ID OPRM_RAT Reviewed; 398 AA. AC P33535; Q2TV20; Q2TV21; Q4VWM5; Q4VWM7; Q4VWX7; Q4VWX8; Q62846; Q64064; AC Q64120; DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1994, sequence version 1. DT 11-DEC-2019, entry version 165. DE RecName: Full=Mu-type opioid receptor; DE Short=M-OR-1; DE Short=MOR-1; DE AltName: Full=Opioid receptor B; GN Name=Oprm1; Synonyms=Ror-b; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=8394245; DOI=10.1016/0014-5793(93)81011-n; RA Fukuda K., Kato S., Mori K., Nishi M., Takeshima H.; RT "Primary structures and expression from cDNAs of rat opioid receptor RT delta- and mu-subtypes."; RL FEBS Lett. 327:311-314(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=8234282; DOI=10.1073/pnas.90.21.10230; RA Wang J.-B., Imai Y., Epler M.C., Gregor P., Spivak C., Uhl G.R.; RT "Mu opiate receptor: cDNA cloning and expression."; RL Proc. Natl. Acad. Sci. U.S.A. 90:10230-10234(1993). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND SUBCELLULAR LOCATION. RC TISSUE=Brain; RX PubMed=8393525; RA Chen Y., Mestek A., Liu J., Hurley J.A., Yu L.; RT "Molecular cloning and functional expression of a mu-opioid receptor from RT rat brain."; RL Mol. Pharmacol. 44:8-12(1993). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC STRAIN=Sprague-Dawley; TISSUE=Brain; RA Bunzow J.R., Grandy D.K., Kelly M.; RL Submitted (SEP-1993) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND SUBCELLULAR LOCATION. RC STRAIN=Sprague-Dawley; TISSUE=Olfactory bulb; RX PubMed=8240812; DOI=10.1016/0896-6273(93)90120-g; RA Thompson R.C., Mansour A., Akil H., Watson S.J.; RT "Cloning and pharmacological characterization of a rat mu opioid RT receptor."; RL Neuron 11:903-913(1993). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=8189219; DOI=10.1046/j.1471-4159.1994.62062099.x; RA Zastawny R.L., George S.R., Nguyen T., Cheng R., Tsatsos J., RA Briones-Urbina R., O'Dowd B.F.; RT "Cloning, characterization, and distribution of a mu-opioid receptor in rat RT brain."; RL J. Neurochem. 62:2099-2105(1994). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 5). RC STRAIN=Sprague-Dawley; RA Pan Y.-X., Xu J., Pasternak G.W.; RT "Identification and characterization of two new alternatively spliced RT variants from the rat mu opioid receptor gene, Oprm."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 6; 7 AND 8). RC STRAIN=Sprague-Dawley; RX PubMed=15525342; DOI=10.1111/j.1471-4159.2004.02767.x; RA Pasternak D.A., Pan L., Xu J., Yu R., Xu M.M., Pasternak G.W., Pan Y.X.; RT "Identification of three new alternatively spliced variants of the rat mu RT opioid receptor gene: dissociation of affinity and efficacy."; RL J. Neurochem. 91:881-890(2004). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Brown Norway; RX PubMed=15057822; DOI=10.1038/nature02426; RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., RA Mockrin S., Collins F.S.; RT "Genome sequence of the Brown Norway rat yields insights into mammalian RT evolution."; RL Nature 428:493-521(2004). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 101-340. RC TISSUE=Macrophage; RX PubMed=7733926; DOI=10.1006/bbrc.1995.1538; RA Sedqi M., Roy S., Ramakrishnan S., Elde R., Loh H.H.; RT "Complementary DNA cloning of a mu-opioid receptor from rat peritoneal RT macrophages."; RL Biochem. Biophys. Res. Commun. 209:563-574(1995). RN [11] RP NUCLEOTIDE SEQUENCE [MRNA] OF 356-398 (ISOFORM 4). RX PubMed=7532594; DOI=10.1016/0014-5793(95)00028-8; RA Zimprich A., Simon T., Hoellt V.; RT "Cloning and expression of an isoform of the rat mu opioid receptor RT (rMOR1B) which differs in agonist induced desensitization from rMOR1."; RL FEBS Lett. 359:142-146(1995). RN [12] RP FUNCTION. RX PubMed=1846076; DOI=10.1016/0896-6273(91)90117-i; RA Schroeder J.E., Fischbach P.S., Zheng D., McCleskey E.W.; RT "Activation of mu opioid receptors inhibits transient high- and low- RT threshold Ca2+ currents, but spares a sustained current."; RL Neuron 6:13-20(1991). RN [13] RP FUNCTION. RX PubMed=7678862; DOI=10.1523/jneurosci.13-02-00867.1993; RA Schroeder J.E., McCleskey E.W.; RT "Inhibition of Ca2+ currents by a mu-opioid in a defined subset of rat RT sensory neurons."; RL J. Neurosci. 13:867-873(1993). RN [14] RP FUNCTION, AND MUTAGENESIS OF ASP-114; ASP-147 AND HIS-297. RX PubMed=8051154; RA Surratt C.K., Johnson P.S., Moriwaki A., Seidleck B.K., Blaschak C.J., RA Wang J.B., Uhl G.R.; RT "-mu opiate receptor. Charged transmembrane domain amino acids are critical RT for agonist recognition and intrinsic activity."; RL J. Biol. Chem. 269:20548-20553(1994). RN [15] RP FUNCTION, AND COUPLING TO G-PROTEINS. RX PubMed=7595566; DOI=10.1046/j.1471-4159.1995.65062682.x; RA Chan J.S., Chiu T.T., Wong Y.H.; RT "Activation of type II adenylyl cyclase by the cloned mu-opioid receptor: RT coupling to multiple G proteins."; RL J. Neurochem. 65:2682-2689(1995). RN [16] RP FUNCTION, AND MUTAGENESIS OF ASP-114. RX PubMed=9224819; DOI=10.1124/mol.52.1.105; RA Chakrabarti S., Yang W., Law P.Y., Loh H.H.; RT "The mu-opioid receptor down-regulates differently from the delta-opioid RT receptor: requirement of a high affinity receptor/G protein complex RT formation."; RL Mol. Pharmacol. 52:105-113(1997). RN [17] RP PALMITOYLATION, AND MUTAGENESIS OF CYS-346 AND CYS-351. RX PubMed=9877183; DOI=10.1016/s0014-5793(98)01547-6; RA Chen C., Shahabi V., Xu W., Liu-Chen L.Y.; RT "Palmitoylation of the rat mu opioid receptor."; RL FEBS Lett. 441:148-152(1998). RN [18] RP COUPLING TO GNA15, AND FUNCTION. RX PubMed=9572309; RA Lee J.W., Joshi S., Chan J.S., Wong Y.H.; RT "Differential coupling of mu-, delta-, and kappa-opioid receptors to G RT alpha16-mediated stimulation of phospholipase C."; RL J. Neurochem. 70:2203-2211(1998). RN [19] RP PHOSPHORYLATION, AND MUTAGENESIS OF TYR-91; TYR-96; TYR-166; TYR-336 AND RP THR-394. RX PubMed=10488100; DOI=10.1074/jbc.274.39.27610; RA Pak Y., O'Dowd B.F., Wang J.B., George S.R.; RT "Agonist-induced, G protein-dependent and -independent down-regulation of RT the mu opioid receptor. The receptor is a direct substrate for protein- RT tyrosine kinase."; RL J. Biol. Chem. 274:27610-27616(1999). RN [20] RP PHOSPHORYLATION AT THR-394, AND MUTAGENESIS OF THR-394. RX PubMed=10820022; DOI=10.1021/bi991938b; RA Deng H.B., Yu Y., Pak Y., O'Dowd B.F., George S.R., Surratt C.K., Uhl G.R., RA Wang J.B.; RT "Role for the C-terminus in agonist-induced mu opioid receptor RT phosphorylation and desensitization."; RL Biochemistry 39:5492-5499(2000). RN [21] RP RECEPTOR HETEROOLIGOMERIZATION, 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 [22] RP PHOSPHORYLATION BY GRK2. RX PubMed=10744734; DOI=10.1074/jbc.275.14.10443; RA Carman C.V., Barak L.S., Chen C., Liu-Chen L.Y., Onorato J.J., RA Kennedy S.P., Caron M.G., Benovic J.L.; RT "Mutational analysis of Gbetagamma and phospholipid interaction with G RT protein-coupled receptor kinase 2."; RL J. Biol. Chem. 275:10443-10452(2000). RN [23] RP MUTAGENESIS OF ASP-147 AND ASP-164. RX PubMed=11580279; DOI=10.1021/bi0100945; RA Li J., Huang P., Chen C., de Riel J.K., Weinstein H., Liu-Chen L.Y.; RT "Constitutive activation of the mu opioid receptor by mutation of RT D3.49(164), but not D3.32(147): D3.49(164) is critical for stabilization of RT the inactive form of the receptor and for its expression."; RL Biochemistry 40:12039-12050(2001). RN [24] RP MUTAGENESIS OF THR-279. RX PubMed=11695897; DOI=10.1021/bi010917q; RA Huang P., Li J., Chen C., Visiers I., Weinstein H., Liu-Chen L.Y.; RT "Functional role of a conserved motif in TM6 of the rat mu opioid receptor: RT constitutively active and inactive receptors result from substitutions of RT Thr6.34(279) with Lys and Asp."; RL Biochemistry 40:13501-13509(2001). RN [25] RP MUTAGENESIS OF THR-180. RX PubMed=11060299; DOI=10.1074/jbc.m007437200; RA Celver J.P., Lowe J., Kovoor A., Gurevich V.V., Chavkin C.; RT "Threonine 180 is required for G-protein-coupled receptor kinase 3- and RT beta-arrestin 2-mediated desensitization of the mu-opioid receptor in RT Xenopus oocytes."; RL J. Biol. Chem. 276:4894-4900(2001). RN [26] RP PHOSPHORYLATION AT SER-363; THR-370 AND SER-375, AND MUTAGENESIS OF RP SER-363; THR-370 AND SER-375. RX PubMed=11278523; DOI=10.1074/jbc.m009571200; RA El Kouhen R., Burd A.L., Erickson-Herbrandson L.J., Chang C.Y., Law P.Y., RA Loh H.H.; RT "Phosphorylation of Ser363, Thr370, and Ser375 residues within the carboxyl RT tail differentially regulates mu-opioid receptor internalization."; RL J. Biol. Chem. 276:12774-12780(2001). RN [27] RP MUTAGENESIS OF LEU-275 AND THR-279. RX PubMed=12356297; DOI=10.1021/bi026067b; RA Huang P., Visiers I., Weinstein H., Liu-Chen L.Y.; RT "The local environment at the cytoplasmic end of TM6 of the mu opioid RT receptor differs from those of rhodopsin and monoamine receptors: RT introduction of an ionic lock between the cytoplasmic ends of helices 3 and RT 6 by a L6.30(275)E mutation inactivates the mu opioid receptor and reduces RT the constitutive activity of its T6.34(279)K mutant."; RL Biochemistry 41:11972-11980(2002). RN [28] RP RECEPTOR HETEROOLIGOMERIZATION, AND INTERACTION WITH SSTR2. RX PubMed=11896051; DOI=10.1074/jbc.m110373200; RA Pfeiffer M., Koch T., Schroder H., Laugsch M., Hollt V., Schulz S.; RT "Heterodimerization of somatostatin and opioid receptors cross-modulates RT phosphorylation, internalization, and desensitization."; RL J. Biol. Chem. 277:19762-19772(2002). RN [29] RP INTERACTION WITH PLD2. RX PubMed=12519790; DOI=10.1074/jbc.m206709200; RA Koch T., Brandenburg L.O., Schulz S., Liang Y., Klein J., Hollt V.; RT "ADP-ribosylation factor-dependent phospholipase D2 activation is required RT for agonist-induced mu-opioid receptor endocytosis."; RL J. Biol. Chem. 278:9979-9985(2003). RN [30] RP RECEPTOR HETEROOLIGOMERIZATION, AND INTERACTION WITH ADRA2A. RX PubMed=14645661; DOI=10.1124/mol.64.6.1317; RA Jordan B.A., Gomes I., Rios C., Filipovska J., Devi L.A.; RT "Functional interactions between mu opioid and alpha 2A-adrenergic RT receptors."; RL Mol. Pharmacol. 64:1317-1324(2003). RN [31] RP RECEPTOR HETEROOLIGOMERIZATION, AND INTERACTION WITH CCR5. RX PubMed=14729105; DOI=10.1016/j.ejphar.2003.10.033; RA Chen C., Li J., Bot G., Szabo I., Rogers T.J., Liu-Chen L.Y.; RT "Heterodimerization and cross-desensitization between the mu-opioid RT receptor and the chemokine CCR5 receptor."; RL Eur. J. Pharmacol. 483:175-186(2004). RN [32] RP INTERACTION WITH GNAS. RX PubMed=15857684; DOI=10.1016/j.molbrainres.2004.12.016; RA Chakrabarti S., Regec A., Gintzler A.R.; RT "Biochemical demonstration of mu-opioid receptor association with Gsalpha: RT enhancement following morphine exposure."; RL Brain Res. Mol. Brain Res. 135:217-224(2005). RN [33] RP FUNCTION. RX PubMed=15944153; DOI=10.1074/jbc.m502593200; RA Belcheva M.M., Clark A.L., Haas P.D., Serna J.S., Hahn J.W., Kiss A., RA Coscia C.J.; RT "Mu and kappa opioid receptors activate ERK/MAPK via different protein RT kinase C isoforms and secondary messengers in astrocytes."; RL J. Biol. Chem. 280:27662-27669(2005). RN [34] RP RECEPTOR HETEROOLIGOMERIZATION, AND INTERACTION WITH OPRD1. RX PubMed=17384143; DOI=10.1096/fj.06-7793com; RA Rozenfeld R., Devi L.A.; RT "Receptor heterodimerization leads to a switch in signaling: beta- RT arrestin2-mediated ERK activation by mu-delta opioid receptor RT heterodimers."; RL FASEB J. 21:2455-2465(2007). RN [35] RP INTERACTION WITH GPM6A. RX PubMed=17548356; DOI=10.1074/jbc.m700941200; RA Wu D.F., Koch T., Liang Y.J., Stumm R., Schulz S., Schroder H., Hollt V.; RT "Membrane glycoprotein M6a interacts with the micro-opioid receptor and RT facilitates receptor endocytosis and recycling."; RL J. Biol. Chem. 282:22239-22247(2007). RN [36] RP INTERACTION WITH SYP. RX PubMed=17005904; DOI=10.1124/mol.106.026062; RA Liang Y.J., Wu D.F., Yang L.Q., Hollt V., Koch T.; RT "Interaction of the mu-opioid receptor with synaptophysin influences RT receptor trafficking and signaling."; RL Mol. Pharmacol. 71:123-131(2007). RN [37] RP FUNCTION, RECEPTOR HETEROOLIGOMERIZATION, AND INTERACTION WITH CNR1. 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 [38] RP MUTAGENESIS OF SER-363; THR-370 AND SER-375. RX PubMed=18558479; DOI=10.1016/j.cellsig.2008.05.004; RA Chu J., Zheng H., Loh H.H., Law P.Y.; RT "Morphine-induced mu-opioid receptor rapid desensitization is independent RT of receptor phosphorylation and beta-arrestins."; RL Cell. Signal. 20:1616-1624(2008). RN [39] RP FUNCTION. RX PubMed=17947509; DOI=10.1124/mol.107.039842; RA Zheng H., Loh H.H., Law P.Y.; RT "Beta-arrestin-dependent mu-opioid receptor-activated extracellular signal- RT regulated kinases (ERKs) Translocate to Nucleus in Contrast to G protein- RT dependent ERK activation."; RL Mol. Pharmacol. 73:178-190(2008). RN [40] RP INTERACTION WITH RGS4. RX PubMed=19324084; DOI=10.1016/j.cellsig.2009.03.013; RA Leontiadis L.J., Papakonstantinou M.P., Georgoussi Z.; RT "Regulator of G protein signaling 4 confers selectivity to specific G RT proteins to modulate mu- and delta-opioid receptor signaling."; RL Cell. Signal. 21:1218-1228(2009). RN [41] RP PHOSPHORYLATION AT TYR-166, AND MUTAGENESIS OF TYR-166. RX PubMed=19959593; DOI=10.1124/mol.109.060558; RA Clayton C.C., Bruchas M.R., Lee M.L., Chavkin C.; RT "Phosphorylation of the mu-opioid receptor at tyrosine 166 (Tyr3.51) in the RT DRY motif reduces agonist efficacy."; RL Mol. Pharmacol. 77:339-347(2010). RN [42] RP FUNCTION, AND MUTAGENESIS OF SER-375. RX PubMed=21292762; DOI=10.1074/jbc.m110.177089; RA Zheng H., Chu J., Zhang Y., Loh H.H., Law P.Y.; RT "Modulating micro-opioid receptor phosphorylation switches agonist- RT dependent signaling as reflected in PKCepsilon activation and dendritic RT spine stability."; RL J. Biol. Chem. 286:12724-12733(2011). CC -!- FUNCTION: Receptor for endogenous opioids such as beta-endorphin and CC endomorphin. Receptor for natural and synthetic opioids including CC morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and CC methadone. Agonist binding to the receptor induces coupling to an CC 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. The agonist- and cell type-specific activity is CC predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G CC alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and CC Alpha-2, and to a lesser extent to pertussis toxin-insensitive G alpha CC proteins GNAZ and GNA15. They mediate an array of downstream cellular CC responses, including inhibition of adenylate cyclase activity and both CC N-type and L-type calcium channels, activation of inward rectifying CC 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. Also CC couples to adenylate cyclase stimulatory G alpha proteins. The CC selective temporal coupling to G-proteins and subsequent signaling can CC be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4. 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. Beta-arrestins associate with the GPRK- CC phosphorylated receptor and uncouple it from the G-protein thus CC terminating signal transduction. The phosphorylated receptor is CC internalized through endocytosis via clathrin-coated pits which CC involves beta-arrestins. The activation of the ERK pathway occurs CC either in a G-protein-dependent or a beta-arrestin-dependent manner and CC is regulated by agonist-specific receptor phosphorylation. 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 Receptor down-regulation pathways are varying with the agonist and CC occur dependent or independent of G-protein coupling. Endogenous CC ligands induce rapid desensitization, endocytosis and recycling. CC Heterooligomerization with other GPCRs can modulate agonist binding, CC signaling and trafficking properties. Involved in neurogenesis. CC {ECO:0000269|PubMed:15944153, ECO:0000269|PubMed:16682964, CC ECO:0000269|PubMed:17947509, ECO:0000269|PubMed:1846076, CC ECO:0000269|PubMed:21292762, ECO:0000269|PubMed:7595566, CC ECO:0000269|PubMed:7678862, ECO:0000269|PubMed:8051154, CC ECO:0000269|PubMed:8240812, ECO:0000269|PubMed:8393525, CC ECO:0000269|PubMed:9224819, ECO:0000269|PubMed:9572309}. 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:11896051, PubMed:14645661, CC PubMed:14729105, PubMed:17384143, PubMed:16682964). Interacts with CC heterotrimeric G proteins; interaction with a heterotrimeric complex CC containing GNAI1, GNB1 and GNG2 stabilizes the active conformation of CC the receptor and increases its affinity for endomorphin-2, the CC synthetic opioid peptide DAMGO and for morphinan agonists (By CC similarity). Interacts with PPL; the interaction disrupts agonist- CC mediated G-protein activation. Interacts (via C-terminus) with DNAJB4 CC (via C-terminus). Interacts with calmodulin; the interaction inhibits CC the constitutive activity of OPRM1; it abolishes basal and attenuates CC agonist-stimulated G-protein coupling (By similarity). Interacts with CC FLNA, PLD2, RANBP9 and WLS and GPM6A (PubMed:12519790, CC PubMed:17548356). Interacts with RTP4 (By similarity). Interacts with CC SYP and GNAS (PubMed:15857684, PubMed:17005904). Interacts with RGS9, CC RGS17, RGS20, RGS4, PPP1R9B and HINT1 (By similarity). CC {ECO:0000250|UniProtKB:P35372, ECO:0000250|UniProtKB:P42866, CC ECO:0000269|PubMed:10842167, ECO:0000269|PubMed:11896051, CC ECO:0000269|PubMed:12519790, ECO:0000269|PubMed:14645661, CC ECO:0000269|PubMed:14729105, ECO:0000269|PubMed:15857684, CC ECO:0000269|PubMed:16682964, ECO:0000269|PubMed:17005904, CC ECO:0000269|PubMed:17384143, ECO:0000269|PubMed:17548356, CC ECO:0000269|PubMed:19324084}. CC -!- INTERACTION: CC Q812E9:Gpm6a; NbExp=7; IntAct=EBI-4392569, EBI-6113756; CC P70498:Pld2; NbExp=3; IntAct=EBI-4392569, EBI-6140589; CC P07825:Syp; NbExp=8; IntAct=EBI-4392569, EBI-976085; CC Q6P689:Wls; NbExp=2; IntAct=EBI-4392569, EBI-6113235; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:8240812, CC ECO:0000269|PubMed:8393525}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:P42866}. 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=8; CC Name=1; CC IsoId=P33535-1; Sequence=Displayed; CC Name=2; Synonyms=MOR1A; CC IsoId=P33535-2; Sequence=VSP_041828; CC Name=3; Synonyms=MOR1R; CC IsoId=P33535-3; Sequence=VSP_041829; CC Name=4; Synonyms=MOR1B; CC IsoId=P33535-4; Sequence=VSP_041830; CC Name=5; Synonyms=MOR1B2; CC IsoId=P33535-5; Sequence=VSP_041831; CC Name=6; Synonyms=MOR1C1; CC IsoId=P33535-6; Sequence=VSP_041832; CC Name=7; Synonyms=MOR-1C2; CC IsoId=P33535-7; Sequence=VSP_041833; CC Name=8; Synonyms=rMOR-1D; CC IsoId=P33535-8; Sequence=VSP_041834; CC -!- TISSUE SPECIFICITY: Brain. Is expressed in the cerebral cortex, caudate CC putamen, nucleus accumbens, septal nuclei, thalamus, hippocampus, and CC habenula. Not detected in cerebellum. 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:0000269|PubMed:10488100, ECO:0000269|PubMed:10744734, CC ECO:0000269|PubMed:10820022, ECO:0000269|PubMed:11278523, CC ECO:0000269|PubMed:19959593}. 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:0000250|UniProtKB:P42866}. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. CC {ECO:0000255|PROSITE-ProRule:PRU00521}. CC -!- SEQUENCE CAUTION: CC Sequence=AAQ77387.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D16349; BAA03852.1; -; mRNA. DR EMBL; L20684; AAA41643.1; -; mRNA. DR EMBL; L13069; AAA41630.1; -; mRNA. DR EMBL; U02083; AAA70049.1; -; mRNA. DR EMBL; L22455; AAA16075.1; -; mRNA. DR EMBL; U35424; AAA79180.1; -; mRNA. DR EMBL; AY309003; AAQ77387.1; ALT_FRAME; mRNA. DR EMBL; AY309004; AAQ77388.1; -; mRNA. DR EMBL; AY225402; AAP44725.1; -; mRNA. DR EMBL; AY225403; AAP44726.1; -; mRNA. DR EMBL; AY309000; AAQ77384.1; -; mRNA. DR EMBL; AY309002; AAQ77386.1; -; mRNA. DR EMBL; S77863; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; S75669; AAB33530.2; -; mRNA. DR PIR; I56504; I56504. DR PIR; I56517; I56517. DR PIR; S69010; S69010. DR RefSeq; NP_001033686.1; NM_001038597.2. [P33535-2] DR RefSeq; NP_001033688.2; NM_001038599.2. [P33535-5] DR RefSeq; NP_001033689.1; NM_001038600.2. [P33535-6] DR RefSeq; NP_001033690.1; NM_001038601.2. [P33535-7] DR RefSeq; NP_001291664.1; NM_001304735.1. [P33535-1] DR RefSeq; NP_001291666.1; NM_001304737.1. [P33535-1] DR RefSeq; NP_001291667.1; NM_001304738.1. [P33535-1] DR RefSeq; NP_001291669.1; NM_001304740.1. [P33535-1] DR RefSeq; NP_037203.1; NM_013071.2. [P33535-1] DR SMR; P33535; -. DR BioGrid; 247631; 1. DR CORUM; P33535; -. DR IntAct; P33535; 6. DR STRING; 10116.ENSRNOP00000051290; -. DR BindingDB; P33535; -. DR ChEMBL; CHEMBL270; -. DR DrugCentral; P33535; -. DR GuidetoPHARMACOLOGY; 319; -. DR iPTMnet; P33535; -. DR PhosphoSitePlus; P33535; -. DR SwissPalm; P33535; -. DR PaxDb; P33535; -. DR PRIDE; P33535; -. DR Ensembl; ENSRNOT00000024682; ENSRNOP00000024682; ENSRNOG00000018191. [P33535-6] DR Ensembl; ENSRNOT00000079628; ENSRNOP00000072626; ENSRNOG00000018191. [P33535-8] DR Ensembl; ENSRNOT00000083308; ENSRNOP00000074079; ENSRNOG00000018191. [P33535-1] DR Ensembl; ENSRNOT00000092034; ENSRNOP00000068988; ENSRNOG00000018191. [P33535-7] DR GeneID; 25601; -. DR KEGG; rno:25601; -. DR CTD; 4988; -. DR RGD; 3234; Oprm1. DR eggNOG; KOG3656; Eukaryota. DR eggNOG; ENOG410XRW9; LUCA. DR GeneTree; ENSGT00940000158236; -. DR HOGENOM; HOG000230486; -. DR InParanoid; P33535; -. DR KO; K04215; -. DR OMA; PAWYWEN; -. DR OrthoDB; 1011272at2759; -. DR TreeFam; TF315737; -. DR Reactome; R-RNO-111885; Opioid Signalling. DR Reactome; R-RNO-202040; G-protein activation. DR Reactome; R-RNO-375276; Peptide ligand-binding receptors. DR Reactome; R-RNO-418594; G alpha (i) signalling events. DR PRO; PR:P33535; -. DR Proteomes; UP000002494; Chromosome 1. DR Bgee; ENSRNOG00000018191; Expressed in 1 organ(s), highest expression level in brain. DR ExpressionAtlas; P33535; baseline and differential. DR Genevisible; P33535; RN. DR GO; GO:0030424; C:axon; ISS:UniProtKB. DR GO; GO:0005623; C:cell; IEA:GOC. DR GO; GO:0005737; C:cytoplasm; IDA:RGD. DR GO; GO:0030425; C:dendrite; IDA:RGD. DR GO; GO:0032839; C:dendrite cytoplasm; IDA:RGD. DR GO; GO:0032590; C:dendrite membrane; IDA:RGD. DR GO; GO:0005768; C:endosome; ISS:UniProtKB. DR GO; GO:0005925; C:focal adhesion; IDA:RGD. DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central. DR GO; GO:0099055; C:integral component of postsynaptic membrane; IDA:SynGO. DR GO; GO:0099056; C:integral component of presynaptic membrane; IDA:SynGO. DR GO; GO:0016020; C:membrane; IDA:RGD. DR GO; GO:0045121; C:membrane raft; IDA:RGD. DR GO; GO:0043204; C:perikaryon; IDA:RGD. DR GO; GO:0097444; C:spine apparatus; IDA:SynGO. DR GO; GO:0004979; F:beta-endorphin receptor activity; ISO:RGD. DR GO; GO:0031005; F:filamin binding; IMP:RGD. DR GO; GO:0004930; F:G protein-coupled receptor activity; IDA:RGD. DR GO; GO:0001965; F:G-protein alpha-subunit binding; ISS:UniProtKB. DR GO; GO:0031681; F:G-protein beta-subunit binding; IPI:RGD. DR GO; GO:0038047; F:morphine receptor activity; IDA:RGD. DR GO; GO:0042923; F:neuropeptide binding; IBA:GO_Central. DR GO; GO:0004985; F:opioid receptor activity; ISO:RGD. DR GO; GO:0042277; F:peptide binding; IBA:GO_Central. DR GO; GO:0008022; F:protein C-terminus binding; IPI:RGD. DR GO; GO:0019904; F:protein domain specific binding; IPI:RGD. DR GO; GO:0005245; F:voltage-gated calcium channel activity; IMP:UniProtKB. DR GO; GO:0002438; P:acute inflammatory response to antigenic stimulus; IEP:RGD. DR GO; GO:0007191; P:adenylate cyclase-activating dopamine receptor signaling pathway; ISO:RGD. DR GO; GO:0007197; P:adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway; IDA:GO_Central. DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IDA:RGD. DR GO; GO:0031635; P:adenylate cyclase-inhibiting opioid receptor signaling pathway; IDA:RGD. DR GO; GO:0048149; P:behavioral response to ethanol; ISO:RGD. DR GO; GO:0042755; P:eating behavior; IMP:RGD. DR GO; GO:0044849; P:estrous cycle; IEP:RGD. DR GO; GO:0060079; P:excitatory postsynaptic potential; IDA:RGD. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:RGD. DR GO; GO:0006955; P:immune response; TAS:RGD. DR GO; GO:0007626; P:locomotory behavior; ISO:RGD. DR GO; GO:0106072; P:negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:RGD. 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:0038003; P:opioid receptor signaling pathway; IDA:RGD. DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0032100; P:positive regulation of appetite; IMP:RGD. DR GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; ISO:RGD. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISO:RGD. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB. DR GO; GO:0050769; P:positive regulation of neurogenesis; ISS:UniProtKB. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISO:RGD. DR GO; GO:0080135; P:regulation of cellular response to stress; ISO:RGD. DR GO; GO:2000310; P:regulation of NMDA receptor activity; IMP:UniProtKB. DR GO; GO:0051930; P:regulation of sensory perception of pain; IDA:RGD. DR GO; GO:0042220; P:response to cocaine; IEP:RGD. DR GO; GO:0045471; P:response to ethanol; IDA:RGD. DR GO; GO:0032094; P:response to food; IEP:RGD. DR GO; GO:0070848; P:response to growth factor; IEP:RGD. DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD. DR GO; GO:0043278; P:response to morphine; IEP:RGD. DR GO; GO:0009314; P:response to radiation; IEP:RGD. DR GO; GO:0019233; P:sensory perception of pain; ISS:UniProtKB. DR GO; GO:0042060; P:wound healing; IEP:RGD. 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 Alternative splicing; Cell membrane; Cell projection; Disulfide bond; KW Endosome; G-protein coupled receptor; Glycoprotein; Lipoprotein; Membrane; KW Palmitate; Phosphoprotein; Receptor; Reference proteome; Transducer; KW Transmembrane; Transmembrane helix; Ubl conjugation. FT CHAIN 1..398 FT /note="Mu-type opioid receptor" FT /id="PRO_0000069978" FT TOPO_DOM 1..66 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TRANSMEM 67..91 FT /note="Helical; Name=1" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TOPO_DOM 92..104 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TRANSMEM 105..129 FT /note="Helical; Name=2" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TOPO_DOM 130..140 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TRANSMEM 141..163 FT /note="Helical; Name=3" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TOPO_DOM 164..183 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TRANSMEM 184..205 FT /note="Helical; Name=4" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TOPO_DOM 206..228 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TRANSMEM 229..253 FT /note="Helical; Name=5" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TOPO_DOM 254..277 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TRANSMEM 278..304 FT /note="Helical; Name=6" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TOPO_DOM 305..312 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TRANSMEM 313..336 FT /note="Helical; Name=7" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TOPO_DOM 337..398 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P42866" FT MOTIF 332..336 FT /note="NPxxY; plays a role in stabilizing the activated FT conformation of the receptor" FT /evidence="ECO:0000250|UniProtKB:P42866" FT MOD_RES 166 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:19959593" FT MOD_RES 363 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11278523" FT MOD_RES 370 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:11278523" FT MOD_RES 375 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11278523" FT MOD_RES 394 FT /note="Phosphothreonine" FT /evidence="ECO:0000305|PubMed:10820022" 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 CARBOHYD 53 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 140..217 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521" FT VAR_SEQ 387..398 FT /note="LENLEAETAPLP -> VCAF (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15525342" FT /id="VSP_041828" FT VAR_SEQ 387..398 FT /note="LENLEAETAPLP -> GAEL (in isoform 3)" FT /evidence="ECO:0000303|Ref.7" FT /id="VSP_041829" FT VAR_SEQ 387..398 FT /note="LENLEAETAPLP -> KIVLF (in isoform 4)" FT /evidence="ECO:0000303|PubMed:7532594" FT /id="VSP_041830" FT VAR_SEQ 387..398 FT /note="LENLEAETAPLP -> EPQSVET (in isoform 5)" FT /evidence="ECO:0000303|Ref.7" FT /id="VSP_041831" FT VAR_SEQ 387..398 FT /note="LENLEAETAPLP -> PALAVSVAQIFTGYPSPTHGEKPCKSYRDRPRPCGR FT TWSLKSRAESNVEHFHCGAALIYNNVNFI (in isoform 6)" FT /evidence="ECO:0000303|PubMed:15525342" FT /id="VSP_041832" FT VAR_SEQ 387..398 FT /note="LENLEAETAPLP -> PALAVSVAQIFTGYPSPTHGEKPCKSYRDRPRPCGR FT TWSLKSRAESNVEHFHCGAALIYNNELKIGPVSWLQMPAHVLVRPW (in isoform FT 7)" FT /evidence="ECO:0000303|PubMed:15525342" FT /id="VSP_041833" FT VAR_SEQ 387..398 FT /note="LENLEAETAPLP -> T (in isoform 8)" FT /evidence="ECO:0000303|PubMed:15525342" FT /id="VSP_041834" FT MUTAGEN 91 FT /note="Y->A: Abolishes agonist-induced G-protein- FT independent receptor internalization; when associated with FT A-96, A-166 and A-336." FT /evidence="ECO:0000269|PubMed:10488100" FT MUTAGEN 96 FT /note="Y->A: Abolishes agonist-induced G-protein- FT independent receptor internalization; when associated with FT A-91, A-166 and A-336." FT /evidence="ECO:0000269|PubMed:10488100" FT MUTAGEN 114 FT /note="D->A,N: Impairs agonist affinity, agonist-induced FT inhibition of adenylate cyclase and coupling to G- FT proteins." FT /evidence="ECO:0000269|PubMed:8051154, FT ECO:0000269|PubMed:9224819" FT MUTAGEN 114 FT /note="D->E: No effect on inhibition of adenylate cyclase." FT /evidence="ECO:0000269|PubMed:8051154, FT ECO:0000269|PubMed:9224819" FT MUTAGEN 147 FT /note="D->A: No effect on constitutive activation. Impairs FT agonist affinity and agonist-induced inhibition of FT adenylate cyclase." FT /evidence="ECO:0000269|PubMed:11580279, FT ECO:0000269|PubMed:8051154" FT MUTAGEN 147 FT /note="D->E: Impairs agonist affinity and increases FT agonist-induced inhibition of adenylate cyclase." FT /evidence="ECO:0000269|PubMed:11580279, FT ECO:0000269|PubMed:8051154" FT MUTAGEN 147 FT /note="D->N: No effect on constitutive activation." FT /evidence="ECO:0000269|PubMed:11580279, FT ECO:0000269|PubMed:8051154" FT MUTAGEN 164 FT /note="D->E: Reduces basal activity." FT /evidence="ECO:0000269|PubMed:11580279" FT MUTAGEN 164 FT /note="D->H,M,Q,Y: Constitutive active." FT /evidence="ECO:0000269|PubMed:11580279" FT MUTAGEN 166 FT /note="Y->A: Abolishes agonist-induced G-protein- FT independent receptor internalization; when associated with FT A-91, A-96 and A-336." FT /evidence="ECO:0000269|PubMed:10488100, FT ECO:0000269|PubMed:19959593" FT MUTAGEN 166 FT /note="Y->F: Decrease in phosphorylation, no decrease in G- FT protein binding." FT /evidence="ECO:0000269|PubMed:10488100, FT ECO:0000269|PubMed:19959593" FT MUTAGEN 180 FT /note="T->A: Impairs ARRB2- and GRK3-mediated receptor FT desensitization." FT /evidence="ECO:0000269|PubMed:11060299" FT MUTAGEN 275 FT /note="L->E: No effect on constitutive activation. Some FT constitutive activity; when associated with K-279." FT /evidence="ECO:0000269|PubMed:12356297" FT MUTAGEN 279 FT /note="T->D: Receptor inactivation." FT /evidence="ECO:0000269|PubMed:11695897, FT ECO:0000269|PubMed:12356297" FT MUTAGEN 279 FT /note="T->K: Constitutive active. Some constitutive FT activity; when associated with E-275." FT /evidence="ECO:0000269|PubMed:11695897, FT ECO:0000269|PubMed:12356297" FT MUTAGEN 297 FT /note="H->A: Impairs agonist affinity and increases FT agonist-induced inhibition of adenylate cyclase." FT /evidence="ECO:0000269|PubMed:8051154" FT MUTAGEN 336 FT /note="Y->A: Abolishes agonist-induced G-protein- FT independent receptor internalization; when associated with FT A-91, A-96 and A-166." FT /evidence="ECO:0000269|PubMed:10488100" FT MUTAGEN 346 FT /note="C->A: No change in palmitoylation. No change in FT palmitoylation; when associated with A-351." FT /evidence="ECO:0000269|PubMed:9877183" FT MUTAGEN 351 FT /note="C->A: No change in palmitoylation; when associated FT with A-346." FT /evidence="ECO:0000269|PubMed:9877183" FT MUTAGEN 363 FT /note="S->A: Abolishes basal phosphorylation; when FT associated with A-370. Abolishes basal and agonist-induced FT phosphorylation; when associated with A-370 and A-375. FT Accelerates agonist-induced receptor internalization." FT /evidence="ECO:0000269|PubMed:11278523, FT ECO:0000269|PubMed:18558479" FT MUTAGEN 370 FT /note="T->A: Abolishes basal phosphorylation; when FT associated with A-363. Abolishes basal and agonist-induced FT phosphorylation; when associated with A-363 and A-375. FT Accelerates agonist-induced receptor internalization." FT /evidence="ECO:0000269|PubMed:11278523, FT ECO:0000269|PubMed:18558479" FT MUTAGEN 375 FT /note="S->A: Reduces agonist-induced receptor FT internalization. Abolishes morphine-induced FT phosphorylation. Restores agonist-specific PRKCE activity. FT Abolishes basal and agonist-induced phosphorylation; when FT associated with A-363 and A-370." FT /evidence="ECO:0000269|PubMed:11278523, FT ECO:0000269|PubMed:18558479, ECO:0000269|PubMed:21292762" FT MUTAGEN 394 FT /note="T->A: Impairs phosphorylation and abolishes agonist- FT mediated acute receptor desensitization." FT /evidence="ECO:0000269|PubMed:10488100, FT ECO:0000269|PubMed:10820022" FT CONFLICT 237 FT /note="F -> G (in Ref. 6; AAA79180)" FT /evidence="ECO:0000305" FT CONFLICT 238 FT /note="I -> V (in Ref. 7; AAQ77386)" FT /evidence="ECO:0000305" FT CONFLICT 245 FT /note="V -> I (in Ref. 3; AAA41630, 4; AAA70049 and 10; FT S77863)" FT /evidence="ECO:0000305" SQ SEQUENCE 398 AA; 44494 MW; 9C916DE7C1C33743 CRC64; MDSSTGPGNT SDCSDPLAQA SCSPAPGSWL NLSHVDGNQS DPCGLNRTGL GGNDSLCPQT GSPSMVTAIT IMALYSIVCV VGLFGNFLVM YVIVRYTKMK TATNIYIFNL ALADALATST LPFQSVNYLM GTWPFGTILC KIVISIDYYN MFTSIFTLCT MSVDRYIAVC HPVKALDFRT PRNAKIVNVC NWILSSAIGL PVMFMATTKY RQGSIDCTLT FSHPTWYWEN LLKICVFIFA FIMPVLIITV CYGLMILRLK SVRMLSGSKE KDRNLRRITR MVLVVVAVFI VCWTPIHIYV IIKALITIPE TTFQTVSWHF CIALGYTNSC LNPVLYAFLD ENFKRCFREF CIPTSSTIEQ QNSTRVRQNT REHPSTANTV DRTNHQLENL EAETAPLP //