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Protein

Mu-type opioid receptor

Gene

OPRM1

Organism
Cavia porcellus (Guinea pig)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Protein inferred from homologyi

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
OrganismiCavia porcellus (Guinea pig)
Taxonomic identifieri10141 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaHystricognathiCaviidaeCavia
Proteomesi
  • UP000005447 Componenti: Unassembled WGS sequence

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini‹1 – 9›9CytoplasmicBy similarity
Transmembranei10 – 3425Helical; Name=2By similarityAdd
BLAST
Topological domaini35 – 4511ExtracellularBy similarityAdd
BLAST
Transmembranei46 – 6823Helical; Name=3By similarityAdd
BLAST
Topological domaini69 – 8820CytoplasmicBy similarityAdd
BLAST
Transmembranei89 – ›98›10Helical; Name=4By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL3038518.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini‹1 – ›98›98Mu-type opioid receptorPRO_0000069971Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei71 – 711PhosphotyrosineBy 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. Phosphorylated on tyrosine residues; the phosphorylation is involved in agonist-induced G-protein-independent receptor down-regulation (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

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

STRINGi10141.ENSCPOP00000017994.

Chemistry

BindingDBiP97266.

Structurei

3D structure databases

ProteinModelPortaliP97266.
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.
InParanoidiP97266.

Family and domain databases

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

Sequencei

Sequence statusi: Fragment.

P97266-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
YTKMKTATNI YIFNLALADA LATSTLPFQS VNYLMGTWPF GTILCKIVIS
60 70 80 90
IDYYNMFTSI FTLCTMSVDR YIAVCHPVKA LDFRTPRNAK TVNVCNWI
Length:98
Mass (Da):11,161
Last modified:May 1, 1997 - v1
Checksum:iBEDB096924E0B9BE
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Non-terminal residuei1 – 11
Non-terminal residuei98 – 981

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U67928 Genomic DNA. Translation: AAB39617.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U67928 Genomic DNA. Translation: AAB39617.1.

3D structure databases

ProteinModelPortaliP97266.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10141.ENSCPOP00000017994.

Chemistry

BindingDBiP97266.
ChEMBLiCHEMBL3038518.

Protein family/group databases

GPCRDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
HOGENOMiHOG000230486.
InParanoidiP97266.

Family and domain databases

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

Publicationsi

  1. Ronnekleiv O.K., Bosch M.A., Cunningham M.J., Wagner E.J., Grandy D.K., Kelly M.J.
    Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. Cited for: SUBCELLULAR LOCATION, RECEPTOR INTERNALIZATION.

Entry informationi

Entry nameiOPRM_CAVPO
AccessioniPrimary (citable) accession number: P97266
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: May 1, 1997
Last modified: July 6, 2016
This is version 96 of the entry and version 1 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.