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Protein

Mu-type opioid receptor

Gene

OPRM1

Organism
Macaca mulatta (Rhesus macaque)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Receptor for endogenous opioids such as beta-endorphin and endomorphin. 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 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. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Names & Taxonomyi

Protein namesi
Recommended name:
Mu-type opioid receptor
Short name:
M-OR-1
Short name:
MOR-1
Gene namesi
Name:OPRM1
Synonyms:MOR1
OrganismiMacaca mulatta (Rhesus macaque)
Taxonomic identifieri9544 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniCercopithecidaeCercopithecinaeMacaca
Proteomesi
  • UP000006718 Componenti: Unplaced

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 6868ExtracellularBy similarityAdd
BLAST
Transmembranei69 – 9325Helical; Name=1By similarityAdd
BLAST
Topological domaini94 – 10613CytoplasmicBy similarityAdd
BLAST
Transmembranei107 – 13125Helical; Name=2By similarityAdd
BLAST
Topological domaini132 – 14211ExtracellularBy similarityAdd
BLAST
Transmembranei143 – 16523Helical; Name=3By similarityAdd
BLAST
Topological domaini166 – 18520CytoplasmicBy similarityAdd
BLAST
Transmembranei186 – 20722Helical; Name=4By similarityAdd
BLAST
Topological domaini208 – 23023ExtracellularBy similarityAdd
BLAST
Transmembranei231 – 25525Helical; Name=5By similarityAdd
BLAST
Topological domaini256 – 28328CytoplasmicBy similarityAdd
BLAST
Transmembranei284 – 30724Helical; Name=6By similarityAdd
BLAST
Topological domaini308 – 3147ExtracellularBy similarity
Transmembranei315 – 33824Helical; Name=7By similarityAdd
BLAST
Topological domaini339 – 40062CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL5799.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 400400Mu-type opioid receptorPRO_0000069974Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi9 – 91N-linked (GlcNAc...)Sequence analysis
Glycosylationi12 – 121N-linked (GlcNAc...)Sequence analysis
Glycosylationi33 – 331N-linked (GlcNAc...)Sequence analysis
Glycosylationi40 – 401N-linked (GlcNAc...)Sequence analysis
Glycosylationi48 – 481N-linked (GlcNAc...)Sequence analysis
Disulfide bondi142 ↔ 219PROSITE-ProRule annotation
Modified residuei168 – 1681PhosphotyrosineBy similarity
Lipidationi353 – 3531S-palmitoyl cysteineSequence analysis
Modified residuei365 – 3651PhosphoserineBy similarity
Modified residuei372 – 3721PhosphothreonineBy similarity
Modified residuei377 – 3771PhosphoserineBy similarity

Post-translational modificationi

Phosphorylated. 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).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 (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

Interactioni

Subunit structurei

Forms 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 RTP4, SYP, GNAS, RGS9, RGS17, RGS20, RGS4, PPP1R9B, HINT1, GPM6A, FLNA, PLD2, RANBP9 and WLS (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9544.ENSMMUP00000029873.

Chemistry

BindingDBiQ9MYW9.

Structurei

3D structure databases

ProteinModelPortaliQ9MYW9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
HOGENOMiHOG000230486.
HOVERGENiHBG106919.
InParanoidiQ9MYW9.
KOiK04215.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR000105. Mu_opioid_rcpt.
IPR001418. Opioid_rcpt.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR00537. MUOPIOIDR.
PR00384. OPIOIDR.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9MYW9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDSSAVPTNA SNCTDALAHS SCSPARSPGS WVNLSHLDGN LSDPCGPNRT
60 70 80 90 100
DLGGRDSLCP PTGSPSMITA ITIMALYSIV CVVGLFGNFL VMYVIVRYTK
110 120 130 140 150
MKTATNIYIF NLALADALVT STLPFQSVNY LMGTWPFGTI LCKIVISIDY
160 170 180 190 200
YNMSTSIFTL CTMSVDRYIA VCHPVKALDF RTPRNAKIIN VCNWILSSAI
210 220 230 240 250
GLPVMFMATT KYRQGSIDCT LTFSHPSWYW ENLLKICVFI FAFIMPVLII
260 270 280 290 300
TVCYGLMILR LKSVRMLSGS KEKDRNLRRI TRMVLVVVAV FIICWTPIHI
310 320 330 340 350
YVIIKALVTI PETTFQTVSW HFCIALGYTN SCLNPVLYAF LDEDFKRCFR
360 370 380 390 400
EFCIPTSSNI EQQNSTRIRQ NTRDHPSTAN TVDRTNHQLE NLEAETAPLP
Length:400
Mass (Da):44,809
Last modified:May 10, 2005 - v2
Checksum:i1AD812A961CAAEFF
GO

Polymorphismi

Variant Arg-26 is associated with higher beta-endorphin affinity, lower blood cortisol levels and higher aggressive threat behavior.1 Publication

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti26 – 261R → P.1 Publication
Natural varianti344 – 3441D → N.1 Publication
Natural varianti392 – 3921L → P.1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF286024 mRNA. Translation: AAF97249.2.
RefSeqiNP_001027996.1. NM_001032824.1.
UniGeneiMmu.3487.

Genome annotation databases

GeneIDi574141.
KEGGimcc:574141.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF286024 mRNA. Translation: AAF97249.2.
RefSeqiNP_001027996.1. NM_001032824.1.
UniGeneiMmu.3487.

3D structure databases

ProteinModelPortaliQ9MYW9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9544.ENSMMUP00000029873.

Chemistry

BindingDBiQ9MYW9.
ChEMBLiCHEMBL5799.

Protein family/group databases

GPCRDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi574141.
KEGGimcc:574141.

Organism-specific databases

CTDi4988.

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
HOGENOMiHOG000230486.
HOVERGENiHBG106919.
InParanoidiQ9MYW9.
KOiK04215.

Miscellaneous databases

PROiQ9MYW9.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR000105. Mu_opioid_rcpt.
IPR001418. Opioid_rcpt.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR00537. MUOPIOIDR.
PR00384. OPIOIDR.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "A mu-opioid receptor single nucleotide polymorphism in rhesus monkey: association with stress response and aggression."
    Miller G.M., Bendor J., Tiefenbacher S., Yang H., Novak M.A., Madras B.K.
    Mol. Psychiatry 9:99-108(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS PRO-26; ASN-344 AND PRO-392.
    Tissue: Corpus striatum.

Entry informationi

Entry nameiOPRM_MACMU
AccessioniPrimary (citable) accession number: Q9MYW9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 23, 2002
Last sequence update: May 10, 2005
Last modified: July 6, 2016
This is version 97 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.