC3; A1YAC4; A5H7G2; Q4U2P4; Q4U2Q6; Q548C6;
AC Q60768; Q6YC50; Q8CAN5; Q8CGW2; Q8CH73; Q8CH74; Q8CH75; Q8VBU3; Q8VBU6;
AC Q8VBX8; Q8VI69; Q8VI70; Q8VI71; Q8VIN3; Q8VIN4; Q8VIN5; Q8VIN6; Q8VIP0;
AC Q8VIP1; Q9JIY1; Q9R0D1; Q9R1L9; Q9R1M0;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Mu-type opioid receptor;
DE Short=M-OR-1;
DE Short=MOR-1;
GN Name=Oprm1; Synonyms=Mor, Oprm;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=8090773; DOI=10.1073/pnas.91.19.9081;
RA Min B.H., Augustin L.B., Felsheim R.F., Fuchs J.A., Loh H.H.;
RT "Genomic structure analysis of promoter sequence of a mouse mu opioid
RT receptor gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:9081-9085(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=7649256; DOI=10.1016/0014-5793(95)00757-z;
RA Rossi G.C., Pan Y.X., Brown G.P., Pasternak G.W.;
RT "Antisense mapping the MOR-1 opioid receptor: evidence for alternative
RT splicing and a novel morphine-6 beta-glucuronide receptor.";
RL FEBS Lett. 369:192-196(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=7797593; DOI=10.1074/jbc.270.26.15877;
RA Kaufman D.L., Keith D.E., Anton B., Tian J., Magendzo K., Newman D.,
RA Tran T., Lee D.S., Wen C., Xia Y., Lusis A.J., Evans C.J.;
RT "Characterization of the murine mu opioid receptor gene.";
RL J. Biol. Chem. 270:15877-15883(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 8; 9 AND 10).
RC STRAIN=C57BL/6J;
RX PubMed=10419560; DOI=10.1124/mol.56.2.396;
RA Pan Y.X., Xu J., Bolan E., Abbadie C., Chang A., Zuckerman A., Rossi G.,
RA Pasternak G.W.;
RT "Identification and characterization of three new alternatively spliced mu-
RT opioid receptor isoforms.";
RL Mol. Pharmacol. 56:396-403(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=CD-1;
RA Pan Y.-X., Xu J., Chang A., Pasternak G.W.;
RT "Identification and characterization of a mouse spliced mu-opioid receptor
RT isoform (MOR-1A).";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 11).
RC STRAIN=CD-1;
RX PubMed=10682855; DOI=10.1016/s0014-5793(00)01095-4;
RA Pan Y.X., Xu J., Bolan E., Chang A., Mahurter L., Rossi G., Pasternak G.W.;
RT "Isolation and expression of a novel alternatively spliced mu opioid
RT receptor isoform, MOR-1F.";
RL FEBS Lett. 466:337-340(2000).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6By x BALB/cBy; TISSUE=Brain;
RX PubMed=11160404; DOI=10.1523/jneurosci.21-04-01334.2001;
RA Ikeda K., Kobayashi T., Ichikawa T., Kumanishi T., Niki H., Yano R.;
RT "The untranslated region of (mu)-opioid receptor mRNA contributes to
RT reduced opioid sensitivity in CXBK mice.";
RL J. Neurosci. 21:1334-1339(2001).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 14; 15 AND 16).
RC STRAIN=C57BL/6By x BALB/cBy;
RX PubMed=11717463; DOI=10.1073/pnas.241296098;
RA Pan Y.X., Xu J., Mahurter L., Bolan E., Xu M., Pasternak G.W.;
RT "Generation of the mu opioid receptor (MOR-1) protein by three new splice
RT variants of the Oprm gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:14084-14089(2001).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 13).
RA Pan Y., Xu J., Xu M., Pasternak G.W.;
RT "Identification and characterization of a novel splice variant from mouse
RT mu opioid receptor gene (Oprm).";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 12).
RC STRAIN=CD-1;
RA Xu J., Pasternak G.W.;
RT "Identification and characterization of a new isoform from mouse mu opioid
RT receptor gene Oprm.";
RL Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3; 4; 5; 6 AND 7).
RC STRAIN=CD-1;
RX PubMed=15939800; DOI=10.1124/mol.105.011858;
RA Pan Y.X., Xu J., Bolan E., Moskowitz H.S., Xu M., Pasternak G.W.;
RT "Identification of four novel exon 5 splice variants of the mouse mu-opioid
RT receptor gene: functional consequences of C-terminal splicing.";
RL Mol. Pharmacol. 68:866-875(2005).
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 8).
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [13]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 10; 17; 18 AND 19).
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=17398041; DOI=10.1016/j.gene.2007.02.004;
RA Doyle G.A., Sheng X.R., Lin S.S., Press D.M., Grice D.E., Buono R.J.,
RA Ferraro T.N., Berrettini W.H.;
RT "Identification of five mouse mu-opioid receptor (MOR) gene (Oprm1) splice
RT variants containing a newly identified alternatively spliced exon.";
RL Gene 395:98-107(2007).
RN [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [15]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [16]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 8).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [17]
RP FUNCTION.
RX PubMed=6933569; DOI=10.1073/pnas.77.9.5512;
RA Inturrisi C.E., Umans J.G., Wolff D., Stern A.S., Lewis R.V., Stein S.,
RA Udenfriend S.;
RT "Analgesic activity of the naturally occurring heptapeptide
RT [Met]enkephalin-Arg6-Phe7.";
RL Proc. Natl. Acad. Sci. U.S.A. 77:5512-5514(1980).
RN [18]
RP FUNCTION.
RX PubMed=9037090; DOI=10.1073/pnas.94.4.1544;
RA Sora I., Takahashi N., Funada M., Ujike H., Revay R.S., Donovan D.M.,
RA Miner L.L., Uhl G.R.;
RT "Opiate receptor knockout mice define mu receptor roles in endogenous
RT nociceptive responses and morphine-induced analgesia.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:1544-1549(1997).
RN [19]
RP FUNCTION, AND COUPLING TO GNAZ.
RX PubMed=9767386; DOI=10.1046/j.1460-9568.1998.00267.x;
RA Garzon J., Castro M., Sanchez-Blazquez P.;
RT "Influence of Gz and Gi2 transducer proteins in the affinity of opioid
RT agonists to mu receptors.";
RL Eur. J. Neurosci. 10:2557-2564(1998).
RN [20]
RP RECEPTOR HETEROOLIGOMERIZATION, FUNCTION, AND INTERACTION WITH OPRD1.
RX PubMed=10842167; DOI=10.1074/jbc.m000345200;
RA George S.R., Fan T., Xie Z., Tse R., Tam V., Varghese G., O'Dowd B.F.;
RT "Oligomerization of mu- and delta-opioid receptors. Generation of novel
RT functional properties.";
RL J. Biol. Chem. 275:26128-26135(2000).
RN [21]
RP RECEPTOR HETEROOLIGOMERIZATION, AND INTERACTION WITH OPRL1.
RX PubMed=12270145; DOI=10.1016/s0006-291x(02)02258-1;
RA Pan Y.X., Bolan E., Pasternak G.W.;
RT "Dimerization of morphine and orphanin FQ/nociceptin receptors: generation
RT of a novel opioid receptor subtype.";
RL Biochem. Biophys. Res. Commun. 297:659-663(2002).
RN [22]
RP FUNCTION, RECEPTOR DESENSITIZATION, SUBCELLULAR LOCATION, AND RECEPTOR
RP INTERNALIZATION.
RX PubMed=12642578; DOI=10.1074/jbc.m300525200;
RA Borgland S.L., Connor M., Osborne P.B., Furness J.B., Christie M.J.;
RT "Opioid agonists have different efficacy profiles for G protein activation,
RT rapid desensitization, and endocytosis of mu-opioid receptors.";
RL J. Biol. Chem. 278:18776-18784(2003).
RN [23]
RP RECEPTOR RECYCLING, AND MUTAGENESIS OF LEU-387 AND LEU-390.
RX PubMed=12939277; DOI=10.1074/jbc.m304504200;
RA Tanowitz M., von Zastrow M.;
RT "A novel endocytic recycling signal that distinguishes the membrane
RT trafficking of naturally occurring opioid receptors.";
RL J. Biol. Chem. 278:45978-45986(2003).
RN [24]
RP ALTERNATIVE SPLICING.
RX PubMed=14991152; DOI=10.1007/s00109-003-0514-z;
RA Kvam T.M., Baar C., Rakvag T.T., Kaasa S., Krokan H.E., Skorpen F.;
RT "Genetic analysis of the murine mu opioid receptor: increased complexity of
RT Oprm gene splicing.";
RL J. Mol. Med. 82:250-255(2004).
RN [25]
RP FUNCTION, AND INTERACTION WITH RGS17 AND RGS20.
RX PubMed=15827571; DOI=10.1038/sj.npp.1300726;
RA Garzan J., Rodriguez-Munoz M., Lopez-Fando A., Sanchez-Blazquez P.;
RT "The RGSZ2 protein exists in a complex with mu-opioid receptors and
RT regulates the desensitizing capacity of Gz proteins.";
RL Neuropsychopharmacology 30:1632-1648(2005).
RN [26]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16682964; DOI=10.1038/sj.bjp.0706757;
RA Rios C., Gomes I., Devi L.A.;
RT "mu opioid and CB1 cannabinoid receptor interactions: reciprocal inhibition
RT of receptor signaling and neuritogenesis.";
RL Br. J. Pharmacol. 148:387-395(2006).
RN [27]
RP FUNCTION, AND INTERACTION WITH RGS9.
RX PubMed=17725581; DOI=10.1111/j.1471-4159.2007.04812.x;
RA Psifogeorgou K., Papakosta P., Russo S.J., Neve R.L., Kardassis D.,
RA Gold S.J., Zachariou V.;
RT "RGS9-2 is a negative modulator of mu-opioid receptor function.";
RL J. Neurochem. 103:617-625(2007).
RN [28]
RP INTERACTION WITH PPP1R9B.
RX PubMed=18439408; DOI=10.1016/j.neuron.2008.02.006;
RA Charlton J.J., Allen P.B., Psifogeorgou K., Chakravarty S., Gomes I.,
RA Neve R.L., Devi L.A., Greengard P., Nestler E.J., Zachariou V.;
RT "Multiple actions of spinophilin regulate mu opioid receptor function.";
RL Neuron 58:238-247(2008).
RN [29]
RP UBIQUITINATION, RECEPTOR HETEROOLIGOMERIZATION, AND INTERACTION WITH OPRD1
RP AND RTP4.
RX PubMed=18836069; DOI=10.1073/pnas.0804106105;
RA Decaillot F.M., Rozenfeld R., Gupta A., Devi L.A.;
RT "Cell surface targeting of mu-delta opioid receptor heterodimers by RTP4.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:16045-16050(2008).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-363, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [31]
RP FUNCTION (ISOFORM 9), AND INTERACTION WITH GRPR.
RX PubMed=22000021; DOI=10.1016/j.cell.2011.08.043;
RA Liu X.Y., Liu Z.C., Sun Y.G., Ross M., Kim S., Tsai F.F., Li Q.F.,
RA Jeffry J., Kim J.Y., Loh H.H., Chen Z.F.;
RT "Unidirectional cross-activation of GRPR by MOR1D uncouples itch and
RT analgesia induced by opioids.";
RL Cell 147:447-458(2011).
RN [32]
RP INTERACTION WITH HINT1.
RX PubMed=21153910; DOI=10.1007/s00018-010-0598-x;
RA Rodriguez-Munoz M., Sanchez-Blazquez P., Vicente-Sanchez A., Bailon C.,
RA Martin-Aznar B., Garzon J.;
RT "The histidine triad nucleotide-binding protein 1 supports mu-opioid
RT receptor-glutamate NMDA receptor cross-regulation.";
RL Cell. Mol. Life Sci. 68:2933-2949(2011).
RN [33]
RP RECEPTOR HETEROOLIGOMERIZATION, FUNCTION, AND INTERACTION WITH OPRD1.
RX PubMed=21422164; DOI=10.1124/jpet.111.179093;
RA Milan-Lobo L., Whistler J.L.;
RT "Heteromerization of the mu- and delta-opioid receptors produces ligand-
RT biased antagonism and alters mu-receptor trafficking.";
RL J. Pharmacol. Exp. Ther. 337:868-875(2011).
RN [34]
RP FUNCTION.
RX PubMed=35201898; DOI=10.1126/science.abl5130;
RA Trieu B.H., Remmers B.C., Toddes C., Brandner D.D., Lefevre E.M.,
RA Kocharian A., Retzlaff C.L., Dick R.M., Mashal M.A., Gauthier E.A., Xie W.,
RA Zhang Y., More S.S., Rothwell P.E.;
RT "Angiotensin-converting enzyme gates brain circuit-specific plasticity via
RT an endogenous opioid.";
RL Science 2022:eabl5130-eabl5130(2022).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 52-360 IN COMPLEX WITH MORPHINAN
RP ANTAGONIST, FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, AND DISULFIDE BOND.
RX PubMed=22437502; DOI=10.1038/nature10954;
RA Manglik A., Kruse A.C., Kobilka T.S., Thian F.S., Mathiesen J.M.,
RA Sunahara R.K., Pardo L., Weis W.I., Kobilka B.K., Granier S.;
RT "Crystal structure of the micro-opioid receptor bound to a morphinan
RT antagonist.";
RL Nature 485:321-326(2012).
RN [36] {ECO:0007744|PDB:5C1M}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 52-347 IN COMPLEX WITH MORPHINAN
RP AGONIST, FUNCTION, INTERACTION WITH GNAI1; GNB1 AND GNG2, SUBUNIT,
RP DISULFIDE BONDS, SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=26245379; DOI=10.1038/nature14886;
RA Huang W., Manglik A., Venkatakrishnan A.J., Laeremans T., Feinberg E.N.,
RA Sanborn A.L., Kato H.E., Livingston K.E., Thorsen T.S., Kling R.C.,
RA Granier S., Gmeiner P., Husbands S.M., Traynor J.R., Weis W.I.,
RA Steyaert J., Dror R.O., Kobilka B.K.;
RT "Structural insights into u-opioid receptor activation.";
RL Nature 524:315-321(2015).
CC -!- FUNCTION: Receptor for endogenous opioids such as beta-endorphin and
CC endomorphin (PubMed:21422164, PubMed:22437502, PubMed:10842167,
CC PubMed:16682964, PubMed:26245379, PubMed:7797593, PubMed:9037090).
CC Receptor for natural and synthetic opioids including morphine, heroin,
CC DAMGO, fentanyl, etorphine, buprenorphin and methadone
CC (PubMed:16682964, PubMed:7797593, PubMed:9037090). Also activated by
CC enkephalin peptides, such as Met-enkephalin or Met-enkephalin-Arg-Phe,
CC with higher affinity for Met-enkephalin-Arg-Phe (PubMed:6933569,
CC PubMed:35201898). Agonist binding to the receptor induces coupling to
CC an inactive GDP-bound heterotrimeric G-protein complex and subsequent
CC exchange of GDP for GTP in the G-protein alpha subunit leading to
CC dissociation of the G-protein complex with the free GTP-bound G-protein
CC alpha and the G-protein beta-gamma dimer activating downstream cellular
CC effectors (PubMed:10842167, PubMed:21422164, PubMed:22437502). The
CC agonist- and cell type-specific activity is predominantly coupled to
CC pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2,
CC GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extent to
CC pertussis toxin-insensitive G alpha proteins GNAZ and GNA15
CC (PubMed:9767386, PubMed:26245379). They mediate an array of downstream
CC cellular responses, including inhibition of adenylate cyclase activity
CC and both N-type and L-type calcium channels, activation of inward
CC rectifying potassium channels, mitogen-activated protein kinase (MAPK),
CC phospholipase C (PLC), phosphoinositide/protein kinase (PKC),
CC phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B (By
CC similarity). Also couples to adenylate cyclase stimulatory G alpha
CC proteins (By similarity). The selective temporal coupling to G-proteins
CC and subsequent signaling can be regulated by RGSZ proteins, such as
CC RGS9, RGS17 and RGS4 (PubMed:15827571, PubMed:17725581).
CC Phosphorylation by members of the GPRK subfamily of Ser/Thr protein
CC kinases and association with beta-arrestins is involved in short-term
CC receptor desensitization (By similarity). Beta-arrestins associate with
CC the GPRK-phosphorylated receptor and uncouple it from the G-protein
CC thus terminating signal transduction (By similarity). The
CC phosphorylated receptor is internalized through endocytosis via
CC clathrin-coated pits which involves beta-arrestins (PubMed:12642578).
CC The activation of the ERK pathway occurs either in a G-protein-
CC dependent or a beta-arrestin-dependent manner and is regulated by
CC agonist-specific receptor phosphorylation (By similarity). Acts as a
CC class A G-protein coupled receptor (GPCR) which dissociates from beta-
CC arrestin at or near the plasma membrane and undergoes rapid recycling
CC (By similarity). Receptor down-regulation pathways are varying with the
CC agonist and occur dependent or independent of G-protein coupling.
CC Endogenous ligands induce rapid desensitization, endocytosis and
CC recycling (By similarity). Heterooligomerization with other GPCRs can
CC modulate agonist binding, signaling and trafficking properties (By
CC similarity). {ECO:0000250|UniProtKB:P33535,
CC ECO:0000269|PubMed:10842167, ECO:0000269|PubMed:12642578,
CC ECO:0000269|PubMed:15827571, ECO:0000269|PubMed:16682964,
CC ECO:0000269|PubMed:17725581, ECO:0000269|PubMed:21422164,
CC ECO:0000269|PubMed:22437502, ECO:0000269|PubMed:26245379,
CC ECO:0000269|PubMed:35201898, ECO:0000269|PubMed:6933569,
CC ECO:0000269|PubMed:7797593, ECO:0000269|PubMed:9037090,
CC ECO:0000269|PubMed:9767386}.
CC -!- FUNCTION: [Isoform 9]: Isoform 9 is involved in morphine-induced
CC scratching and seems to cross-activate GRPR in response to morphine.
CC {ECO:0000269|PubMed:22000021}.
CC -!- SUBUNIT: Forms homooligomers and heterooligomers with other GPCRs, such
CC as OPRD1, OPRK1, OPRL1, NPFFR2, ADRA2A, SSTR2, CNR1 and CCR5 (probably
CC in dimeric forms) (PubMed:10842167, PubMed:12270145, PubMed:18836069,
CC PubMed:21422164). Interacts with heterotrimeric G proteins; interaction
CC with a heterotrimeric complex containing GNAI1, GNB1 and GNG2
CC stabilizes the active conformation of the receptor and increases its
CC affinity for endomorphin-2, the synthetic opioid peptide DAMGO and for
CC morphinan agonists (PubMed:26245379). Interacts with PPL; the
CC interaction disrupts agonist-mediated G-protein activation. Interacts
CC (via C-terminus) with DNAJB4 (via C-terminus). Interacts with
CC calmodulin; the interaction inhibits the constitutive activity of
CC OPRM1; it abolishes basal and attenuates agonist-stimulated G-protein
CC coupling. Interacts with FLNA, PLD2, RANBP9 and WLS and GPM6A (By
CC similarity). Interacts with RTP4 (PubMed:18836069). Interacts with SYP
CC and GNAS (By similarity). Interacts with RGS9, RGS17, RGS20, RGS4,
CC PPP1R9B and HINT1 (PubMed:15827571, PubMed:17725581, PubMed:18439408,
CC PubMed:21153910). Isoform 9 interacts with GRPR (PubMed:22000021).
CC {ECO:0000250|UniProtKB:P33535, ECO:0000250|UniProtKB:P35372,
CC ECO:0000269|PubMed:10842167, ECO:0000269|PubMed:12270145,
CC ECO:0000269|PubMed:15827571, ECO:0000269|PubMed:17725581,
CC ECO:0000269|PubMed:18439408, ECO:0000269|PubMed:18836069,
CC ECO:0000269|PubMed:21153910, ECO:0000269|PubMed:21422164,
CC ECO:0000269|PubMed:22000021, ECO:0000269|PubMed:22437502,
CC ECO:0000269|PubMed:26245379}.
CC -!- INTERACTION:
CC P42866; P04899: GNAI2; Xeno; NbExp=2; IntAct=EBI-5282656, EBI-353997;
CC P42866; P63092-2: GNAS; Xeno; NbExp=2; IntAct=EBI-5282656, EBI-7607528;
CC P42866-9; P21729: Grpr; NbExp=4; IntAct=EBI-6049667, EBI-6049651;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12642578,
CC ECO:0000269|PubMed:22437502, ECO:0000269|PubMed:7797593}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:12642578,
CC ECO:0000269|PubMed:22437502, ECO:0000269|PubMed:26245379,
CC ECO:0000269|PubMed:7797593}. Cell projection, axon
CC {ECO:0000250|UniProtKB:P97266}. Perikaryon
CC {ECO:0000250|UniProtKB:P97266}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:P97266}. Endosome
CC {ECO:0000250|UniProtKB:P97266}. Note=Is rapidly internalized after
CC agonist binding. {ECO:0000250|UniProtKB:P97266}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=19;
CC Comment=Additional isoforms seem to exist. Functional relevance for
CC short isoforms with one transmembrane domain only is unsure and these
CC isoforms are not included.;
CC Name=1; Synonyms=MOR-1, MOR-H, MOR-1J, MOR-1T;
CC IsoId=P42866-1; Sequence=Displayed;
CC Name=2; Synonyms=MOR-1A;
CC IsoId=P42866-2; Sequence=VSP_042339;
CC Name=3; Synonyms=MOR-1B1;
CC IsoId=P42866-3; Sequence=VSP_042340;
CC Name=4; Synonyms=MOR-1B2;
CC IsoId=P42866-4; Sequence=VSP_042341;
CC Name=5; Synonyms=MOR-1B3, MOR-1Q;
CC IsoId=P42866-5; Sequence=VSP_042342;
CC Name=6; Synonyms=MOR-1B4, MOR-1R;
CC IsoId=P42866-6; Sequence=VSP_042343;
CC Name=7; Synonyms=MOR-1B5, MOR-1P;
CC IsoId=P42866-7; Sequence=VSP_042344;
CC Name=8; Synonyms=MOR-1C;
CC IsoId=P42866-8; Sequence=VSP_042345;
CC Name=9; Synonyms=MOR-1D;
CC IsoId=P42866-9; Sequence=VSP_042346;
CC Name=10; Synonyms=MOR-1E, MOR-1Eiii, MOR-1Eiv;
CC IsoId=P42866-10; Sequence=VSP_042333;
CC Name=11; Synonyms=MOR-1F;
CC IsoId=P42866-11; Sequence=VSP_042334;
CC Name=12; Synonyms=MOR-1O;
CC IsoId=P42866-12; Sequence=VSP_042335;
CC Name=13; Synonyms=MOR-1P, MOR-1R;
CC IsoId=P42866-13; Sequence=VSP_042336;
CC Name=14; Synonyms=MOR-1G;
CC IsoId=P42866-14; Sequence=VSP_042332;
CC Name=15; Synonyms=MOR-1M;
CC IsoId=P42866-15; Sequence=VSP_042332, VSP_042345;
CC Name=16; Synonyms=MOR-1N;
CC IsoId=P42866-16; Sequence=VSP_042332, VSP_042346;
CC Name=17; Synonyms=MOR-1U;
CC IsoId=P42866-17; Sequence=VSP_042337;
CC Name=18; Synonyms=MOR-1V;
CC IsoId=P42866-18; Sequence=VSP_042338;
CC Name=19; Synonyms=MOR-1W;
CC IsoId=P42866-19; Sequence=VSP_042347;
CC -!- PTM: Phosphorylated. Differentially phosphorylated in basal and
CC agonist-induced conditions. Agonist-mediated phosphorylation modulates
CC receptor internalization. Phosphorylated by GRK2 in a agonist-dependent
CC manner. Phosphorylation at Tyr-166 requires receptor activation, is
CC dependent on non-receptor protein tyrosine kinase Src and results in a
CC decrease in agonist efficacy by reducing G-protein coupling efficiency.
CC Phosphorylated on tyrosine residues; the phosphorylation is involved in
CC agonist-induced G-protein-independent receptor down-regulation.
CC Phosphorylation at Ser-375 is involved in G-protein-dependent but not
CC beta-arrestin-dependent activation of the ERK pathway.
CC {ECO:0000250|UniProtKB:P33535}.
CC -!- PTM: Ubiquitinated. A basal ubiquitination seems not to be related to
CC degradation. Ubiquitination is increased upon formation of OPRM1:OPRD1
CC oligomers leading to proteasomal degradation; the ubiquitination is
CC diminished by RTP4. {ECO:0000269|PubMed:18836069}.
CC -!- DISRUPTION PHENOTYPE: During adult neurogenesis in hippocampus,
CC increased numbers of granule cells maturing into neurons, larger
CC granule cell layers and increased numbers of granule cells.
CC {ECO:0000269|PubMed:16682964}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; U10561; AAB60673.1; -; Genomic_DNA.
DR EMBL; U10558; AAB60673.1; JOINED; Genomic_DNA.
DR EMBL; U10559; AAB60673.1; JOINED; Genomic_DNA.
DR EMBL; U10560; AAB60673.1; JOINED; Genomic_DNA.
DR EMBL; U26915; AAA81170.1; -; mRNA.
DR EMBL; U19380; AAA86878.1; -; mRNA.
DR EMBL; AF062753; AAD54415.1; -; mRNA.
DR EMBL; AF074973; AAD51861.1; -; mRNA.
DR EMBL; AF074974; AAD51862.1; -; mRNA.
DR EMBL; AF167565; AAL55581.1; -; mRNA.
DR EMBL; AF167568; AAF79213.1; -; mRNA.
DR EMBL; AB047546; BAB63338.1; -; mRNA.
DR EMBL; AF062755; AAL34927.1; -; mRNA.
DR EMBL; AF260311; AAL34400.1; -; mRNA.
DR EMBL; AF074972; AAL34394.1; -; mRNA.
DR EMBL; AF400246; AAL34507.1; -; mRNA.
DR EMBL; AF400247; AAL34508.1; -; mRNA.
DR EMBL; AF400248; AAL34509.1; -; mRNA.
DR EMBL; AY036621; AAK74188.1; -; mRNA.
DR EMBL; AY160190; AAO18365.1; -; mRNA.
DR EMBL; AF167566; AAL55582.1; -; mRNA.
DR EMBL; AF167567; AAL55583.1; -; mRNA.
DR EMBL; AF346812; AAO13792.1; -; mRNA.
DR EMBL; AF346813; AAO13793.1; -; mRNA.
DR EMBL; AF346814; AAO13794.1; -; mRNA.
DR EMBL; AK038389; BAC29982.1; -; mRNA.
DR EMBL; DQ363376; ABC94862.1; -; mRNA.
DR EMBL; DQ363377; ABC94863.1; -; mRNA.
DR EMBL; DQ868787; ABI95796.1; -; mRNA.
DR EMBL; DQ868788; ABI95797.2; -; mRNA.
DR EMBL; EF105311; ABN45760.1; -; mRNA.
DR EMBL; EF105312; ABN45761.1; -; mRNA.
DR EMBL; EF105313; ABN45762.1; -; mRNA.
DR EMBL; EF105314; ABN45763.1; -; mRNA.
DR EMBL; CH466562; EDL03560.1; -; Genomic_DNA.
DR EMBL; CH466562; EDL03561.1; -; Genomic_DNA.
DR EMBL; CH466562; EDL03562.1; -; Genomic_DNA.
DR EMBL; AC153981; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC155718; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC164171; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC119545; AAI19546.1; -; mRNA.
DR CCDS; CCDS56687.1; -. [P42866-8]
DR CCDS; CCDS78783.1; -. [P42866-14]
DR CCDS; CCDS78784.1; -. [P42866-15]
DR CCDS; CCDS78785.1; -. [P42866-16]
DR CCDS; CCDS78787.1; -. [P42866-1]
DR CCDS; CCDS78788.1; -. [P42866-9]
DR CCDS; CCDS83672.1; -. [P42866-4]
DR CCDS; CCDS83673.1; -. [P42866-3]
DR CCDS; CCDS83674.1; -. [P42866-2]
DR PIR; A57510; A57510.
DR RefSeq; NP_001034741.1; NM_001039652.2. [P42866-8]
DR RefSeq; NP_001289722.1; NM_001302793.1. [P42866-1]
DR RefSeq; NP_001289723.1; NM_001302794.1. [P42866-14]
DR RefSeq; NP_001289724.1; NM_001302795.1. [P42866-15]
DR RefSeq; NP_001289725.1; NM_001302796.1. [P42866-16]
DR RefSeq; NP_001291866.1; NM_001304937.1. [P42866-2]
DR RefSeq; NP_001291867.1; NM_001304938.1. [P42866-3]
DR RefSeq; NP_001291877.1; NM_001304948.1. [P42866-4]
DR RefSeq; NP_001291879.1; NM_001304950.1. [P42866-9]
DR RefSeq; NP_001291884.1; NM_001304955.1. [P42866-17]
DR RefSeq; XP_017169315.1; XM_017313826.1.
DR RefSeq; XP_017169316.1; XM_017313827.1. [P42866-6]
DR PDB; 4DKL; X-ray; 2.80 A; A=52-360.
DR PDB; 5C1M; X-ray; 2.10 A; A=52-347.
DR PDB; 6DDE; EM; 3.50 A; R=9-358.
DR PDB; 6DDF; EM; 3.50 A; R=9-358.
DR PDBsum; 4DKL; -.
DR PDBsum; 5C1M; -.
DR PDBsum; 6DDE; -.
DR PDBsum; 6DDF; -.
DR AlphaFoldDB; P42866; -.
DR SMR; P42866; -.
DR BioGRID; 201972; 3.
DR DIP; DIP-46148N; -.
DR IntAct; P42866; 11.
DR MINT; P42866; -.
DR STRING; 10090.ENSMUSP00000101236; -.
DR BindingDB; P42866; -.
DR ChEMBL; CHEMBL2858; -.
DR DrugCentral; P42866; -.
DR GuidetoPHARMACOLOGY; 319; -.
DR GlyGen; P42866; 4 sites.
DR iPTMnet; P42866; -.
DR PhosphoSitePlus; P42866; -.
DR SwissPalm; P42866; -.
DR jPOST; P42866; -.
DR PaxDb; P42866; -.
DR PRIDE; P42866; -.
DR ProteomicsDB; 294202; -. [P42866-1]
DR ProteomicsDB; 294203; -. [P42866-2]
DR ProteomicsDB; 294204; -. [P42866-3]
DR ProteomicsDB; 294205; -. [P42866-4]
DR ProteomicsDB; 294206; -. [P42866-5]
DR ProteomicsDB; 294207; -. [P42866-6]
DR ProteomicsDB; 294208; -. [P42866-7]
DR ProteomicsDB; 294209; -. [P42866-8]
DR ProteomicsDB; 294210; -. [P42866-9]
DR ProteomicsDB; 294211; -. [P42866-10]
DR ProteomicsDB; 294212; -. [P42866-11]
DR ProteomicsDB; 294213; -. [P42866-12]
DR ProteomicsDB; 294214; -. [P42866-13]
DR ProteomicsDB; 294215; -. [P42866-14]
DR ProteomicsDB; 294216; -. [P42866-15]
DR ProteomicsDB; 294217; -. [P42866-16]
DR ProteomicsDB; 294218; -. [P42866-17]
DR ProteomicsDB; 294219; -. [P42866-18]
DR ProteomicsDB; 294220; -. [P42866-19]
DR ABCD; P42866; 1 sequenced antibody.
DR Antibodypedia; 2929; 590 antibodies from 40 providers.
DR DNASU; 18390; -.
DR Ensembl; ENSMUST00000000783; ENSMUSP00000000783; ENSMUSG00000000766. [P42866-6]
DR Ensembl; ENSMUST00000052751; ENSMUSP00000060329; ENSMUSG00000000766. [P42866-9]
DR Ensembl; ENSMUST00000056385; ENSMUSP00000060590; ENSMUSG00000000766. [P42866-1]
DR Ensembl; ENSMUST00000063036; ENSMUSP00000053498; ENSMUSG00000000766. [P42866-16]
DR Ensembl; ENSMUST00000092729; ENSMUSP00000090405; ENSMUSG00000000766. [P42866-7]
DR Ensembl; ENSMUST00000092731; ENSMUSP00000090407; ENSMUSG00000000766. [P42866-5]
DR Ensembl; ENSMUST00000092734; ENSMUSP00000090410; ENSMUSG00000000766. [P42866-1]
DR Ensembl; ENSMUST00000105602; ENSMUSP00000101227; ENSMUSG00000000766. [P42866-2]
DR Ensembl; ENSMUST00000105605; ENSMUSP00000101230; ENSMUSG00000000766. [P42866-3]
DR Ensembl; ENSMUST00000105607; ENSMUSP00000101232; ENSMUSG00000000766. [P42866-1]
DR Ensembl; ENSMUST00000105611; ENSMUSP00000101236; ENSMUSG00000000766. [P42866-8]
DR Ensembl; ENSMUST00000105615; ENSMUSP00000101240; ENSMUSG00000000766. [P42866-15]
DR Ensembl; ENSMUST00000135502; ENSMUSP00000135143; ENSMUSG00000000766. [P42866-12]
DR Ensembl; ENSMUST00000144264; ENSMUSP00000115836; ENSMUSG00000000766. [P42866-19]
DR Ensembl; ENSMUST00000147171; ENSMUSP00000117950; ENSMUSG00000000766. [P42866-14]
DR Ensembl; ENSMUST00000154906; ENSMUSP00000114342; ENSMUSG00000000766. [P42866-4]
DR GeneID; 18390; -.
DR KEGG; mmu:18390; -.
DR UCSC; uc007eff.2; mouse. [P42866-9]
DR UCSC; uc007efl.2; mouse. [P42866-17]
DR UCSC; uc007efn.1; mouse. [P42866-8]
DR UCSC; uc007efp.2; mouse. [P42866-15]
DR UCSC; uc007efq.2; mouse. [P42866-16]
DR UCSC; uc007eft.1; mouse. [P42866-12]
DR UCSC; uc007efw.3; mouse. [P42866-1]
DR UCSC; uc007egc.2; mouse. [P42866-14]
DR UCSC; uc007ege.2; mouse. [P42866-3]
DR UCSC; uc007egf.2; mouse. [P42866-2]
DR UCSC; uc056yga.1; mouse. [P42866-4]
DR CTD; 4988; -.
DR MGI; MGI:97441; Oprm1.
DR VEuPathDB; HostDB:ENSMUSG00000000766; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00940000158236; -.
DR InParanoid; P42866; -.
DR OMA; GNNMEID; -.
DR OrthoDB; 1011272at2759; -.
DR TreeFam; TF315737; -.
DR Reactome; R-MMU-111885; Opioid Signalling.
DR Reactome; R-MMU-202040; G-protein activation.
DR Reactome; R-MMU-375276; Peptide ligand-binding receptors.
DR Reactome; R-MMU-418594; G alpha (i) signalling events.
DR BioGRID-ORCS; 18390; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Oprm1; mouse.
DR PRO; PR:P42866; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; P42866; protein.
DR Bgee; ENSMUSG00000000766; Expressed in medial habenular nucleus and 40 other tissues.
DR ExpressionAtlas; P42866; baseline and differential.
DR Genevisible; P42866; MM.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0032839; C:dendrite cytoplasm; ISO:MGI.
DR GO; GO:0032590; C:dendrite membrane; ISO:MGI.
DR GO; GO:0005768; C:endosome; ISS:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; ISO:MGI.
DR GO; GO:0099056; C:integral component of presynaptic membrane; ISO:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0043204; C:perikaryon; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0042383; C:sarcolemma; ISO:MGI.
DR GO; GO:0097444; C:spine apparatus; ISO:MGI.
DR GO; GO:0004979; F:beta-endorphin receptor activity; ISO:MGI.
DR GO; GO:0031005; F:filamin binding; ISO:MGI.
DR GO; GO:0004985; F:G protein-coupled opioid receptor activity; IDA:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; ISS:UniProtKB.
DR GO; GO:0001965; F:G-protein alpha-subunit binding; ISS:UniProtKB.
DR GO; GO:0031681; F:G-protein beta-subunit binding; ISO:MGI.
DR GO; GO:0038047; F:morphine receptor activity; ISS:UniProtKB.
DR GO; GO:0042923; F:neuropeptide binding; IBA:GO_Central.
DR GO; GO:0042277; F:peptide binding; IBA:GO_Central.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; ISO:MGI.
DR GO; GO:0007191; P:adenylate cyclase-activating dopamine receptor signaling pathway; IDA:MGI.
DR GO; GO:0007197; P:adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IDA:MGI.
DR GO; GO:0031635; P:adenylate cyclase-inhibiting opioid receptor signaling pathway; ISO:MGI.
DR GO; GO:0048149; P:behavioral response to ethanol; ISO:MGI.
DR GO; GO:0042755; P:eating behavior; ISO:MGI.
DR GO; GO:0060079; P:excitatory postsynaptic potential; ISO:MGI.
DR GO; GO:0038003; P:G protein-coupled opioid receptor signaling pathway; ISO:MGI.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0007626; P:locomotory behavior; IMP:MGI.
DR GO; GO:0106072; P:negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; ISS:UniProtKB.
DR GO; GO:0051481; P:negative regulation of cytosolic calcium ion concentration; ISS:UniProtKB.
DR GO; GO:0045019; P:negative regulation of nitric oxide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0061358; P:negative regulation of Wnt protein secretion; ISS:UniProtKB.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IBA:GO_Central.
DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0032100; P:positive regulation of appetite; ISO:MGI.
DR GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; ISO:MGI.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISO:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0050769; P:positive regulation of neurogenesis; IMP:UniProtKB.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISO:MGI.
DR GO; GO:0080135; P:regulation of cellular response to stress; ISO:MGI.
DR GO; GO:2000310; P:regulation of NMDA receptor activity; ISS:UniProtKB.
DR GO; GO:0051930; P:regulation of sensory perception of pain; ISO:MGI.
DR GO; GO:0045471; P:response to ethanol; ISO:MGI.
DR GO; GO:0019233; P:sensory perception of pain; IMP:UniProtKB.
DR DisProt; DP00974; -.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR000105; Mu_opioid_rcpt.
DR InterPro; IPR001418; Opioid_rcpt.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR00537; MUOPIOIDR.
DR PRINTS; PR00384; OPIOIDR.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cell projection;
KW Disulfide bond; Endosome; G-protein coupled receptor; Glycoprotein;
KW Lipoprotein; Membrane; Palmitate; Phosphoprotein; Receptor;
KW Reference proteome; Transducer; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT CHAIN 1..398
FT /note="Mu-type opioid receptor"
FT /id="PRO_0000069975"
FT TOPO_DOM 1..66
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:22437502,
FT ECO:0000269|PubMed:26245379"
FT TRANSMEM 67..91
FT /note="Helical; Name=1"
FT /evidence="ECO:0000269|PubMed:22437502,
FT ECO:0000269|PubMed:26245379"
FT TOPO_DOM 92..104
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:22437502,
FT ECO:0000269|PubMed:26245379"
FT TRANSMEM 105..129
FT /note="Helical; Name=2"
FT /evidence="ECO:0000269|PubMed:22437502,
FT ECO:0000269|PubMed:26245379"
FT TOPO_DOM 130..140
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:22437502,
FT ECO:0000269|PubMed:26245379"
FT TRANSMEM 141..163
FT /note="Helical; Name=3"
FT /evidence="ECO:0000269|PubMed:22437502,
FT ECO:0000269|PubMed:26245379"
FT TOPO_DOM 164..183
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:22437502,
FT ECO:0000269|PubMed:26245379"
FT TRANSMEM 184..205
FT /note="Helical; Name=4"
FT /evidence="ECO:0000269|PubMed:22437502,
FT ECO:0000269|PubMed:26245379"
FT TOPO_DOM 206..228
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:22437502,
FT ECO:0000269|PubMed:26245379"
FT TRANSMEM 229..253
FT /note="Helical; Name=5"
FT /evidence="ECO:0000269|PubMed:22437502,
FT ECO:0000269|PubMed:26245379"
FT TOPO_DOM 254..277
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:22437502,
FT ECO:0000269|PubMed:26245379"
FT TRANSMEM 278..304
FT /note="Helical; Name=6"
FT /evidence="ECO:0000269|PubMed:22437502,
FT ECO:0000269|PubMed:26245379"
FT TOPO_DOM 305..312
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:22437502,
FT ECO:0000269|PubMed:26245379"
FT TRANSMEM 313..336
FT /note="Helical; Name=7"
FT /evidence="ECO:0000269|PubMed:22437502,
FT ECO:0000269|PubMed:26245379"
FT TOPO_DOM 337..398
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:22437502,
FT ECO:0000269|PubMed:26245379"
FT REGION 362..383
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 332..336
FT /note="NPxxY; plays a role in stabilizing the activated
FT conformation of the receptor"
FT /evidence="ECO:0000269|PubMed:26245379"
FT MOD_RES 166
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P33535"
FT MOD_RES 363
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 370
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P33535"
FT MOD_RES 375
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P33535"
FT MOD_RES 394
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P33535"
FT LIPID 351
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000255"
FT CARBOHYD 9
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 31
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 38
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 46
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 140..217
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521,
FT ECO:0000269|PubMed:22437502, ECO:0000269|PubMed:26245379,
FT ECO:0007744|PDB:4DKL, ECO:0007744|PDB:5C1M"
FT VAR_SEQ 1..94
FT /note="MDSSAGPGNISDCSDPLAPASCSPAPGSWLNLSHVDGNQSDPCGPNRTGLGG
FT SHSLCPQTGSPSMVTAITIMALYSIVCVVGLFGNFLVMYVIV -> MMEAFSKSAFQKL
FT RQRDGNQEGKSYL (in isoform 14, isoform 15 and isoform 16)"
FT /evidence="ECO:0000303|PubMed:11717463"
FT /id="VSP_042332"
FT VAR_SEQ 387..398
FT /note="LENLEAETAPLP -> KKKLDSQRGCVQHPV (in isoform 10)"
FT /evidence="ECO:0000303|PubMed:10419560,
FT ECO:0000303|PubMed:17398041"
FT /id="VSP_042333"
FT VAR_SEQ 387..398
FT /note="LENLEAETAPLP -> APCACVPGANRGQTKASDLLDLELETVGSHQADAET
FT NPGPYEGSKCAEPLAISLVPLY (in isoform 11)"
FT /evidence="ECO:0000303|PubMed:10682855"
FT /id="VSP_042334"
FT VAR_SEQ 387..398
FT /note="LENLEAETAPLP -> PTLAVSVAQIFTGYPSPTHVEKPCKSCMDR (in
FT isoform 12)"
FT /evidence="ECO:0000303|Ref.10"
FT /id="VSP_042335"
FT VAR_SEQ 387..398
FT /note="LENLEAETAPLP -> IMKFEAIYPKLSFKSWALKYFTFIREKKRNTKAGAL
FT PTCHAGSPSQAHRGVAAWLLPLRHMGPSYPS (in isoform 13)"
FT /evidence="ECO:0000303|Ref.9"
FT /id="VSP_042336"
FT VAR_SEQ 387..398
FT /note="LENLEAETAPLP -> PTLAVSVAQIFTGYPSPTHVEKPCKSCMDSVDCYNR
FT KQQTGSLRKNKKKKKRRKNKQNILEAGISRGMRNLLPDDGPRQESGEGQLGR (in
FT isoform 17)"
FT /evidence="ECO:0000303|PubMed:17398041"
FT /id="VSP_042337"
FT VAR_SEQ 387..398
FT /note="LENLEAETAPLP -> KQEKTKTKSAWEIWEQKEHTLLLGETHLTIQHLS
FT (in isoform 18)"
FT /evidence="ECO:0000303|PubMed:17398041"
FT /id="VSP_042338"
FT VAR_SEQ 387..398
FT /note="LENLEAETAPLP -> VCAF (in isoform 2)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_042339"
FT VAR_SEQ 387..398
FT /note="LENLEAETAPLP -> KIDLF (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15939800"
FT /id="VSP_042340"
FT VAR_SEQ 387..398
FT /note="LENLEAETAPLP -> KLLMWRAMPTFKRHLAIMLSLDN (in isoform
FT 4)"
FT /evidence="ECO:0000303|PubMed:15939800"
FT /id="VSP_042341"
FT VAR_SEQ 387..398
FT /note="LENLEAETAPLP -> TSLTLQ (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15939800"
FT /id="VSP_042342"
FT VAR_SEQ 387..398
FT /note="LENLEAETAPLP -> AHQKPQECLKCRCLSLTILVICLHFQHQQFFIMIKK
FT NVS (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:15939800"
FT /id="VSP_042343"
FT VAR_SEQ 387..398
FT /note="LENLEAETAPLP -> CV (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:15939800"
FT /id="VSP_042344"
FT VAR_SEQ 387..398
FT /note="LENLEAETAPLP -> PTLAVSVAQIFTGYPSPTHVEKPCKSCMDRGMRNLL
FT PDDGPRQESGEGQLGR (in isoform 8 and isoform 15)"
FT /evidence="ECO:0000303|PubMed:10419560,
FT ECO:0000303|PubMed:11717463, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_042345"
FT VAR_SEQ 387..398
FT /note="LENLEAETAPLP -> RNEEPSS (in isoform 9 and isoform
FT 16)"
FT /evidence="ECO:0000303|PubMed:10419560,
FT ECO:0000303|PubMed:11717463"
FT /id="VSP_042346"
FT VAR_SEQ 388..398
FT /note="ENLEAETAPLP -> AFGCCNEHHDQR (in isoform 19)"
FT /evidence="ECO:0000303|PubMed:17398041"
FT /id="VSP_042347"
FT MUTAGEN 387
FT /note="L->A: Abolishes receptor recycling; when associated
FT with A-390."
FT /evidence="ECO:0000269|PubMed:12939277"
FT MUTAGEN 390
FT /note="L->A: Abolishes receptor recycling; when associated
FT with A-387."
FT /evidence="ECO:0000269|PubMed:12939277"
FT CONFLICT 22
FT /note="C -> W (in Ref. 3; AAA86878)"
FT /evidence="ECO:0000305"
FT STRAND 54..56
FT /evidence="ECO:0007829|PDB:5C1M"
FT HELIX 65..95
FT /evidence="ECO:0007829|PDB:5C1M"
FT TURN 96..99
FT /evidence="ECO:0007829|PDB:5C1M"
FT HELIX 102..118
FT /evidence="ECO:0007829|PDB:5C1M"
FT HELIX 121..129
FT /evidence="ECO:0007829|PDB:5C1M"
FT HELIX 136..170
FT /evidence="ECO:0007829|PDB:5C1M"
FT HELIX 172..178
FT /evidence="ECO:0007829|PDB:5C1M"
FT HELIX 181..205
FT /evidence="ECO:0007829|PDB:5C1M"
FT STRAND 206..211
FT /evidence="ECO:0007829|PDB:5C1M"
FT STRAND 214..219
FT /evidence="ECO:0007829|PDB:5C1M"
FT STRAND 222..224
FT /evidence="ECO:0007829|PDB:4DKL"
FT HELIX 225..240
FT /evidence="ECO:0007829|PDB:5C1M"
FT HELIX 242..261
FT /evidence="ECO:0007829|PDB:5C1M"
FT TURN 263..265
FT /evidence="ECO:0007829|PDB:6DDF"
FT HELIX 268..305
FT /evidence="ECO:0007829|PDB:5C1M"
FT HELIX 312..336
FT /evidence="ECO:0007829|PDB:5C1M"
FT TURN 337..339
FT /evidence="ECO:0007829|PDB:5C1M"
FT HELIX 341..346
FT /evidence="ECO:0007829|PDB:5C1M"
SQ SEQUENCE 398 AA; 44421 MW; DFE1C758E2DA197E CRC64;
MDSSAGPGNI SDCSDPLAPA SCSPAPGSWL NLSHVDGNQS DPCGPNRTGL GGSHSLCPQT
GSPSMVTAIT IMALYSIVCV VGLFGNFLVM YVIVRYTKMK TATNIYIFNL ALADALATST
LPFQSVNYLM GTWPFGNILC KIVISIDYYN MFTSIFTLCT MSVDRYIAVC HPVKALDFRT
PRNAKIVNVC NWILSSAIGL PVMFMATTKY RQGSIDCTLT FSHPTWYWEN LLKICVFIFA
FIMPVLIITV CYGLMILRLK SVRMLSGSKE KDRNLRRITR MVLVVVAVFI VCWTPIHIYV
IIKALITIPE TTFQTVSWHF CIALGYTNSC LNPVLYAFLD ENFKRCFREF CIPTSSTIEQ
QNSARIRQNT REHPSTANTV DRTNHQLENL EAETAPLP
