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MGP002164

UniProt Annotations

Entry Information
Gene Nameopioid receptor, mu 1
Protein EntryOPRM_HUMAN
UniProt IDP35372
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=18; Comment=Additional isoforms seem to exist.; Name=1; IsoId=P35372-1; Sequence=Displayed; Name=2; Synonyms=MOR1A, MOR-1A; IsoId=P35372-2; Sequence=VSP_001896; Name=3; Synonyms=MOR-1R, MOR-1X; IsoId=P35372-3; Sequence=VSP_037695; Note=Ref.4 (AAK74189) sequence is in conflict in position: 402:Q->H. {ECO:0000305}; Name=4; Synonyms=MOR-1B3; IsoId=P35372-4; Sequence=VSP_037696; Name=5; Synonyms=MOR-1C, MOR-1O; IsoId=P35372-5; Sequence=VSP_037697; Name=6; Synonyms=MOR-1V, MOR-1Y, MOR-1Y2, MOR-1Y3; IsoId=P35372-6; Sequence=VSP_037698; Note=May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.; Name=7; Synonyms=MOR-1B1; IsoId=P35372-7; Sequence=VSP_037699; Name=8; Synonyms=MOR-1B2; IsoId=P35372-8; Sequence=VSP_037700; Name=9; Synonyms=MOR-1B5; IsoId=P35372-9; Sequence=VSP_037701; Note=Ref.5 (AAQ77392) sequence differs from that shown due to a polymorphism leading to premature termination of translation (position: 411:Q->Stop). {ECO:0000305}; Name=10; Synonyms=MOR-1i; IsoId=P35372-10; Sequence=VSP_037693; Name=11; Synonyms=MOR-1B4; IsoId=P35372-11; Sequence=VSP_037694; Name=12; Synonyms=MOR-1G1, MOR-1K; IsoId=P35372-12; Sequence=VSP_042327; Name=13; Synonyms=MOR-1G2; IsoId=P35372-13; Sequence=VSP_042328; Name=14; Synonyms=Mu3; IsoId=P35372-14; Sequence=VSP_042327, VSP_042331; Name=15; Synonyms=MOR-1W; IsoId=P35372-15; Sequence=VSP_042327, VSP_001896; Name=16; Synonyms=SV1; IsoId=P35372-16; Sequence=VSP_042330; Name=17; Synonyms=SV2; IsoId=P35372-17; Sequence=VSP_042329; Name=18; Synonyms=hMOR-1Z; IsoId=P35372-18; Sequence=VSP_047577, VSP_047578;
FunctionReceptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone. 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. 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 extend to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15. 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. Also couples to adenylate cyclase stimulatory G alpha proteins. The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4. Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization. Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction. The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins. 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. 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. Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling. Endogenous ligands induce rapid desensitization, endocytosis and recycling whereas morphine induces only low desensitization and endocytosis. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis. Isoform 12 couples to GNAS and is proposed to be involved in excitatory effects. Isoform 16 and isoform 17 do not bind agonists but may act through oligomerization with binding- competent OPRM1 isoforms and reduce their ligand binding activity.
InteractionQ9Y679:AUP1; NbExp=4; IntAct=EBI-2624570, EBI-1058701; Q92905:COPS5; NbExp=5; IntAct=EBI-2624570, EBI-594661; Q8TEW6:DOK4; NbExp=4; IntAct=EBI-2624570, EBI-6918542; P21333:FLNA; NbExp=5; IntAct=EBI-2624570, EBI-350432; P35212:GJA4; NbExp=2; IntAct=EBI-2624570, EBI-6918707; Q96S59:RANBP9; NbExp=5; IntAct=EBI-2624570, EBI-636085; Q8IUQ4:SIAH1; NbExp=4; IntAct=EBI-2624570, EBI-747107; O43255:SIAH2; NbExp=3; IntAct=EBI-2624570, EBI-948141; Q9P0L0:VAPA; NbExp=3; IntAct=EBI-2624570, EBI-1059156; Q5T9L3:WLS; NbExp=10; IntAct=EBI-2624570, EBI-2868748; Q15942:ZYX; NbExp=2; IntAct=EBI-2624570, EBI-444225;
MiscellaneousOPRM1 is the main physiological target for most clinically important opioid analgesics. OPRM1-mediated inhibition of voltage-gated calcium channels on central presynaptic terminals of primary afferent nociceptors is thought to be one of the primary mechanisms mediating analgesia at the spinal level. Opioid-induced hyperalgesic responses are observed following both acute and chronic dosing associated with cellular excitation.
PolymorphismVariant Asp-40 does not show altered binding affinities for most opioid peptides and alkaloids tested, but it binds beta-endorphin, an endogenous opioid that activates the mu opioid receptor, approximately 3 times more tightly than the most common allelic form.
PtmPhosphorylated. Differentially phosphorylated in basal and agonist-induced conditions. Agonist-mediated phosphorylation modulates receptor internalization. Phosphorylated by ADRBK1 in a agonist-dependent manner. Phosphorylation at Tyr-168 requires receptor activation, is dependent on non-receptor protein tyrosine kinase Src and results in a decrease in agonist efficacy by reducing G-protein coupling efficiency. Phosphorylated on tyrosine residues; the phosphorylation is involved in agonist-induced G- protein-independent receptor down-regulation. Phosphorylation at Ser-377 is involved in G-protein-dependent but not beta-arrestin- dependent activation of the ERK pathway (By similarity). {ECO:0000250}.
PtmUbiquitinated. A basal ubiquitination seems not to be related to degradation. Ubiquitination is increased upon formation of OPRM1:OPRD1 oligomers leading to proteasomal degradation; the ubiquitination is diminished by RTP4 (By similarity). {ECO:0000250}.
Sequence CautionSequence=CAI20458.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=EAW47705.1; Type=Erroneous initiation; Evidence={ECO:0000305};
SimilarityBelongs to the G-protein coupled receptor 1 family. {ECO:0000255|PROSITE-ProRule:PRU00521}.
Subcellular LocationCell membrane {ECO:0000269|PubMed:16580639}; Multi-pass membrane protein {ECO:0000269|PubMed:16580639}.
Subcellular LocationIsoform 12: Cytoplasm {ECO:0000269|PubMed:20525224}.
SubunitForms homooligomers and heterooligomers with other GPCRs, such as OPRD1, OPRK1, OPRL1, NPFFR2, ADRA2A, SSTR2, CNR1 and CCR5 (probably in dimeric forms). Interacts with PPL; the interaction disrupts agonist-mediated G-protein activation. Interacts (via C- terminus) with DNAJB4 (via C-terminus). Interacts with calmodulin; the interaction inhibits the constitutive activity of OPRM1; it abolishes basal and attenuates agonist-stimulated G-protein coupling. Interacts with FLNA, PLD2, RANBP9 and WLS. Interacts with GPM6A, RTP4, SYP, GNAS, RGS9, RGS17, RGS20, RGS4, PPP1R9B and HINT1 (By similarity). {ECO:0000250}.
Tissue SpecificityExpressed in brain. Isoform 16 and isoform 17 are detected in brain. {ECO:0000269|PubMed:16580639}.
Web ResourceName=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/oprm1/";
Web ResourceName=Wikipedia; Note=Mu opioid receptor entry; URL="http://en.wikipedia.org/wiki/Mu_opioid_receptor";
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