InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Oprm1

Summary

InnateDB Protein

IDBP-534323.4

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Oprm1

Protein Name

opioid receptor, mu 1

Synonyms

M-OR-1; MOP-R; mor; MOR-1; MOR-1O; muOR; Oprm;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000117950

InnateDB Gene

IDBG-130147 (Oprm1)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:10842167, ECO:0000269PubMed:16682964, ECO:0000269PubMed:21422164, ECO:0000269PubMed:22437502, ECO:0000269PubMed:7797593, ECO:0000269PubMed:9037090}.

Subcellular Localization

Cell membrane {ECO:0000269PubMed:12642578, ECO:0000269PubMed:22437502, ECO:0000269PubMed:7797593}; Multi- pass membrane protein {ECO:0000269PubMed:12642578, ECO:0000269PubMed:22437502, ECO:0000269PubMed:7797593}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 8 experimentally validated interaction(s) in this database.
They are also associated with 9 interaction(s) predicted by orthology.

Experimentally validated
Total	8 [view]
Protein-Protein	8 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	9 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001965	G-protein alpha-subunit binding
GO:0004930	G-protein coupled receptor activity
GO:0004979	beta-endorphin receptor activity
GO:0004985	opioid receptor activity
GO:0005245	voltage-gated calcium channel activity
GO:0005515	protein binding
GO:0038047	morphine receptor activity

Biological Process

GO:0007186	G-protein coupled receptor signaling pathway
GO:0007191	adenylate cyclase-activating dopamine receptor signaling pathway
GO:0007193	adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway
GO:0007194	negative regulation of adenylate cyclase activity
GO:0007200	phospholipase C-activating G-protein coupled receptor signaling pathway
GO:0007204	positive regulation of cytosolic calcium ion concentration
GO:0007218	neuropeptide signaling pathway
GO:0007626	locomotory behavior
GO:0019233	sensory perception of pain
GO:0033554	cellular response to stress
GO:0038003	opioid receptor signaling pathway
GO:0043950	positive regulation of cAMP-mediated signaling
GO:0043951	negative regulation of cAMP-mediated signaling
GO:0045019	negative regulation of nitric oxide biosynthetic process
GO:0045429	positive regulation of nitric oxide biosynthetic process
GO:0048149	behavioral response to ethanol
GO:0050769	positive regulation of neurogenesis
GO:0050795	regulation of behavior
GO:0051481	negative regulation of cytosolic calcium ion concentration
GO:0061358	negative regulation of Wnt protein secretion
GO:0070374	positive regulation of ERK1 and ERK2 cascade
GO:0070588	calcium ion transmembrane transport
GO:0071315	cellular response to morphine
GO:2000310	regulation of N-methyl-D-aspartate selective glutamate receptor activity

Cellular Component

GO:0005886	plasma membrane
GO:0016020	membrane
GO:0016021	integral component of membrane

Protein Structure and Domains

PDB ID

MGI:97441

InterPro

IPR000105 Mu opioid receptor
IPR000276 G protein-coupled receptor, rhodopsin-like
IPR000405 Galanin receptor family
IPR000611 Neuropeptide Y receptor family
IPR001418 Opioid receptor
IPR009150 Neuropeptide B/W receptor family
IPR017452 GPCR, rhodopsin-like, 7TM
IPR019426 7TM GPCR, serpentine receptor class v (Srv)

PFAM

PF00001
PF10323

PRINTS

PR00537
PR00237
PR00663
PR01012
PR00384
PR01855

PIRSF

SMART

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

P42866