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P41145 (OPRK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Kappa-type opioid receptor

Short name=K-OR-1
Short name=KOR-1
Gene names
Name:OPRK1
Synonyms:OPRK
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length380 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain. Plays a role in mediating reduced physical activity upon treatment with synthetic opioids. Plays a role in the regulation of salivation in response to synthetic opioids. May play a role in arousal and regulation of autonomic and neuroendocrine functions. Ref.1 Ref.2 Ref.10 Ref.15

Subunit structure

Interacts with SLC9A3R1. Interacts with GABARAPL1. Ref.10 Ref.11

Subcellular location

Cell membrane; Multi-pass membrane protein Ref.1 Ref.2 Ref.10 Ref.15.

Tissue specificity

Detected in brain and placenta. Ref.1 Ref.2

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Ontologies

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

Traceable author statement Ref.2. Source: ProtInc

adenylate cyclase-inhibiting opioid receptor signaling pathway

Inferred from direct assay Ref.15. Source: UniProtKB

behavior

Traceable author statement Ref.2. Source: ProtInc

defense response to virus

Inferred from direct assay PubMed 8755601. Source: UniProtKB

immune response

Inferred from direct assay PubMed 8755601. Source: UniProtKB

locomotory behavior

Inferred from sequence or structural similarity. Source: UniProtKB

opioid receptor signaling pathway

Inferred from direct assay PubMed 8755601. Source: UniProtKB

phospholipase C-activating G-protein coupled receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of saliva secretion

Inferred from sequence or structural similarity. Source: UniProtKB

sensory perception

Traceable author statement Ref.2. Source: ProtInc

sensory perception of pain

Inferred from sequence or structural similarity. Source: UniProtKB

synaptic transmission

Traceable author statement Ref.2. Source: ProtInc

   Cellular_componentintegral component of membrane

Inferred from direct assay Ref.15. Source: UniProtKB

integral component of plasma membrane

Inferred from mutant phenotype Ref.2. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functiondynorphin receptor activity

Inferred from direct assay PubMed 8755601. Source: UniProtKB

opioid receptor activity

Inferred from direct assay Ref.15. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.11. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

GABARAPL1Q9H0R85EBI-925028,EBI-3464833

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P41145-1)

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: P41145-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-89: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 380380Kappa-type opioid receptor
PRO_0000069967

Regions

Topological domain1 – 5757Extracellular
Transmembrane58 – 8528Helical; Name=1
Topological domain86 – 9510Cytoplasmic
Transmembrane96 – 11924Helical; Name=2
Topological domain120 – 13213Extracellular
Transmembrane133 – 15422Helical; Name=3
Topological domain155 – 17319Cytoplasmic
Transmembrane174 – 19623Helical; Name=4
Topological domain197 – 22226Extracellular
Transmembrane223 – 24725Helical; Name=5
Topological domain248 – 27427Cytoplasmic
Transmembrane275 – 29622Helical; Name=6
Topological domain297 – 31115Extracellular
Transmembrane312 – 33322Helical; Name=7
Topological domain334 – 38047Cytoplasmic

Amino acid modifications

Lipidation3451S-palmitoyl cysteine Potential
Glycosylation251N-linked (GlcNAc...) Ref.12
Glycosylation391N-linked (GlcNAc...) Ref.12
Disulfide bond131 ↔ 210 Ref.15

Natural variations

Alternative sequence1 – 8989Missing in isoform 2.
VSP_055313
Natural variant3741D → N.
Corresponds to variant rs9282808 [ dbSNP | Ensembl ].
VAR_028067

Experimental info

Sequence conflict21D → E in AAA20985. Ref.1
Sequence conflict21D → E in AAM21070. Ref.4

Secondary structure

................................ 380
Helix Strand Turn

Details...

Sequences

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

Last modified October 17, 2006. Version 2.
Checksum: 3DA6E9F90FB48825

FASTA38042,645
        10         20         30         40         50         60 
MDSPIQIFRG EPGPTCAPSA CLPPNSSAWF PGWAEPDSNG SAGSEDAQLE PAHISPAIPV 

        70         80         90        100        110        120 
IITAVYSVVF VVGLVGNSLV MFVIIRYTKM KTATNIYIFN LALADALVTT TMPFQSTVYL 

       130        140        150        160        170        180 
MNSWPFGDVL CKIVISIDYY NMFTSIFTLT MMSVDRYIAV CHPVKALDFR TPLKAKIINI 

       190        200        210        220        230        240 
CIWLLSSSVG ISAIVLGGTK VREDVDVIEC SLQFPDDDYS WWDLFMKICV FIFAFVIPVL 

       250        260        270        280        290        300 
IIIVCYTLMI LRLKSVRLLS GSREKDRNLR RITRLVLVVV AVFVVCWTPI HIFILVEALG 

       310        320        330        340        350        360 
STSHSTAALS SYYFCIALGY TNSSLNPILY AFLDENFKRC FRDFCFPLKM RMERQSTSRV 

       370        380 
RNTVQDPAYL RDIDGMNKPV 

« Hide

Isoform 2 [UniParc].

Checksum: 86448C346FF7E35A
Show »

FASTA29133,319

References

« Hide 'large scale' references
[1]"Isolation of a human kappa opioid receptor cDNA from placenta."
Mansson E., Bare L.A., Yang D.
Biochem. Biophys. Res. Commun. 202:1431-1437(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Placenta.
[2]"Kappa-opioid receptor in humans: cDNA and genomic cloning, chromosomal assignment, functional expression, pharmacology, and expression pattern in the central nervous system."
Simonin F., Gaveriaus-Ruff C., Befort K., Lannes B., Micheletti G., Mattei M.-G., Charon G., Bloch B., Kieffer B.
Proc. Natl. Acad. Sci. U.S.A. 92:7006-7010(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Placenta.
[3]"Cloning of a human kappa opioid receptor from the brain."
Zhu J., Chen C., Xue J.-C., Kunapuli S., Deriel J.K., Liu-Chen L.-Y.
Life Sci. 56:PL201-PL207(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Brain.
[4]"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
Puhl H.L. III, Ikeda S.R., Aronstam R.S.
Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[6]"DNA sequence and analysis of human chromosome 8."
Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. expand/collapse author list , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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 1).
Tissue: Placenta.
[8]"Human kappa opiate receptor second extracellular loop elevates dynorphin's affinity for human mu/kappa chimeras."
Wang J.B., Johnson P.S., Wu J.M., Wang W.F., Uhl G.R.
J. Biol. Chem. 269:25966-25969(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 136-279 (ISOFORMS 1/2).
Tissue: Brain.
[9]"Mapping of the human kappa opioid receptor gene to chromosome 8q11.2-q12: no evidence for multiple kappa opioid receptor genes."
Grandy D.K.
Submitted (DEC-1994) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 132-203 (ISOFORMS 1/2).
[10]"Ezrin-radixin-moesin-binding phosphoprotein-50/Na+/H+ exchanger regulatory factor (EBP50/NHERF) blocks U50,488H-induced down-regulation of the human kappa opioid receptor by enhancing its recycling rate."
Li J.-G., Chen C., Liu-Chen L.-Y.
J. Biol. Chem. 277:27545-27552(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SLC9A3R1, FUNCTION, SUBCELLULAR LOCATION.
[11]"GEC1 interacts with the kappa opioid receptor and enhances expression of the receptor."
Chen C., Li J.-G., Chen Y., Huang P., Wang Y., Liu-Chen L.-Y.
J. Biol. Chem. 281:7983-7993(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GABARAPL1.
[12]"N-glycosylation of the human kappa opioid receptor enhances its stability but slows its trafficking along the biosynthesis pathway."
Li J.G., Chen C., Liu-Chen L.Y.
Biochemistry 46:10960-10970(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-25 AND ASN-39.
[13]"The role of kappa-opioid receptor activation in mediating antinociception and addiction."
Wang Y.H., Sun J.F., Tao Y.M., Chi Z.Q., Liu J.G.
Acta Pharmacol. Sin. 31:1065-1070(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[14]"Kinase cascades and ligand-directed signaling at the kappa opioid receptor."
Bruchas M.R., Chavkin C.
Psychopharmacology 210:137-147(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[15]"Structure of the human kappa-opioid receptor in complex with JDTic."
Wu H., Wacker D., Mileni M., Katritch V., Han G.W., Vardy E., Liu W., Thompson A.A., Huang X.P., Carroll F.I., Mascarella S.W., Westkaemper R.B., Mosier P.D., Roth B.L., Cherezov V., Stevens R.C.
Nature 485:327-332(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 43-358 IN COMPLEX WITH ANTAGONIST, FUNCTION, SUBCELLULAR LOCATION, DISULFIDE BOND.
+Additional computationally mapped references.

Web resources

Wikipedia

Kappa opioid receptor entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U11053 mRNA. Translation: AAA20985.1.
U17298 mRNA. Translation: AAC50158.1.
L37362 mRNA. Translation: AAA63906.1.
AF498922 mRNA. Translation: AAM21070.1.
AK310233 mRNA. No translation available.
AC009646 Genomic DNA. No translation available.
BC099912 mRNA. Translation: AAH99912.1.
L36130 mRNA. Translation: AAA63646.1.
U16860 Genomic DNA. Translation: AAA56758.1.
CCDSCCDS6152.1.
PIRJC2338.
RefSeqNP_000903.2. NM_000912.3.
UniGeneHs.106795.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2A0Dmodel-A1-380[»]
2IQNmodel-A55-348[»]
4DJHX-ray2.90A/B43-358[»]
ProteinModelPortalP41145.
SMRP41145. Positions 40-347.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111031. 3 interactions.
IntActP41145. 9 interactions.
MINTMINT-236997.
STRING9606.ENSP00000265572.

Chemistry

BindingDBP41145.
ChEMBLCHEMBL2095151.
DrugBankDB00921. Buprenorphine.
DB00611. Butorphanol.
DB00907. Cocaine.
DB00318. Codeine.
DB01209. Dezocine.
DB00956. Hydrocodone.
DB00327. Hydromorphone.
DB00454. Meperidine.
DB00370. Mirtazapine.
DB00295. Morphine.
DB00844. Nalbuphine.
DB00704. Naltrexone.
DB00497. Oxycodone.
DB00652. Pentazocine.
DB00647. Propoxyphene.
DB00193. Tramadol.
GuidetoPHARMACOLOGY318.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP41145.

Polymorphism databases

DMDM116242691.

Proteomic databases

PaxDbP41145.
PRIDEP41145.

Protocols and materials databases

DNASU4986.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265572; ENSP00000265572; ENSG00000082556.
ENST00000520287; ENSP00000429706; ENSG00000082556.
GeneID4986.
KEGGhsa:4986.
UCSCuc003xrh.1. human.

Organism-specific databases

CTD4986.
GeneCardsGC08M054138.
HGNCHGNC:8154. OPRK1.
HPACAB022595.
MIM165196. gene.
neXtProtNX_P41145.
PharmGKBPA31943.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG317066.
HOGENOMHOG000230486.
HOVERGENHBG106919.
InParanoidP41145.
KOK04214.
OMAPFQSTEY.
OrthoDBEOG7BKCVQ.
PhylomeDBP41145.
TreeFamTF315737.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkP41145.

Gene expression databases

ArrayExpressP41145.
BgeeP41145.
CleanExHS_OPRK1.
GenevestigatorP41145.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR000452. Kappa_opi_rcpt.
IPR001418. Opioid_rcpt.
[Graphical view]
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00237. GPCRRHODOPSN.
PR00532. KAPPAOPIOIDR.
PR00384. OPIOIDR.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWiki%CE%9A-opioid_receptor.
GenomeRNAi4986.
NextBio19194.
PROP41145.
SOURCESearch...

Entry information

Entry nameOPRK_HUMAN
AccessionPrimary (citable) accession number: P41145
Secondary accession number(s): E5RHC9, Q499G4
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: October 17, 2006
Last modified: July 9, 2014
This is version 134 of the entry and version 2 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 polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries