Target name

P42866: Mu-type opioid receptor


  Protein function

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 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. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis. Isoform 9 is involved in morphine-induced scratching and seems to cross-activate GRPR in response to morphine.

  Database links

Uniprot primary ID P42866
PDB ID 4DKL 5C1M
DrugBank ID
BioGrid ID 201972
GuidetoPHARMACOLOGY ID 319
PharmGKB ID
KEGG ID mmu:18390
DIP ID DIP-46148N
STRING ID 10090.ENSMUSP00000101236
IntAct ID P42866
DMDM
BRENDA
Reactome R-MMU-111885 R-MMU-418594 R-MMU-375276 R-MMU-202040
SignaLink
BioCyc
Entrez Gene (Gene ID) 18390
BindingDB P42866

  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 0.945 0.005 0.917 0.005 0.931 0.003 0.931 0.003 0.980 0.000 0.863 0.008 Download
Estate fingerprints 0.918 0.008 0.812 0.005 0.865 0.005 0.875 0.005 0.933 0.005 0.735 0.011 Download
MACCS fingerprints 0.840 0.005 0.858 0.003 0.849 0.003 0.848 0.004 0.939 0.003 0.695 0.007 Download
Daylight fingerprints 0.839 0.010 0.919 0.005 0.879 0.006 0.872 0.006 0.900 0.000 0.760 0.011 Download
ECFP2 fingerprints 0.968 0.004 0.968 0.005 0.968 0.004 0.969 0.003 0.990 0.000 0.936 0.005 Download
ECFP4 fingerprints 0.937 0.007 0.981 0.000 0.959 0.003 0.959 0.003 0.990 0.000 0.925 0.007 Download
ECFP6 fingerprints 0.928 0.004 0.990 0.000 0.959 0.003 0.959 0.003 0.990 0.000 0.920 0.005 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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