P21918 (DRD5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	477 AA.
Sequence status	Complete.
Protein existence	Evidence 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	Defects in DRD5 are a cause of benign essential blepharospasm (BEB) [MIM:606798]. BEB is 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. Ref.9
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Dystonia
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	activation of adenylate cyclase activity by dopamine receptor signaling pathway Inferred from direct assay Ref.1. Source: UniProtKB activation of phospholipase C activity by dopamine receptor signaling pathway Traceable author statement. Source: BHF-UCL cellular calcium ion homeostasis Traceable author statement. Source: BHF-UCL negative regulation of NAD(P)H oxidase activity Inferred from direct assay. Source: UniProtKB reactive oxygen species metabolic process Inferred from direct assay. Source: UniProtKB synaptic transmission, dopaminergic Non-traceable author statement. Source: UniProtKB
Cellular component	integral to plasma membrane Non-traceable author statement Ref.1. Source: UniProtKB
Molecular function	dopamine binding Inferred from direct assay Ref.1. Source: UniProtKB dopamine receptor activity, coupled via Gs Traceable author statement. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 477	477	D(1B) dopamine receptor		PRO_0000069405
Regions
	Topological domain	1 – 39	39	Extracellular Potential
	Transmembrane	40 – 66	27	Helical; Name=1; Potential
	Topological domain	67 – 77	11	Cytoplasmic Potential
	Transmembrane	78 – 104	27	Helical; Name=2; Potential
	Topological domain	105 – 114	10	Extracellular Potential
	Transmembrane	115 – 136	22	Helical; Name=3; Potential
	Topological domain	137 – 158	22	Cytoplasmic Potential
	Transmembrane	159 – 180	22	Helical; Name=4; Potential
	Topological domain	181 – 223	43	Extracellular Potential
	Transmembrane	224 – 246	23	Helical; Name=5; Potential
	Topological domain	247 – 296	50	Cytoplasmic Potential
	Transmembrane	297 – 320	24	Helical; Name=6; Potential
	Topological domain	321 – 340	20	Extracellular Potential
	Transmembrane	341 – 360	20	Helical; Name=7; Potential
	Topological domain	361 – 477	117	Cytoplasmic Potential
Amino acid modifications
	Lipidation	375	1	S-palmitoyl cysteine By similarity
	Glycosylation	7	1	N-linked (GlcNAc...) Ref.8
	Glycosylation	222	1	N-linked (GlcNAc...) Potential
	Disulfide bond	113 ↔ 217		By similarity
Natural variations
	Natural variant	62	1	C → S. Corresponds to variant rs2227840 [ dbSNP | Ensembl ].		VAR_029210
	Natural variant	88	1	L → R. Ref.11 Corresponds to variant rs6282 [ dbSNP | Ensembl ].		VAR_011837
	Natural variant	110	1	G → E. Corresponds to variant rs2227849 [ dbSNP | Ensembl ].		VAR_029211
	Natural variant	207	1	F → V. Corresponds to variant rs2227845 [ dbSNP | Ensembl ].		VAR_029212
	Natural variant	233	1	S → N. Corresponds to variant rs2227843 [ dbSNP | Ensembl ].		VAR_029213
	Natural variant	238	1	V → I. Corresponds to variant rs2227852 [ dbSNP | Ensembl ].		VAR_024254
	Natural variant	247	1	R → H. Corresponds to variant rs2227847 [ dbSNP | Ensembl ].		VAR_029214
	Natural variant	269	1	A → V. Ref.10 Corresponds to variant rs2227842 [ dbSNP | Ensembl ].		VAR_003458
	Natural variant	286	1	A → V. Corresponds to variant rs2227850 [ dbSNP | Ensembl ].		VAR_029215
	Natural variant	297	1	T → P. Corresponds to variant rs2227851 [ dbSNP | Ensembl ].		VAR_061217
	Natural variant	330	1	P → Q. Ref.10 Corresponds to variant rs1800762 [ dbSNP | Ensembl ].		VAR_003459
	Natural variant	351	1	N → D. Ref.10		VAR_003460
	Natural variant	453	1	S → C. Ref.10		VAR_003461
Experimental info
	Mutagenesis	7	1	N → Q: Impairs subcellular location. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	P21918 [UniParc]. Last modified March 1, 1992. Version 2. Checksum: BACCB85E5A72F9CA	FASTA	477	52,951
	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

References

	« Hide 'large scale' referencesShow '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: 1826762] [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: 1833775] [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: 1834671] [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. , 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: 14702039] [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. , 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: 15489334] [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: 10531415] [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: 11781417] [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: 7633397] [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: 10391209] [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.
IPI	IPI00011227.
PIR	DYHUD5. S15080.
RefSeq	NP_000789.1. NM_000798.4.
UniGene	Hs.380681.
3D structure databases
ProteinModelPortal	P21918.
SMR	P21918. Positions 39-373.
ModBase	Search...
Protein-protein interaction databases
STRING	P21918.
Protein family/group databases
GPCRDB	Search...
Polymorphism databases
DMDM	118214.
Proteomic databases
PRIDE	P21918.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000304374; ENSP00000306129; ENSG00000169676.
GeneID	1816.
KEGG	hsa:1816.
UCSC	uc003gmb.2. human.
Organism-specific databases
CTD	1816.
GeneCards	GC04P009783.
H-InvDB	HIX0004089.
HGNC	HGNC:3026. DRD5.
MIM	126453. gene+phenotype. 606798. phenotype.
neXtProt	NX_P21918.
Orphanet	93955. Benign essential blepharospasm.
PharmGKB	PA148.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG17430.
HOGENOM	HBG445348.
HOVERGEN	HBG106962.
InParanoid	P21918.
OMA	EGPFDRM.
OrthoDB	EOG4PVNZH.
PhylomeDB	P21918.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	P21918.
Bgee	P21918.
CleanEx	HS_DRD5.
Genevestigator	P21918.
GermOnline	ENSG00000169676. Homo sapiens.
Family and domain databases
InterPro	IPR000276. 7TM_GPCR_Rhodpsn. IPR000497. Dopa_1B_rcpt. IPR000929. Dopamine_rcpt. IPR017452. GPCR_Rhodpsn_supfam. [Graphical view]
KO	K05840.
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00566. DOPAMINED1BR. PR00242. DOPAMINER. PR00237. GPCRRHODOPSN.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00714. Apomorphine. DB01038. Carphenazine. DB00800. Fenoldopam. DB01624. Zuclopenthixol.
NextBio	7405.
SOURCE	Search...

Entry information

Entry name

DRD5_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 137 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.