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P35377 (OPRX_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Nociceptin receptor
Alternative name(s):
K3 opiate receptor
Kappa-type 3 opioid receptor
Short name=KOR-3
ORGC
Orphanin FQ receptor
Gene names
Name:Oprl1
Synonyms:Oor, Oprl
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length367 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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. Ref.3 Ref.5 Ref.10 Ref.11 Ref.12

Subcellular location

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. Ref.3 Ref.5

Tissue specificity

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. Ref.5 Ref.6 Ref.8

Post-translational modification

Phosphorylation at Ser-360 requires ADRBK2 By similarity.

Disruption phenotype

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. Ref.9 Ref.10 Ref.11

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]
Isoform KOR3 (identifier: P35377-1)

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 KOR3A (identifier: P35377-2)

The sequence of this isoform differs from the canonical sequence as follows:
     75-99: RHTKMKTATNIYIFNLALADTLVLL → SWEGIEGNWRQQAHQDEDCYQHLHI
     100-367: Missing.
Isoform KOR3B (identifier: P35377-3)

The sequence of this isoform differs from the canonical sequence as follows:
     76-111: HTKMKTATNIYIFNLALADTLVLLTLPFQGTDILLG → QCPENPLRGVLRETEERRQHLSLLIPSTNSHSGTPR
     112-367: Missing.
Isoform KOR3C (identifier: P35377-4)

The sequence of this isoform differs from the canonical sequence as follows:
     76-95: HTKMKTATNIYIFNLALADT → QHCALGRSLMNFTGSALKTL
     96-367: Missing.
Isoform KOR3D (identifier: P35377-5)

The sequence of this isoform differs from the canonical sequence as follows:
     71-75: Missing.
Isoform KOR3E (identifier: P35377-6)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 367367Nociceptin receptor
PRO_0000069981

Regions

Topological domain1 – 4545Extracellular By similarity
Transmembrane46 – 7126Helical; Name=1; By similarity
Topological domain72 – 8413Cytoplasmic By similarity
Transmembrane85 – 10622Helical; Name=2; By similarity
Topological domain107 – 12115Extracellular By similarity
Transmembrane122 – 14322Helical; Name=3; By similarity
Topological domain144 – 16219Cytoplasmic By similarity
Transmembrane163 – 18523Helical; Name=4; By similarity
Topological domain186 – 20823Extracellular By similarity
Transmembrane209 – 23325Helical; Name=5; By similarity
Topological domain234 – 26128Cytoplasmic By similarity
Transmembrane262 – 28221Helical; Name=6; By similarity
Topological domain283 – 29715Extracellular By similarity
Transmembrane298 – 31922Helical; Name=7; By similarity
Topological domain320 – 36748Cytoplasmic By similarity

Sites

Site1071Important for G protein-mediated signaling By similarity
Site1271Important for G protein-mediated signaling By similarity

Amino acid modifications

Lipidation3311S-palmitoyl cysteine Potential
Glycosylation211N-linked (GlcNAc...) Potential
Glycosylation261N-linked (GlcNAc...) Potential
Glycosylation361N-linked (GlcNAc...) Potential
Disulfide bond120 ↔ 197 By similarity

Natural variations

Alternative sequence71 – 755Missing in isoform KOR3D.
VSP_001898
Alternative sequence75 – 9925RHTKM…TLVLL → SWEGIEGNWRQQAHQDEDCY QHLHI in isoform KOR3A.
VSP_001899
Alternative sequence76 – 11136HTKMK…DILLG → QCPENPLRGVLRETEERRQH LSLLIPSTNSHSGTPR in isoform KOR3B.
VSP_001903
Alternative sequence76 – 9520HTKMK…ALADT → QHCALGRSLMNFTGSALKTL in isoform KOR3C.
VSP_001901
Alternative sequence96 – 367272Missing in isoform KOR3C.
VSP_001902
Alternative sequence100 – 367268Missing in isoform KOR3A.
VSP_001900
Alternative sequence112 – 367256Missing in isoform KOR3B.
VSP_001904
Alternative sequence194 – 21320EIECL…GPVFA → GQWAVLLPDQSVPHGSCRPL in isoform KOR3E.
VSP_001905
Alternative sequence214 – 367154Missing in isoform KOR3E.
VSP_001906

Experimental info

Sequence conflict348 – 3492SI → TV in AAA81333. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform KOR3 [UniParc].

Last modified June 1, 1994. Version 1.
Checksum: E498CA9FE5276026

FASTA36740,491
        10         20         30         40         50         60 
MESLFPAPFW EVLYGSHFQG NLSLLNETVP HHLLLNASHS AFLPLGLKVT IVGLYLAVCI 

        70         80         90        100        110        120 
GGLLGNCLVM YVILRHTKMK TATNIYIFNL ALADTLVLLT LPFQGTDILL GFWPFGNALC 

       130        140        150        160        170        180 
KTVIAIDYYN MFTSTFTLTA MSVDRYVAIC HPIRALDVRT SSKAQAVNVA IWALASVVGV 

       190        200        210        220        230        240 
PVAIMGSAQV EDEEIECLVE IPAPQDYWGP VFAICIFLFS FIIPVLIISV CYSLMIRRLR 

       250        260        270        280        290        300 
GVRLLSGSRE KDRNLRRITR LVLVVVAVFV GCWTPVQVFV LVQGLGVQPG SETAVAILRF 

       310        320        330        340        350        360 
CTALGYVNSC LNPILYAFLD ENFKACFRKF CCASALHREM QVSDRVRSIA KDVGLGCKTS 


ETVPRPA 

« Hide

Isoform KOR3A [UniParc].

Checksum: 9165BB34BB5CFC80
Show »

FASTA9911,129
Isoform KOR3B [UniParc].

Checksum: 3901CF41856A774F
Show »

FASTA11112,314
Isoform KOR3C [UniParc].

Checksum: 0E495CD1381489CC
Show »

FASTA9510,353
Isoform KOR3D [UniParc].

Checksum: 8B9A7C66E35E3A3D
Show »

FASTA36239,846
Isoform KOR3E [UniParc].

Checksum: 0444B4CFD7DB4751
Show »

FASTA21323,205

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRI49022.
JC2421.
RefSeqNP_001239494.1. NM_001252565.1.
NP_035142.1. NM_011012.5.
XP_006500645.1. XM_006500582.1.
UniGeneMm.285075.

3D structure databases

ProteinModelPortalP35377.
SMRP35377. Positions 44-328.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBP35377.
ChEMBLCHEMBL3621.
GuidetoPHARMACOLOGY320.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP35377.

Proteomic databases

PRIDEP35377.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000071585; 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]
GeneID18389.
KEGGmmu:18389.
UCSCuc008onj.2. mouse. [P35377-1]
uc008ono.1. mouse. [P35377-5]

Organism-specific databases

CTD4987.
MGIMGI:97440. Oprl1.

Phylogenomic databases

eggNOGNOG299442.
GeneTreeENSGT00630000089574.
HOVERGENHBG106919.
InParanoidP35377.
KOK04216.
OMAVFAICIF.
OrthoDBEOG7BKCVQ.
PhylomeDBP35377.
TreeFamTF315737.

Gene expression databases

BgeeP35377.
CleanExMM_OPRL1.
GenevestigatorP35377.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR001418. Opioid_rcpt.
IPR001420. X_opioid_rcpt.
[Graphical view]
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00237. GPCRRHODOPSN.
PR00384. OPIOIDR.
PR00547. XOPIOIDR.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSOPRL1. mouse.
NextBio293984.
PROP35377.
SOURCESearch...

Entry information

Entry nameOPRX_MOUSE
AccessionPrimary (citable) accession number: P35377
Secondary accession number(s): Q60645 expand/collapse secondary AC list , Q8VI74, Q9QUT5, Q9Z2M8, Q9Z2M9, Q9Z2N0
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: April 16, 2014
This is version 129 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

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries