Human Gene OPRM1 (ENST00000330432.12)
  Description: Homo sapiens opioid receptor mu 1 (OPRM1), transcript variant MOR-1S, mRNA. (from RefSeq NM_001285522)
RefSeq Summary (NM_000914): 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]. Sequence Note:.
Gencode Transcript: ENST00000330432.12
Gencode Gene: ENSG00000112038.18
Transcript (Including UTRs)
   Position: hg38 chr6:154,039,240-154,132,356 Size: 93,117 Total Exon Count: 4 Strand: +
Coding Region
   Position: hg38 chr6:154,039,545-154,118,721 Size: 79,177 Coding Exon Count: 4 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated at UCSC: 2021-01-14 15:32:12

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr6:154,039,240-154,132,356)mRNA (may differ from genome)Protein (400 aa)
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UniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: OPRM_HUMAN
DESCRIPTION: RecName: Full=Mu-type opioid receptor; Short=M-OR-1; Short=MOR-1; AltName: Full=Mu opiate receptor; AltName: Full=Mu opioid receptor; Short=MOP; Short=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.
SUBUNIT: Forms homooligomers and heterooligomers with other GPCRs, such as OPRD1, OPRK1, OPRL1, NPFFR2, ADRA2A, SSTR2, CNR1 and CCR5 (probably in dimeric forms). Interacts with PPL; the interaction disrupts agonist-mediated G-protein activation. Interacts (via C- terminus) with DNAJB4 (via C-terminus). Interacts with calmodulin; the interaction inhibits the constitutive activity of OPRM1; it abolishes basal and attenuates agonist-stimulated G-protein coupling. Interacts with FLNA, PLD2, RANBP9 and WLS. Interacts with GPM6A, RTP4, SYP, GNAS, RGS9, RGS17, RGS20, RGS4, PPP1R9B and HINT1 (By similarity).
INTERACTION: P21333:FLNA; NbExp=5; IntAct=EBI-2624570, EBI-350432; Q5T9L3:WLS; NbExp=7; IntAct=EBI-2624570, EBI-2868748;
SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
SUBCELLULAR LOCATION: Isoform 12: Cytoplasm.
TISSUE SPECIFICITY: Expressed in brain. Isoform 16 and isoform 17 are detected in brain.
PTM: Phosphorylated. Differentially phosphorylated in basal and agonist-induced conditions. Agonist-mediated phosphorylation modulates receptor internalization. Phosphorylated by ADRBK1 in a agonist-dependent manner. Phosphorylation at Tyr-168 requires receptor activation, is dependent on non-receptor protein tyrosine kinase Src and results in a decrease in agonist efficacy by reducing G-protein coupling efficiency. Phosphorylated on tyrosine residues; the phosphorylation is involved in agoinist-induced G- protein-indepenedent receptor down-regulation. Phosphorylation at Ser-377 is involved in G-protein-dependent but not beta-arrestin- dependent activation of the ERK pathway (By similarity).
PTM: Ubiquitinated. A basal ubiquitination seems not to be related to degradation. Ubiquitination is increased upon formation of OPRM1:OPRD1 oligomers leading to proteasomal degradation; the ubiquitination is diminished by RTP4 (By similarity).
POLYMORPHISM: Variant Asp-40 does not show altered binding affinities for most opioid peptides and alkaloids tested, but it binds beta-endorphin, an endogenous opioid that activates the mu opioid receptor, approximately 3 times more tightly than the most common allelic form.
MISCELLANEOUS: OPRM1 is the main physiological target for most clinically important opioid analgesics. OPRM1-mediated inhibition of voltage-gated calcium channels on central presynaptic terminals of primary afferent nociceptors is thought to be one of the primary mechanisms mediating analgesia at the spinal level. Opioid-induced hyperalgesic responses are observed following both acute and chronic dosing associated with cellular excitation.
SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
SEQUENCE CAUTION: Sequence=CAI20458.1; Type=Erroneous initiation; Sequence=EAW47705.1; Type=Erroneous initiation;
WEB RESOURCE: Name=Wikipedia; Note=Mu opioid receptor entry; URL="http://en.wikipedia.org/wiki/Mu_opioid_receptor";
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/oprm1/";

-  MalaCards Disease Associations
  MalaCards Gene Search: OPRM1
Diseases sorted by gene-association score: oprm1-related altered drug metabolism* (100), substance dependence (34), drug dependence (32), opiate dependence (27), heroin dependence (25), neonatal abstinence syndrome (24), morphine dependence (24), opioid abuse (24), opioid dependence 1 (18), complex partial epilepsy (16), withdrawal disorder (16), pain agnosia (13), agnosia (13), pertussis (12), alcohol dependence (11), cyclic vomiting syndrome (10), cocaine dependence (9), chronic pain (8), somatoform disorder (8), histrionic personality disorder (8), tetanus neonatorum (8), specific developmental disorder (7), constipation (6), narcissistic personality disorder (6), hemiplegic migraine (5), nicotine dependence, protection against (5), mental retardation, x-linked syndromic, lubs type (4), idiopathic generalized epilepsy (3), disease of mental health (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 1.16 RPKM in Testis
Total median expression: 2.49 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -117.70305-0.386 Picture PostScript Text
3' UTR -3753.8113635-0.275 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000276 - 7TM_GPCR_Rhodpsn
IPR017452 - GPCR_Rhodpsn_supfam
IPR000105 - Mu_opioid_rcpt
IPR001418 - Opioid_rcpt

Pfam Domains:
PF00001 - 7 transmembrane receptor (rhodopsin family)

ModBase Predicted Comparative 3D Structure on P35372
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0001965 G-protein alpha-subunit binding
GO:0004871 signal transducer activity
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:0008022 protein C-terminus binding
GO:0019904 protein domain specific binding
GO:0031005 filamin binding
GO:0031681 G-protein beta-subunit binding
GO:0038047 morphine receptor activity
GO:0042923 neuropeptide binding

Biological Process:
GO:0002438 acute inflammatory response to antigenic stimulus
GO:0007165 signal transduction
GO:0007186 G-protein coupled receptor signaling pathway
GO:0007187 G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
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:0007268 chemical synaptic transmission
GO:0007600 sensory perception
GO:0007626 locomotory behavior
GO:0008285 negative regulation of cell proliferation
GO:0009314 response to radiation
GO:0019221 cytokine-mediated signaling pathway
GO:0019233 sensory perception of pain
GO:0031635 adenylate cyclase-inhibiting opioid receptor signaling pathway
GO:0032094 response to food
GO:0032100 positive regulation of appetite
GO:0032496 response to lipopolysaccharide
GO:0038003 opioid receptor signaling pathway
GO:0042060 wound healing
GO:0042220 response to cocaine
GO:0042755 eating behavior
GO:0043278 response to morphine
GO:0043950 positive regulation of cAMP-mediated signaling
GO:0043951 negative regulation of cAMP-mediated signaling
GO:0044849 estrous cycle
GO:0045019 negative regulation of nitric oxide biosynthetic process
GO:0045429 positive regulation of nitric oxide biosynthetic process
GO:0045471 response to ethanol
GO:0048149 behavioral response to ethanol
GO:0050769 positive regulation of neurogenesis
GO:0051481 negative regulation of cytosolic calcium ion concentration
GO:0051930 regulation of sensory perception of pain
GO:0060079 excitatory postsynaptic potential
GO:0061358 negative regulation of Wnt protein secretion
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0070588 calcium ion transmembrane transport
GO:0070848 response to growth factor
GO:0071315 cellular response to morphine
GO:0080135 regulation of cellular response to stress
GO:2000310 regulation of N-methyl-D-aspartate selective glutamate receptor activity

Cellular Component:
GO:0005623 cell
GO:0005737 cytoplasm
GO:0005768 endosome
GO:0005783 endoplasmic reticulum
GO:0005794 Golgi apparatus
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0005925 focal adhesion
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0030424 axon
GO:0030425 dendrite
GO:0032590 dendrite membrane
GO:0032839 dendrite cytoplasm
GO:0042383 sarcolemma
GO:0042995 cell projection
GO:0043005 neuron projection
GO:0043204 perikaryon
GO:0045121 membrane raft
GO:0098794 postsynapse


-  Descriptions from all associated GenBank mRNAs
  AY036623 - Homo sapiens mu opioid receptor variant MOR-1C (OPRM) mRNA, complete cds, alternatively spliced.
DQ680044 - Homo sapiens mu opioid receptor splice variant MOR-1H (OPRM1) mRNA, partial cds, alternatively spliced.
EU340241 - Homo sapiens mu opioid receptor splice variant hMOR-1i (OPRM1) mRNA, complete cds, alternatively spliced.
EU340242 - Homo sapiens mu opioid receptor splice variant hMOR-1G1 (OPRM1) mRNA, complete cds, alternatively spliced.
EU340243 - Homo sapiens mu opioid receptor splice variant hMOR-1G2 (OPRM1) mRNA, complete cds, alternatively spliced.
FJ041291 - Homo sapiens mu opioid receptor hMOR-1a (OPRM1) mRNA, complete cds, alternatively spliced.
FJ041292 - Homo sapiens mu opioid receptor splice variant hMOR-1b (OPRM1) mRNA, complete cds, alternatively spliced.
JX914655 - Homo sapiens micro opioid receptor isoform hMOR-1A2 (OPRM1) mRNA, complete cds, alternatively spliced.
FJ041290 - Homo sapiens mu opioid receptor splice variant hMOR-1S (OPRM1) mRNA, complete cds, alternatively spliced.
L29301 - Homo sapiens opioid receptor mRNA, complete cds.
L25119 - Human Mu opiate receptor (MOR1) mRNA, complete cds.
JD509580 - Sequence 490604 from Patent EP1572962.
JD349269 - Sequence 330293 from Patent EP1572962.
U12569 - Human mu opioid receptor variant (MOR1) mRNA, complete cds.
AB590577 - Synthetic construct DNA, clone: pFN21AB6696, Homo sapiens OPRM1 gene for opioid receptor, mu 1, without stop codon, in Flexi system.
JD248435 - Sequence 229459 from Patent EP1572962.
AK309655 - Homo sapiens cDNA, FLJ99696.
AK313901 - Homo sapiens cDNA, FLJ94538, highly similar to Homo sapiens opioid receptor, mu 1 (OPRM1), mRNA.
JD444683 - Sequence 425707 from Patent EP1572962.
AY225404 - Homo sapiens cell-line Be(2)C neuroblastoma Mu opioid receptor isoform MOR-1B1 (OPRM) mRNA, complete cds, alternatively spliced.
AY364230 - Homo sapiens mu opioid receptor variant MOR-1V (OPRM1) mRNA, complete cds, alternatively spliced.
AY309001 - Homo sapiens mu opioid receptor splice variant hMOR-1A (OPRM1) mRNA, complete cds; alternatively spliced.
AY036622 - Homo sapiens mu opioid receptor variant MOR-1R (OPRM) mRNA, complete cds, alternatively spliced.
AY309007 - Homo sapiens mu opioid receptor splice variant hMOR-1B4 (OPRM1) mRNA, complete cds; alternatively spliced.
AY309008 - Homo sapiens mu opioid receptor splice variant hMOR-1B5 (OPRM1) mRNA, complete cds; alternatively spliced.
AY309005 - Homo sapiens mu opioid receptor splice variant hMOR-1B2 (OPRM1) mRNA, complete cds; alternatively spliced.
AY309006 - Homo sapiens mu opioid receptor splice variant hMOR-1B3 (OPRM1) mRNA, complete cds; alternatively spliced.
AY309009 - Homo sapiens mu opioid receptor splice variant hMOR-1Y (OPRM1) mRNA, complete cds, alternatively spliced.
FJ041294 - Homo sapiens mu opioid receptor splice variant hMOR-1Y2 (OPRM1) mRNA, complete cds, alternatively spliced.
FJ041293 - Homo sapiens mu opioid receptor splice variant hMOR-1Y3 (OPRM1) mRNA, complete cds, alternatively spliced.
HQ699462 - Homo sapiens mu opioid receptor splice variant hMOR-1Z (OPRM1) mRNA, complete cds, alternatively spliced.
BC074927 - Homo sapiens opioid receptor, mu 1, mRNA (cDNA clone MGC:103880 IMAGE:30915262), complete cds.
KJ891728 - Synthetic construct Homo sapiens clone ccsbBroadEn_01122 OPRM1 gene, encodes complete protein.
KR712076 - Synthetic construct Homo sapiens clone CCSBHm_00035393 OPRM1 (OPRM1) mRNA, encodes complete protein.
KR712077 - Synthetic construct Homo sapiens clone CCSBHm_00035394 OPRM1 (OPRM1) mRNA, encodes complete protein.
KR712078 - Synthetic construct Homo sapiens clone CCSBHm_00035396 OPRM1 (OPRM1) mRNA, encodes complete protein.
KR712079 - Synthetic construct Homo sapiens clone CCSBHm_00035397 OPRM1 (OPRM1) mRNA, encodes complete protein.
AY521028 - Homo sapiens mu opioid receptor 1 (OPRM1) mRNA, complete cds.
GQ258059 - Homo sapiens opioid receptor mu 1 transcript variant hMOR-1JL (OPRM1) mRNA, partial cds, alternatively spliced.
EU360599 - Homo sapiens mu opioid receptor splice variant hMOR-1K2 (OPRM1) mRNA, complete cds, alternatively spliced.
EU362990 - Homo sapiens mu opioid receptor splice variant hMOR-1K1 (OPRM1) mRNA, complete cds, alternatively spliced.
EF666090 - Homo sapiens mu opioid receptor splice variant hMOR-1K1 (OPRM1) mRNA, partial sequence; alternatively spliced.
AY364890 - Homo sapiens mu opioid receptor variant MOR1W (OPRM1) mRNA, complete cds, alternatively spliced.
AY195733 - Homo sapiens mu3 opiate receptor mRNA, complete cds, alternatively spliced.
JD270981 - Sequence 252005 from Patent EP1572962.
JD327800 - Sequence 308824 from Patent EP1572962.
JD166915 - Sequence 147939 from Patent EP1572962.
JD418893 - Sequence 399917 from Patent EP1572962.
JD491116 - Sequence 472140 from Patent EP1572962.
JD302418 - Sequence 283442 from Patent EP1572962.
JD553781 - Sequence 534805 from Patent EP1572962.
JD243268 - Sequence 224292 from Patent EP1572962.
JD079662 - Sequence 60686 from Patent EP1572962.
JD064539 - Sequence 45563 from Patent EP1572962.
JD074171 - Sequence 55195 from Patent EP1572962.
MN308215 - UNVERIFIED: Homo sapiens isolate SV3 opioid receptor mu 1-like mRNA, complete sequence.
MN308213 - UNVERIFIED: Homo sapiens isolate MOR-1TM1 opioid receptor mu 1-like mRNA, complete sequence.
MN308214 - Homo sapiens isolate MOR-1TM2 opioid receptor mu 1 (OPRM1) mRNA, complete cds, alternatively spliced.
MN308216 - Homo sapiens isolate MOR-6TM1 opioid receptor mu 1 (OPRM1) mRNA, partial cds, alternatively spliced.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04080 - Neuroactive ligand-receptor interaction

Reactome (by CSHL, EBI, and GO)

Protein P35372 (Reactome details) participates in the following event(s):

R-HSA-112042 Opioid binds MOR
R-HSA-167427 Opioid dissociates from MOR
R-HSA-167408 The high affinity receptor complex binds to G-protein
R-HSA-112271 The receptor:G-protein complex dissociates
R-HSA-374298 Opioid receptors bind opioid peptides
R-HSA-167419 The receptor:G-protein complex releases GDP
R-HSA-167429 The receptor:G-protein complex binds GTP
R-HSA-749454 The Ligand:GPCR:Gi complex dissociates
R-HSA-749456 Liganded Gi-activating GPCRs bind inactive heterotrimeric G-protein Gi
R-HSA-380073 Liganded Gi-activating GPCR acts as a GEF for Gi
R-HSA-111885 Opioid Signalling
R-HSA-202040 G-protein activation
R-HSA-375276 Peptide ligand-binding receptors
R-HSA-6785807 Interleukin-4 and 13 signaling
R-HSA-418594 G alpha (i) signalling events
R-HSA-373076 Class A/1 (Rhodopsin-like receptors)
R-HSA-449147 Signaling by Interleukins
R-HSA-388396 GPCR downstream signalling
R-HSA-500792 GPCR ligand binding
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-372790 Signaling by GPCR
R-HSA-168256 Immune System
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: B0FXJ1, B2R9S7, B8Q1L7, B8Q1L8, B8Q1L9, ENST00000330432.1, ENST00000330432.10, ENST00000330432.11, ENST00000330432.2, ENST00000330432.3, ENST00000330432.4, ENST00000330432.5, ENST00000330432.6, ENST00000330432.7, ENST00000330432.8, ENST00000330432.9, G8XRH6, G8XRH8, MOR1, NM_001285522, OPRM_HUMAN, P35372, Q12930, Q4VWM1, Q4VWM2, Q4VWM3, Q4VWM4, Q4VWM6, Q4VWX6, Q5TDA1, Q6UPP1, Q6UQ80, Q7Z2D8, Q86V80, Q8IWW3, Q8IWW4, Q9UCZ4, Q9UN57, uc003qpr.1, uc003qpr.2, uc003qpr.3, uc003qpr.4, uc003qpr.5
UCSC ID: ENST00000330432.12
RefSeq Accession: NM_000914
Protein: P35372 (aka OPRM_HUMAN)
CCDS: CCDS47504.1, CCDS47505.1, CCDS47506.1, CCDS47508.1, CCDS55069.1, CCDS55070.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.