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Details on Person UniProt:P35372-5 OPRM1
| Class:Id | ReferenceIsoform:436145 |
|---|---|
| _chainChangeLog | chain:1-400 added on Fri February 6 2015 |
| _displayName | UniProt:P35372-5 OPRM1 |
| _timestamp | 2026-02-20 22:46:53 |
| chain | chain:1-400 |
| checksum | 1DABEBEC9AFF6F66 |
| comment | FUNCTION 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).FUNCTION Couples to GNAS and is proposed to be involved in excitatory effects.FUNCTION Does not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity.FUNCTION Does not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity.SUBUNIT 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).INTERACTION Is rapidly internalized after agonist binding.SUBCELLULAR LOCATION Additional isoforms seem to exist.TISSUE SPECIFICITY Expressed in brain. Isoform 16 and isoform 17 are detected in brain.PTM Phosphorylated. Differentially phosphorylated in basal and agonist-induced conditions. Agonist-mediated phosphorylation modulates receptor internalization. Phosphorylated by GRK2 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).PTM Ubiquitinated. A basal ubiquitination does not seem to be related to degradation. Ubiquitination is increased upon formation of OPRM1:OPRD1 oligomers leading to proteasomal degradation; the ubiquitination is diminished by RTP4.POLYMORPHISM Variant 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.MISCELLANEOUS OPRM1 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.MISCELLANEOUS May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.SIMILARITY Belongs to the G-protein coupled receptor 1 family.SEQUENCE CAUTION Mu opioid receptor entry |
| created | [InstanceEdit:435871] Kanapin, AA |
| description | recommendedName: Mu-type opioid receptor shortName: M-OR-1 shortName: MOR-1 alternativeName: Mu opiate receptor alternativeName: Mu opioid receptor shortName: MOP shortName: hMOP |
| geneName | OPRM1 MOR1 |
| identifier | P35372 |
| isoformParent | |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing Cell membrane Cell projection Cytoplasm Disulfide bond Endosome G-protein coupled receptor Glycoprotein Lipoprotein Membrane Palmitate Phosphoprotein Proteomics identification Receptor Reference proteome Transducer Transmembrane Transmembrane helix Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | OPRM1 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:6797366] ENSEMBL:ENSG00000112038 OPRM1 [Homo sapiens] |
| secondaryIdentifier | OPRM_HUMAN B0FXJ1 B2R9S7 B8Q1L7 B8Q1L8 B8Q1L9 E7EWZ3 G8XRH6 G8XRH8 Q12930 Q4VWM1 Q4VWM2 Q4VWM3 Q4VWM4 Q4VWM6 Q4VWX6 Q5TDA1 Q6UPP1 Q6UQ80 Q7Z2D8 Q86V80 Q8IWW3 Q8IWW4 Q9UCZ4 Q9UN57 |
| sequenceLength | 400 |
| species | [Species:48887] Homo sapiens |
| variantIdentifier | P35372-5 |
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No pathways have been reviewed or authored by UniProt:P35372-5 OPRM1 (436145)
