ID OPRM_HUMAN Reviewed; 400 AA. AC P35372; B0FXJ1; B2R9S7; B8Q1L7; B8Q1L8; B8Q1L9; E7EWZ3; G8XRH6; G8XRH8; AC Q12930; Q4VWM1; Q4VWM2; Q4VWM3; Q4VWM4; Q4VWM6; Q4VWX6; Q5TDA1; Q6UPP1; AC Q6UQ80; Q7Z2D8; Q86V80; Q8IWW3; Q8IWW4; Q9UCZ4; Q9UN57; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 15-JUL-1998, sequence version 2. DT 24-JAN-2024, entry version 217. DE RecName: Full=Mu-type opioid receptor; DE Short=M-OR-1; DE Short=MOR-1; DE AltName: Full=Mu opiate receptor; DE AltName: Full=Mu opioid receptor; DE Short=MOP; DE Short=hMOP; GN Name=OPRM1; Synonyms=MOR1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND SUBCELLULAR LOCATION. RC TISSUE=Brain; RX PubMed=7905839; DOI=10.1016/0014-5793(94)80368-4; RA Wang J.-B., Johnson P.S., Persico A.M., Hawkins A.L., Griffin C.A., RA Uhl G.R.; RT "Human mu opiate receptor. cDNA and genomic clones, pharmacologic RT characterization and chromosomal assignment."; RL FEBS Lett. 338:217-222(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT ASP-40, FUNCTION, AND RP SUBCELLULAR LOCATION. RC TISSUE=Brain; RX PubMed=7957926; DOI=10.1016/0014-5793(94)01129-x; RA Bare L.A., Mansson E., Yang D.; RT "Expression of two variants of the human mu opioid receptor mRNA in SK-N-SH RT cells and human brain."; RL FEBS Lett. 354:213-216(1994). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND SUBCELLULAR LOCATION. RC TISSUE=Brain; RX PubMed=7891175; DOI=10.1523/jneurosci.15-03-02396.1995; RA Mestek A. Jr., Hurley J.H., Bye L.S., Campbell A.D., Chen Y., Tian M., RA Liu J., Schulman H., Yu L.; RT "The human mu opioid receptor: modulation of functional desensitization by RT calcium/calmodulin-dependent protein kinase and protein kinase C."; RL J. Neurosci. 15:2396-2406(1995). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 5), FUNCTION, AND SUBCELLULAR RP LOCATION. RX PubMed=12589820; DOI=10.1016/s0006-291x(03)00089-5; RA Pan Y.X., Xu J., Mahurter L., Xu M., Gilbert A.K., Pasternak G.W.; RT "Identification and characterization of two new human mu opioid receptor RT splice variants, hMOR-1O and hMOR-1X."; RL Biochem. Biophys. Res. Commun. 301:1057-1061(2003). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 14), FUNCTION, AND SUBCELLULAR RP LOCATION. RX PubMed=12734358; DOI=10.4049/jimmunol.170.10.5118; RA Cadet P., Mantione K.J., Stefano G.B.; RT "Molecular identification and functional expression of mu 3, a novel RT alternatively spliced variant of the human mu opiate receptor gene."; RL J. Immunol. 170:5118-5123(2003). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 4; 6; 7; 8; 9 AND 11), AND VARIANT RP 411-GLN--VAL-420 DEL (ISOFORM 9). RX PubMed=15893644; DOI=10.1016/j.neuroscience.2004.12.033; RA Pan L., Xu J., Yu R., Xu M.-M., Pan Y.-X., Pasternak G.W.; RT "Identification and characterization of six new alternatively spliced RT variants of the human mu opioid receptor gene, Oprm."; RL Neuroscience 133:209-220(2005). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 10; 12 AND 13). RX PubMed=19077058; DOI=10.1111/j.1471-4159.2008.05833.x; RA Xu J., Xu M., Hurd Y.L., Pasternak G.W., Pan Y.X.; RT "Isolation and characterization of new exon 11-associated N-terminal splice RT variants of the human mu opioid receptor gene."; RL J. Neurochem. 108:962-972(2009). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 6 AND 15). RC TISSUE=Brain; RA Baar C., Kvam T.-M., Rakvag T.T., Kaasa S., Skorpen F.; RT "Novel variants of the human mu opioid receptor are generated by RT alternative splicing and transcription from different positions in the RT OPRM1 gene."; RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 18). RA Xu J., Pasternak G.W., Pan Y.; RT "Isolation and expression of alternatively spliced variants encoding RT proteins with single transmembrane domain in mu opioid receptor genes."; RL Submitted (DEC-2010) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 12). RC TISSUE=Brain; RX PubMed=19103668; DOI=10.1093/hmg/ddn439; RA Shabalina S.A., Zaykin D.V., Gris P., Ogurtsov A.Y., Gauthier J., RA Shibata K., Tchivileva I.E., Belfer I., Mishra B., Kiselycznyk C., RA Wallace M.R., Staud R., Spiridonov N.A., Max M.B., Goldman D., RA Fillingim R.B., Maixner W., Diatchenko L.; RT "Expansion of the human mu-opioid receptor gene architecture: novel RT functional variants."; RL Hum. Mol. Genet. 18:1037-1051(2009). RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RA Kopatz S.A., Aronstam R.S., Sharma S.V.; RT "cDNA clones of human proteins involved in signal transduction sequenced by RT the Guthrie cDNA resource center (www.cdna.org)."; RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases. RN [13] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-6; ASP-40; CYS-147; RP ASP-152; CYS-265 AND ASN-274. RG NIEHS SNPs program; RL Submitted (NOV-2006) to the EMBL/GenBank/DDBJ databases. RN [14] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 6 AND 10). RA Xu J., Xu M., Pasternak G.W., Pan Y.; RT "Isolation and characterization of two alternatively spliced variants from RT the human mu opioid receptor, OPRM1, gene."; RL Submitted (AUG-2008) to the EMBL/GenBank/DDBJ databases. RN [15] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [16] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [17] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [18] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-20, AND VARIANT VAL-6. RC TISSUE=Blood; RA Metha S., Glendenning M., Kutlar A., Kutlar F.; RT "An homozygous Ala 6 Val (GCC->GTC) mutation was detected on human mu RT opioid receptor gene of an African American individual with sickle cell RT anemia."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [19] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-47. RX PubMed=10393893; DOI=10.1073/pnas.96.14.7752; RA Uhl G.R., Sora I., Wang Z.; RT "The mu opiate receptor as a candidate gene for pain: polymorphisms, RT variations in expression, nociception, and opiate responses."; RL Proc. Natl. Acad. Sci. U.S.A. 96:7752-7755(1999). RN [20] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 229-374. RX PubMed=7488213; DOI=10.1006/bbrc.1995.2709; RA Chuang T.K., Killam K.F. Jr., Chuang L.F., Kung H.F., Sheng W.S., RA Chao C.C., Yu L., Chuang R.Y.; RT "Mu opioid receptor gene expression in immune cells."; RL Biochem. Biophys. Res. Commun. 216:922-930(1995). RN [21] 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 [22] RP MUTAGENESIS OF CYS-142 AND CYS-219, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=10529478; DOI=10.1016/s0169-328x(99)00241-7; RA Zhang P., Johnson P.S., Zollner C., Wang W., Wang Z., Montes A.E., RA Seidleck B.K., Blaschak C.J., Surratt C.K.; RT "Mutation of human mu opioid receptor extracellular 'disulfide cysteine' RT residues alters ligand binding but does not prevent receptor targeting to RT the cell plasma membrane."; RL Brain Res. Mol. Brain Res. 72:195-204(1999). RN [23] RP INTERACTION WITH CALMODULIN, AND MUTAGENESIS OF LYS-273. RX PubMed=10419536; DOI=10.1074/jbc.274.31.22081; RA Wang D., Sadee W., Quillan J.M.; RT "Calmodulin binding to G protein-coupling domain of opioid receptors."; RL J. Biol. Chem. 274:22081-22088(1999). RN [24] RP REVIEW. RX PubMed=10836142; DOI=10.1146/annurev.pharmtox.40.1.389; RA Law P.Y., Wong Y.H., Loh H.H.; RT "Molecular mechanisms and regulation of opioid receptor signaling."; RL Annu. Rev. Pharmacol. Toxicol. 40:389-430(2000). RN [25] RP INTERACTION WITH CALMODULIN, AND MUTAGENESIS OF LYS-273 AND ARG-275. RX PubMed=10899953; DOI=10.1046/j.1471-4159.2000.0750763.x; RA Wang D., Surratt C.K., Sadee W.; RT "Calmodulin regulation of basal and agonist-stimulated G protein coupling RT by the mu-opioid receptor (OP(3)) in morphine-pretreated cell."; RL J. Neurochem. 75:763-771(2000). RN [26] RP RECEPTOR HETEROOLIGOMERIZATION, AND INTERACTION WITH CCR5. RX PubMed=12413885; DOI=10.1006/excr.2002.5638; RA Suzuki S., Chuang L.F., Yau P., Doi R.H., Chuang R.Y.; RT "Interactions of opioid and chemokine receptors: oligomerization of mu, RT kappa, and delta with CCR5 on immune cells."; RL Exp. Cell Res. 280:192-200(2002). RN [27] RP FUNCTION, AND COUPLING TO GNAI1 AND GNAI2. RX PubMed=12068084; DOI=10.1046/j.1471-4159.2002.00946.x; RA Massotte D., Brillet K., Kieffer B., Milligan G.; RT "Agonists activate Gi1 alpha or Gi2 alpha fused to the human mu opioid RT receptor differently."; RL J. Neurochem. 81:1372-1382(2002). RN [28] RP INTERACTION WITH PPL. RX PubMed=12810704; DOI=10.1074/jbc.m305866200; RA Feng G.J., Kellett E., Scorer C.A., Wilde J., White J.H., Milligan G.; RT "Selective interactions between helix VIII of the human mu-opioid receptors RT and the C terminus of periplakin disrupt G protein activation."; RL J. Biol. Chem. 278:33400-33407(2003). RN [29] RP INTERACTION WITH FLNA. RX PubMed=14573758; DOI=10.1124/mol.64.5.1092; RA Onoprishvili I., Andria M.L., Kramer H.K., Ancevska-Taneva N., Hiller J.M., RA Simon E.J.; RT "Interaction between the mu opioid receptor and filamin A is involved in RT receptor regulation and trafficking."; RL Mol. Pharmacol. 64:1092-1100(2003). RN [30] RP HOMOOLIGOMERIZATION, RECEPTOR HETEROOLIGOMERIZATION, AND INTERACTION WITH RP OPRD1 AND OPRK1. RX PubMed=15778451; DOI=10.1124/mol.104.010272; RA Wang D., Sun X., Bohn L.M., Sadee W.; RT "Opioid receptor homo- and heterodimerization in living cells by RT quantitative bioluminescence resonance energy transfer."; RL Mol. Pharmacol. 67:2173-2184(2005). RN [31] RP HOMOOLIGOMERIZATION. RX PubMed=15967873; DOI=10.1124/mol.105.013847; RA Pascal G., Milligan G.; RT "Functional complementation and the analysis of opioid receptor RT homodimerization."; RL Mol. Pharmacol. 68:905-915(2005). RN [32] RP ALTERNATIVE SPLICING (ISOFORMS 16 AND 17), FUNCTION (ISOFORMS 16 AND 17), RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND SUBUNIT. RX PubMed=16580639; DOI=10.1016/j.bbrc.2006.03.084; RA Choi H.S., Kim C.S., Hwang C.K., Song K.Y., Wang W., Qiu Y., Law P.Y., RA Wei L.N., Loh H.H.; RT "The opioid ligand binding of human mu-opioid receptor is modulated by RT novel splice variants of the receptor."; RL Biochem. Biophys. Res. Commun. 343:1132-1140(2006). RN [33] RP INTERACTION WITH DNAJB4. RX PubMed=16542645; DOI=10.1016/j.brainres.2006.01.125; RA Ancevska-Taneva N., Onoprishvili I., Andria M.L., Hiller J.M., Simon E.J.; RT "A member of the heat shock protein 40 family, hlj1, binds to the carboxyl RT tail of the human mu opioid receptor."; RL Brain Res. 1081:28-33(2006). RN [34] RP RECEPTOR HETEROOLIGOMERIZATION, AND INTERACTION WITH NPFFR2. RX PubMed=17224450; DOI=10.1074/jbc.m606946200; RA Roumy M., Lorenzo C., Mazeres S., Bouchet S., Zajac J.M., Mollereau C.; RT "Physical association between neuropeptide FF and micro-opioid receptors as RT a possible molecular basis for anti-opioid activity."; RL J. Biol. Chem. 282:8332-8342(2007). RN [35] RP REVIEW. RX PubMed=19300905; DOI=10.1007/s00018-009-0008-4; RA Lopez A., Salome L.; RT "Membrane functional organisation and dynamic of mu-opioid receptors."; RL Cell. Mol. Life Sci. 66:2093-2108(2009). RN [36] RP INTERACTION WITH RANBP9. RX PubMed=19788913; DOI=10.1016/j.neulet.2009.09.048; RA Talbot J.N., Skifter D.A., Bianchi E., Monaghan D.T., Toews M.L., RA Murrin L.C.; RT "Regulation of mu opioid receptor internalization by the scaffold protein RT RanBPM."; RL Neurosci. Lett. 466:154-158(2009). RN [37] RP INTERACTION WITH WLS. RX PubMed=20214800; DOI=10.1186/1471-2202-11-33; RA Jin J., Kittanakom S., Wong V., Reyes B.A., Van Bockstaele E.J., RA Stagljar I., Berrettini W., Levenson R.; RT "Interaction of the mu-opioid receptor with GPR177 (Wntless) inhibits Wnt RT secretion: potential implications for opioid dependence."; RL BMC Neurosci. 11:33-33(2010). RN [38] RP FUNCTION (ISOFORM 12), AND SUBCELLULAR LOCATION (ISOFORM 12). RX PubMed=20525224; DOI=10.1186/1744-8069-6-33; RA Gris P., Gauthier J., Cheng P., Gibson D.G., Gris D., Laur O., Pierson J., RA Wentworth S., Nackley A.G., Maixner W., Diatchenko L.; RT "A novel alternatively spliced isoform of the mu-opioid receptor: RT functional antagonism."; RL Mol. Pain 6:33-33(2010). RN [39] RP VARIANTS VAL-6; ASP-40 AND CYS-147. RX PubMed=9399694; DOI=10.1038/sj.mp.4000331; RA Bergen A.W., Kokoszka J., Peterson R., Long J.C., Virkkunen M., RA Linnoila M., Goldman D.; RT "Mu opioid receptor gene variants: lack of association with alcohol RT dependence."; RL Mol. Psychiatry 2:490-494(1997). RN [40] RP VARIANTS VAL-6; ASP-40 AND HIS-260, CHARACTERIZATION OF VARIANT ASP-40, RP POLYMORPHISM, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=9689128; DOI=10.1073/pnas.95.16.9608; RA Bond C., LaForge K.S., Tian M., Melia D., Zhang S., Borg L., Gong J., RA Schluger J., Strong J.A., Leal S.M., Tischfield J.A., Kreek M.J., Yu L.; RT "Single-nucleotide polymorphism in the human mu opioid receptor gene alters RT beta-endorphin binding and activity: possible implications for opiate RT addiction."; RL Proc. Natl. Acad. Sci. U.S.A. 95:9608-9613(1998). CC -!- FUNCTION: Receptor for endogenous opioids such as beta-endorphin and CC endomorphin (PubMed:12589820, PubMed:7891175, PubMed:7905839, CC PubMed:10529478, PubMed:7957926, PubMed:9689128). Receptor for natural CC and synthetic opioids including morphine, heroin, DAMGO, fentanyl, CC etorphine, buprenorphin and methadone (PubMed:12589820, PubMed:7891175, CC PubMed:7905839, PubMed:7957926, PubMed:10529478, PubMed:9689128, CC PubMed:10836142, PubMed:19300905). Also activated by enkephalin CC peptides, such as Met-enkephalin or Met-enkephalin-Arg-Phe, with higher CC affinity for Met-enkephalin-Arg-Phe (By similarity). Agonist binding to CC the receptor induces coupling to an inactive GDP-bound heterotrimeric CC G-protein complex and subsequent exchange of GDP for GTP in the G- CC protein alpha subunit leading to dissociation of the G-protein complex CC with the free GTP-bound G-protein alpha and the G-protein beta-gamma CC dimer activating downstream cellular effectors (PubMed:7905839). 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:12068084). 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 (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 (By similarity). Phosphorylation by members of the CC GPRK subfamily of Ser/Thr protein kinases and association with beta- CC arrestins is involved in short-term receptor desensitization (By CC similarity). Beta-arrestins associate with the GPRK-phosphorylated CC receptor and uncouple it from the G-protein thus terminating signal CC transduction (By similarity). The phosphorylated receptor is CC internalized through endocytosis via clathrin-coated pits which CC involves beta-arrestins (By similarity). The activation of the ERK CC pathway occurs either in a G-protein-dependent or a beta-arrestin- CC dependent manner and is regulated by agonist-specific receptor CC phosphorylation (By similarity). Acts as a class A G-protein coupled CC receptor (GPCR) which dissociates from beta-arrestin at or near the CC plasma membrane and undergoes rapid recycling (By similarity). Receptor CC down-regulation pathways are varying with the agonist and occur CC dependent or independent of G-protein coupling (By similarity). 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:10529478, ECO:0000269|PubMed:12068084, CC ECO:0000269|PubMed:12589820, ECO:0000269|PubMed:7891175, CC ECO:0000269|PubMed:7905839, ECO:0000269|PubMed:7957926, CC ECO:0000269|PubMed:9689128, ECO:0000303|PubMed:10836142, CC ECO:0000303|PubMed:19300905}. CC -!- FUNCTION: [Isoform 12]: Couples to GNAS and is proposed to be involved CC in excitatory effects. {ECO:0000269|PubMed:20525224}. CC -!- FUNCTION: [Isoform 16]: Does not bind agonists but may act through CC oligomerization with binding-competent OPRM1 isoforms and reduce their CC ligand binding activity. {ECO:0000269|PubMed:16580639}. CC -!- FUNCTION: [Isoform 17]: Does not bind agonists but may act through CC oligomerization with binding-competent OPRM1 isoforms and reduce their CC ligand binding activity. {ECO:0000269|PubMed:16580639}. 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:12413885, PubMed:15778451, PubMed:15967873, CC PubMed:17224450). 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 (By similarity). Interacts with PPL; the interaction CC disrupts agonist-mediated G-protein activation (PubMed:12810704). CC Interacts (via C-terminus) with DNAJB4 (via C-terminus) CC (PubMed:16542645). Interacts with calmodulin; the interaction inhibits CC the constitutive activity of OPRM1; it abolishes basal and attenuates CC agonist-stimulated G-protein coupling (PubMed:10419536, CC PubMed:10899953). Interacts with FLNA, PLD2, RANBP9 and WLS and GPM6A CC (PubMed:12519790, PubMed:14573758, PubMed:19788913, PubMed:20214800). CC Interacts with RTP4 (By similarity). Interacts with SYP and GNAS (By CC similarity). Interacts with RGS9, RGS17, RGS20, RGS4, PPP1R9B and HINT1 CC (By similarity). {ECO:0000250|UniProtKB:P33535, CC ECO:0000250|UniProtKB:P42866, ECO:0000269|PubMed:10419536, CC ECO:0000269|PubMed:10899953, ECO:0000269|PubMed:12413885, CC ECO:0000269|PubMed:12519790, ECO:0000269|PubMed:12810704, CC ECO:0000269|PubMed:14573758, ECO:0000269|PubMed:15778451, CC ECO:0000269|PubMed:15967873, ECO:0000269|PubMed:16542645, CC ECO:0000269|PubMed:17224450, ECO:0000269|PubMed:19788913, CC ECO:0000269|PubMed:20214800}. CC -!- INTERACTION: CC P35372; Q9Y679: AUP1; NbExp=4; IntAct=EBI-2624570, EBI-1058701; CC P35372; Q92905: COPS5; NbExp=5; IntAct=EBI-2624570, EBI-594661; CC P35372; Q8TEW6: DOK4; NbExp=4; IntAct=EBI-2624570, EBI-6918542; CC P35372; P21333: FLNA; NbExp=5; IntAct=EBI-2624570, EBI-350432; CC P35372; P35212: GJA4; NbExp=3; IntAct=EBI-2624570, EBI-6918707; CC P35372; Q9H3P2: NELFA; NbExp=2; IntAct=EBI-2624570, EBI-5461341; CC P35372; PRO_0000008243 [P01210]: PENK; NbExp=3; IntAct=EBI-2624570, EBI-6656055; CC P35372; Q96S59: RANBP9; NbExp=5; IntAct=EBI-2624570, EBI-636085; CC P35372; Q8IUQ4: SIAH1; NbExp=4; IntAct=EBI-2624570, EBI-747107; CC P35372; O43255: SIAH2; NbExp=3; IntAct=EBI-2624570, EBI-948141; CC P35372; Q9P0L0: VAPA; NbExp=4; IntAct=EBI-2624570, EBI-1059156; CC P35372; Q5T9L3: WLS; NbExp=11; IntAct=EBI-2624570, EBI-2868748; CC P35372; Q15942: ZYX; NbExp=2; IntAct=EBI-2624570, EBI-444225; CC P35372-10; Q08AM2: ADAM33; NbExp=3; IntAct=EBI-12807478, EBI-10225815; CC P35372-10; P20292: ALOX5AP; NbExp=3; IntAct=EBI-12807478, EBI-3904621; CC P35372-10; P27449: ATP6V0C; NbExp=3; IntAct=EBI-12807478, EBI-721179; CC P35372-10; O15342: ATP6V0E1; NbExp=3; IntAct=EBI-12807478, EBI-12935759; CC P35372-10; O14523: C2CD2L; NbExp=3; IntAct=EBI-12807478, EBI-12822627; CC P35372-10; Q9P0B6: CCDC167; NbExp=3; IntAct=EBI-12807478, EBI-9083477; CC P35372-10; Q8IX05: CD302; NbExp=3; IntAct=EBI-12807478, EBI-14259393; CC P35372-10; P51798: CLCN7; NbExp=3; IntAct=EBI-12807478, EBI-4402346; CC P35372-10; P78369: CLDN10; NbExp=3; IntAct=EBI-12807478, EBI-13372810; CC P35372-10; Q8N7P3: CLDN22; NbExp=3; IntAct=EBI-12807478, EBI-17766761; CC P35372-10; P56748: CLDN8; NbExp=3; IntAct=EBI-12807478, EBI-10215641; CC P35372-10; Q2HXU8-2: CLEC12B; NbExp=3; IntAct=EBI-12807478, EBI-12811991; CC P35372-10; Q9BXN2-6: CLEC7A; NbExp=3; IntAct=EBI-12807478, EBI-11989440; CC P35372-10; O95406: CNIH1; NbExp=3; IntAct=EBI-12807478, EBI-12172273; CC P35372-10; Q4LDR2: CTXN3; NbExp=3; IntAct=EBI-12807478, EBI-12019274; CC P35372-10; P49447: CYB561; NbExp=3; IntAct=EBI-12807478, EBI-8646596; CC P35372-10; Q08426: EHHADH; NbExp=3; IntAct=EBI-12807478, EBI-2339219; CC P35372-10; P54849: EMP1; NbExp=3; IntAct=EBI-12807478, EBI-4319440; CC P35372-10; P54852: EMP3; NbExp=3; IntAct=EBI-12807478, EBI-3907816; CC P35372-10; Q01628: IFITM3; NbExp=3; IntAct=EBI-12807478, EBI-7932862; CC P35372-10; O43561-2: LAT; NbExp=3; IntAct=EBI-12807478, EBI-8070286; CC P35372-10; Q9UBY5: LPAR3; NbExp=3; IntAct=EBI-12807478, EBI-12033434; CC P35372-10; Q8N386: LRRC25; NbExp=3; IntAct=EBI-12807478, EBI-11304917; CC P35372-10; P21145: MAL; NbExp=3; IntAct=EBI-12807478, EBI-3932027; CC P35372-10; Q13021: MALL; NbExp=3; IntAct=EBI-12807478, EBI-750078; CC P35372-10; Q9H492: MAP1LC3A; NbExp=3; IntAct=EBI-12807478, EBI-720768; CC P35372-10; Q9BXW4: MAP1LC3C; NbExp=3; IntAct=EBI-12807478, EBI-2603996; CC P35372-10; Q9GZY8-5: MFF; NbExp=3; IntAct=EBI-12807478, EBI-11956541; CC P35372-10; P42857: NSG1; NbExp=3; IntAct=EBI-12807478, EBI-6380741; CC P35372-10; Q8IV08: PLD3; NbExp=3; IntAct=EBI-12807478, EBI-2689908; CC P35372-10; Q01453: PMP22; NbExp=3; IntAct=EBI-12807478, EBI-2845982; CC P35372-10; Q9NS64: RPRM; NbExp=3; IntAct=EBI-12807478, EBI-1052363; CC P35372-10; O95968: SCGB1D1; NbExp=3; IntAct=EBI-12807478, EBI-12825395; CC P35372-10; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-12807478, EBI-8652744; CC P35372-10; Q8N6R1: SERP2; NbExp=3; IntAct=EBI-12807478, EBI-749270; CC P35372-10; Q9BRI3: SLC30A2; NbExp=3; IntAct=EBI-12807478, EBI-8644112; CC P35372-10; Q9NVC3: SLC38A7; NbExp=3; IntAct=EBI-12807478, EBI-10314552; CC P35372-10; Q8IVJ1: SLC41A1; NbExp=3; IntAct=EBI-12807478, EBI-12266234; CC P35372-10; Q0VAQ4: SMAGP; NbExp=3; IntAct=EBI-12807478, EBI-10226799; CC P35372-10; Q9Y6I9: TEX264; NbExp=3; IntAct=EBI-12807478, EBI-10329860; CC P35372-10; P48230: TM4SF4; NbExp=3; IntAct=EBI-12807478, EBI-8650934; CC P35372-10; P55061: TMBIM6; NbExp=3; IntAct=EBI-12807478, EBI-1045825; CC P35372-10; Q5W0B7: TMEM236; NbExp=3; IntAct=EBI-12807478, EBI-13378608; CC P35372-10; A5PKU2: TUSC5; NbExp=3; IntAct=EBI-12807478, EBI-11988865; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10529478, CC ECO:0000269|PubMed:12589820, ECO:0000269|PubMed:16580639, CC ECO:0000269|PubMed:7891175, ECO:0000269|PubMed:7905839, CC ECO:0000269|PubMed:7957926, ECO:0000269|PubMed:9689128}; Multi-pass CC membrane protein {ECO:0000269|PubMed:16580639}. 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 -!- SUBCELLULAR LOCATION: [Isoform 12]: Cytoplasm CC {ECO:0000269|PubMed:20525224}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=18; CC Comment=Additional isoforms seem to exist.; CC Name=1; CC IsoId=P35372-1; Sequence=Displayed; CC Name=2; Synonyms=MOR1A, MOR-1A; CC IsoId=P35372-2; Sequence=VSP_001896; CC Name=3; Synonyms=MOR-1R, MOR-1X; CC IsoId=P35372-3; Sequence=VSP_037695; CC Name=4; Synonyms=MOR-1B3; CC IsoId=P35372-4; Sequence=VSP_037696; CC Name=5; Synonyms=MOR-1C, MOR-1O; CC IsoId=P35372-5; Sequence=VSP_037697; CC Name=6; Synonyms=MOR-1V, MOR-1Y, MOR-1Y2, MOR-1Y3; CC IsoId=P35372-6; Sequence=VSP_037698; CC Name=7; Synonyms=MOR-1B1; CC IsoId=P35372-7; Sequence=VSP_037699; CC Name=8; Synonyms=MOR-1B2; CC IsoId=P35372-8; Sequence=VSP_037700; CC Name=9; Synonyms=MOR-1B5; CC IsoId=P35372-9; Sequence=VSP_037701; CC Name=10; Synonyms=MOR-1i; CC IsoId=P35372-10; Sequence=VSP_037693; CC Name=11; Synonyms=MOR-1B4; CC IsoId=P35372-11; Sequence=VSP_037694; CC Name=12; Synonyms=MOR-1G1, MOR-1K; CC IsoId=P35372-12; Sequence=VSP_042327; CC Name=13; Synonyms=MOR-1G2; CC IsoId=P35372-13; Sequence=VSP_042328; CC Name=14; Synonyms=Mu3; CC IsoId=P35372-14; Sequence=VSP_042327, VSP_042331; CC Name=15; Synonyms=MOR-1W; CC IsoId=P35372-15; Sequence=VSP_042327, VSP_001896; CC Name=16; Synonyms=SV1; CC IsoId=P35372-16; Sequence=VSP_042330; CC Name=17; Synonyms=SV2; CC IsoId=P35372-17; Sequence=VSP_042329; CC Name=18; Synonyms=hMOR-1Z; CC IsoId=P35372-18; Sequence=VSP_047577, VSP_047578; CC -!- TISSUE SPECIFICITY: Expressed in brain. Isoform 16 and isoform 17 are CC detected in brain. {ECO:0000269|PubMed:16580639}. 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-168 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-377 is involved in G-protein-dependent but not CC beta-arrestin-dependent activation of the ERK pathway (By similarity). 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:0000250|UniProtKB:P42866}. CC -!- POLYMORPHISM: Variant Asp-40 does not show altered binding affinities CC for most opioid peptides and alkaloids tested, but it binds beta- CC endorphin, an endogenous opioid that activates the mu opioid receptor, CC approximately 3 times more tightly than the most common allelic form. CC {ECO:0000269|PubMed:9689128}. CC -!- MISCELLANEOUS: OPRM1 is the main physiological target for most CC clinically important opioid analgesics. OPRM1-mediated inhibition of CC voltage-gated calcium channels on central presynaptic terminals of CC primary afferent nociceptors is thought to be one of the primary CC mechanisms mediating analgesia at the spinal level. Opioid-induced CC hyperalgesic responses are observed following both acute and chronic CC dosing associated with cellular excitation. CC -!- MISCELLANEOUS: [Isoform 6]: May be produced at very low levels due to a CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA CC decay. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. CC {ECO:0000255|PROSITE-ProRule:PRU00521}. CC -!- SEQUENCE CAUTION: CC Sequence=EAW47705.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Mu opioid receptor entry; CC URL="https://en.wikipedia.org/wiki/Mu_opioid_receptor"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/oprm1/"; 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; L25119; AAA20580.1; -; mRNA. DR EMBL; U12569; AAB60354.1; -; mRNA. DR EMBL; L29301; AAA73958.1; -; mRNA. DR EMBL; AY036622; AAK74189.1; -; mRNA. DR EMBL; AY036623; AAK74190.1; -; mRNA. DR EMBL; AY195733; AAO21305.1; -; mRNA. DR EMBL; AY225404; AAP44727.1; -; mRNA. DR EMBL; AY309001; AAQ77385.1; -; mRNA. DR EMBL; AY309005; AAQ77389.1; -; mRNA. DR EMBL; AY309006; AAQ77390.1; -; mRNA. DR EMBL; AY309007; AAQ77391.1; -; mRNA. DR EMBL; AY309008; AAQ77392.1; -; mRNA. DR EMBL; AY309009; AAQ77393.1; -; mRNA. DR EMBL; EU340241; ACA49726.1; -; mRNA. DR EMBL; EU340242; ACA49727.1; -; mRNA. DR EMBL; EU340243; ACA49728.1; -; mRNA. DR EMBL; AY364230; AAR12887.1; -; mRNA. DR EMBL; AY364890; AAR11568.1; -; mRNA. DR EMBL; HQ699462; AET97615.1; -; mRNA. DR EMBL; EU360599; ABY61366.1; -; mRNA. DR EMBL; EU362990; ABY66530.1; -; mRNA. DR EMBL; AK313901; BAG36624.1; -; mRNA. DR EMBL; AY521028; AAS00462.1; -; mRNA. DR EMBL; AY587764; AAS83107.1; -; Genomic_DNA. DR EMBL; FJ041292; ACM90350.1; -; mRNA. DR EMBL; FJ041293; ACM90351.1; -; mRNA. DR EMBL; FJ041294; ACM90352.1; -; mRNA. DR EMBL; AL132774; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL136444; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL445220; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471051; EAW47705.1; ALT_INIT; Genomic_DNA. DR EMBL; BC074927; AAH74927.1; -; mRNA. DR EMBL; AY292290; AAP44409.1; -; Genomic_DNA. DR EMBL; AY292291; AAP44410.1; -; Genomic_DNA. DR EMBL; AF153500; AAD44318.1; -; Genomic_DNA. DR CCDS; CCDS43517.1; -. [P35372-5] DR CCDS; CCDS43518.1; -. [P35372-3] DR CCDS; CCDS47503.1; -. [P35372-10] DR CCDS; CCDS47504.1; -. [P35372-7] DR CCDS; CCDS47505.1; -. [P35372-8] DR CCDS; CCDS47506.1; -. [P35372-4] DR CCDS; CCDS47507.1; -. [P35372-9] DR CCDS; CCDS47508.1; -. [P35372-2] DR CCDS; CCDS55068.1; -. [P35372-13] DR CCDS; CCDS55069.1; -. [P35372-11] DR CCDS; CCDS55070.1; -. [P35372-1] DR CCDS; CCDS55071.1; -. [P35372-12] DR PIR; I56553; I56553. DR PIR; S65693; S65693. DR RefSeq; NP_000905.3; NM_000914.4. [P35372-1] DR RefSeq; NP_001008503.2; NM_001008503.2. [P35372-5] DR RefSeq; NP_001008504.2; NM_001008504.3. [P35372-2] DR RefSeq; NP_001008505.2; NM_001008505.2. [P35372-3] DR RefSeq; NP_001138751.1; NM_001145279.3. [P35372-10] DR RefSeq; NP_001138752.1; NM_001145280.3. [P35372-12] DR RefSeq; NP_001138753.1; NM_001145281.2. [P35372-13] DR RefSeq; NP_001138754.1; NM_001145282.2. [P35372-7] DR RefSeq; NP_001138755.1; NM_001145283.2. [P35372-8] DR RefSeq; NP_001138756.1; NM_001145284.3. [P35372-4] DR RefSeq; NP_001138757.1; NM_001145285.2. [P35372-11] DR RefSeq; NP_001138758.1; NM_001145286.2. [P35372-9] DR RefSeq; NP_001138759.1; NM_001145287.2. [P35372-12] DR RefSeq; NP_001272452.1; NM_001285523.2. DR RefSeq; NP_001272453.1; NM_001285524.1. [P35372-10] DR RefSeq; NP_001272455.1; NM_001285526.1. [P35372-12] DR RefSeq; NP_001272456.1; NM_001285527.1. [P35372-15] DR RefSeq; NP_001272457.1; NM_001285528.2. [P35372-14] DR RefSeq; XP_016866395.1; XM_017010906.1. DR PDB; 8EF5; EM; 3.30 A; M/R=2-368. DR PDB; 8EF6; EM; 3.20 A; M/R=2-368. DR PDB; 8EFB; EM; 3.20 A; R=2-368. DR PDB; 8EFL; EM; 3.20 A; M/R=2-368. DR PDB; 8EFO; EM; 2.80 A; M/R=2-368. DR PDB; 8EFQ; EM; 3.30 A; R=2-368. DR PDB; 8F7Q; EM; 3.22 A; M/R=2-388. DR PDB; 8F7R; EM; 3.28 A; M/R=2-388. DR PDBsum; 8EF5; -. DR PDBsum; 8EF6; -. DR PDBsum; 8EFB; -. DR PDBsum; 8EFL; -. DR PDBsum; 8EFO; -. DR PDBsum; 8EFQ; -. DR PDBsum; 8F7Q; -. DR PDBsum; 8F7R; -. DR AlphaFoldDB; P35372; -. DR EMDB; EMD-28066; -. DR EMDB; EMD-28069; -. DR EMDB; EMD-28077; -. DR EMDB; EMD-28085; -. DR EMDB; EMD-28086; -. DR EMDB; EMD-28088; -. DR EMDB; EMD-28909; -. DR SMR; P35372; -. DR BioGRID; 111033; 137. DR IntAct; P35372; 123. DR MINT; P35372; -. DR STRING; 9606.ENSP00000394624; -. DR BindingDB; P35372; -. DR ChEMBL; CHEMBL233; -. DR DrugBank; DB01571; 3-Methylfentanyl. DR DrugBank; DB01439; 3-Methylthiofentanyl. DR DrugBank; DB00802; Alfentanil. DR DrugBank; DB06274; Alvimopan. DR DrugBank; DB06288; Amisulpride. DR DrugBank; DB00321; Amitriptyline. DR DrugBank; DB00913; Anileridine. DR DrugBank; DB01238; Aripiprazole. DR DrugBank; DB00921; Buprenorphine. DR DrugBank; DB00611; Butorphanol. DR DrugBank; DB09173; Butyrfentanyl. DR DrugBank; DB09061; Cannabidiol. DR DrugBank; DB01535; Carfentanil. DR DrugBank; DB00318; Codeine. DR DrugBank; DB00514; Dextromethorphan. DR DrugBank; DB00647; Dextropropoxyphene. DR DrugBank; DB01209; Dezocine. DR DrugBank; DB01452; Diamorphine. DR DrugBank; DB01565; Dihydromorphine. DR DrugBank; DB01444; Dimethylthiambutene. DR DrugBank; DB01081; Diphenoxylate. DR DrugBank; DB01548; Diprenorphine. DR DrugBank; DB09272; Eluxadoline. DR DrugBank; DB05492; Epicept NP-1. DR DrugBank; DB01466; Ethylmorphine. DR DrugBank; DB01497; Etorphine. DR DrugBank; DB00813; Fentanyl. DR DrugBank; DB00956; Hydrocodone. DR DrugBank; DB00327; Hydromorphone. DR DrugBank; DB01221; Ketamine. DR DrugBank; DB06738; Ketobemidone. DR DrugBank; DB01227; Levacetylmethadol. DR DrugBank; DB00504; Levallorphan. DR DrugBank; DB00854; Levorphanol. DR DrugBank; DB05509; LI-301. DR DrugBank; DB00836; Loperamide. DR DrugBank; DB14146; Loxicodegol. DR DrugBank; DB14009; Medical Cannabis. DR DrugBank; DB00454; Meperidine. DR DrugBank; DB12668; Metenkefalin. DR DrugBank; DB00333; Methadone. DR DrugBank; DB01433; Methadyl acetate. DR DrugBank; DB06800; Methylnaltrexone. DR DrugBank; DB00295; Morphine. DR DrugBank; DB06409; Morphine glucuronide. DR DrugBank; DB14011; Nabiximols. DR DrugBank; DB00844; Nalbuphine. DR DrugBank; DB11691; Naldemedine. DR DrugBank; DB06230; Nalmefene. DR DrugBank; DB09049; Naloxegol. DR DrugBank; DB01183; Naloxone. DR DrugBank; DB00704; Naltrexone. DR DrugBank; DB14881; Oliceridine. DR DrugBank; DB00904; Ondansetron. DR DrugBank; DB11130; Opium. DR DrugBank; DB00497; Oxycodone. DR DrugBank; DB01192; Oxymorphone. DR DrugBank; DB00652; Pentazocine. DR DrugBank; DB11186; Pentoxyverine. DR DrugBank; DB09209; Pholcodine. DR DrugBank; DB00899; Remifentanil. DR DrugBank; DB12543; Samidorphan. DR DrugBank; DB00708; Sufentanil. DR DrugBank; DB06204; Tapentadol. DR DrugBank; DB09289; Tianeptine. DR DrugBank; DB00193; Tramadol. DR DrugBank; DB09089; Trimebutine. DR DrugBank; DB05046; V1003. DR DrugCentral; P35372; -. DR GuidetoPHARMACOLOGY; 319; -. DR TCDB; 9.A.14.13.18; the g-protein-coupled receptor (gpcr) family. DR GlyCosmos; P35372; 5 sites, No reported glycans. DR GlyGen; P35372; 5 sites. DR iPTMnet; P35372; -. DR PhosphoSitePlus; P35372; -. DR SwissPalm; P35372; -. DR BioMuta; OPRM1; -. DR DMDM; 2851402; -. DR MassIVE; P35372; -. DR PaxDb; 9606-ENSP00000394624; -. DR PeptideAtlas; P35372; -. DR ProteomicsDB; 55039; -. [P35372-10] DR Antibodypedia; 2929; 659 antibodies from 40 providers. DR DNASU; 4988; -. DR Ensembl; ENST00000229768.9; ENSP00000229768.5; ENSG00000112038.18. [P35372-3] DR Ensembl; ENST00000330432.12; ENSP00000328264.7; ENSG00000112038.18. [P35372-1] DR Ensembl; ENST00000337049.8; ENSP00000338381.4; ENSG00000112038.18. [P35372-5] DR Ensembl; ENST00000414028.6; ENSP00000399359.2; ENSG00000112038.18. [P35372-4] DR Ensembl; ENST00000419506.6; ENSP00000403549.2; ENSG00000112038.18. [P35372-9] DR Ensembl; ENST00000428397.6; ENSP00000411903.2; ENSG00000112038.18. [P35372-2] DR Ensembl; ENST00000434900.6; ENSP00000394624.2; ENSG00000112038.18. [P35372-10] DR Ensembl; ENST00000435918.6; ENSP00000413752.2; ENSG00000112038.18. [P35372-8] DR Ensembl; ENST00000452687.6; ENSP00000410497.2; ENSG00000112038.18. [P35372-7] DR Ensembl; ENST00000518759.5; ENSP00000430260.1; ENSG00000112038.18. [P35372-13] DR Ensembl; ENST00000519083.5; ENSP00000431048.1; ENSG00000112038.18. [P35372-6] DR Ensembl; ENST00000520708.5; ENSP00000430876.1; ENSG00000112038.18. [P35372-12] DR Ensembl; ENST00000522236.1; ENSP00000429373.1; ENSG00000112038.18. [P35372-12] DR Ensembl; ENST00000522555.5; ENSP00000429719.1; ENSG00000112038.18. [P35372-12] DR Ensembl; ENST00000522739.5; ENSP00000428018.1; ENSG00000112038.18. [P35372-6] DR Ensembl; ENST00000524150.2; ENSP00000430575.1; ENSG00000112038.18. [P35372-18] DR Ensembl; ENST00000524163.5; ENSP00000430097.1; ENSG00000112038.18. [P35372-11] DR GeneID; 4988; -. DR KEGG; hsa:4988; -. DR MANE-Select; ENST00000330432.12; ENSP00000328264.7; NM_000914.5; NP_000905.3. DR UCSC; uc003qpn.4; human. [P35372-1] DR AGR; HGNC:8156; -. DR CTD; 4988; -. DR DisGeNET; 4988; -. DR GeneCards; OPRM1; -. DR HGNC; HGNC:8156; OPRM1. DR HPA; ENSG00000112038; Tissue enhanced (brain, testis). DR MIM; 600018; gene. DR neXtProt; NX_P35372; -. DR OpenTargets; ENSG00000112038; -. DR PharmGKB; PA31945; -. DR VEuPathDB; HostDB:ENSG00000112038; -. DR eggNOG; KOG3656; Eukaryota. DR GeneTree; ENSGT00940000158236; -. DR HOGENOM; CLU_009579_8_1_1; -. DR InParanoid; P35372; -. DR OMA; CGNFTDN; -. DR OrthoDB; 5393360at2759; -. DR PhylomeDB; P35372; -. DR TreeFam; TF315737; -. DR PathwayCommons; P35372; -. DR Reactome; R-HSA-111885; Opioid Signalling. DR Reactome; R-HSA-202040; G-protein activation. DR Reactome; R-HSA-375276; Peptide ligand-binding receptors. DR Reactome; R-HSA-418594; G alpha (i) signalling events. DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling. DR Reactome; R-HSA-9022699; MECP2 regulates neuronal receptors and channels. DR SignaLink; P35372; -. DR SIGNOR; P35372; -. DR BioGRID-ORCS; 4988; 11 hits in 1151 CRISPR screens. DR ChiTaRS; OPRM1; human. DR GeneWiki; %CE%9C-opioid_receptor; -. DR GenomeRNAi; 4988; -. DR Pharos; P35372; Tclin. DR PRO; PR:P35372; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; P35372; Protein. DR Bgee; ENSG00000112038; Expressed in primordial germ cell in gonad and 54 other cell types or tissues. DR ExpressionAtlas; P35372; baseline and differential. DR GO; GO:0030424; C:axon; ISS:UniProtKB. DR GO; GO:0030425; C:dendrite; ISS:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; TAS:ProtInc. DR GO; GO:0005768; C:endosome; ISS:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; TAS:ProtInc. DR GO; GO:0043005; C:neuron projection; IBA:GO_Central. DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0045202; C:synapse; IEA:GOC. DR GO; GO:0004979; F:beta-endorphin receptor activity; IMP:UniProtKB. DR GO; GO:0004930; F:G protein-coupled receptor activity; ISS:UniProtKB. DR GO; GO:0001965; F:G-protein alpha-subunit binding; IDA:UniProtKB. DR GO; GO:0031681; F:G-protein beta-subunit binding; IBA:GO_Central. DR GO; GO:0038047; F:morphine receptor activity; ISS:UniProtKB. DR GO; GO:0042923; F:neuropeptide binding; IBA:GO_Central. DR GO; GO:0005245; F:voltage-gated calcium channel activity; ISS:UniProtKB. DR GO; GO:0007197; P:adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0048149; P:behavioral response to ethanol; IMP:UniProtKB. DR GO; GO:0038003; P:G protein-coupled opioid receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0007187; P:G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; TAS:ProtInc. DR GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; IDA:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:ProtInc. DR GO; GO:0051481; P:negative regulation of cytosolic calcium ion concentration; IDA:UniProtKB. DR GO; GO:0045019; P:negative regulation of nitric oxide biosynthetic process; IDA:UniProtKB. DR GO; GO:0061358; P:negative regulation of Wnt protein secretion; IMP: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:0043950; P:positive regulation of cAMP-mediated signaling; IDA:UniProtKB. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:UniProtKB. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB. DR GO; GO:0050769; P:positive regulation of neurogenesis; ISS:UniProtKB. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IDA:UniProtKB. DR GO; GO:0080135; P:regulation of cellular response to stress; IMP:UniProtKB. DR GO; GO:2000310; P:regulation of NMDA receptor activity; ISS:UniProtKB. DR GO; GO:0007600; P:sensory perception; NAS:UniProtKB. DR GO; GO:0019233; P:sensory perception of pain; ISS:UniProtKB. DR CDD; cd15090; 7tmA_Mu_opioid_R; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR InterPro; IPR000105; Mu_opioid_rcpt. DR InterPro; IPR001418; Opioid_rcpt. DR PANTHER; PTHR24229:SF7; MU-TYPE OPIOID RECEPTOR; 1. DR PANTHER; PTHR24229; NEUROPEPTIDES RECEPTOR; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR00237; GPCRRHODOPSN. DR PRINTS; PR00537; MUOPIOIDR. DR PRINTS; PR00384; OPIOIDR. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1. DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1. DR Genevisible; P35372; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Cell projection; KW Cytoplasm; Disulfide bond; Endosome; G-protein coupled receptor; KW Glycoprotein; Lipoprotein; Membrane; Palmitate; Phosphoprotein; Receptor; KW Reference proteome; Transducer; Transmembrane; Transmembrane helix; KW Ubl conjugation. FT CHAIN 1..400 FT /note="Mu-type opioid receptor" FT /id="PRO_0000069972" FT TOPO_DOM 1..68 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TRANSMEM 69..93 FT /note="Helical; Name=1" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TOPO_DOM 94..106 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TRANSMEM 107..131 FT /note="Helical; Name=2" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TOPO_DOM 132..142 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TRANSMEM 143..165 FT /note="Helical; Name=3" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TOPO_DOM 166..185 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TRANSMEM 186..207 FT /note="Helical; Name=4" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TOPO_DOM 208..230 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TRANSMEM 231..255 FT /note="Helical; Name=5" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TOPO_DOM 256..279 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TRANSMEM 280..306 FT /note="Helical; Name=6" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TOPO_DOM 307..314 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TRANSMEM 315..338 FT /note="Helical; Name=7" FT /evidence="ECO:0000250|UniProtKB:P42866" FT TOPO_DOM 339..400 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P42866" FT MOTIF 334..338 FT /note="NPxxY; plays a role in stabilizing the activated FT conformation of the receptor" FT /evidence="ECO:0000250|UniProtKB:P42866" FT MOD_RES 168 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P33535" FT MOD_RES 365 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P42866" FT MOD_RES 372 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P33535" FT MOD_RES 377 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P33535" FT MOD_RES 396 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P33535" FT LIPID 353 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000255" FT CARBOHYD 9 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 12 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 33 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 40 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 48 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 142..219 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521" FT VAR_SEQ 1..100 FT /note="Missing (in isoform 12, isoform 14 and isoform 15)" FT /evidence="ECO:0000303|PubMed:12734358, FT ECO:0000303|PubMed:19077058, ECO:0000303|PubMed:19103668, FT ECO:0000303|Ref.8" FT /id="VSP_042327" FT VAR_SEQ 1..96 FT /note="MDSSAAPTNASNCTDALAYSSCSPAPSPGSWVNLSHLDGNLSDPCGPNRTDL FT GGRDSLCPPTGSPSMITAITIMALYSIVCVVGLFGNFLVMYVIV -> MMRAKSISTKA FT GKPS (in isoform 13)" FT /evidence="ECO:0000303|PubMed:19077058" FT /id="VSP_042328" FT VAR_SEQ 1 FT /note="M -> MCLHRRVPSEETYSLDRFAQNPPLFPPPSLPASESRMAHAPLLQRCG FT AARTGFCKKQQELWQRRKEAAEALGTRKVSVLLATSHSGARPAVSTM (in isoform FT 10)" FT /evidence="ECO:0000303|PubMed:19077058, ECO:0000303|Ref.14" FT /id="VSP_037693" FT VAR_SEQ 97..400 FT /note="RYTKMKTATNIYIFNLALADALATSTLPFQSVNYLMGTWPFGTILCKIVISI FT DYYNMFTSIFTLCTMSVDRYIAVCHPVKALDFRTPRNAKIINVCNWILSSAIGLPVMFM FT ATTKYRQGSIDCTLTFSHPTWYWENLLKICVFIFAFIMPVLIITVCYGLMILRLKSVRM FT LSGSKEKDRNLRRITRMVLVVVAVFIVCWTPIHIYVIIKALVTIPETTFQTVSWHFCIA FT LGYTNSCLNPVLYAFLDENFKRCFREFCIPTSSNIEQQNSTRIRQNTRDHPSTANTVDR FT TNHQLENLEAETAPLP -> SSSWF (in isoform 17)" FT /evidence="ECO:0000305" FT /id="VSP_042329" FT VAR_SEQ 98..400 FT /note="YTKMKTATNIYIFNLALADALATSTLPFQSVNYLMGTWPFGTILCKIVISID FT YYNMFTSIFTLCTMSVDRYIAVCHPVKALDFRTPRNAKIINVCNWILSSAIGLPVMFMA FT TTKYRQGSIDCTLTFSHPTWYWENLLKICVFIFAFIMPVLIITVCYGLMILRLKSVRML FT SGSKEKDRNLRRITRMVLVVVAVFIVCWTPIHIYVIIKALVTIPETTFQTVSWHFCIAL FT GYTNSCLNPVLYAFLDENFKRCFREFCIPTSSNIEQQNSTRIRQNTRDHPSTANTVDRT FT NHQLENLEAETAPLP -> YSWFVIGGPEGRRKQRRLGEDKRARGCGEKG (in FT isoform 16)" FT /evidence="ECO:0000305" FT /id="VSP_042330" FT VAR_SEQ 98..186 FT /note="YTKMKTATNIYIFNLALADALATSTLPFQSVNYLMGTWPFGTILCKIVISID FT YYNMFTSIFTLCTMSVDRYIAVCHPVKALDFRTPRNA -> FHRLYTNILSSNLVLGKP FT AEDLCFHLRLHYASAHHYRVLWTDDLAPQECPHALWLQRKGQESSKDHQDGAGGGGCVH FT RLLDSHSHLRHH (in isoform 18)" FT /evidence="ECO:0000303|Ref.9" FT /id="VSP_047577" FT VAR_SEQ 187..400 FT /note="Missing (in isoform 18)" FT /evidence="ECO:0000303|Ref.9" FT /id="VSP_047578" FT VAR_SEQ 389..400 FT /note="LENLEAETAPLP -> S (in isoform 11)" FT /evidence="ECO:0000303|PubMed:15893644" FT /id="VSP_037694" FT VAR_SEQ 389..400 FT /note="LENLEAETAPLP -> NYYIIHRCCCNTPLISQKPVLLWFCD (in FT isoform 14)" FT /evidence="ECO:0000303|PubMed:12734358" FT /id="VSP_042331" FT VAR_SEQ 389..400 FT /note="LENLEAETAPLP -> VRSL (in isoform 2 and isoform 15)" FT /evidence="ECO:0000303|PubMed:15893644, FT ECO:0000303|PubMed:7957926, ECO:0000303|Ref.8" FT /id="VSP_001896" FT VAR_SEQ 389..400 FT /note="LENLEAETAPLP -> CLPIPSLSCWALEQGCLVVYPGPLQGPLVRYDLPAI FT LHSSCLRGNTAPSPSGGAFLLS (in isoform 3)" FT /evidence="ECO:0000303|PubMed:12589820" FT /id="VSP_037695" FT VAR_SEQ 389..400 FT /note="LENLEAETAPLP -> GPPAKFVADQLAGSS (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15893644" FT /id="VSP_037696" FT VAR_SEQ 389..400 FT /note="LENLEAETAPLP -> PPLAVSMAQIFTRYPPPTHREKTCNDYMKR (in FT isoform 5)" FT /evidence="ECO:0000303|PubMed:12589820" FT /id="VSP_037697" FT VAR_SEQ 389..400 FT /note="LENLEAETAPLP -> IRDPISNLPRVSVF (in isoform 6)" FT /evidence="ECO:0000303|PubMed:15893644, ECO:0000303|Ref.14, FT ECO:0000303|Ref.8" FT /id="VSP_037698" FT VAR_SEQ 389..400 FT /note="LENLEAETAPLP -> KIDLFQKSSLLNCEHTKG (in isoform 7)" FT /evidence="ECO:0000303|PubMed:15893644" FT /id="VSP_037699" FT VAR_SEQ 389..400 FT /note="LENLEAETAPLP -> RERRQKSDW (in isoform 8)" FT /evidence="ECO:0000303|PubMed:15893644" FT /id="VSP_037700" FT VAR_SEQ 389..400 FT /note="LENLEAETAPLP -> VELNLDCHCENAKPWPLSYNAGQSPFPFPGRV (in FT isoform 9)" FT /evidence="ECO:0000303|PubMed:15893644" FT /id="VSP_037701" FT VARIANT 6 FT /note="A -> V (in dbSNP:rs1799972)" FT /evidence="ECO:0000269|PubMed:9399694, FT ECO:0000269|PubMed:9689128, ECO:0000269|Ref.13, FT ECO:0000269|Ref.18" FT /id="VAR_009525" FT VARIANT 40 FT /note="N -> D (in dbSNP:rs1799971)" FT /evidence="ECO:0000269|PubMed:7957926, FT ECO:0000269|PubMed:9399694, ECO:0000269|PubMed:9689128, FT ECO:0000269|Ref.13" FT /id="VAR_009524" FT VARIANT 63 FT /note="G -> V (in dbSNP:rs9282817)" FT /id="VAR_049426" FT VARIANT 66 FT /note="S -> F (in dbSNP:rs9282819)" FT /id="VAR_049427" FT VARIANT 147 FT /note="S -> C (in dbSNP:rs17174794)" FT /evidence="ECO:0000269|PubMed:9399694, ECO:0000269|Ref.13" FT /id="VAR_009526" FT VARIANT 152 FT /note="N -> D (in dbSNP:rs17174801)" FT /evidence="ECO:0000269|Ref.13" FT /id="VAR_019252" FT VARIANT 260 FT /note="R -> H (in dbSNP:rs1799974)" FT /evidence="ECO:0000269|PubMed:9689128" FT /id="VAR_009527" FT VARIANT 265 FT /note="R -> C (in dbSNP:rs17174822)" FT /evidence="ECO:0000269|Ref.13" FT /id="VAR_019253" FT VARIANT 274 FT /note="D -> N (in dbSNP:rs17174829)" FT /evidence="ECO:0000269|Ref.13" FT /id="VAR_019254" FT VARIANT 388..400 FT /note="Missing" FT /evidence="ECO:0000269|PubMed:15893644" FT /id="VAR_082952" FT MUTAGEN 142 FT /note="C->A,S: Abolishes ligand binding; when associated FT with A-219 or S-219." FT /evidence="ECO:0000269|PubMed:10529478" FT MUTAGEN 219 FT /note="C->A,S: Abolishes ligand binding; when associated FT with A-142 or S-142." FT /evidence="ECO:0000269|PubMed:10529478" FT MUTAGEN 273 FT /note="K->A: Impairs interaction with calmodulin." FT /evidence="ECO:0000269|PubMed:10419536, FT ECO:0000269|PubMed:10899953" FT MUTAGEN 275 FT /note="R->A: Impairs interaction with calmodulin." FT /evidence="ECO:0000269|PubMed:10899953" FT CONFLICT 26 FT /note="P -> L (in Ref. 11; BAG36624)" FT /evidence="ECO:0000305" FT CONFLICT 51 FT /note="D -> N (in Ref. 1; AAA20580)" FT /evidence="ECO:0000305" FT CONFLICT 109 FT /note="I -> V (in Ref. 6; AAQ77391)" FT /evidence="ECO:0000305" FT CONFLICT 207 FT /note="M -> I (in Ref. 2; AAB60354)" FT /evidence="ECO:0000305" FT CONFLICT 234 FT /note="L -> V (in Ref. 1; AAA20580)" FT /evidence="ECO:0000305" FT HELIX 68..97 FT /evidence="ECO:0007829|PDB:8EFO" FT TURN 98..101 FT /evidence="ECO:0007829|PDB:8EFO" FT HELIX 104..132 FT /evidence="ECO:0007829|PDB:8EFO" FT HELIX 139..172 FT /evidence="ECO:0007829|PDB:8EFO" FT HELIX 174..180 FT /evidence="ECO:0007829|PDB:8EFO" FT HELIX 183..207 FT /evidence="ECO:0007829|PDB:8EFO" FT STRAND 208..213 FT /evidence="ECO:0007829|PDB:8EFO" FT STRAND 216..221 FT /evidence="ECO:0007829|PDB:8EFO" FT HELIX 227..242 FT /evidence="ECO:0007829|PDB:8EFO" FT HELIX 244..263 FT /evidence="ECO:0007829|PDB:8EFO" FT TURN 265..267 FT /evidence="ECO:0007829|PDB:8EFO" FT STRAND 268..270 FT /evidence="ECO:0007829|PDB:8EFO" FT HELIX 271..307 FT /evidence="ECO:0007829|PDB:8EFO" FT HELIX 314..338 FT /evidence="ECO:0007829|PDB:8EFO" FT TURN 339..341 FT /evidence="ECO:0007829|PDB:8EFO" FT HELIX 343..351 FT /evidence="ECO:0007829|PDB:8EFO" FT CONFLICT P35372-3:402 FT /note="Q -> H (in Ref. 4; AAK74189)" FT /evidence="ECO:0000305" FT VARIANT P35372-9:411..420 FT /note="Missing" FT /evidence="ECO:0000269|PubMed:15893644" FT /id="VAR_082953" SQ SEQUENCE 400 AA; 44779 MW; 1DABEBEC9AFF6F66 CRC64; MDSSAAPTNA SNCTDALAYS SCSPAPSPGS WVNLSHLDGN LSDPCGPNRT DLGGRDSLCP PTGSPSMITA ITIMALYSIV CVVGLFGNFL VMYVIVRYTK MKTATNIYIF NLALADALAT STLPFQSVNY LMGTWPFGTI LCKIVISIDY YNMFTSIFTL CTMSVDRYIA VCHPVKALDF RTPRNAKIIN VCNWILSSAI GLPVMFMATT KYRQGSIDCT LTFSHPTWYW ENLLKICVFI FAFIMPVLII TVCYGLMILR LKSVRMLSGS KEKDRNLRRI TRMVLVVVAV FIVCWTPIHI YVIIKALVTI PETTFQTVSW HFCIALGYTN SCLNPVLYAF LDENFKRCFR EFCIPTSSNI EQQNSTRIRQ NTRDHPSTAN TVDRTNHQLE NLEAETAPLP //