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P21918 (DRD5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 160. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
D(1B) dopamine receptor
Alternative name(s):
D(5) dopamine receptor
D1beta dopamine receptor
Dopamine D5 receptor
Gene names
Name:DRD5
Synonyms:DRD1B, DRD1L2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length477 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase. Ref.3

Subcellular location

Cell membrane; Multi-pass membrane protein.

Tissue specificity

Neuron-specific, localized primarily within limbic regions of the brain. Ref.3

Involvement in disease

Benign essential blepharospasm (BEB) [MIM:606798]: A primary focal dystonia affecting the orbicularis oculi muscles. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. BEB usually begins in middle age. Initial symptoms include eye irritation and frequent blinking, progressing to involuntary spasms of eyelid closure. Patients have normal eyes. The visual disturbance is due solely to the forced closure of the eyelids. In severe cases, this can lead to functional blindness.
Note: Disease susceptibility may be associated with variations affecting the gene represented in this entry. Ref.9

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DiseaseDystonia
   DomainTransmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Lipoprotein
Palmitate
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of adenylate cyclase activity

Traceable author statement PubMed 9457173. Source: BHF-UCL

adenylate cyclase-activating G-protein coupled receptor signaling pathway

Inferred from direct assay PubMed 11500503. Source: UniProtKB

adenylate cyclase-activating dopamine receptor signaling pathway

Inferred from direct assay Ref.1. Source: UniProtKB

associative learning

Inferred from electronic annotation. Source: Ensembl

cellular calcium ion homeostasis

Traceable author statement PubMed 9457173. Source: BHF-UCL

cellular response to catecholamine stimulus

Inferred from direct assay PubMed 18403039. Source: BHF-UCL

long term synaptic depression

Inferred from electronic annotation. Source: Ensembl

negative regulation of NAD(P)H oxidase activity

Inferred from direct assay PubMed 16352863. Source: UniProtKB

negative regulation of blood pressure

Inferred from electronic annotation. Source: Ensembl

norepinephrine-epinephrine vasoconstriction involved in regulation of systemic arterial blood pressure

Inferred from electronic annotation. Source: Ensembl

phospholipase C-activating dopamine receptor signaling pathway

Traceable author statement PubMed 9457173. Source: BHF-UCL

positive regulation of adenylate cyclase activity

Inferred from direct assay Ref.1. Source: UniProtKB

positive regulation of adenylate cyclase activity involved in G-protein coupled receptor signaling pathway

Inferred from electronic annotation. Source: InterPro

reactive oxygen species metabolic process

Inferred from direct assay PubMed 16352863. Source: UniProtKB

regulation of female receptivity

Inferred from electronic annotation. Source: Ensembl

regulation of systemic arterial blood pressure by vasopressin

Inferred from electronic annotation. Source: Ensembl

response to amphetamine

Inferred from electronic annotation. Source: Ensembl

response to cocaine

Inferred from electronic annotation. Source: Ensembl

sensitization

Inferred from electronic annotation. Source: Ensembl

synaptic transmission

Non-traceable author statement PubMed 7727453. Source: UniProtKB

synaptic transmission, dopaminergic

Non-traceable author statement PubMed 11036203. Source: UniProtKB

transmission of nerve impulse

Inferred from electronic annotation. Source: Ensembl

wound healing

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentbrush border membrane

Inferred from electronic annotation. Source: Ensembl

integral component of plasma membrane

Non-traceable author statement Ref.1. Source: UniProtKB

plasma membrane

Inferred from direct assay Ref.8PubMed 11500503. Source: UniProtKB

   Molecular_functiondopamine binding

Inferred from direct assay Ref.1. Source: UniProtKB

dopamine neurotransmitter receptor activity

Inferred from direct assay Ref.1. Source: UniProtKB

dopamine neurotransmitter receptor activity, coupled via Gs

Traceable author statement PubMed 9457173. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 477477D(1B) dopamine receptor
PRO_0000069405

Regions

Topological domain1 – 3939Extracellular Potential
Transmembrane40 – 6627Helical; Name=1; Potential
Topological domain67 – 7711Cytoplasmic Potential
Transmembrane78 – 10427Helical; Name=2; Potential
Topological domain105 – 11410Extracellular Potential
Transmembrane115 – 13622Helical; Name=3; Potential
Topological domain137 – 15822Cytoplasmic Potential
Transmembrane159 – 18022Helical; Name=4; Potential
Topological domain181 – 22343Extracellular Potential
Transmembrane224 – 24623Helical; Name=5; Potential
Topological domain247 – 29650Cytoplasmic Potential
Transmembrane297 – 32024Helical; Name=6; Potential
Topological domain321 – 34020Extracellular Potential
Transmembrane341 – 36020Helical; Name=7; Potential
Topological domain361 – 477117Cytoplasmic Potential

Amino acid modifications

Lipidation3751S-palmitoyl cysteine By similarity
Glycosylation71N-linked (GlcNAc...) Ref.8
Glycosylation2221N-linked (GlcNAc...) Potential
Disulfide bond113 ↔ 217 By similarity

Natural variations

Natural variant621C → S.
Corresponds to variant rs2227840 [ dbSNP | Ensembl ].
VAR_029210
Natural variant881L → R. Ref.11
Corresponds to variant rs6282 [ dbSNP | Ensembl ].
VAR_011837
Natural variant1101G → E.
Corresponds to variant rs2227849 [ dbSNP | Ensembl ].
VAR_029211
Natural variant2071F → V.
Corresponds to variant rs2227845 [ dbSNP | Ensembl ].
VAR_029212
Natural variant2331S → N.
Corresponds to variant rs2227843 [ dbSNP | Ensembl ].
VAR_029213
Natural variant2381V → I.
Corresponds to variant rs2227852 [ dbSNP | Ensembl ].
VAR_024254
Natural variant2471R → H.
Corresponds to variant rs2227847 [ dbSNP | Ensembl ].
VAR_029214
Natural variant2691A → V. Ref.10
Corresponds to variant rs2227842 [ dbSNP | Ensembl ].
VAR_003458
Natural variant2861A → V.
Corresponds to variant rs2227850 [ dbSNP | Ensembl ].
VAR_029215
Natural variant2971T → P.
Corresponds to variant rs2227851 [ dbSNP | Ensembl ].
VAR_061217
Natural variant3301P → Q. Ref.10
Corresponds to variant rs1800762 [ dbSNP | Ensembl ].
VAR_003459
Natural variant3511N → D. Ref.10
VAR_003460
Natural variant4531S → C. Ref.10
VAR_003461

Experimental info

Mutagenesis71N → Q: Impairs subcellular location. Ref.8

Sequences

Sequence LengthMass (Da)Tools
P21918 [UniParc].

Last modified March 1, 1992. Version 2.
Checksum: BACCB85E5A72F9CA

FASTA47752,951
        10         20         30         40         50         60 
MLPPGSNGTA YPGQFALYQQ LAQGNAVGGS AGAPPLGPSQ VVTACLLTLL IIWTLLGNVL 

        70         80         90        100        110        120 
VCAAIVRSRH LRANMTNVFI VSLAVSDLFV ALLVMPWKAV AEVAGYWPFG AFCDVWVAFD 

       130        140        150        160        170        180 
IMCSTASILN LCVISVDRYW AISRPFRYKR KMTQRMALVM VGLAWTLSIL ISFIPVQLNW 

       190        200        210        220        230        240 
HRDQAASWGG LDLPNNLANW TPWEEDFWEP DVNAENCDSS LNRTYAISSS LISFYIPVAI 

       250        260        270        280        290        300 
MIVTYTRIYR IAQVQIRRIS SLERAAEHAQ SCRSSAACAP DTSLRASIKK ETKVLKTLSV 

       310        320        330        340        350        360 
IMGVFVCCWL PFFILNCMVP FCSGHPEGPP AGFPCVSETT FDVFVWFGWA NSSLNPVIYA 

       370        380        390        400        410        420 
FNADFQKVFA QLLGCSHFCS RTPVETVNIS NELISYNQDI VFHKEIAAAY IHMMPNAVTP 

       430        440        450        460        470 
GNREVDNDEE EGPFDRMFQI YQTSPDGDPV AESVWELDCE GEISLDKITP FTPNGFH 

« Hide

References

« Hide 'large scale' references
[1]"Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1."
Sunahara R.K., Guan H.-C., O'Dowd B.F., Seeman P., Laurier L.G., Ng G., George S.R., Torchia J., van Tol H.H.M., Niznik H.B.
Nature 350:614-619(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Brain.
[2]"Multiple human D5 dopamine receptor genes: a functional receptor and two pseudogenes."
Grandy D.K., Zhang Y., Bouvier C., Zhou Q.-Y., Johnson R.A., Allen L., Buck K., Bunzow J.R., Salon J., Civelli O.
Proc. Natl. Acad. Sci. U.S.A. 88:9175-9179(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Molecular cloning and characterization of a high affinity dopamine receptor (D1 beta) and its pseudogene."
Weinshank R.L., Adham N., Macchi M., Olsen M.A., Branchek T.A., Hartig P.R.
J. Biol. Chem. 266:22427-22435(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, TISSUE SPECIFICITY.
Tissue: Spleen.
[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 (JUL-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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].
Tissue: Amygdala.
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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].
Tissue: Ovary.
[8]"N-linked glycosylation is required for plasma membrane localization of D5, but not D1, dopamine receptors in transfected mammalian cells."
Karpa K.D., Lidow M.S., Pickering M.T., Levenson R., Bergson C.
Mol. Pharmacol. 56:1071-1078(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-7, MUTAGENESIS OF ASN-7.
[9]"A polymorphism in the dopamine receptor DRD5 is associated with blepharospasm."
Misbahuddin A., Placzek M.R., Chaudhuri K.R., Wood N.W., Bhatia K.P., Warner T.T.
Neurology 58:124-126(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN BEB.
[10]"The D5 dopamine receptor gene in schizophrenia: identification of a nonsense change and multiple missense changes but lack of association with disease."
Sobell J.L., Lind T.J., Sigurdson D.C., Zald D.H., Snitz B.E., Grove W.M., Heston L.L., Sommer S.S.
Hum. Mol. Genet. 4:507-514(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VAL-269; GLN-330; ASP-351 AND CYS-453.
[11]"Characterization of single-nucleotide polymorphisms in coding regions of human genes."
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.
Nat. Genet. 22:231-238(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ARG-88.
[12]Erratum
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.
Nat. Genet. 23:373-373(1999)
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X58454 Genomic DNA. Translation: CAA41360.1.
M67439 Genomic DNA. Translation: AAA52329.1.
AY136750 mRNA. Translation: AAN01276.1.
AK313897 mRNA. Translation: BAG36620.1.
CH471069 Genomic DNA. Translation: EAW92679.1.
BC009748 mRNA. Translation: AAH09748.1.
PIRDYHUD5. S15080.
RefSeqNP_000789.1. NM_000798.4.
UniGeneHs.380681.

3D structure databases

ProteinModelPortalP21918.
SMRP21918. Positions 46-374.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108150. 3 interactions.
STRING9606.ENSP00000306129.

Chemistry

BindingDBP21918.
ChEMBLCHEMBL2096905.
DrugBankDB00714. Apomorphine.
DB01038. Carphenazine.
DB00800. Fenoldopam.
DB01624. Zuclopenthixol.
GuidetoPHARMACOLOGY218.

Protein family/group databases

GPCRDBSearch...

Polymorphism databases

DMDM118214.

Proteomic databases

PaxDbP21918.
PRIDEP21918.

Protocols and materials databases

DNASU1816.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000304374; ENSP00000306129; ENSG00000169676.
GeneID1816.
KEGGhsa:1816.
UCSCuc003gmb.4. human.

Organism-specific databases

CTD1816.
GeneCardsGC04P009783.
H-InvDBHIX0029583.
HGNCHGNC:3026. DRD5.
HPAHPA048930.
MIM126453. gene+phenotype.
606798. phenotype.
neXtProtNX_P21918.
Orphanet93962. Autosomal dominant cervical dystonia.
93955. Benign essential blepharospasm.
PharmGKBPA148.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG262978.
HOGENOMHOG000239242.
HOVERGENHBG106962.
InParanoidP21918.
KOK05840.
OMARAENCDS.
OrthoDBEOG780RMN.
PhylomeDBP21918.
TreeFamTF325181.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

BgeeP21918.
CleanExHS_DRD5.
GenevestigatorP21918.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR000497. Dopamine_D5_rcpt.
IPR000929. Dopamine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERPTHR24249:SF45. PTHR24249:SF45. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00566. DOPAMINED1BR.
PR00242. DOPAMINER.
PR00237. GPCRRHODOPSN.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiDopamine_receptor_D5.
GenomeRNAi1816.
NextBio7405.
PROP21918.
SOURCESearch...

Entry information

Entry nameDRD5_HUMAN
AccessionPrimary (citable) accession number: P21918
Secondary accession number(s): B2R9S3, Q8NEQ8
Entry history
Integrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: March 1, 1992
Last modified: April 16, 2014
This is version 160 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

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 4

Human chromosome 4: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries