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P35377

- OPRX_MOUSE

UniProt

P35377 - OPRX_MOUSE

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Protein
Nociceptin receptor
Gene
Oprl1, Oor, Oprl
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript leveli

Functioni

G-protein coupled opioid receptor that functions as receptor for the endogenous neuropeptide nociceptin. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling via G proteins mediates inhibition of adenylate cyclase activity and calcium channel activity. Arrestins modulate signaling via G proteins and mediate the activation of alternative signaling pathways that lead to the activation of MAP kinases. Plays a role in modulating nociception and the perception of pain. Plays a role in the regulation of locomotor activity by the neuropeptide nociceptin.5 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei107 – 1071Important for G protein-mediated signaling By similarity
Sitei127 – 1271Important for G protein-mediated signaling By similarity

GO - Molecular functioni

  1. G-protein coupled receptor activity Source: UniProtKB
  2. nociceptin receptor activity Source: UniProtKB
Complete GO annotation...

GO - Biological processi

  1. adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway Source: UniProtKB
  2. behavior Source: UniProtKB-KW
  3. opioid receptor signaling pathway Source: GOC
  4. positive regulation of cytosolic calcium ion concentration Source: Ensembl
  5. sensory perception of pain Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Behavior

Names & Taxonomyi

Protein namesi
Recommended name:
Nociceptin receptor
Alternative name(s):
K3 opiate receptor
Kappa-type 3 opioid receptor
Short name:
KOR-3
ORGC
Orphanin FQ receptor
Gene namesi
Name:Oprl1
Synonyms:Oor, Oprl
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 2

Organism-specific databases

MGIiMGI:97440. Oprl1.

Subcellular locationi

Cell membrane; Multi-pass membrane protein. Cytoplasmic vesicle By similarity
Note: Ligand binding leads to receptor internalization into cytoplasmic vesicles, decreasing the amount of available receptor at the cell surface. Internalization requires phosphorylation at Ser-360. Can recycle to the cell membrane By similarity.2 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 4545Extracellular By similarity
Add
BLAST
Transmembranei46 – 7126Helical; Name=1; By similarity
Add
BLAST
Topological domaini72 – 8413Cytoplasmic By similarity
Add
BLAST
Transmembranei85 – 10622Helical; Name=2; By similarity
Add
BLAST
Topological domaini107 – 12115Extracellular By similarity
Add
BLAST
Transmembranei122 – 14322Helical; Name=3; By similarity
Add
BLAST
Topological domaini144 – 16219Cytoplasmic By similarity
Add
BLAST
Transmembranei163 – 18523Helical; Name=4; By similarity
Add
BLAST
Topological domaini186 – 20823Extracellular By similarity
Add
BLAST
Transmembranei209 – 23325Helical; Name=5; By similarity
Add
BLAST
Topological domaini234 – 26128Cytoplasmic By similarity
Add
BLAST
Transmembranei262 – 28221Helical; Name=6; By similarity
Add
BLAST
Topological domaini283 – 29715Extracellular By similarity
Add
BLAST
Transmembranei298 – 31922Helical; Name=7; By similarity
Add
BLAST
Topological domaini320 – 36748Cytoplasmic By similarity
Add
BLAST

GO - Cellular componenti

  1. cytoplasmic membrane-bounded vesicle Source: UniProtKB-SubCell
  2. integral component of plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Membrane

Pathology & Biotechi

Disruption phenotypei

Mutant mice do not show altered basal nociception, but are no longer susceptible to modulation of nociception by the neuropeptide nociceptin. Contrary to wild-type, they do not show reduced locomotion in response to the neuropeptide nociceptin. In addition, mutant mice show subtle hearing defects.3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 367367Nociceptin receptor
PRO_0000069981Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi21 – 211N-linked (GlcNAc...) Reviewed prediction
Glycosylationi26 – 261N-linked (GlcNAc...) Reviewed prediction
Glycosylationi36 – 361N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi120 ↔ 197 By similarity
Lipidationi331 – 3311S-palmitoyl cysteine Reviewed prediction

Post-translational modificationi

Phosphorylation at Ser-360 requires ADRBK2 By similarity.

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PRIDEiP35377.

PTM databases

PhosphoSiteiP35377.

Expressioni

Tissue specificityi

In the brain, isoform KOR3 and isoform KOR3C are most abundant in hypothalamus and periaqueductal gray. Isoform KOR3A is highly expressed in cortex, striatum and brainstem. Isoform KOR3D is highly expressed in cerebellum, hypothalamus and brainstem. Detected in spleen lymphocytes.3 Publications

Gene expression databases

BgeeiP35377.
CleanExiMM_OPRL1.
GenevestigatoriP35377.

Interactioni

Structurei

3D structure databases

ProteinModelPortaliP35377.
SMRiP35377. Positions 44-328.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG299442.
GeneTreeiENSGT00630000089574.
HOVERGENiHBG106919.
InParanoidiP35377.
KOiK04216.
OMAiVFAICIF.
OrthoDBiEOG7BKCVQ.
PhylomeDBiP35377.
TreeFamiTF315737.

Family and domain databases

Gene3Di1.20.1070.10. 1 hit.
InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR001418. Opioid_rcpt.
IPR001420. X_opioid_rcpt.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR00384. OPIOIDR.
PR00547. XOPIOIDR.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequences (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. Align

Isoform KOR3 (identifier: P35377-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MESLFPAPFW EVLYGSHFQG NLSLLNETVP HHLLLNASHS AFLPLGLKVT    50
IVGLYLAVCI GGLLGNCLVM YVILRHTKMK TATNIYIFNL ALADTLVLLT 100
LPFQGTDILL GFWPFGNALC KTVIAIDYYN MFTSTFTLTA MSVDRYVAIC 150
HPIRALDVRT SSKAQAVNVA IWALASVVGV PVAIMGSAQV EDEEIECLVE 200
IPAPQDYWGP VFAICIFLFS FIIPVLIISV CYSLMIRRLR GVRLLSGSRE 250
KDRNLRRITR LVLVVVAVFV GCWTPVQVFV LVQGLGVQPG SETAVAILRF 300
CTALGYVNSC LNPILYAFLD ENFKACFRKF CCASALHREM QVSDRVRSIA 350
KDVGLGCKTS ETVPRPA 367
Length:367
Mass (Da):40,491
Last modified:June 1, 1994 - v1
Checksum:iE498CA9FE5276026
GO
Isoform KOR3A (identifier: P35377-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     75-99: RHTKMKTATNIYIFNLALADTLVLL → SWEGIEGNWRQQAHQDEDCYQHLHI
     100-367: Missing.

Show »
Length:99
Mass (Da):11,129
Checksum:i9165BB34BB5CFC80
GO
Isoform KOR3B (identifier: P35377-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     76-111: HTKMKTATNIYIFNLALADTLVLLTLPFQGTDILLG → QCPENPLRGVLRETEERRQHLSLLIPSTNSHSGTPR
     112-367: Missing.

Show »
Length:111
Mass (Da):12,314
Checksum:i3901CF41856A774F
GO
Isoform KOR3C (identifier: P35377-4) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     76-95: HTKMKTATNIYIFNLALADT → QHCALGRSLMNFTGSALKTL
     96-367: Missing.

Show »
Length:95
Mass (Da):10,353
Checksum:i0E495CD1381489CC
GO
Isoform KOR3D (identifier: P35377-5) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     71-75: Missing.

Show »
Length:362
Mass (Da):39,846
Checksum:i8B9A7C66E35E3A3D
GO
Isoform KOR3E (identifier: P35377-6) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     194-213: EIECLVEIPAPQDYWGPVFA → GQWAVLLPDQSVPHGSCRPL
     214-367: Missing.

Show »
Length:213
Mass (Da):23,205
Checksum:i0444B4CFD7DB4751
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei71 – 755Missing in isoform KOR3D.
VSP_001898
Alternative sequencei75 – 9925RHTKM…TLVLL → SWEGIEGNWRQQAHQDEDCY QHLHI in isoform KOR3A.
VSP_001899Add
BLAST
Alternative sequencei76 – 11136HTKMK…DILLG → QCPENPLRGVLRETEERRQH LSLLIPSTNSHSGTPR in isoform KOR3B.
VSP_001903Add
BLAST
Alternative sequencei76 – 9520HTKMK…ALADT → QHCALGRSLMNFTGSALKTL in isoform KOR3C.
VSP_001901Add
BLAST
Alternative sequencei96 – 367272Missing in isoform KOR3C.
VSP_001902Add
BLAST
Alternative sequencei100 – 367268Missing in isoform KOR3A.
VSP_001900Add
BLAST
Alternative sequencei112 – 367256Missing in isoform KOR3B.
VSP_001904Add
BLAST
Alternative sequencei194 – 21320EIECL…GPVFA → GQWAVLLPDQSVPHGSCRPL in isoform KOR3E.
VSP_001905Add
BLAST
Alternative sequencei214 – 367154Missing in isoform KOR3E.
VSP_001906Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti348 – 3492SI → TV in AAA81333. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U04952 mRNA. Translation: AAA03730.1.
D31667 Genomic DNA. Translation: BAA06509.1.
X91813 mRNA. Translation: CAA62922.1.
U32932, U32928, U32930 Genomic DNA. Translation: AAC52669.1.
U09421 mRNA. Translation: AAA81333.1.
AF043276 mRNA. Translation: AAC64507.1.
AF043277 mRNA. Translation: AAC64508.1.
AF043278 mRNA. Translation: AAC64509.1.
AF062381 mRNA. Translation: AAF21258.1.
AF075605 mRNA. Translation: AAF21781.1.
AF126469 mRNA. Translation: AAL54889.1.
BC050885 mRNA. Translation: AAH50885.1.
U14165 mRNA. Translation: AAA87899.1.
CCDSiCCDS17222.1. [P35377-1]
PIRiI49022.
JC2421.
RefSeqiNP_001239494.1. NM_001252565.1. [P35377-1]
NP_035142.1. NM_011012.5. [P35377-1]
XP_006500645.1. XM_006500582.1. [P35377-5]
UniGeneiMm.285075.

Genome annotation databases

EnsembliENSMUST00000071585; ENSMUSP00000071513; ENSMUSG00000027584. [P35377-1]
ENSMUST00000108766; ENSMUSP00000104397; ENSMUSG00000027584. [P35377-6]
ENSMUST00000108767; ENSMUSP00000104398; ENSMUSG00000027584. [P35377-1]
ENSMUST00000108768; ENSMUSP00000104399; ENSMUSG00000027584. [P35377-1]
ENSMUST00000183693; ENSMUSP00000138810; ENSMUSG00000027584. [P35377-4]
ENSMUST00000184127; ENSMUSP00000139119; ENSMUSG00000027584. [P35377-3]
GeneIDi18389.
KEGGimmu:18389.
UCSCiuc008onj.2. mouse. [P35377-1]
uc008ono.1. mouse. [P35377-5]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U04952 mRNA. Translation: AAA03730.1 .
D31667 Genomic DNA. Translation: BAA06509.1 .
X91813 mRNA. Translation: CAA62922.1 .
U32932 , U32928 , U32930 Genomic DNA. Translation: AAC52669.1 .
U09421 mRNA. Translation: AAA81333.1 .
AF043276 mRNA. Translation: AAC64507.1 .
AF043277 mRNA. Translation: AAC64508.1 .
AF043278 mRNA. Translation: AAC64509.1 .
AF062381 mRNA. Translation: AAF21258.1 .
AF075605 mRNA. Translation: AAF21781.1 .
AF126469 mRNA. Translation: AAL54889.1 .
BC050885 mRNA. Translation: AAH50885.1 .
U14165 mRNA. Translation: AAA87899.1 .
CCDSi CCDS17222.1. [P35377-1 ]
PIRi I49022.
JC2421.
RefSeqi NP_001239494.1. NM_001252565.1. [P35377-1 ]
NP_035142.1. NM_011012.5. [P35377-1 ]
XP_006500645.1. XM_006500582.1. [P35377-5 ]
UniGenei Mm.285075.

3D structure databases

ProteinModelPortali P35377.
SMRi P35377. Positions 44-328.
ModBasei Search...

Chemistry

BindingDBi P35377.
ChEMBLi CHEMBL3621.
GuidetoPHARMACOLOGYi 320.

Protein family/group databases

GPCRDBi Search...

PTM databases

PhosphoSitei P35377.

Proteomic databases

PRIDEi P35377.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000071585 ; ENSMUSP00000071513 ; ENSMUSG00000027584 . [P35377-1 ]
ENSMUST00000108766 ; ENSMUSP00000104397 ; ENSMUSG00000027584 . [P35377-6 ]
ENSMUST00000108767 ; ENSMUSP00000104398 ; ENSMUSG00000027584 . [P35377-1 ]
ENSMUST00000108768 ; ENSMUSP00000104399 ; ENSMUSG00000027584 . [P35377-1 ]
ENSMUST00000183693 ; ENSMUSP00000138810 ; ENSMUSG00000027584 . [P35377-4 ]
ENSMUST00000184127 ; ENSMUSP00000139119 ; ENSMUSG00000027584 . [P35377-3 ]
GeneIDi 18389.
KEGGi mmu:18389.
UCSCi uc008onj.2. mouse. [P35377-1 ]
uc008ono.1. mouse. [P35377-5 ]

Organism-specific databases

CTDi 4987.
MGIi MGI:97440. Oprl1.

Phylogenomic databases

eggNOGi NOG299442.
GeneTreei ENSGT00630000089574.
HOVERGENi HBG106919.
InParanoidi P35377.
KOi K04216.
OMAi VFAICIF.
OrthoDBi EOG7BKCVQ.
PhylomeDBi P35377.
TreeFami TF315737.

Miscellaneous databases

ChiTaRSi OPRL1. mouse.
NextBioi 293984.
PROi P35377.
SOURCEi Search...

Gene expression databases

Bgeei P35377.
CleanExi MM_OPRL1.
Genevestigatori P35377.

Family and domain databases

Gene3Di 1.20.1070.10. 1 hit.
InterProi IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR001418. Opioid_rcpt.
IPR001420. X_opioid_rcpt.
[Graphical view ]
Pfami PF00001. 7tm_1. 1 hit.
[Graphical view ]
PRINTSi PR00237. GPCRRHODOPSN.
PR00384. OPIOIDR.
PR00547. XOPIOIDR.
PROSITEi PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. Yasuda K., Jones E., Reisine T., Bell G.I.
    Submitted (JAN-1994) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE (ISOFORM KOR3).
    Strain: C57BL/6N.
    Tissue: Brain.
  2. "Structure and chromosomal mapping of genes for the mouse kappa-opioid receptor and an opioid receptor homologue (MOR-C)."
    Nishi M., Takeshima H., Mori M., Nakagawara K., Takeuchi T.
    Biochem. Biophys. Res. Commun. 205:1353-1357(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM KOR3).
  3. "Functional selectivity of orphanin FQ for its receptor coexpressed with potassium channel subunits in Xenopus laevis oocytes."
    Matthes H.W.D., Seward E.P., Kieffer B., North R.A.
    Mol. Pharmacol. 50:447-450(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM KOR3), FUNCTION, SUBCELLULAR LOCATION.
    Tissue: Brain.
  4. Pan Y.-X., Xu J., Pasternak G.W.
    Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE (ISOFORM KOR3).
  5. "Cloning and functional characterization through antisense mapping of a kappa 3-related opioid receptor."
    Pan Y.-X., Cheng J., Xu J., Rossi G., Jacobson E., Ryan-Moro J., Brooks A.I., Dean G.E., Standifer K.M., Pasternak G.W.
    Mol. Pharmacol. 47:1180-1188(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM KOR3), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  6. "Identification and differential regional expression of KOR-3/ORL-1 gene splice variants in mouse brain."
    Pan Y.-X., Xu J., Wan B.-L., Zuckerman A., Pasternak G.W.
    FEBS Lett. 435:65-68(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS KOR3A; KOR3B; KOR3C; KOR3D AND KOR3E), TISSUE SPECIFICITY.
    Strain: C57BL/6.
    Tissue: Brain.
  7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM KOR3).
    Strain: C57BL/6.
    Tissue: Brain.
  8. "Functional role and sequence analysis of a lymphocyte orphan opioid receptor."
    Halford W.P., Gebhardt B.M., Carr D.J.J.
    J. Neuroimmunol. 59:91-101(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-357 (ISOFORM KOR3), TISSUE SPECIFICITY.
    Strain: BALB/c.
    Tissue: Spleen.
  9. "Unrestrained nociceptive response and disregulation of hearing ability in mice lacking the nociceptin/orphaninFQ receptor."
    Nishi M., Houtani T., Noda Y., Mamiya T., Sato K., Doi T., Kuno J., Takeshima H., Nukada T., Nabeshima T., Yamashita T., Noda T., Sugimoto T.
    EMBO J. 16:1858-1864(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  10. "Lack of the nociceptin receptor does not affect acute or chronic nociception in mice."
    Bertorelli R., Bastia E., Citterio F., Corradini L., Forlani A., Ongini E.
    Peptides 23:1589-1596(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  11. "Normal sensitivity to acute pain, but increased inflammatory hyperalgesia in mice lacking the nociceptin precursor polypeptide or the nociceptin receptor."
    Depner U.B., Reinscheid R.K., Takeshima H., Brune K., Zeilhofer H.U.
    Eur. J. Neurosci. 17:2381-2387(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  12. "Effects of spinally administered bifunctional nociceptin/orphanin FQ peptide receptor/mu-opioid receptor ligands in mouse models of neuropathic and inflammatory pain."
    Sukhtankar D.D., Zaveri N.T., Husbands S.M., Ko M.C.
    J. Pharmacol. Exp. Ther. 346:11-22(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiOPRX_MOUSE
AccessioniPrimary (citable) accession number: P35377
Secondary accession number(s): Q60645
, Q8VI74, Q9QUT5, Q9Z2M8, Q9Z2M9, Q9Z2N0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: July 9, 2014
This is version 131 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi