Tclin OPRM1 Mu-type opioid receptor

Protein Summary

Description

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:7905839, PubMed:7957926, PubMed:7891175, PubMed:12589820, PubMed:9689128). 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 (PubMed:7905839). 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 extent to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15 (PubMed:12068084). 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 (PubMed:20525224). 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 (PubMed:16580639). This gene encodes one of at least three opioid receptors in humans; the mu opioid receptor (MOR). The MOR is the principal target of endogenous opioid peptides and opioid analgesic agents such as beta-endorphin and enkephalins. The MOR also has an important role in dependence to other drugs of abuse, such as nicotine, cocaine, and alcohol via its modulation of the dopamine system. The NM_001008503.2:c.118A>G allele has been associated with opioid and alcohol addiction and variations in pain sensitivity but evidence for it having a causal role is conflicting. Multiple transcript variants encoding different isoforms have been found for this gene. Though the canonical MOR belongs to the superfamily of 7-transmembrane-spanning G-protein-coupled receptors some isoforms of this gene have only 6 transmembrane domains. [provided by RefSeq, Oct 2013]

Uniprot Accession IDs

• P35372
• B0FXJ1
• B2R9S7
• B8Q1L7
• B8Q1L8
• B8Q1L9
• E7EWZ3
• G8XRH6
• G8XRH8
• Q12930
• Q4VWM1
• Q4VWM2
• Q4VWM3
• Q4VWM4
• Q4VWM6
• Q4VWX6
• Q5TDA1
• Q6UPP1
• Q6UQ80
• Q7Z2D8
• Q86V80
• Q8IWW3
• Q8IWW4
• Q9UCZ4
• Q9UN57
• M-OR-1

Gene Name

• OPRM1

Ensembl ID

• ENST00000229768
• ENSP00000229768
• ENSG00000112038
• ENST00000330432
• ENSP00000328264
• ENST00000337049
• ENSP00000338381
• ENST00000414028
• ENSP00000399359
• ENST00000419506
• ENSP00000403549
• ENST00000428397
• ENSP00000411903
• ENST00000434900
• ENSP00000394624
• ENST00000435918
• ENSP00000413752
• ENST00000452687
• ENSP00000410497
• ENST00000518759
• ENSP00000430260
• ENST00000519083
• ENSP00000431048
• ENST00000520708
• ENSP00000430876
• ENST00000522236
• ENSP00000429373
• ENST00000522555
• ENSP00000429719
• ENST00000522739
• ENSP00000428018
• ENST00000524150
• ENSP00000430575
• ENST00000524163
• ENSP00000430097

Symbol

• MOR1
• MOP
• MOR
• LMOR
• MOR1
• OPRM
• M-OR-1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
drug	1
molecular function	1
biological process	0.99
ligand (chemical)	0.99
kinase	0.96

Protein Classes

PANTHER Classes

Protein / Receptor / G-protein Coupled Receptor / Mu-type Opioid Receptor

DTO Classes

Protein / G-protein Coupled Receptor / Class A Rhodopsin Like / Mu-type Opioid Receptor

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 3424.4   (req: < 5)

Gene RIFs: 488   (req: <= 3)

Antibodies: 512   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 3424.4   (req: >= 5)

Gene RIFs: 488   (req: > 3)

Antibodies: 512   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 48

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 2600

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 42