Target name

P35372: Mu-type opioid receptor


  Protein 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. 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 isoforms Alpha-1 and Alpha-2, 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 whereas morphine induces only low desensitization and endocytosis. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis. Isoform 12 couples to GNAS and is proposed to be involved in excitatory effects. Isoform 16 and isoform 17 do not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity.

  Database links

Uniprot primary ID P35372
PDB ID
DrugBank ID DB00327 DB00956 DB00652 DB00611 DB01221 DB01433 DB00904
BioGrid ID 111033
GuidetoPHARMACOLOGY ID 319
PharmGKB ID PA31945
KEGG ID hsa:4988
DIP ID
STRING ID 9606.ENSP00000394624
IntAct ID P35372
DMDM 2851402
BRENDA
Reactome R-HSA-418594 R-HSA-111885 R-HSA-202040 R-HSA-375276
SignaLink
BioCyc
Entrez Gene (Gene ID) 4988
BindingDB P35372

  Model Performance Metrics

Fingerprint type Sensitivity SEN_std Specificity SPE_std Accuracy ACC_std F1-score F1-score_std AUC AUC_std MCC MCC_std Download model
FP2 fingerprints 0.850 0.000 0.790 0.000 0.820 0.000 0.830 0.000 0.900 0.000 0.650 0.000 Download
Estate fingerprints 0.817 0.005 0.743 0.005 0.780 0.000 0.790 0.000 0.870 0.000 0.562 0.004 Download
MACCS fingerprints 0.849 0.003 0.709 0.004 0.779 0.003 0.790 0.000 0.860 0.000 0.559 0.003 Download
Daylight fingerprints 0.730 0.000 0.850 0.000 0.790 0.000 0.778 0.004 0.840 0.000 0.580 0.000 Download
ECFP2 fingerprints 0.910 0.000 0.894 0.000 0.902 0.004 0.903 0.005 0.960 0.000 0.810 0.000 Download
ECFP4 fingerprints 0.910 0.000 0.950 0.000 0.930 0.000 0.930 0.000 0.970 0.000 0.860 0.000 Download
ECFP6 fingerprints 0.880 0.000 0.960 0.000 0.920 0.000 0.918 0.004 0.970 0.000 0.840 0.000 Download

  Download datasets

Positive dataset Negative dataset


Copyright @ 2012-2014 Computational Biology & Drug Design Group,
School of Pharmaceutical Sciences, Central South University. All rights reserved.

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