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DrugBank target: P35372

DrugBank target: P35372 (OPRM_HUMAN)     

Mu-type opioid receptor

Mu opiate receptor, Mu opioid receptor, M-OR-1, MOR-1, MOP, hMOP.

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..

Structures

There are currently no structures for this UniProt code in the PDB.

Schematic diagram of Pfam domains in target sequence

Key:    PfamA domain

Sequence length: 400 a.a.

Approved drugs targeting this protein

The DrugBank database identifies 33 drugs for this target protein:

 

 
Generic name: DB06274 alvimopan
Formula: C25H32N2O4
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB00708 sufentanil
Formula: C22H30N2O2S
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB00704 naltrexone
Formula: C20H23No4
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB01192 oxymorphone
Formula: C17H19No4
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB01183 naloxone
Formula: C19H21No4
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB01081 diphenoxylate
Formula: C30H32N2O2
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB00836 loperamide
Formula: C29H33Cln2O2
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB06800 methylnaltrexone
Formula: C21H26No4
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB00913 anileridine
Formula: C22H28N2O2
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB00854 levorphanol
Formula: C17H23No
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB00899 remifentanil
Formula: C20H28N2O5
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB00956 hydrocodone
Formula: C18H21No3
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB00802 alfentanil
Formula: C21H32N6O3
Structure: There are no structures of this molecule in the PDB.
Generic name: DB00295 morphine
MOI
Formula: C17H19No3
Structure: There is one PDB structure containing this molecule but it is not bound to the above target protein.
 
Generic name: DB06204 tapentadol
Formula: C14H23No
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB00647 propoxyphene
Formula: C22H29No2
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB00844 nalbuphine
Formula: C21H27No4
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB01452 heroin
Formula: C21H23No5
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB00652 pentazocine
Formula: C19H27No
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB00497 oxycodone
Formula: C18H21No4
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB00504 levallorphan
Formula: C19H25No
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB00333 methadone
Formula: C21H27No
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB00327 hydromorphone
Formula: C17H19No3
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB00921 buprenorphine
Formula: C29H41No4
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB01466 ethylmorphine
Formula: C19H23No3
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB00611 butorphanol
Formula: C21H29No2
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB00904 ondansetron
Formula: C18H19N3O
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB01433 methadyl acetate
Formula: C23H31No2
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB01209 dezocine
Formula: C16H23No
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB00318 codeine
Formula: C18H21No3
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB00813 fentanyl
Formula: C22H28N2O
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB00193 tramadol
Formula: C16H25No2
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB01227 levomethadyl acetate
Formula: C23H31No2
Structure: There are no structures of this molecule in the PDB.

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