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OPRM_SAIBB
ID   OPRM_SAIBB              Reviewed;         400 AA.
AC   Q5IS84;
DT   25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT   15-FEB-2005, sequence version 1.
DT   03-AUG-2022, entry version 86.
DE   RecName: Full=Mu-type opioid receptor;
DE            Short=M-OR-1;
DE            Short=MOR-1;
GN   Name=OPRM1;
OS   Saimiri boliviensis boliviensis (Bolivian squirrel monkey).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Platyrrhini; Cebidae;
OC   Saimiriinae; Saimiri.
OX   NCBI_TaxID=39432;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=15620360; DOI=10.1016/j.cell.2004.11.040;
RA   Dorus S., Vallender E.J., Evans P.D., Anderson J.R., Gilbert S.L.,
RA   Mahowald M., Wyckoff G.J., Malcom C.M., Lahn B.T.;
RT   "Accelerated evolution of nervous system genes in the origin of Homo
RT   sapiens.";
RL   Cell 119:1027-1040(2004).
CC   -!- FUNCTION: Receptor for endogenous opioids such as beta-endorphin and
CC       endomorphin. Receptor for natural and synthetic opioids including
CC       morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and
CC       methadone. Also activated by enkephalin peptides, such as Met-
CC       enkephalin or Met-enkephalin-Arg-Phe, with higher affinity for Met-
CC       enkephalin-Arg-Phe. Agonist binding to the receptor induces coupling to
CC       an inactive GDP-bound heterotrimeric G-protein complex and subsequent
CC       exchange of GDP for GTP in the G-protein alpha subunit leading to
CC       dissociation of the G-protein complex with the free GTP-bound G-protein
CC       alpha and the G-protein beta-gamma dimer activating downstream cellular
CC       effectors. The agonist- and cell type-specific activity is
CC       predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G
CC       alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1, and to a lesser extent
CC       to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15. They
CC       mediate an array of downstream cellular responses, including inhibition
CC       of adenylate cyclase activity and both N-type and L-type calcium
CC       channels, activation of inward rectifying potassium channels, mitogen-
CC       activated protein kinase (MAPK), phospholipase C (PLC),
CC       phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K)
CC       and regulation of NF-kappa-B. Also couples to adenylate cyclase
CC       stimulatory G alpha proteins. The selective temporal coupling to G-
CC       proteins and subsequent signaling can be regulated by RGSZ proteins,
CC       such as RGS9, RGS17 and RGS4. Phosphorylation by members of the GPRK
CC       subfamily of Ser/Thr protein kinases and association with beta-
CC       arrestins is involved in short-term receptor desensitization. Beta-
CC       arrestins associate with the GPRK-phosphorylated receptor and uncouple
CC       it from the G-protein thus terminating signal transduction. The
CC       phosphorylated receptor is internalized through endocytosis via
CC       clathrin-coated pits which involves beta-arrestins. The activation of
CC       the ERK pathway occurs either in a G-protein-dependent or a beta-
CC       arrestin-dependent manner and is regulated by agonist-specific receptor
CC       phosphorylation. Acts as a class A G-protein coupled receptor (GPCR)
CC       which dissociates from beta-arrestin at or near the plasma membrane and
CC       undergoes rapid recycling. Receptor down-regulation pathways are
CC       varying with the agonist and occur dependent or independent of G-
CC       protein coupling. Endogenous ligands induce rapid desensitization,
CC       endocytosis and recycling. Heterooligomerization with other GPCRs can
CC       modulate agonist binding, signaling and trafficking properties.
CC       Involved in neurogenesis. {ECO:0000250|UniProtKB:P33535,
CC       ECO:0000250|UniProtKB:P35372, ECO:0000250|UniProtKB:P42866}.
CC   -!- SUBUNIT: Forms homooligomers and heterooligomers with other GPCRs, such
CC       as OPRD1, OPRK1, OPRL1, NPFFR2, ADRA2A, SSTR2, CNR1 and CCR5 (probably
CC       in dimeric forms). Interacts with heterotrimeric G proteins;
CC       interaction with a heterotrimeric complex containing GNAI1, GNB1 and
CC       GNG2 stabilizes the active conformation of the receptor and increases
CC       its affinity for endomorphin-2, the synthetic opioid peptide DAMGO and
CC       for morphinan agonists (By similarity). Interacts with PPL; the
CC       interaction disrupts agonist-mediated G-protein activation. Interacts
CC       (via C-terminus) with DNAJB4 (via C-terminus). Interacts with
CC       calmodulin; the interaction inhibits the constitutive activity of
CC       OPRM1; it abolishes basal and attenuates agonist-stimulated G-protein
CC       coupling. Interacts with FLNA, PLD2, RANBP9 and WLS and GPM6A (By
CC       similarity). Interacts with RTP4 (By similarity). Interacts with SYP
CC       and GNAS (By similarity). Interacts with RGS9, RGS17, RGS20, RGS4,
CC       PPP1R9B and HINT1. {ECO:0000250|UniProtKB:P33535,
CC       ECO:0000250|UniProtKB:P35372, ECO:0000250|UniProtKB:P42866}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P42866};
CC       Multi-pass membrane protein {ECO:0000250|UniProtKB:P42866}. Cell
CC       projection, axon {ECO:0000250|UniProtKB:P97266}. Perikaryon
CC       {ECO:0000250|UniProtKB:P97266}. Cell projection, dendrite
CC       {ECO:0000250|UniProtKB:P97266}. Endosome
CC       {ECO:0000250|UniProtKB:P97266}. Note=Is rapidly internalized after
CC       agonist binding. {ECO:0000250|UniProtKB:P97266}.
CC   -!- PTM: Phosphorylated. Differentially phosphorylated in basal and
CC       agonist-induced conditions. Agonist-mediated phosphorylation modulates
CC       receptor internalization. Phosphorylated by GRK2 in a agonist-dependent
CC       manner. Phosphorylation at Tyr-168 requires receptor activation, is
CC       dependent on non-receptor protein tyrosine kinase Src and results in a
CC       decrease in agonist efficacy by reducing G-protein coupling efficiency.
CC       Phosphorylated on tyrosine residues; the phosphorylation is involved in
CC       agonist-induced G-protein-independent receptor down-regulation.
CC       Phosphorylation at Ser-377 is involved in G-protein-dependent but not
CC       beta-arrestin-dependent activation of the ERK pathway (By similarity).
CC       {ECO:0000250|UniProtKB:P33535}.
CC   -!- PTM: Ubiquitinated. A basal ubiquitination seems not to be related to
CC       degradation. Ubiquitination is increased upon formation of OPRM1:OPRD1
CC       oligomers leading to proteasomal degradation; the ubiquitination is
CC       diminished by RTP4. {ECO:0000250|UniProtKB:P42866}.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR   EMBL; AY665244; AAV74282.1; -; mRNA.
DR   RefSeq; NP_001266908.1; NM_001279979.1.
DR   AlphaFoldDB; Q5IS84; -.
DR   SMR; Q5IS84; -.
DR   STRING; 39432.ENSSBOP00000020184; -.
DR   Ensembl; ENSSBOT00000037002; ENSSBOP00000020175; ENSSBOG00000026674.
DR   GeneID; 101042291; -.
DR   CTD; 4988; -.
DR   GeneTree; ENSGT00940000158236; -.
DR   Proteomes; UP000233220; Unplaced.
DR   GO; GO:0030424; C:axon; ISS:UniProtKB.
DR   GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR   GO; GO:0005768; C:endosome; ISS:UniProtKB.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0045202; C:synapse; IEA:GOC.
DR   GO; GO:0004979; F:beta-endorphin receptor activity; IEA:InterPro.
DR   GO; GO:0004930; F:G protein-coupled receptor activity; ISS:UniProtKB.
DR   GO; GO:0001965; F:G-protein alpha-subunit binding; ISS:UniProtKB.
DR   GO; GO:0038047; F:morphine receptor activity; ISS:UniProtKB.
DR   GO; GO:0005245; F:voltage-gated calcium channel activity; ISS:UniProtKB.
DR   GO; GO:0007197; P:adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:0038003; P:G protein-coupled opioid receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; ISS:UniProtKB.
DR   GO; GO:0051481; P:negative regulation of cytosolic calcium ion concentration; ISS:UniProtKB.
DR   GO; GO:0045019; P:negative regulation of nitric oxide biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0061358; P:negative regulation of Wnt protein secretion; ISS:UniProtKB.
DR   GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR   GO; GO:0050769; P:positive regulation of neurogenesis; ISS:UniProtKB.
DR   GO; GO:2000310; P:regulation of NMDA receptor activity; ISS:UniProtKB.
DR   GO; GO:0019233; P:sensory perception of pain; ISS:UniProtKB.
DR   InterPro; IPR000276; GPCR_Rhodpsn.
DR   InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR   InterPro; IPR000105; Mu_opioid_rcpt.
DR   InterPro; IPR001418; Opioid_rcpt.
DR   Pfam; PF00001; 7tm_1; 1.
DR   PRINTS; PR00237; GPCRRHODOPSN.
DR   PRINTS; PR00537; MUOPIOIDR.
DR   PRINTS; PR00384; OPIOIDR.
DR   PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR   PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE   2: Evidence at transcript level;
KW   Cell membrane; Cell projection; Disulfide bond; Endosome;
KW   G-protein coupled receptor; Glycoprotein; Lipoprotein; Membrane; Palmitate;
KW   Phosphoprotein; Receptor; Reference proteome; Transducer; Transmembrane;
KW   Transmembrane helix; Ubl conjugation.
FT   CHAIN           1..400
FT                   /note="Mu-type opioid receptor"
FT                   /id="PRO_0000246162"
FT   TOPO_DOM        1..68
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:P42866"
FT   TRANSMEM        69..93
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000250|UniProtKB:P42866"
FT   TOPO_DOM        94..106
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P42866"
FT   TRANSMEM        107..131
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000250|UniProtKB:P42866"
FT   TOPO_DOM        132..142
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:P42866"
FT   TRANSMEM        143..165
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000250|UniProtKB:P42866"
FT   TOPO_DOM        166..185
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P42866"
FT   TRANSMEM        186..207
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000250|UniProtKB:P42866"
FT   TOPO_DOM        208..230
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:P42866"
FT   TRANSMEM        231..255
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000250|UniProtKB:P42866"
FT   TOPO_DOM        256..279
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P42866"
FT   TRANSMEM        280..306
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000250|UniProtKB:P42866"
FT   TOPO_DOM        307..314
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:P42866"
FT   TRANSMEM        315..338
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000250|UniProtKB:P42866"
FT   TOPO_DOM        339..400
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P42866"
FT   MOTIF           334..338
FT                   /note="NPxxY; plays a role in stabilizing the activated
FT                   conformation of the receptor"
FT                   /evidence="ECO:0000250|UniProtKB:P42866"
FT   MOD_RES         168
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P33535"
FT   MOD_RES         365
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P42866"
FT   MOD_RES         372
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P33535"
FT   MOD_RES         377
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P33535"
FT   MOD_RES         396
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P33535"
FT   LIPID           353
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        9
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        12
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        33
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        40
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        48
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        142..219
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
SQ   SEQUENCE   400 AA;  44559 MW;  9AE5DEE957354023 CRC64;
     MDSSAVPANA SNCTDPLAPS TCSPAPGPGS WVNLSHLDGN LSDPCGPNRT DLGGSDSPCP
     PTGSPSMITA ITIMALYSIV CVVGLFGNFL VMYVIVRYTK MKTATNIYIF NLALADALAT
     STLPFQSVNY LMGTWPFGTI LCKIVISIDY YNMFTSIFTL CTMSVDRYIA VCHPVKALDF
     RTPRNAKIVN VCNWIISSAI GLPVMFMATT KYRQGSIDCT LTFSHPTWYW ENLLKICVFI
     FAFIMPVLII TVCYGLMILR LKSVRMLSGS KEKDRNLRRI TRMVLVVVAV FIVCWTPIHI
     YVIIKALVTI PETTFQTVSW HFCIALGYTN SCLNPVLYAF LDENFKRCFR EFCIPTPSAI
     EQQNSARIRQ NTRDHPSTAN TVDRTNHQLE NLEAETAPLP
 
 
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