{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P35372","secondaryAccessions":["B0FXJ1","B2R9S7","B8Q1L7","B8Q1L8","B8Q1L9","E7EWZ3","G8XRH6","G8XRH8","Q12930","Q4VWM1","Q4VWM2","Q4VWM3","Q4VWM4","Q4VWM6","Q4VWX6","Q5TDA1","Q6UPP1","Q6UQ80","Q7Z2D8","Q86V80","Q8IWW3","Q8IWW4","Q9UCZ4","Q9UN57"],"uniProtkbId":"OPRM_HUMAN","entryAudit":{"firstPublicDate":"1994-06-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1998-07-15","entryVersion":227,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Mu-type opioid receptor"},"shortNames":[{"value":"M-OR-1"},{"value":"MOR-1"}]},"alternativeNames":[{"fullName":{"value":"Mu opiate receptor"}},{"fullName":{"value":"Mu opioid receptor"},"shortNames":[{"value":"MOP"},{"value":"hMOP"}]}]},"genes":[{"geneName":{"value":"OPRM1"},"synonyms":[{"value":"MOR1"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P33535"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10529478"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12068084"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12589820"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7891175"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7905839"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7957926"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9689128"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"10836142"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"19300905"}],"value":"Receptor for endogenous opioids such as beta-endorphin and endomorphin (PubMed:10529478, PubMed:12589820, PubMed:7891175, PubMed:7905839, PubMed:7957926, PubMed:9689128). Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone (PubMed:10529478, PubMed:10836142, PubMed:12589820, PubMed:19300905, PubMed:7891175, PubMed:7905839, PubMed:7957926, PubMed:9689128). Also activated by enkephalin peptides, such as Met-enkephalin or Met-enkephalin-Arg-Phe, with higher affinity for Met-enkephalin-Arg-Phe (By similarity). Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G protein complex and subsequent exchange of GDP for GTP in the G protein alpha subunit leading to dissociation of the G protein complex with the free GTP-bound G protein alpha and the G protein beta-gamma dimer activating downstream cellular effectors (PubMed:7905839). The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extent to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15 (PubMed:12068084). They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B (By similarity). Also couples to adenylate cyclase stimulatory G alpha proteins (By similarity). The selective temporal coupling to G proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4 (By similarity). Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization (By similarity). Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G protein thus terminating signal transduction (By similarity). The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins (By similarity). The activation of the ERK pathway occurs either in a G protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation (By similarity). Acts as a class A G protein-coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling (By similarity). Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G protein coupling (By similarity). Endogenous ligands induce rapid desensitization, endocytosis and recycling (By similarity). Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties (By similarity)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20525224"}],"value":"Couples to GNAS and is proposed to be involved in excitatory effects"}],"commentType":"FUNCTION","molecule":"Isoform 12"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16580639"}],"value":"Does not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity"}],"commentType":"FUNCTION","molecule":"Isoform 16"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16580639"}],"value":"Does not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity"}],"commentType":"FUNCTION","molecule":"Isoform 17"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P33535"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P42866"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10419536"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10899953"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12413885"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12519790"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12810704"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14573758"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15778451"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15967873"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16542645"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17224450"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19788913"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20214800"}],"value":"Forms homooligomers and heterooligomers with other GPCRs, such as OPRD1, OPRK1, OPRL1, NPFFR2, ADRA2A, SSTR2, CNR1 and CCR5 (probably in dimeric forms) (PubMed:12413885, PubMed:15778451, PubMed:15967873, PubMed:17224450). Interacts with heterotrimeric G proteins; interaction with a heterotrimeric complex containing GNAI1, GNB1 and GNG2 stabilizes the active conformation of the receptor and increases its affinity for endomorphin-2, the synthetic opioid peptide DAMGO and for morphinan agonists (By similarity). Interacts with PPL; the interaction disrupts agonist-mediated G protein activation (PubMed:12810704). Interacts (via C-terminus) with DNAJB4 (via C-terminus) (PubMed:16542645). Interacts with calmodulin; the interaction inhibits the constitutive activity of OPRM1; it abolishes basal and attenuates agonist-stimulated G protein coupling (PubMed:10419536, PubMed:10899953). Interacts with FLNA, PLD2, RANBP9 and WLS and GPM6A (PubMed:12519790, PubMed:14573758, PubMed:19788913, PubMed:20214800). Interacts with RTP4 (By similarity). Interacts with SYP and GNAS (By similarity). Interacts with RGS9, RGS17, RGS20, RGS4, PPP1R9B and HINT1 (By similarity). Interacts with SIGMAR1 (By similarity)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P35372","intActId":"EBI-2624570"},"interactantTwo":{"uniProtKBAccession":"Q9Y679","geneName":"AUP1","intActId":"EBI-1058701"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P35372","intActId":"EBI-2624570"},"interactantTwo":{"uniProtKBAccession":"Q92905","geneName":"COPS5","intActId":"EBI-594661"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P35372","intActId":"EBI-2624570"},"interactantTwo":{"uniProtKBAccession":"Q8TEW6","geneName":"DOK4","intActId":"EBI-6918542"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P35372","intActId":"EBI-2624570"},"interactantTwo":{"uniProtKBAccession":"P21333","geneName":"FLNA","intActId":"EBI-350432"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P35372","intActId":"EBI-2624570"},"interactantTwo":{"uniProtKBAccession":"P35212","geneName":"GJA4","intActId":"EBI-6918707"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P35372","intActId":"EBI-2624570"},"interactantTwo":{"uniProtKBAccession":"Q9H3P2","geneName":"NELFA","intActId":"EBI-5461341"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P35372","intActId":"EBI-2624570"},"interactantTwo":{"uniProtKBAccession":"P01210","geneName":"PENK","chainId":"PRO_0000008243","intActId":"EBI-6656055"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P35372","intActId":"EBI-2624570"},"interactantTwo":{"uniProtKBAccession":"O60894","geneName":"RAMP1","intActId":"EBI-962893"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P35372","intActId":"EBI-2624570"},"interactantTwo":{"uniProtKBAccession":"O60895","geneName":"RAMP2","intActId":"EBI-9009040"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P35372","intActId":"EBI-2624570"},"interactantTwo":{"uniProtKBAccession":"O60896","geneName":"RAMP3","intActId":"EBI-720447"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P35372","intActId":"EBI-2624570"},"interactantTwo":{"uniProtKBAccession":"Q96S59","geneName":"RANBP9","intActId":"EBI-636085"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P35372","intActId":"EBI-2624570"},"interactantTwo":{"uniProtKBAccession":"Q8IUQ4","geneName":"SIAH1","intActId":"EBI-747107"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P35372","intActId":"EBI-2624570"},"interactantTwo":{"uniProtKBAccession":"O43255","geneName":"SIAH2","intActId":"EBI-948141"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P35372","intActId":"EBI-2624570"},"interactantTwo":{"uniProtKBAccession":"Q9P0L0","geneName":"VAPA","intActId":"EBI-1059156"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P35372","intActId":"EBI-2624570"},"interactantTwo":{"uniProtKBAccession":"Q5T9L3","geneName":"WLS","intActId":"EBI-2868748"},"numberOfExperiments":11,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P35372","intActId":"EBI-2624570"},"interactantTwo":{"uniProtKBAccession":"Q15942","geneName":"ZYX","intActId":"EBI-444225"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P35372-10","intActId":"EBI-12807478"},"interactantTwo":{"uniProtKBAccession":"Q08AM2","geneName":"ADAM33","intActId":"EBI-10225815"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P35372-10","intActId":"EBI-12807478"},"interactantTwo":{"uniProtKBAccession":"P20292","geneName":"ALOX5AP","intActId":"EBI-3904621"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P35372-10","intActId":"EBI-12807478"},"interactantTwo":{"uniProtKBAccession":"P27449","geneName":"ATP6V0C","intActId":"EBI-721179"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P35372-10","intActId":"EBI-12807478"},"interactantTwo":{"uniProtKBAccession":"O15342","geneName":"ATP6V0E1","intActId":"EBI-12935759"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P35372-10","intActId":"EBI-12807478"},"interactantTwo":{"uniProtKBAccession":"O14523","geneName":"C2CD2L","intActId":"EBI-12822627"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P35372-10","intActId":"EBI-12807478"},"interactantTwo":{"uniProtKBAccession":"Q9P0B6","geneName":"CCDC167","intActId":"EBI-9083477"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P35372-10","intActId":"EBI-12807478"},"interactantTwo":{"uniProtKBAccessio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