OPRM_RAT
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 03-AUG-2022, entry version 177.
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; DOI=10.1016/s0021-9258(17)32028-8;
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.
RX PubMed=8624732; DOI=10.1016/0006-8993(95)00928-j;
RA Mansour A., Hoversten M.T., Taylor L.P., Watson S.J., Akil H.;
RT "The cloned mu, delta and kappa receptors and their endogenous ligands:
RT evidence for two opioid peptide recognition cores.";
RL Brain Res. 700:89-98(1995).
RN [16]
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 [17]
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 [18]
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 [19]
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 [20]
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 [21]
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 [22]
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 [23]
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 [24]
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 [25]
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 [26]
RP FUNCTION, AND 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 [27]
RP FUNCTION, PHOSPHORYLATION AT SER-363; THR-370 AND SER-375, AND MUTAGENESIS
RP OF 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 [28]
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 [29]
RP FUNCTION, 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 [30]
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 [31]
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 [32]
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 [33]
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 [34]
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 [35]
RP FUNCTION, 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 [36]
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 [37]
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 [38]
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 [39]
RP FUNCTION, AND 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 [40]
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 [41]
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 [42]
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 [43]
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 (PubMed:15944153, PubMed:16682964, PubMed:1846076,
CC PubMed:21292762, PubMed:7595566, PubMed:7678862, PubMed:8051154,
CC PubMed:8240812, PubMed:8393525, PubMed:9224819, PubMed:9572309,
CC PubMed:11060299, PubMed:17384143, PubMed:18558479, PubMed:17947509).
CC Receptor for natural and synthetic opioids including morphine, heroin,
CC DAMGO, fentanyl, etorphine, buprenorphin and methadone
CC (PubMed:15944153, PubMed:16682964, PubMed:1846076, PubMed:21292762,
CC PubMed:7595566, PubMed:7678862, PubMed:8051154, PubMed:8240812,
CC PubMed:8393525, PubMed:9224819, PubMed:9572309, PubMed:11060299,
CC PubMed:17384143, PubMed:18558479, PubMed:17947509). 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:8624732).
CC Agonist binding to the receptor induces coupling to an inactive GDP-
CC bound heterotrimeric G-protein complex and subsequent exchange of GDP
CC for GTP in the G-protein alpha subunit leading to dissociation of the
CC G-protein complex with the free GTP-bound G-protein alpha and the G-
CC protein beta-gamma dimer activating downstream cellular effectors
CC (PubMed:9224819, PubMed:16682964). The agonist- and cell type-specific
CC activity is predominantly coupled to pertussis toxin-sensitive G(i) and
CC G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1
CC and Alpha-2, and to a lesser extent to pertussis toxin-insensitive G
CC alpha proteins GNAZ and GNA15 (PubMed:9224819, PubMed:9572309). They
CC mediate an array of downstream cellular responses, including inhibition
CC of adenylate cyclase activity and both N-type and L-type calcium
CC channels, activation of inward rectifying potassium channels, mitogen-
CC activated protein kinase (MAPK), phospholipase C (PLC),
CC phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K)
CC and regulation of NF-kappa-B (PubMed:7595566, PubMed:15944153,
CC PubMed:21292762, PubMed:9572309). Also couples to adenylate cyclase
CC stimulatory G alpha proteins (PubMed:7595566). The selective temporal
CC coupling to G-proteins and subsequent signaling can be regulated by
CC RGSZ proteins, such as RGS9, RGS17 and RGS4. Phosphorylation by members
CC of the GPRK subfamily of Ser/Thr protein kinases and association with
CC beta-arrestins is involved in short-term receptor desensitization
CC (PubMed:11060299, PubMed:17384143, PubMed:18558479, PubMed:17947509).
CC Beta-arrestins associate with the GPRK-phosphorylated receptor and
CC uncouple it from the G-protein thus terminating signal transduction.
CC The phosphorylated receptor is internalized through endocytosis via
CC clathrin-coated pits which involves beta-arrestins. The activation of
CC the ERK pathway occurs either in a G-protein-dependent or a beta-
CC arrestin-dependent manner and is regulated by agonist-specific receptor
CC phosphorylation (PubMed:11278523, PubMed:11896051, PubMed:15944153).
CC Acts as a class A G-protein coupled receptor (GPCR) which dissociates
CC from beta-arrestin at or near the plasma membrane and undergoes rapid
CC recycling. Receptor down-regulation pathways are varying with the
CC agonist and occur dependent or independent of G-protein coupling
CC (PubMed:11060299, PubMed:17384143, PubMed:18558479, PubMed:17947509).
CC Endogenous ligands induce rapid desensitization, endocytosis and
CC recycling. Heterooligomerization with other GPCRs can modulate agonist
CC binding, signaling and trafficking properties (PubMed:17384143,
CC PubMed:16682964). {ECO:0000269|PubMed:11060299,
CC ECO:0000269|PubMed:11278523, ECO:0000269|PubMed:11896051,
CC ECO:0000269|PubMed:15944153, ECO:0000269|PubMed:16682964,
CC ECO:0000269|PubMed:17384143, ECO:0000269|PubMed:17947509,
CC ECO:0000269|PubMed:1846076, ECO:0000269|PubMed:18558479,
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:8624732, ECO:0000269|PubMed:9224819,
CC 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 P33535; Q812E9: Gpm6a; NbExp=7; IntAct=EBI-4392569, EBI-6113756;
CC P33535; P70498: Pld2; NbExp=3; IntAct=EBI-4392569, EBI-6140589;
CC P33535; P07825: Syp; NbExp=8; IntAct=EBI-4392569, EBI-976085;
CC P33535; 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};
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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 AlphaFoldDB; P33535; -.
DR SMR; P33535; -.
DR BioGRID; 247631; 5.
DR CORUM; P33535; -.
DR IntAct; P33535; 6.
DR STRING; 10116.ENSRNOP00000051290; -.
DR BindingDB; P33535; -.
DR ChEMBL; CHEMBL270; -.
DR DrugCentral; P33535; -.
DR GuidetoPHARMACOLOGY; 319; -.
DR GlyGen; P33535; 5 sites.
DR iPTMnet; P33535; -.
DR PhosphoSitePlus; P33535; -.
DR SwissPalm; P33535; -.
DR PaxDb; P33535; -.
DR GeneID; 25601; -.
DR KEGG; rno:25601; -.
DR CTD; 4988; -.
DR RGD; 3234; Oprm1.
DR VEuPathDB; HostDB:ENSRNOG00000018191; -.
DR eggNOG; KOG3656; Eukaryota.
DR InParanoid; P33535; -.
DR OMA; GNNMEID; -.
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 brain and 3 other tissues.
DR ExpressionAtlas; P33535; baseline and differential.
DR Genevisible; P33535; RN.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
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:0043005; C:neuron projection; IBA:GO_Central.
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:0004985; F:G protein-coupled opioid receptor activity; ISO: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: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:0038003; P:G protein-coupled opioid receptor signaling pathway; IBA:GO_Central.
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: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: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: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 REGION 361..385
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: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
