OPRX_MOUSE
ID OPRX_MOUSE Reviewed; 367 AA.
AC P35377; Q60645; Q8VI74; Q9QUT5; Q9Z2M8; Q9Z2M9; Q9Z2N0;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Nociceptin receptor;
DE AltName: Full=K3 opiate receptor;
DE AltName: Full=Kappa-type 3 opioid receptor;
DE Short=KOR-3;
DE AltName: Full=ORGC;
DE AltName: Full=Orphanin FQ receptor;
GN Name=Oprl1; Synonyms=Oor, Oprl;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE (ISOFORM KOR3).
RC STRAIN=C57BL/6N; TISSUE=Brain;
RA Yasuda K., Jones E., Reisine T., Bell G.I.;
RL Submitted (JAN-1994) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM KOR3).
RX PubMed=7802669; DOI=10.1006/bbrc.1994.2814;
RA Nishi M., Takeshima H., Mori M., Nakagawara K., Takeuchi T.;
RT "Structure and chromosomal mapping of genes for the mouse kappa-opioid
RT receptor and an opioid receptor homologue (MOR-C).";
RL Biochem. Biophys. Res. Commun. 205:1353-1357(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM KOR3), FUNCTION, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Brain;
RX PubMed=8794880;
RA Matthes H.W.D., Seward E.P., Kieffer B., North R.A.;
RT "Functional selectivity of orphanin FQ for its receptor coexpressed with
RT potassium channel subunits in Xenopus laevis oocytes.";
RL Mol. Pharmacol. 50:447-450(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE (ISOFORM KOR3).
RA Pan Y.-X., Xu J., Pasternak G.W.;
RL Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM KOR3), FUNCTION, SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RX PubMed=7603458;
RA Pan Y.-X., Cheng J., Xu J., Rossi G., Jacobson E., Ryan-Moro J.,
RA Brooks A.I., Dean G.E., Standifer K.M., Pasternak G.W.;
RT "Cloning and functional characterization through antisense mapping of a
RT kappa 3-related opioid receptor.";
RL Mol. Pharmacol. 47:1180-1188(1995).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS KOR3A; KOR3B; KOR3C; KOR3D AND KOR3E),
RP AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=9755860; DOI=10.1016/s0014-5793(98)01039-4;
RA Pan Y.-X., Xu J., Wan B.-L., Zuckerman A., Pasternak G.W.;
RT "Identification and differential regional expression of KOR-3/ORL-1 gene
RT splice variants in mouse brain.";
RL FEBS Lett. 435:65-68(1998).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM KOR3).
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-357 (ISOFORM KOR3), AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ; TISSUE=Spleen;
RX PubMed=7797625; DOI=10.1016/0165-5728(95)00030-6;
RA Halford W.P., Gebhardt B.M., Carr D.J.J.;
RT "Functional role and sequence analysis of a lymphocyte orphan opioid
RT receptor.";
RL J. Neuroimmunol. 59:91-101(1995).
RN [9]
RP DISRUPTION PHENOTYPE.
RX PubMed=9155012; DOI=10.1093/emboj/16.8.1858;
RA Nishi M., Houtani T., Noda Y., Mamiya T., Sato K., Doi T., Kuno J.,
RA Takeshima H., Nukada T., Nabeshima T., Yamashita T., Noda T., Sugimoto T.;
RT "Unrestrained nociceptive response and disregulation of hearing ability in
RT mice lacking the nociceptin/orphaninFQ receptor.";
RL EMBO J. 16:1858-1864(1997).
RN [10]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=12217419; DOI=10.1016/s0196-9781(02)00102-x;
RA Bertorelli R., Bastia E., Citterio F., Corradini L., Forlani A., Ongini E.;
RT "Lack of the nociceptin receptor does not affect acute or chronic
RT nociception in mice.";
RL Peptides 23:1589-1596(2002).
RN [11]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=12814369; DOI=10.1046/j.1460-9568.2003.02676.x;
RA Depner U.B., Reinscheid R.K., Takeshima H., Brune K., Zeilhofer H.U.;
RT "Normal sensitivity to acute pain, but increased inflammatory hyperalgesia
RT in mice lacking the nociceptin precursor polypeptide or the nociceptin
RT receptor.";
RL Eur. J. Neurosci. 17:2381-2387(2003).
RN [12]
RP FUNCTION.
RX PubMed=23652222; DOI=10.1124/jpet.113.203984;
RA Sukhtankar D.D., Zaveri N.T., Husbands S.M., Ko M.C.;
RT "Effects of spinally administered bifunctional nociceptin/orphanin FQ
RT peptide receptor/mu-opioid receptor ligands in mouse models of neuropathic
RT and inflammatory pain.";
RL J. Pharmacol. Exp. Ther. 346:11-22(2013).
CC -!- FUNCTION: G-protein coupled opioid receptor that functions as receptor
CC for the endogenous neuropeptide nociceptin. Ligand binding causes a
CC conformation change that triggers signaling via guanine nucleotide-
CC binding proteins (G proteins) and modulates the activity of down-stream
CC effectors. Signaling via G proteins mediates inhibition of adenylate
CC cyclase activity and calcium channel activity. Arrestins modulate
CC signaling via G proteins and mediate the activation of alternative
CC signaling pathways that lead to the activation of MAP kinases. Plays a
CC role in modulating nociception and the perception of pain. Plays a role
CC in the regulation of locomotor activity by the neuropeptide nociceptin.
CC {ECO:0000269|PubMed:12217419, ECO:0000269|PubMed:12814369,
CC ECO:0000269|PubMed:23652222, ECO:0000269|PubMed:7603458,
CC ECO:0000269|PubMed:8794880}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC Cytoplasmic vesicle {ECO:0000250}. Note=Ligand binding leads to
CC receptor internalization into cytoplasmic vesicles, decreasing the
CC amount of available receptor at the cell surface. Internalization
CC requires phosphorylation at Ser-360. Can recycle to the cell membrane
CC (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=KOR3;
CC IsoId=P35377-1; Sequence=Displayed;
CC Name=KOR3A;
CC IsoId=P35377-2; Sequence=VSP_001899, VSP_001900;
CC Name=KOR3B;
CC IsoId=P35377-3; Sequence=VSP_001903, VSP_001904;
CC Name=KOR3C;
CC IsoId=P35377-4; Sequence=VSP_001901, VSP_001902;
CC Name=KOR3D;
CC IsoId=P35377-5; Sequence=VSP_001898;
CC Name=KOR3E;
CC IsoId=P35377-6; Sequence=VSP_001905, VSP_001906;
CC -!- TISSUE SPECIFICITY: In the brain, isoform KOR3 and isoform KOR3C are
CC most abundant in hypothalamus and periaqueductal gray. Isoform KOR3A is
CC highly expressed in cortex, striatum and brainstem. Isoform KOR3D is
CC highly expressed in cerebellum, hypothalamus and brainstem. Detected in
CC spleen lymphocytes. {ECO:0000269|PubMed:7603458,
CC ECO:0000269|PubMed:7797625, ECO:0000269|PubMed:9755860}.
CC -!- PTM: Phosphorylation at Ser-360 requires GRK3. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice do not show altered basal
CC nociception, but are no longer susceptible to modulation of nociception
CC by the neuropeptide nociceptin. Contrary to wild-type, they do not show
CC reduced locomotion in response to the neuropeptide nociceptin. In
CC addition, mutant mice show subtle hearing defects.
CC {ECO:0000269|PubMed:12217419, ECO:0000269|PubMed:12814369,
CC ECO:0000269|PubMed:9155012}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; U04952; AAA03730.1; -; mRNA.
DR EMBL; D31667; BAA06509.1; -; Genomic_DNA.
DR EMBL; X91813; CAA62922.1; -; mRNA.
DR EMBL; U32932; AAC52669.1; -; Genomic_DNA.
DR EMBL; U32928; AAC52669.1; JOINED; Genomic_DNA.
DR EMBL; U32930; AAC52669.1; JOINED; Genomic_DNA.
DR EMBL; U09421; AAA81333.1; -; mRNA.
DR EMBL; AF043276; AAC64507.1; -; mRNA.
DR EMBL; AF043277; AAC64508.1; -; mRNA.
DR EMBL; AF043278; AAC64509.1; -; mRNA.
DR EMBL; AF062381; AAF21258.1; -; mRNA.
DR EMBL; AF075605; AAF21781.1; -; mRNA.
DR EMBL; AF126469; AAL54889.1; -; mRNA.
DR EMBL; BC050885; AAH50885.1; -; mRNA.
DR EMBL; U14165; AAA87899.1; -; mRNA.
DR CCDS; CCDS17222.1; -. [P35377-1]
DR PIR; I49022; I49022.
DR PIR; JC2421; JC2421.
DR RefSeq; NP_001239494.1; NM_001252565.1. [P35377-1]
DR RefSeq; NP_001305848.1; NM_001318919.1.
DR RefSeq; NP_001305849.1; NM_001318920.1. [P35377-5]
DR RefSeq; NP_035142.1; NM_011012.5. [P35377-1]
DR RefSeq; XP_006500645.1; XM_006500582.2. [P35377-5]
DR RefSeq; XP_017171812.1; XM_017316323.1. [P35377-1]
DR RefSeq; XP_017171814.1; XM_017316325.1. [P35377-1]
DR AlphaFoldDB; P35377; -.
DR SMR; P35377; -.
DR STRING; 10090.ENSMUSP00000071513; -.
DR BindingDB; P35377; -.
DR ChEMBL; CHEMBL3621; -.
DR GuidetoPHARMACOLOGY; 320; -.
DR GlyGen; P35377; 3 sites.
DR PhosphoSitePlus; P35377; -.
DR SwissPalm; P35377; -.
DR PaxDb; P35377; -.
DR PRIDE; P35377; -.
DR Antibodypedia; 29994; 241 antibodies from 29 providers.
DR DNASU; 18389; -.
DR Ensembl; ENSMUST00000071585; ENSMUSP00000071513; ENSMUSG00000027584. [P35377-1]
DR Ensembl; ENSMUST00000108766; ENSMUSP00000104397; ENSMUSG00000027584. [P35377-6]
DR Ensembl; ENSMUST00000108767; ENSMUSP00000104398; ENSMUSG00000027584. [P35377-1]
DR Ensembl; ENSMUST00000108768; ENSMUSP00000104399; ENSMUSG00000027584. [P35377-1]
DR Ensembl; ENSMUST00000183693; ENSMUSP00000138810; ENSMUSG00000027584. [P35377-4]
DR Ensembl; ENSMUST00000184127; ENSMUSP00000139119; ENSMUSG00000027584. [P35377-3]
DR GeneID; 18389; -.
DR KEGG; mmu:18389; -.
DR UCSC; uc008onj.2; mouse. [P35377-1]
DR UCSC; uc008ono.1; mouse. [P35377-5]
DR UCSC; uc008onq.1; mouse. [P35377-6]
DR CTD; 4987; -.
DR MGI; MGI:97440; Oprl1.
DR VEuPathDB; HostDB:ENSMUSG00000027584; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00940000160661; -.
DR HOGENOM; CLU_009579_8_1_1; -.
DR InParanoid; P35377; -.
DR OMA; SNWFNNG; -.
DR OrthoDB; 1011272at2759; -.
DR PhylomeDB; P35377; -.
DR TreeFam; TF315737; -.
DR Reactome; R-MMU-375276; Peptide ligand-binding receptors.
DR Reactome; R-MMU-418594; G alpha (i) signalling events.
DR BioGRID-ORCS; 18389; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Oprl1; mouse.
DR PRO; PR:P35377; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P35377; protein.
DR Bgee; ENSMUSG00000027584; Expressed in neural tube lateral wall and 126 other tissues.
DR ExpressionAtlas; P35377; baseline and differential.
DR Genevisible; P35377; MM.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0004930; F:G protein-coupled receptor activity; ISS:UniProtKB.
DR GO; GO:0042923; F:neuropeptide binding; IBA:GO_Central.
DR GO; GO:0001626; F:nociceptin receptor activity; IMP:UniProtKB.
DR GO; GO:0042277; F:peptide binding; IBA:GO_Central.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:1990708; P:conditioned place preference; ISO:MGI.
DR GO; GO:0042755; P:eating behavior; ISO:MGI.
DR GO; GO:0038003; P:G protein-coupled opioid receptor signaling pathway; ISO:MGI.
DR GO; GO:0106072; P:negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0045776; P:negative regulation of blood pressure; ISO:MGI.
DR GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; ISO:MGI.
DR GO; GO:1901386; P:negative regulation of voltage-gated calcium channel activity; ISO:MGI.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IBA:GO_Central.
DR GO; GO:0051482; P:positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway; ISO:MGI.
DR GO; GO:0060454; P:positive regulation of gastric acid secretion; ISO:MGI.
DR GO; GO:1904058; P:positive regulation of sensory perception of pain; ISO:MGI.
DR GO; GO:0035810; P:positive regulation of urine volume; ISO:MGI.
DR GO; GO:1904059; P:regulation of locomotor rhythm; ISO:MGI.
DR GO; GO:0051930; P:regulation of sensory perception of pain; ISO:MGI.
DR GO; GO:0019233; P:sensory perception of pain; IMP:UniProtKB.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR001418; Opioid_rcpt.
DR InterPro; IPR001420; X_opioid_rcpt.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR00384; OPIOIDR.
DR PRINTS; PR00547; XOPIOIDR.
DR SMART; SM01381; 7TM_GPCR_Srsx; 1.
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 Alternative splicing; Behavior; Cell membrane; Cytoplasmic vesicle;
KW Disulfide bond; G-protein coupled receptor; Glycoprotein; Lipoprotein;
KW Membrane; Palmitate; Phosphoprotein; Receptor; Reference proteome;
KW Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..367
FT /note="Nociceptin receptor"
FT /id="PRO_0000069981"
FT TOPO_DOM 1..45
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 46..71
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250"
FT TOPO_DOM 72..84
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 85..106
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250"
FT TOPO_DOM 107..121
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 122..143
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250"
FT TOPO_DOM 144..162
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 163..185
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250"
FT TOPO_DOM 186..208
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 209..233
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250"
FT TOPO_DOM 234..261
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 262..282
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250"
FT TOPO_DOM 283..297
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 298..319
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250"
FT TOPO_DOM 320..367
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT SITE 107
FT /note="Important for G protein-mediated signaling"
FT /evidence="ECO:0000250"
FT SITE 127
FT /note="Important for G protein-mediated signaling"
FT /evidence="ECO:0000250"
FT LIPID 331
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000255"
FT CARBOHYD 21
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 26
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 36
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 120..197
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VAR_SEQ 71..75
FT /note="Missing (in isoform KOR3D)"
FT /evidence="ECO:0000303|PubMed:9755860"
FT /id="VSP_001898"
FT VAR_SEQ 75..99
FT /note="RHTKMKTATNIYIFNLALADTLVLL -> SWEGIEGNWRQQAHQDEDCYQHL
FT HI (in isoform KOR3A)"
FT /evidence="ECO:0000303|PubMed:9755860"
FT /id="VSP_001899"
FT VAR_SEQ 76..111
FT /note="HTKMKTATNIYIFNLALADTLVLLTLPFQGTDILLG -> QCPENPLRGVLR
FT ETEERRQHLSLLIPSTNSHSGTPR (in isoform KOR3B)"
FT /evidence="ECO:0000303|PubMed:9755860"
FT /id="VSP_001903"
FT VAR_SEQ 76..95
FT /note="HTKMKTATNIYIFNLALADT -> QHCALGRSLMNFTGSALKTL (in
FT isoform KOR3C)"
FT /evidence="ECO:0000303|PubMed:9755860"
FT /id="VSP_001901"
FT VAR_SEQ 96..367
FT /note="Missing (in isoform KOR3C)"
FT /evidence="ECO:0000303|PubMed:9755860"
FT /id="VSP_001902"
FT VAR_SEQ 100..367
FT /note="Missing (in isoform KOR3A)"
FT /evidence="ECO:0000303|PubMed:9755860"
FT /id="VSP_001900"
FT VAR_SEQ 112..367
FT /note="Missing (in isoform KOR3B)"
FT /evidence="ECO:0000303|PubMed:9755860"
FT /id="VSP_001904"
FT VAR_SEQ 194..213
FT /note="EIECLVEIPAPQDYWGPVFA -> GQWAVLLPDQSVPHGSCRPL (in
FT isoform KOR3E)"
FT /evidence="ECO:0000303|PubMed:9755860"
FT /id="VSP_001905"
FT VAR_SEQ 214..367
FT /note="Missing (in isoform KOR3E)"
FT /evidence="ECO:0000303|PubMed:9755860"
FT /id="VSP_001906"
FT CONFLICT 348..349
FT /note="SI -> TV (in Ref. 2; AAA81333)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 367 AA; 40491 MW; E498CA9FE5276026 CRC64;
MESLFPAPFW EVLYGSHFQG NLSLLNETVP HHLLLNASHS AFLPLGLKVT IVGLYLAVCI
GGLLGNCLVM YVILRHTKMK TATNIYIFNL ALADTLVLLT LPFQGTDILL GFWPFGNALC
KTVIAIDYYN MFTSTFTLTA MSVDRYVAIC HPIRALDVRT SSKAQAVNVA IWALASVVGV
PVAIMGSAQV EDEEIECLVE IPAPQDYWGP VFAICIFLFS FIIPVLIISV CYSLMIRRLR
GVRLLSGSRE KDRNLRRITR LVLVVVAVFV GCWTPVQVFV LVQGLGVQPG SETAVAILRF
CTALGYVNSC LNPILYAFLD ENFKACFRKF CCASALHREM QVSDRVRSIA KDVGLGCKTS
ETVPRPA
