Linked Life Data

P42866

Source:http://identifiers.org/uniprot/P42866

Statements in which the resource exists.
SubjectPredicateObjectContext
http://identifiers.org/unip...rdf:typebiopax3:ProteinReferencelld:biopax3
http://identifiers.org/unip...biopax3:commentFUNCTION: 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. 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 and GPM6A. Interacts with RTP4. Interacts with SYP and GNAS (By similarity). Interacts with RGS9, RGS17, RGS20, RGS4, PPP1R9B and HINT1. Isoform 9 interacts with GRPR. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=19; Comment=Additional isoforms seem to exist. Functional relevance for short isoforms with one transmembrane domain only is unsure and these isoforms are not included; Name=1; Synonyms=MOR-1, MOR-H, MOR-1J, MOR-1T; IsoId=P42866-1; Sequence=Displayed; Name=2; Synonyms=MOR-1A; IsoId=P42866-2; Sequence=VSP_042339; Name=3; Synonyms=MOR-1B1; IsoId=P42866-3; Sequence=VSP_042340; Name=4; Synonyms=MOR-1B2; IsoId=P42866-4; Sequence=VSP_042341; Name=5; Synonyms=MOR-1B3, MOR-1Q; IsoId=P42866-5; Sequence=VSP_042342; Name=6; Synonyms=MOR-1B4, MOR-1R; IsoId=P42866-6; Sequence=VSP_042343; Name=7; Synonyms=MOR-1B5, MOR-1P; IsoId=P42866-7; Sequence=VSP_042344; Name=8; Synonyms=MOR-1C; IsoId=P42866-8; Sequence=VSP_042345; Name=9; Synonyms=MOR-1D; IsoId=P42866-9; Sequence=VSP_042346; Name=10; Synonyms=MOR-1E, MOR-1Eiii, MOR-1Eiv; IsoId=P42866-10; Sequence=VSP_042333; Name=11; Synonyms=MOR-1F; IsoId=P42866-11; Sequence=VSP_042334; Name=12; Synonyms=MOR-1O; IsoId=P42866-12; Sequence=VSP_042335; Name=13; Synonyms=MOR-1P, MOR-1R; IsoId=P42866-13; Sequence=VSP_042336; Name=14; Synonyms=MOR-1G; IsoId=P42866-14; Sequence=VSP_042332; Name=15; Synonyms=MOR-1M; IsoId=P42866-15; Sequence=VSP_042332, VSP_042345; Name=16; Synonyms=MOR-1N; IsoId=P42866-16; Sequence=VSP_042332, VSP_042346; Name=17; Synonyms=MOR-1U; IsoId=P42866-17; Sequence=VSP_042337; Name=18; Synonyms=MOR-1V; IsoId=P42866-18; Sequence=VSP_042338; Name=19; Synonyms=MOR-1W; IsoId=P42866-19; Sequence=VSP_042347; 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-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 agoinist-induced G- protein-indepenedent receptor down-regulation. Phosphorylation at Ser-375 is involved in G-protein-dependent but not beta-arrestin- dependent activation of the ERK pathway. 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. DISRUPTION PHENOTYPE: During adult neurogenesis in hippocampus, increased numbers of granule cells maturing into neurons, larger granule cell layers and increased numbers of granule cells. SIMILARITY: Belongs to the G-protein coupled receptor 1 family. GENE SYNONYMS:Oprm1 Mor Oprm. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.lld:biopax3
http://identifiers.org/unip...biopax3:commentSEQUENCE 398 AA; 44421 MW; DFE1C758E2DA197E CRC64;lld:biopax3
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http://identifiers.org/unip...biopax3:nameMOR-1lld:biopax3
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http://identifiers.org/unip...biopax3:sequenceMDSSAGPGNISDCSDPLAPASCSPAPGSWLNLSHVDGNQSDPCGPNRTGLGGSHSLCPQTGSPSMVTAITIMALYSIVCVVGLFGNFLVMYVIVRYTKMKTATNIYIFNLALADALATSTLPFQSVNYLMGTWPFGNILCKIVISIDYYNMFTSIFTLCTMSVDRYIAVCHPVKALDFRTPRNAKIVNVCNWILSSAIGLPVMFMATTKYRQGSIDCTLTFSHPTWYWENLLKICVFIFAFIMPVLIITVCYGLMILRLKSVRMLSGSKEKDRNLRRITRMVLVVVAVFIVCWTPIHIYVIIKALITIPETTFQTVSWHFCIALGYTNSCLNPVLYAFLDENFKRCFREFCIPTSSTIEQQNSARIRQNTREHPSTANTVDRTNHQLENLEAETAPLPlld:biopax3
http://identifiers.org/unip...biopax3:standardNameMu-type opioid receptorlld:biopax3
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