InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: OPRM1

Summary

InnateDB Protein

IDBP-98198.6

Last Modified

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

Gene Symbol

OPRM1

Protein Name

opioid receptor, mu 1

Synonyms

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

Species

Homo sapiens

Ensembl Protein

ENSP00000328264

InnateDB Gene

IDBG-98194 (OPRM1)

Protein Structure

UniProt Annotation

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.

Subcellular Localization

Cell membrane {ECO:0000269PubMed:16580639}; Multi-pass membrane protein {ECO:0000269PubMed:16580639}.Isoform 12: Cytoplasm {ECO:0000269PubMed:20525224}.

Disease Associations

Tissue Specificity

Expressed in brain. Isoform 16 and isoform 17 are detected in brain. {ECO:0000269PubMed:16580639}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 20 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	20 [view]
Protein-Protein	20 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [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: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:0007187	G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
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:0007600	sensory perception
GO:0008285	negative regulation of cell proliferation
GO:0019233	sensory perception of pain
GO:0033554	cellular response to stress
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: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:2000310	regulation of N-methyl-D-aspartate selective glutamate receptor activity

Cellular Component

GO:0005783	endoplasmic reticulum
GO:0005794	Golgi apparatus
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0016021	integral component of membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000105 Mu opioid receptor
IPR000276 G protein-coupled receptor, rhodopsin-like
IPR000405 Galanin receptor family
IPR000586 Somatostatin receptor family
IPR000611 Neuropeptide Y receptor family
IPR001418 Opioid receptor
IPR009150 Neuropeptide B/W receptor family
IPR017452 GPCR, rhodopsin-like, 7TM
IPR019424 7TM GPCR, olfactory receptor/chemoreceptor Srsx
IPR019430 7TM GPCR, serpentine receptor class x (Srx)

PFAM

PF00001
PF10320
PF10328

PRINTS