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P41146 (OPRX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 141. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | 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):
Kappa-type 3 opioid receptor
Short name=KOR-3
Orphanin FQ receptor
Gene names
Name:OPRL1
Synonyms:OOR, ORL1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length370 AA.
Sequence statusComplete.
Protein existenceEvidence at protein 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.1 Ref.3 Ref.10 Ref.11 Ref.12

Subcellular location

Cell membrane; Multi-pass membrane protein. Cytoplasmic vesicle. 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-363. Can recycle to the cell membrane. Ref.1 Ref.10 Ref.11 Ref.12

Tissue specificity

Detected in blood leukocytes. Ref.9

Induction

By phytohemagglutinin (PHA). Ref.9

Post-translational modification

Phosphorylation at Ser-363 requires ADRBK2.

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
   Biological processBehavior
   Cellular componentCell membrane
Cytoplasmic vesicle
Membrane
   Coding sequence diversityAlternative splicing
   DomainTransmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Lipoprotein
Palmitate
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

Inferred from mutant phenotype Ref.10Ref.1. Source: UniProtKB

behavior

Inferred from electronic annotation. Source: UniProtKB-KW

opioid receptor signaling pathway

Inferred from direct assay Ref.10. Source: GOC

positive regulation of cytosolic calcium ion concentration

Inferred from genetic interaction PubMed 10571060. Source: UniProtKB

sensory perception

Traceable author statement PubMed 7566152. Source: ProtInc

sensory perception of pain

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytoplasmic membrane-bounded vesicle

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of plasma membrane

Inferred from direct assay Ref.10Ref.1. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionG-protein coupled receptor activity

Inferred from mutant phenotype Ref.1. Source: UniProtKB

nociceptin receptor activity

Inferred from direct assay Ref.10. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P41146-1)

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 2 (identifier: P41146-2)

Also known as: KOR-3D;

The sequence of this isoform differs from the canonical sequence as follows:
     74-78: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 370370Nociceptin receptor
PRO_0000069980

Regions

Topological domain1 – 4848Extracellular Ref.12
Transmembrane49 – 7426Helical; Name=1
Topological domain75 – 8713Cytoplasmic Ref.12
Transmembrane88 – 10922Helical; Name=2
Topological domain110 – 12415Extracellular Ref.12
Transmembrane125 – 14622Helical; Name=3
Topological domain147 – 16519Cytoplasmic Ref.12
Transmembrane166 – 18823Helical; Name=4
Topological domain189 – 21123Extracellular Ref.12
Transmembrane212 – 23625Helical; Name=5
Topological domain237 – 26428Cytoplasmic Ref.12
Transmembrane265 – 28521Helical; Name=6
Topological domain286 – 30015Extracellular Ref.12
Transmembrane301 – 32222Helical; Name=7
Topological domain323 – 37048Cytoplasmic Ref.12

Sites

Site1101Important for G protein-mediated signaling
Site1301Important for G protein-mediated signaling

Amino acid modifications

Modified residue3631Phosphoserine Probable
Lipidation3341S-palmitoyl cysteine Potential
Glycosylation211N-linked (GlcNAc...) Potential
Glycosylation281N-linked (GlcNAc...) Potential
Glycosylation391N-linked (GlcNAc...) Potential
Disulfide bond123 ↔ 200 Ref.12

Natural variations

Alternative sequence74 – 785Missing in isoform 2.
VSP_001897

Experimental info

Mutagenesis1071Q → A: Impairs G protein-mediated inhibition of adenylate cyclase. Ref.12
Mutagenesis1101D → A: Abolishes G protein-mediated inhibition of adenylate cyclase. No effect on antagonist-mediated inhibition of G protein-mediated signaling. Ref.12
Mutagenesis1301D → A: Abolishes G protein-mediated inhibition of adenylate cyclase. Abolishes antagonist-mediated inhibition of G protein-mediated signaling. Ref.12
Mutagenesis1311Y → A: Impairs G protein-mediated inhibition of adenylate cyclase. Ref.12
Mutagenesis2801Q → A: Impairs G protein-mediated inhibition of adenylate cyclase. Ref.12
Mutagenesis3091Y → A: Mildly impairs G protein-mediated inhibition of adenylate cyclase. Abolishes antagonist-mediated inhibition of G protein-mediated signaling. Ref.12
Mutagenesis3371S → A: No effect on ligand-mediated internalization; when associated with A-346 and A-351. Ref.11
Mutagenesis3461S → A: No effect on ligand-mediated internalization; when associated with A-337 and A-351. Ref.11
Mutagenesis3511S → A: No effect on ligand-mediated internalization; when associated with A-337 and A-346. Ref.11
Mutagenesis3631S → A: Impairs ligand-mediated internalization. Ref.11

Secondary structure

........................ 370
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 1, 1995. Version 1.
Checksum: 613700C0B4D093BA

FASTA37040,693
        10         20         30         40         50         60 
MEPLFPAPFW EVIYGSHLQG NLSLLSPNHS LLPPHLLLNA SHGAFLPLGL KVTIVGLYLA 

        70         80         90        100        110        120 
VCVGGLLGNC LVMYVILRHT KMKTATNIYI FNLALADTLV LLTLPFQGTD ILLGFWPFGN 

       130        140        150        160        170        180 
ALCKTVIAID YYNMFTSTFT LTAMSVDRYV AICHPIRALD VRTSSKAQAV NVAIWALASV 

       190        200        210        220        230        240 
VGVPVAIMGS AQVEDEEIEC LVEIPTPQDY WGPVFAICIF LFSFIVPVLV ISVCYSLMIR 

       250        260        270        280        290        300 
RLRGVRLLSG SREKDRNLRR ITRLVLVVVA VFVGCWTPVQ VFVLAQGLGV QPSSETAVAI 

       310        320        330        340        350        360 
LRFCTALGYV NSCLNPILYA FLDENFKACF RKFCCASALR RDVQVSDRVR SIAKDVALAC 

       370 
KTSETVPRPA 

« Hide

Isoform 2 (KOR-3D) [UniParc].

Checksum: 56D4D8DF0F277242
Show »

FASTA36540,048

References

« Hide 'large scale' references
[1]"ORL1, a novel member of the opioid receptor family. Cloning, functional expression and localization."
Mollereau C., Parmentier M., Mailleux P., Butour J.-L., Moisand C., Chalon P., Caput D., Vassart G., Meunier C.
FEBS Lett. 341:33-38(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION.
Tissue: Brain stem.
[2]Lee P.H., Zhu J., Liu-Chen L., Chang K.
Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"Nociceptin stimulates neutrophil chemotaxis and recruitment: Inhibition by aspirin-triggered-15-Epi-lipoxin A4."
Serhan C.N., Fierro I.M., Chiang N., Pouliot M.
J. Immunol. 166:3650-3654(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION.
[4]"Identification and characterization of a splice variant of human kappa3-related opioid receptor (KOR-3D) gene."
Pan Y.-X., Xu J., Pasternak G.W.
Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[5]"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
Warren C.N., Aronstam R.S., Sharma S.V.
Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[6]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[7]"The DNA sequence and comparative analysis of human chromosome 20."
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. expand/collapse author list , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"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 1).
Tissue: Brain.
[9]"Expression of alternate forms of brain opioid 'orphan' receptor mRNA in activated human peripheral blood lymphocytes and lymphocytic cell lines."
Wick M.J., Minnerath S.R., Roy S., Ramakrishnan S., Loh H.H.
Brain Res. Mol. Brain Res. 32:342-347(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-333 (ISOFORM 1), TISSUE SPECIFICITY, INDUCTION.
Tissue: Lymphocyte.
[10]"Agonist-induced internalization and desensitization of the human nociceptin receptor expressed in CHO cells."
Spampinato S., Di Toro R., Alessandri M., Murari G.
Cell. Mol. Life Sci. 59:2172-2183(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[11]"Serine 363 is required for nociceptin/orphanin FQ opioid receptor (NOPR) desensitization, internalization, and arrestin signaling."
Zhang N.R., Planer W., Siuda E.R., Zhao H.C., Stickler L., Chang S.D., Baird M.A., Cao Y.Q., Bruchas M.R.
J. Biol. Chem. 287:42019-42030(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF SER-337; SER-346; SER-351 AND SER-363, PHOSPHORYLATION AT SER-363, SUBCELLULAR LOCATION.
[12]"Structure of the nociceptin/orphanin FQ receptor in complex with a peptide mimetic."
Thompson A.A., Liu W., Chun E., Katritch V., Wu H., Vardy E., Huang X.P., Trapella C., Guerrini R., Calo G., Roth B.L., Cherezov V., Stevens R.C.
Nature 485:395-399(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.01 ANGSTROMS) OF 43-339, FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, MUTAGENESIS OF GLN-107; ASP-110; ASP-130; TYR-131; GLN-280 AND TYR-309, DISULFIDE BOND.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X77130 mRNA. Translation: CAA54386.1.
U30185 mRNA. Translation: AAA84913.1.
AF348323 mRNA. Translation: AAK11714.1.
AF126470 mRNA. Translation: AAL54890.1.
AY268428 mRNA. Translation: AAP23195.1.
CR542061 mRNA. Translation: CAG46858.1.
AL121581 Genomic DNA. Translation: CAC17003.2.
AL590548, AL121581 Genomic DNA. Translation: CAD11904.2.
BC038433 mRNA. Translation: AAH38433.1.
L40949 mRNA. Translation: AAA96251.1.
PIRS43087.
RefSeqNP_000904.1. NM_000913.4.
NP_001186948.1. NM_001200019.1.
NP_872588.1. NM_182647.2.
XP_005260263.1. XM_005260206.1.
UniGeneHs.2859.
Hs.736944.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4EA3X-ray3.01A/B43-339[»]
ProteinModelPortalP41146.
SMRP41146. Positions 47-331.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111032. 2 interactions.
IntActP41146. 2 interactions.
STRING9606.ENSP00000336764.

Chemistry

BindingDBP41146.
ChEMBLCHEMBL2014.
GuidetoPHARMACOLOGY320.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP41146.

Polymorphism databases

DMDM730230.

Proteomic databases

PRIDEP41146.

Protocols and materials databases

DNASU4987.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000336866; ENSP00000336843; ENSG00000125510. [P41146-1]
ENST00000349451; ENSP00000336764; ENSG00000125510. [P41146-1]
ENST00000355631; ENSP00000347848; ENSG00000125510. [P41146-1]
GeneID4987.
KEGGhsa:4987.
UCSCuc002yic.3. human. [P41146-1]
uc002yif.4. human. [P41146-2]

Organism-specific databases

CTD4987.
GeneCardsGC20P062711.
HGNCHGNC:8155. OPRL1.
MIM602548. gene.
neXtProtNX_P41146.
PharmGKBPA31944.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG299442.
HOGENOMHOG000230486.
HOVERGENHBG106919.
InParanoidP41146.
KOK04216.
OMAVFAICIF.
OrthoDBEOG7BKCVQ.
PhylomeDBP41146.
TreeFamTF315737.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

BgeeP41146.
CleanExHS_OPRL1.
GenevestigatorP41146.

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

GeneWikiNociceptin_receptor.
GenomeRNAi4987.
NextBio19198.
PROP41146.
SOURCESearch...

Entry information

Entry nameOPRX_HUMAN
AccessionPrimary (citable) accession number: P41146
Secondary accession number(s): Q8TD34, Q8WYH9, Q9H4K4
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: April 16, 2014
This is version 141 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries