P79350 · OPRM_BOVIN
- ProteinMu-type opioid receptor
- GeneOPRM1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids401 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
Function
function
Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone (PubMed:10581406).
Also activated by enkephalin peptides, such as Met-enkephalin or Met-enkephalin-Arg-Phe, with higher affinity for Met-enkephalin-Arg-Phe. 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, and to a lesser extent 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. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis (By similarity).
Also activated by enkephalin peptides, such as Met-enkephalin or Met-enkephalin-Arg-Phe, with higher affinity for Met-enkephalin-Arg-Phe. 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, and to a lesser extent 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. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis (By similarity).
GO annotations
Keywords
- Molecular function
Names & Taxonomy
Protein names
- Recommended nameMu-type opioid receptor
- Short namesM-OR-1; MOR-1
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Artiodactyla > Ruminantia > Pecora > Bovidae > Bovinae > Bos
Accessions
- Primary accessionP79350
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Note: Is rapidly internalized after agonist binding.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-69 | Extracellular | ||||
Sequence: MDSGAVPTNASNCTDPFTHPSSCSPAPSPSSWVNFSHLEGNLSDPCGPNRTELGGSDRLCPSAGSPSMI | ||||||
Transmembrane | 70-94 | Helical; Name=1 | ||||
Sequence: TAIIIMALYSIVCVVGLFGNFLVMY | ||||||
Topological domain | 95-107 | Cytoplasmic | ||||
Sequence: VIVRYTKMKTATN | ||||||
Transmembrane | 108-132 | Helical; Name=2 | ||||
Sequence: IYIFNLALADALATSTLPFQSVNYL | ||||||
Topological domain | 133-143 | Extracellular | ||||
Sequence: MGTWPFGTILC | ||||||
Transmembrane | 144-166 | Helical; Name=3 | ||||
Sequence: KIVISIDYYNMFTSIFTLCTMSV | ||||||
Topological domain | 167-186 | Cytoplasmic | ||||
Sequence: DRYIAVCHPVKALDLRTPRN | ||||||
Transmembrane | 187-208 | Helical; Name=4 | ||||
Sequence: AKIINICNWILSSAIGLPVMFM | ||||||
Topological domain | 209-231 | Extracellular | ||||
Sequence: ATTKYRQGSIDCTLTFSHPTWYW | ||||||
Transmembrane | 232-256 | Helical; Name=5 | ||||
Sequence: ENLLKICVFIFAFIMPILIITVCYG | ||||||
Topological domain | 257-280 | Cytoplasmic | ||||
Sequence: LMILRLKSVRMLSGSKEKDRNLRR | ||||||
Transmembrane | 281-307 | Helical; Name=6 | ||||
Sequence: ITRMVLVVVAVFIVCWTPIHIYVIIKA | ||||||
Topological domain | 308-315 | Extracellular | ||||
Sequence: LITIPETT | ||||||
Transmembrane | 316-339 | Helical; Name=7 | ||||
Sequence: FQTVSWHFCIALGYTNSCLNPVLY | ||||||
Topological domain | 340-401 | Cytoplasmic | ||||
Sequence: AFLDENFKRCFREFCIPTSSTIEQQNSTRIRQNTRDHPSTANTVDRTNHQLENLEAETTPLP |
Keywords
- Cellular component
Phenotypes & Variants
Chemistry
PTM/Processing
Features
Showing features for chain, glycosylation, disulfide bond, modified residue, lipidation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000069970 | 1-401 | Mu-type opioid receptor | |||
Sequence: MDSGAVPTNASNCTDPFTHPSSCSPAPSPSSWVNFSHLEGNLSDPCGPNRTELGGSDRLCPSAGSPSMITAIIIMALYSIVCVVGLFGNFLVMYVIVRYTKMKTATNIYIFNLALADALATSTLPFQSVNYLMGTWPFGTILCKIVISIDYYNMFTSIFTLCTMSVDRYIAVCHPVKALDLRTPRNAKIINICNWILSSAIGLPVMFMATTKYRQGSIDCTLTFSHPTWYWENLLKICVFIFAFIMPILIITVCYGLMILRLKSVRMLSGSKEKDRNLRRITRMVLVVVAVFIVCWTPIHIYVIIKALITIPETTFQTVSWHFCIALGYTNSCLNPVLYAFLDENFKRCFREFCIPTSSTIEQQNSTRIRQNTRDHPSTANTVDRTNHQLENLEAETTPLP | ||||||
Glycosylation | 9 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 12 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 34 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 41 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 49 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 143↔220 | |||||
Sequence: CKIVISIDYYNMFTSIFTLCTMSVDRYIAVCHPVKALDLRTPRNAKIINICNWILSSAIGLPVMFMATTKYRQGSIDC | ||||||
Modified residue | 169 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Lipidation | 354 | S-palmitoyl cysteine | ||||
Sequence: C | ||||||
Modified residue | 366 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 373 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 378 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 397 | Phosphothreonine | ||||
Sequence: T |
Post-translational modification
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-169 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-378 is involved in G-protein-dependent but not beta-arrestin-dependent activation of the ERK pathway (By similarity).
Ubiquitinated. 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.
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Forms homooligomers and heterooligomers with other GPCRs, such as OPRD1, OPRK1, OPRL1, NPFFR2, ADRA2A, SSTR2, CNR1 and CCR5 (probably in dimeric forms). 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. 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 and GPM6A (By similarity).
Interacts with RTP4 (By similarity).
Interacts with SYP and GNAS (By similarity).
Interacts with RGS9, RGS17, RGS20, RGS4, PPP1R9B and HINT1
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 and GPM6A (By similarity).
Interacts with RTP4 (By similarity).
Interacts with SYP and GNAS (By similarity).
Interacts with RGS9, RGS17, RGS20, RGS4, PPP1R9B and HINT1
Protein-protein interaction databases
Chemistry
Structure
Family & Domains
Features
Showing features for motif, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 335-339 | NPxxY; plays a role in stabilizing the activated conformation of the receptor | ||||
Sequence: NPVLY | ||||||
Region | 365-389 | Disordered | ||||
Sequence: NSTRIRQNTRDHPSTANTVDRTNHQ |
Sequence similarities
Belongs to the G-protein coupled receptor 1 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Protein family/group databases
Sequence
- Sequence statusComplete
- Length401
- Mass (Da)45,028
- Last updated1999-07-15 v2
- Checksum6DA8592F29299C6E
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U89677 EMBL· GenBank· DDBJ | AAB49477.2 EMBL· GenBank· DDBJ | mRNA |