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Protein

Mu-type opioid receptor

Gene

OPRM1

Organism
Bos taurus (Bovine)
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. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone (PubMed:10581406). 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 similarity1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionG-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
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

Subcellular locationi

  • Cell membrane 1 Publication; Multi-pass membrane protein By similarity
  • Cell projectionaxon By similarity
  • Perikaryon By similarity
  • Cell projectiondendrite By similarity
  • Endosome By similarity

  • Note: Is rapidly internalized after agonist binding.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 69ExtracellularBy similarityAdd BLAST69
Transmembranei70 – 94Helical; Name=1By similarityAdd BLAST25
Topological domaini95 – 107CytoplasmicBy similarityAdd BLAST13
Transmembranei108 – 132Helical; Name=2By similarityAdd BLAST25
Topological domaini133 – 143ExtracellularBy similarityAdd BLAST11
Transmembranei144 – 166Helical; Name=3By similarityAdd BLAST23
Topological domaini167 – 186CytoplasmicBy similarityAdd BLAST20
Transmembranei187 – 208Helical; Name=4By similarityAdd BLAST22
Topological domaini209 – 231ExtracellularBy similarityAdd BLAST23
Transmembranei232 – 256Helical; Name=5By similarityAdd BLAST25
Topological domaini257 – 280CytoplasmicBy similarityAdd BLAST24
Transmembranei281 – 307Helical; Name=6By similarityAdd BLAST27
Topological domaini308 – 315ExtracellularBy similarity8
Transmembranei316 – 339Helical; Name=7By similarityAdd BLAST24
Topological domaini340 – 401CytoplasmicBy similarityAdd BLAST62

GO - Cellular componenti

Keywords - Cellular componenti

Cell membrane, Cell projection, Endosome, Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3041.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000699701 – 401Mu-type opioid receptorAdd BLAST401

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi9N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi12N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi34N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi41N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi49N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi143 ↔ 220PROSITE-ProRule annotation
Modified residuei169PhosphotyrosineBy similarity1
Lipidationi354S-palmitoyl cysteineSequence analysis1
Modified residuei366PhosphoserineBy similarity1
Modified residuei373PhosphothreonineBy similarity1
Modified residuei378PhosphoserineBy similarity1

Post-translational modificationi

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).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

Keywords - PTMi

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

Proteomic databases

PaxDbiP79350.
PRIDEiP79350.

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 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.By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000026280.

Chemistry databases

BindingDBiP79350.

Structurei

3D structure databases

ProteinModelPortaliP79350.
SMRiP79350.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi335 – 339NPxxY; plays a role in stabilizing the activated conformation of the receptorBy similarity5

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.
InParanoidiP79350.
KOiK04215.

Family and domain databases

InterProiView protein in InterPro
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR000105. Mu_opioid_rcpt.
IPR001418. Opioid_rcpt.
PfamiView protein in Pfam
PF00001. 7tm_1. 1 hit.
PRINTSiPR00237. GPCRRHODOPSN.
PR00537. MUOPIOIDR.
PR00384. OPIOIDR.
PROSITEiView protein in PROSITE
PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.

Sequencei

Sequence statusi: Complete.

P79350-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDSGAVPTNA SNCTDPFTHP SSCSPAPSPS SWVNFSHLEG NLSDPCGPNR
60 70 80 90 100
TELGGSDRLC PSAGSPSMIT AIIIMALYSI VCVVGLFGNF LVMYVIVRYT
110 120 130 140 150
KMKTATNIYI FNLALADALA TSTLPFQSVN YLMGTWPFGT ILCKIVISID
160 170 180 190 200
YYNMFTSIFT LCTMSVDRYI AVCHPVKALD LRTPRNAKII NICNWILSSA
210 220 230 240 250
IGLPVMFMAT TKYRQGSIDC TLTFSHPTWY WENLLKICVF IFAFIMPILI
260 270 280 290 300
ITVCYGLMIL RLKSVRMLSG SKEKDRNLRR ITRMVLVVVA VFIVCWTPIH
310 320 330 340 350
IYVIIKALIT IPETTFQTVS WHFCIALGYT NSCLNPVLYA FLDENFKRCF
360 370 380 390 400
REFCIPTSST IEQQNSTRIR QNTRDHPSTA NTVDRTNHQL ENLEAETTPL

P
Length:401
Mass (Da):45,028
Last modified:July 15, 1999 - v2
Checksum:i6DA8592F29299C6E
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U89677 mRNA. Translation: AAB49477.2.
RefSeqiNP_776833.1. NM_174408.2.
UniGeneiBt.242.

Genome annotation databases

GeneIDi281958.
KEGGibta:281958.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U89677 mRNA. Translation: AAB49477.2.
RefSeqiNP_776833.1. NM_174408.2.
UniGeneiBt.242.

3D structure databases

ProteinModelPortaliP79350.
SMRiP79350.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000026280.

Chemistry databases

BindingDBiP79350.
ChEMBLiCHEMBL3041.

Protein family/group databases

GPCRDBiSearch...

Proteomic databases

PaxDbiP79350.
PRIDEiP79350.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi281958.
KEGGibta:281958.

Organism-specific databases

CTDi4988.

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
HOGENOMiHOG000230486.
HOVERGENiHBG106919.
InParanoidiP79350.
KOiK04215.

Miscellaneous databases

PROiPR:P79350.

Family and domain databases

InterProiView protein in InterPro
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR000105. Mu_opioid_rcpt.
IPR001418. Opioid_rcpt.
PfamiView protein in Pfam
PF00001. 7tm_1. 1 hit.
PRINTSiPR00237. GPCRRHODOPSN.
PR00537. MUOPIOIDR.
PR00384. OPIOIDR.
PROSITEiView protein in PROSITE
PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiOPRM_BOVIN
AccessioniPrimary (citable) accession number: P79350
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 15, 1999
Last modified: May 10, 2017
This is version 121 of the entry and version 2 of the sequence. See 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.