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P33535 (OPRM_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mu-type opioid receptor

Short name=M-OR-1
Short name=MOR-1
Alternative name(s):
Opioid receptor B
Gene names
Name:Oprm1
Synonyms:Ror-b
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length398 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.33 Ref.37 Ref.39 Ref.42

Subunit structure

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 By similarity. Interacts with PLD2. Interacts with RANBP9 and WLS By similarity. Interacts with GPM6A. Interacts with RTP4 By similarity. Interacts with SYP and GNAS. Interacts with RGS9, RGS17 and RGS20 By similarity. Interacts with RGS4. Interacts with PPP1R9B and HINT1 By similarity. Ref.21 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.34 Ref.35 Ref.36 Ref.37 Ref.40

Subcellular location

Cell membrane; Multi-pass membrane protein.

Tissue specificity

Brain. Is expressed in the cerebral cortex, caudate putamen, nucleus accumbens, septal nuclei, thalamus, hippocampus, and habenula. Not detected in cerebellum.

Post-translational modification

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-166 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 agonist-induced G-protein-independent receptor down-regulation. Phosphorylation at Ser-375 is involved in G-protein-dependent but not beta-arrestin-dependent activation of the ERK pathway. Ref.19 Ref.20 Ref.22 Ref.26 Ref.41

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.

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Sequence caution

The sequence AAQ77387.1 differs from that shown. Reason: Frameshift at several positions.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
   DomainTransmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Lipoprotein
Palmitate
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadenylate cyclase-activating dopamine receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

behavioral response to ethanol

Inferred from electronic annotation. Source: Ensembl

calcium ion transmembrane transport

Inferred from mutant phenotype Ref.12. Source: GOC

cellular response to morphine

Inferred from mutant phenotype Ref.16. Source: GOC

cellular response to stress

Inferred from electronic annotation. Source: Ensembl

locomotory behavior

Inferred from electronic annotation. Source: Ensembl

negative regulation of Wnt protein secretion

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of adenylate cyclase activity

Inferred from direct assay Ref.14. Source: UniProtKB

negative regulation of cAMP-mediated signaling

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cytosolic calcium ion concentration

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of nitric oxide biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

phospholipase C-activating G-protein coupled receptor signaling pathway

Inferred from direct assay Ref.18. Source: UniProtKB

positive regulation of ERK1 and ERK2 cascade

Inferred from direct assay Ref.34. Source: UniProtKB

positive regulation of cAMP-mediated signaling

Inferred from electronic annotation. Source: Ensembl

positive regulation of cytosolic calcium ion concentration

Inferred from electronic annotation. Source: Ensembl

positive regulation of neurogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of nitric oxide biosynthetic process

Inferred from electronic annotation. Source: Ensembl

regulation of N-methyl-D-aspartate selective glutamate receptor activity

Inferred from mutant phenotype PubMed 17976846. Source: UniProtKB

regulation of behavior

Inferred from electronic annotation. Source: Ensembl

sensory perception of pain

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentintegral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionG-protein alpha-subunit binding

Inferred from sequence or structural similarity. Source: UniProtKB

G-protein coupled receptor activity

Inferred from mutant phenotype Ref.16. Source: UniProtKB

beta-endorphin receptor activity

Inferred from electronic annotation. Source: Ensembl

morphine receptor activity

Inferred from mutant phenotype Ref.16. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.29Ref.36Ref.35PubMed 20214800. Source: IntAct

voltage-gated calcium channel activity

Inferred from mutant phenotype Ref.12. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 8 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P33535-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P33535-2)

Also known as: MOR1A;

The sequence of this isoform differs from the canonical sequence as follows:
     387-398: LENLEAETAPLP → VCAF
Isoform 3 (identifier: P33535-3)

Also known as: MOR1R;

The sequence of this isoform differs from the canonical sequence as follows:
     387-398: LENLEAETAPLP → GAEL
Isoform 4 (identifier: P33535-4)

Also known as: MOR1B;

The sequence of this isoform differs from the canonical sequence as follows:
     387-398: LENLEAETAPLP → KIVLF
Isoform 5 (identifier: P33535-5)

Also known as: MOR1B2;

The sequence of this isoform differs from the canonical sequence as follows:
     387-398: LENLEAETAPLP → EPQSVET
Isoform 6 (identifier: P33535-6)

Also known as: MOR1C1;

The sequence of this isoform differs from the canonical sequence as follows:
     387-398: LENLEAETAPLP → PALAVSVAQI...ALIYNNVNFI
Isoform 7 (identifier: P33535-7)

Also known as: MOR-1C2;

The sequence of this isoform differs from the canonical sequence as follows:
     387-398: LENLEAETAPLP → PALAVSVAQI...MPAHVLVRPW
Isoform 8 (identifier: P33535-8)

Also known as: rMOR-1D;

The sequence of this isoform differs from the canonical sequence as follows:
     387-398: LENLEAETAPLP → T

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 398398Mu-type opioid receptor
PRO_0000069978

Regions

Topological domain1 – 6666Extracellular By similarity
Transmembrane67 – 9125Helical; Name=1; By similarity
Topological domain92 – 10413Cytoplasmic By similarity
Transmembrane105 – 12925Helical; Name=2; By similarity
Topological domain130 – 14011Extracellular By similarity
Transmembrane141 – 16323Helical; Name=3; By similarity
Topological domain164 – 18320Cytoplasmic By similarity
Transmembrane184 – 20522Helical; Name=4; By similarity
Topological domain206 – 22823Extracellular By similarity
Transmembrane229 – 25325Helical; Name=5; By similarity
Topological domain254 – 28128Cytoplasmic By similarity
Transmembrane282 – 30524Helical; Name=6; By similarity
Topological domain306 – 3127Extracellular By similarity
Transmembrane313 – 33624Helical; Name=7; By similarity
Topological domain337 – 39862Cytoplasmic By similarity

Amino acid modifications

Modified residue1661Phosphotyrosine Ref.41
Modified residue3631Phosphoserine Ref.26
Modified residue3701Phosphothreonine Ref.26
Modified residue3751Phosphoserine Ref.26
Modified residue3941Phosphothreonine Probable
Lipidation3511S-palmitoyl cysteine Potential
Glycosylation91N-linked (GlcNAc...) Potential
Glycosylation311N-linked (GlcNAc...) Potential
Glycosylation381N-linked (GlcNAc...) Potential
Glycosylation461N-linked (GlcNAc...) Potential
Glycosylation531N-linked (GlcNAc...) Potential
Disulfide bond140 ↔ 217 By similarity

Natural variations

Alternative sequence387 – 39812LENLE…TAPLP → VCAF in isoform 2.
VSP_041828
Alternative sequence387 – 39812LENLE…TAPLP → GAEL in isoform 3.
VSP_041829
Alternative sequence387 – 39812LENLE…TAPLP → KIVLF in isoform 4.
VSP_041830
Alternative sequence387 – 39812LENLE…TAPLP → EPQSVET in isoform 5.
VSP_041831
Alternative sequence387 – 39812LENLE…TAPLP → PALAVSVAQIFTGYPSPTHG EKPCKSYRDRPRPCGRTWSL KSRAESNVEHFHCGAALIYN NVNFI in isoform 6.
VSP_041832
Alternative sequence387 – 39812LENLE…TAPLP → PALAVSVAQIFTGYPSPTHG EKPCKSYRDRPRPCGRTWSL KSRAESNVEHFHCGAALIYN NELKIGPVSWLQMPAHVLVR PW in isoform 7.
VSP_041833
Alternative sequence387 – 39812LENLE…TAPLP → T in isoform 8.
VSP_041834

Experimental info

Mutagenesis911Y → A: Abolishes agonist-induced G-protein-independent receptor internalization; when associated with A-96, A-166 and A-336. Ref.19
Mutagenesis961Y → A: Abolishes agonist-induced G-protein-independent receptor internalization; when associated with A-91, A-166 and A-336. Ref.19
Mutagenesis1141D → A or N: Impairs agonist affinity, agonist-induced inhibition of adenylate cyclase and coupling to G-proteins. Ref.14 Ref.16
Mutagenesis1141D → E: No effect on inhibition of adenylate cyclase. Ref.14 Ref.16
Mutagenesis1471D → A: No effect on constitutive activation. Impairs agonist affinity and agonist-induced inhibition of adenylate cyclase. Ref.14 Ref.23
Mutagenesis1471D → E: Impairs agonist affinity and increases agonist-induced inhibition of adenylate cyclase. Ref.14 Ref.23
Mutagenesis1471D → N: No effect on constitutive activation. Ref.14 Ref.23
Mutagenesis1641D → E: Reduces basal activity. Ref.23
Mutagenesis1641D → H, M, Q or Y: Constitutive active. Ref.23
Mutagenesis1661Y → A: Abolishes agonist-induced G-protein-independent receptor internalization; when associated with A-91, A-96 and A-336. Ref.19 Ref.41
Mutagenesis1661Y → F: Decrease in phosphorylation, no decrease in G-protein binding. Ref.19 Ref.41
Mutagenesis1801T → A: Impairs ARRB2- and ADRBK2-mediated receptor desensitization. Ref.25
Mutagenesis2751L → E: No effect on constitutive activation. Some constitutive activity; when associated with K-279. Ref.27
Mutagenesis2791T → D: Receptor inactivation. Ref.24 Ref.27
Mutagenesis2791T → K: Constitutive active. Some constitutive activity; when associated with E-275. Ref.24 Ref.27
Mutagenesis2971H → A: Impairs agonist affinity and increases agonist-induced inhibition of adenylate cyclase. Ref.14
Mutagenesis3361Y → A: Abolishes agonist-induced G-protein-independent receptor internalization; when associated with A-91, A-96 and A-166. Ref.19
Mutagenesis3461C → A: No change in palmitoylation. No change in palmitoylation; when associated with A-351. Ref.17
Mutagenesis3511C → A: No change in palmitoylation; when associated with A-346. Ref.17
Mutagenesis3631S → A: Abolishes basal phosphorylation; when associated with A-370. Abolishes basal and agonist-induced phosphorylation; when associated with A-370 and A-375. Accelerates agonist-induced receptor internalization. Ref.26 Ref.38
Mutagenesis3701T → A: Abolishes basal phosphorylation; when associated with A-363. Abolishes basal and agonist-induced phosphorylation; when associated with A-363 and A-375. Accelerates agonist-induced receptor internalization. Ref.26 Ref.38
Mutagenesis3751S → A: Reduces agonist-induced receptor internalization. Abolishes morphine-induced phosphorylation. Restores agonist-specific PRKCE activity. Abolishes basal and agonist-induced phosphorylation; when associated with A-363 and A-370. Ref.26 Ref.38 Ref.42
Mutagenesis3941T → A: Impairs phosphorylation and abolishes agonist-mediated acute receptor desensitization. Ref.19 Ref.20
Sequence conflict2371F → G in AAA79180. Ref.6
Sequence conflict2381I → V in AAQ77386. Ref.7
Sequence conflict2451V → I in AAA41630. Ref.3
Sequence conflict2451V → I in AAA70049. Ref.4
Sequence conflict2451V → I in S77863. Ref.10

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 1, 1994. Version 1.
Checksum: 9C916DE7C1C33743

FASTA39844,494
        10         20         30         40         50         60 
MDSSTGPGNT SDCSDPLAQA SCSPAPGSWL NLSHVDGNQS DPCGLNRTGL GGNDSLCPQT 

        70         80         90        100        110        120 
GSPSMVTAIT IMALYSIVCV VGLFGNFLVM YVIVRYTKMK TATNIYIFNL ALADALATST 

       130        140        150        160        170        180 
LPFQSVNYLM GTWPFGTILC KIVISIDYYN MFTSIFTLCT MSVDRYIAVC HPVKALDFRT 

       190        200        210        220        230        240 
PRNAKIVNVC NWILSSAIGL PVMFMATTKY RQGSIDCTLT FSHPTWYWEN LLKICVFIFA 

       250        260        270        280        290        300 
FIMPVLIITV CYGLMILRLK SVRMLSGSKE KDRNLRRITR MVLVVVAVFI VCWTPIHIYV 

       310        320        330        340        350        360 
IIKALITIPE TTFQTVSWHF CIALGYTNSC LNPVLYAFLD ENFKRCFREF CIPTSSTIEQ 

       370        380        390 
QNSTRVRQNT REHPSTANTV DRTNHQLENL EAETAPLP 

« Hide

Isoform 2 (MOR1A) [UniParc].

Checksum: 1880D1C9918035A4
Show »

FASTA39043,636
Isoform 3 (MOR1R) [UniParc].

Checksum: 166612B3218035A4
Show »

FASTA39043,586
Isoform 4 (MOR1B) [UniParc].

Checksum: 81767FCF38618035
Show »

FASTA39143,816
Isoform 5 (MOR1B2) [UniParc].

Checksum: A9819A64EBC80041
Show »

FASTA39343,986
Isoform 6 (MOR1C1) [UniParc].

Checksum: F1130789E14DF1F7
Show »

FASTA45150,445
Isoform 7 (MOR-1C2) [UniParc].

Checksum: 55F763EE13B2B6D1
Show »

FASTA46852,410
Isoform 8 (rMOR-1D) [UniParc].

Checksum: BAF18035A454EB66
Show »

FASTA38743,317

References

« Hide 'large scale' references
[1]"Primary structures and expression from cDNAs of rat opioid receptor delta- and mu-subtypes."
Fukuda K., Kato S., Mori K., Nishi M., Takeshima H.
FEBS Lett. 327:311-314(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Brain.
[2]"Mu opiate receptor: cDNA cloning and expression."
Wang J.-B., Imai Y., Epler M.C., Gregor P., Spivak C., Uhl G.R.
Proc. Natl. Acad. Sci. U.S.A. 90:10230-10234(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Brain.
[3]"Molecular cloning and functional expression of a mu-opioid receptor from rat brain."
Chen Y., Mestek A., Liu J., Hurley J.A., Yu L.
Mol. Pharmacol. 44:8-12(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Brain.
[4]Bunzow J.R., Grandy D.K., Kelly M.
Submitted (SEP-1993) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Strain: Sprague-Dawley.
Tissue: Brain.
[5]"Cloning and pharmacological characterization of a rat mu opioid receptor."
Thompson R.C., Mansour A., Akil H., Watson S.J.
Neuron 11:903-913(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Strain: Sprague-Dawley.
Tissue: Olfactory bulb.
[6]"Cloning, characterization, and distribution of a mu-opioid receptor in rat brain."
Zastawny R.L., George S.R., Nguyen T., Cheng R., Tsatsos J., Briones-Urbina R., O'Dowd B.F.
J. Neurochem. 62:2099-2105(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Brain.
[7]"Identification and characterization of two new alternatively spliced variants from the rat mu opioid receptor gene, Oprm."
Pan Y.-X., Xu J., Pasternak G.W.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 5).
Strain: Sprague-Dawley.
[8]"Identification of three new alternatively spliced variants of the rat mu opioid receptor gene: dissociation of affinity and efficacy."
Pasternak D.A., Pan L., Xu J., Yu R., Xu M.M., Pasternak G.W., Pan Y.X.
J. Neurochem. 91:881-890(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 6; 7 AND 8).
Strain: Sprague-Dawley.
[9]"Genome sequence of the Brown Norway rat yields insights into mammalian evolution."
Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M. expand/collapse author list , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S.
Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Brown Norway.
[10]"Complementary DNA cloning of a mu-opioid receptor from rat peritoneal macrophages."
Sedqi M., Roy S., Ramakrishnan S., Elde R., Loh H.H.
Biochem. Biophys. Res. Commun. 209:563-574(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 101-340.
Tissue: Macrophage.
[11]"Cloning and expression of an isoform of the rat mu opioid receptor (rMOR1B) which differs in agonist induced desensitization from rMOR1."
Zimprich A., Simon T., Hoellt V.
FEBS Lett. 359:142-146(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 356-398 (ISOFORM 4).
[12]"Activation of mu opioid receptors inhibits transient high- and low-threshold Ca2+ currents, but spares a sustained current."
Schroeder J.E., Fischbach P.S., Zheng D., McCleskey E.W.
Neuron 6:13-20(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[13]"Inhibition of Ca2+ currents by a mu-opioid in a defined subset of rat sensory neurons."
Schroeder J.E., McCleskey E.W.
J. Neurosci. 13:867-873(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[14]"-mu opiate receptor. Charged transmembrane domain amino acids are critical for agonist recognition and intrinsic activity."
Surratt C.K., Johnson P.S., Moriwaki A., Seidleck B.K., Blaschak C.J., Wang J.B., Uhl G.R.
J. Biol. Chem. 269:20548-20553(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF ASP-114; ASP-147 AND HIS-297.
[15]"Activation of type II adenylyl cyclase by the cloned mu-opioid receptor: coupling to multiple G proteins."
Chan J.S., Chiu T.T., Wong Y.H.
J. Neurochem. 65:2682-2689(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, COUPLING TO G-PROTEINS.
[16]"The mu-opioid receptor down-regulates differently from the delta-opioid receptor: requirement of a high affinity receptor/G protein complex formation."
Chakrabarti S., Yang W., Law P.Y., Loh H.H.
Mol. Pharmacol. 52:105-113(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF ASP-114.
[17]"Palmitoylation of the rat mu opioid receptor."
Chen C., Shahabi V., Xu W., Liu-Chen L.Y.
FEBS Lett. 441:148-152(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PALMITOYLATION, MUTAGENESIS OF CYS-346 AND CYS-351.
[18]"Differential coupling of mu-, delta-, and kappa-opioid receptors to G alpha16-mediated stimulation of phospholipase C."
Lee J.W., Joshi S., Chan J.S., Wong Y.H.
J. Neurochem. 70:2203-2211(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: COUPLING TO GNA15.
[19]"Agonist-induced, G protein-dependent and -independent down-regulation of the mu opioid receptor. The receptor is a direct substrate for protein-tyrosine kinase."
Pak Y., O'Dowd B.F., Wang J.B., George S.R.
J. Biol. Chem. 274:27610-27616(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, MUTAGENESIS OF TYR-91; TYR-96; TYR-166; TYR-336 AND THR-394.
[20]"Role for the C-terminus in agonist-induced mu opioid receptor phosphorylation and desensitization."
Deng H.B., Yu Y., Pak Y., O'Dowd B.F., George S.R., Surratt C.K., Uhl G.R., Wang J.B.
Biochemistry 39:5492-5499(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-394, MUTAGENESIS OF THR-394.
[21]"Oligomerization of mu- and delta-opioid receptors. Generation of novel functional properties."
George S.R., Fan T., Xie Z., Tse R., Tam V., Varghese G., O'Dowd B.F.
J. Biol. Chem. 275:26128-26135(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: RECEPTOR HETEROOLIGOMERIZATION, INTERACTION WITH OPRD1.
[22]"Mutational analysis of Gbetagamma and phospholipid interaction with G protein-coupled receptor kinase 2."
Carman C.V., Barak L.S., Chen C., Liu-Chen L.Y., Onorato J.J., Kennedy S.P., Caron M.G., Benovic J.L.
J. Biol. Chem. 275:10443-10452(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY ADRBK1.
[23]"Constitutive activation of the mu opioid receptor by mutation of D3.49(164), but not D3.32(147): D3.49(164) is critical for stabilization of the inactive form of the receptor and for its expression."
Li J., Huang P., Chen C., de Riel J.K., Weinstein H., Liu-Chen L.Y.
Biochemistry 40:12039-12050(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF ASP-147 AND ASP-164.
[24]"Functional role of a conserved motif in TM6 of the rat mu opioid receptor: constitutively active and inactive receptors result from substitutions of Thr6.34(279) with Lys and Asp."
Huang P., Li J., Chen C., Visiers I., Weinstein H., Liu-Chen L.Y.
Biochemistry 40:13501-13509(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF THR-279.
[25]"Threonine 180 is required for G-protein-coupled receptor kinase 3- and beta-arrestin 2-mediated desensitization of the mu-opioid receptor in Xenopus oocytes."
Celver J.P., Lowe J., Kovoor A., Gurevich V.V., Chavkin C.
J. Biol. Chem. 276:4894-4900(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF THR-180.
[26]"Phosphorylation of Ser363, Thr370, and Ser375 residues within the carboxyl tail differentially regulates mu-opioid receptor internalization."
El Kouhen R., Burd A.L., Erickson-Herbrandson L.J., Chang C.Y., Law P.Y., Loh H.H.
J. Biol. Chem. 276:12774-12780(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-363; THR-370 AND SER-375, MUTAGENESIS OF SER-363; THR-370 AND SER-375.
[27]"The local environment at the cytoplasmic end of TM6 of the mu opioid receptor differs from those of rhodopsin and monoamine receptors: introduction of an ionic lock between the cytoplasmic ends of helices 3 and 6 by a L6.30(275)E mutation inactivates the mu opioid receptor and reduces the constitutive activity of its T6.34(279)K mutant."
Huang P., Visiers I., Weinstein H., Liu-Chen L.Y.
Biochemistry 41:11972-11980(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF LEU-275 AND THR-279.
[28]"Heterodimerization of somatostatin and opioid receptors cross-modulates phosphorylation, internalization, and desensitization."
Pfeiffer M., Koch T., Schroder H., Laugsch M., Hollt V., Schulz S.
J. Biol. Chem. 277:19762-19772(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: RECEPTOR HETEROOLIGOMERIZATION, INTERACTION WITH SSTR2.
[29]"ADP-ribosylation factor-dependent phospholipase D2 activation is required for agonist-induced mu-opioid receptor endocytosis."
Koch T., Brandenburg L.O., Schulz S., Liang Y., Klein J., Hollt V.
J. Biol. Chem. 278:9979-9985(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PLD2.
[30]"Functional interactions between mu opioid and alpha 2A-adrenergic receptors."
Jordan B.A., Gomes I., Rios C., Filipovska J., Devi L.A.
Mol. Pharmacol. 64:1317-1324(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: RECEPTOR HETEROOLIGOMERIZATION, INTERACTION WITH ADRA2A.
[31]"Heterodimerization and cross-desensitization between the mu-opioid receptor and the chemokine CCR5 receptor."
Chen C., Li J., Bot G., Szabo I., Rogers T.J., Liu-Chen L.Y.
Eur. J. Pharmacol. 483:175-186(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: RECEPTOR HETEROOLIGOMERIZATION, INTERACTION WITH CCR5.
[32]"Biochemical demonstration of mu-opioid receptor association with Gsalpha: enhancement following morphine exposure."
Chakrabarti S., Regec A., Gintzler A.R.
Brain Res. Mol. Brain Res. 135:217-224(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GNAS.
[33]"Mu and kappa opioid receptors activate ERK/MAPK via different protein kinase C isoforms and secondary messengers in astrocytes."
Belcheva M.M., Clark A.L., Haas P.D., Serna J.S., Hahn J.W., Kiss A., Coscia C.J.
J. Biol. Chem. 280:27662-27669(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[34]"Receptor heterodimerization leads to a switch in signaling: beta-arrestin2-mediated ERK activation by mu-delta opioid receptor heterodimers."
Rozenfeld R., Devi L.A.
FASEB J. 21:2455-2465(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: RECEPTOR HETEROOLIGOMERIZATION, INTERACTION WITH OPRD1.
[35]"Membrane glycoprotein M6a interacts with the micro-opioid receptor and facilitates receptor endocytosis and recycling."
Wu D.F., Koch T., Liang Y.J., Stumm R., Schulz S., Schroder H., Hollt V.
J. Biol. Chem. 282:22239-22247(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GPM6A.
[36]"Interaction of the mu-opioid receptor with synaptophysin influences receptor trafficking and signaling."
Liang Y.J., Wu D.F., Yang L.Q., Hollt V., Koch T.
Mol. Pharmacol. 71:123-131(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SYP.
[37]"mu opioid and CB1 cannabinoid receptor interactions: reciprocal inhibition of receptor signaling and neuritogenesis."
Rios C., Gomes I., Devi L.A.
Br. J. Pharmacol. 148:387-395(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, RECEPTOR HETEROOLIGOMERIZATION, INTERACTION WITH CNR1.
[38]"Morphine-induced mu-opioid receptor rapid desensitization is independent of receptor phosphorylation and beta-arrestins."
Chu J., Zheng H., Loh H.H., Law P.Y.
Cell. Signal. 20:1616-1624(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF SER-363; THR-370 AND SER-375.
[39]"Beta-arrestin-dependent mu-opioid receptor-activated extracellular signal-regulated kinases (ERKs) Translocate to Nucleus in Contrast to G protein-dependent ERK activation."
Zheng H., Loh H.H., Law P.Y.
Mol. Pharmacol. 73:178-190(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[40]"Regulator of G protein signaling 4 confers selectivity to specific G proteins to modulate mu- and delta-opioid receptor signaling."
Leontiadis L.J., Papakonstantinou M.P., Georgoussi Z.
Cell. Signal. 21:1218-1228(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RGS4.
[41]"Phosphorylation of the mu-opioid receptor at tyrosine 166 (Tyr3.51) in the DRY motif reduces agonist efficacy."
Clayton C.C., Bruchas M.R., Lee M.L., Chavkin C.
Mol. Pharmacol. 77:339-347(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-166, MUTAGENESIS OF TYR-166.
[42]"Modulating micro-opioid receptor phosphorylation switches agonist-dependent signaling as reflected in PKCepsilon activation and dendritic spine stability."
Zheng H., Chu J., Zhang Y., Loh H.H., Law P.Y.
J. Biol. Chem. 286:12724-12733(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF SER-375.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D16349 mRNA. Translation: BAA03852.1.
L20684 mRNA. Translation: AAA41643.1.
L13069 mRNA. Translation: AAA41630.1.
U02083 mRNA. Translation: AAA70049.1.
L22455 mRNA. Translation: AAA16075.1.
U35424 mRNA. Translation: AAA79180.1.
AY309003 mRNA. Translation: AAQ77387.1. Frameshift.
AY309004 mRNA. Translation: AAQ77388.1.
AY225402 mRNA. Translation: AAP44725.1.
AY225403 mRNA. Translation: AAP44726.1.
AY309000 mRNA. Translation: AAQ77384.1.
AY309002 mRNA. Translation: AAQ77386.1.
S77863 mRNA. No translation available.
S75669 mRNA. Translation: AAB33530.2.
PIRI56504.
I56517.
S69010.
RefSeqNP_001033686.1. NM_001038597.2. [P33535-2]
NP_001033688.2. NM_001038599.2. [P33535-5]
NP_001033689.1. NM_001038600.2. [P33535-6]
NP_001033690.1. NM_001038601.2. [P33535-7]
NP_037203.1. NM_013071.2. [P33535-1]
XP_006227931.1. XM_006227869.1. [P33535-3]
UniGeneRn.10118.

3D structure databases

ProteinModelPortalP33535.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP33535. 6 interactions.
STRING10116.ENSRNOP00000057371.

Chemistry

BindingDBP33535.
ChEMBLCHEMBL270.
GuidetoPHARMACOLOGY319.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP33535.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000024682; ENSRNOP00000024682; ENSRNOG00000018191. [P33535-5]
ENSRNOT00000051837; ENSRNOP00000051290; ENSRNOG00000018191. [P33535-1]
GeneID25601.
KEGGrno:25601.

Organism-specific databases

CTD4988.
RGD3234. Oprm1.

Phylogenomic databases

eggNOGNOG279457.
GeneTreeENSGT00630000089574.
HOGENOMHOG000230486.
HOVERGENHBG106919.
InParanoidQ4VWX8.
KOK04215.
OMANSTRVRQ.
OrthoDBEOG7BKCVQ.
TreeFamTF315737.

Gene expression databases

GenevestigatorP33535.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR000105. Mu_opioid_rcpt.
IPR001418. Opioid_rcpt.
[Graphical view]
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00237. GPCRRHODOPSN.
PR00537. MUOPIOIDR.
PR00384. OPIOIDR.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio607309.
PROP33535.

Entry information

Entry nameOPRM_RAT
AccessionPrimary (citable) accession number: P33535
Secondary accession number(s): Q2TV20 expand/collapse secondary AC list , Q2TV21, Q4VWM5, Q4VWM7, Q4VWX7, Q4VWX8, Q62846, Q64064, Q64120
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: June 11, 2014
This is version 121 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries