Reviewed, UniProtKB/Swiss-Prot P09172 (DOPO_HUMAN)

Names and origin

Protein names

Recommended name:
    Dopamine beta-hydroxylase
    EC=1.14.17.1
Alternative name(s):
    Dopamine beta-monooxygenase
Cleaved into the following chain:
    1- Recommended name:
            Soluble dopamine beta-hydroxylase

Gene names

Name:

DBH

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	617 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Conversion of dopamine to noradrenaline.
Catalytic activity	3,4-dihydroxyphenethylamine + ascorbate + O2 = noradrenaline + dehydroascorbate + H2O.
Cofactor	Binds 1 PQQ per subunit. Binds 2 copper ions per subunit.
Pathway	Catecholamine biosynthesis; norepinephrine biosynthesis; norepinephrine from dopamine: step 1/1.
Subunit structure	Homotetramer composed of two non-covalently bound disulfide-linked dimers.
Subcellular location	Soluble dopamine beta-hydroxylase: Cytoplasmic vesicle › secretory vesicle lumen. Cytoplasmic vesicle › secretory vesicle › chromaffin granule lumen. Cytoplasmic vesicle › secretory vesicle membrane; Single-pass type II membrane protein. Cytoplasmic vesicle › secretory vesicle › chromaffin granule membrane; Single-pass type II membrane protein Potential.
Induction	Activity is enhanced by nerve growth factor (in superior cervical ganglia and adrenal medulla). Trans-synaptic stimulation with reserpine, acetylcholine and glucocorticoids.
Polymorphism	There are two main alleles of DBH: DBH-A with Ala-318 and DBH-B with Ser-318.
Involvement in disease	Defects in DBH are the cause of DBH deficiency [MIM:223360]; also called norepinephrine deficiency or noradrenaline deficiency. This disorder is characterized by profound deficits in autonomic and cardiovascular function, but apparently only subtle signs, if any, of central nervous system dysfunction. Ref.11
Sequence similarities	Belongs to the copper type II ascorbate-dependent monooxygenase family. Contains 1 DOMON domain.

Ontologies

Keywords
Biological process	Catecholamine biosynthesis
Cellular component	Cytoplasmic vesicle Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal-anchor Transmembrane
Ligand	Copper Metal-binding Vitamin C
Molecular function	Monooxygenase Oxidoreductase
PTM	Disulfide bond Glycoprotein PQQ
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	catecholamine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW histidine catabolic process Inferred from electronic annotation. Source: InterPro oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW synaptic transmission Traceable author statement. Source: ProtInc
Cellular component	chromaffin granule lumen Inferred from electronic annotation. Source: UniProtKB-SubCell chromaffin granule membrane Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular region Non-traceable author statement. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW membrane fraction Ref.2 Traceable author statement. Source: ProtInc secretory granule lumen Inferred from electronic annotation. Source: UniProtKB-SubCell soluble fraction Ref.2 Traceable author statement. Source: ProtInc
Molecular function	L-ascorbic acid binding Inferred from electronic annotation. Source: UniProtKB-KW copper ion binding Inferred from electronic annotation. Source: UniProtKB-KW dopamine beta-monooxygenase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 617	617	Dopamine beta-hydroxylase		PRO_0000006356
	Chain	40 – 617	578	Soluble dopamine beta-hydroxylase		PRO_0000308209
Regions
	Topological domain	1 – 16	16	Cytoplasmic Potential
	Transmembrane	17 – 37	21	Signal-anchor for type II membrane Potential
	Topological domain	38 – 617	580	Intragranular Potential
	Domain	57 – 173	117	DOMON
Sites
	Active site	230	1	Potential
	Active site	412	1	Potential
	Metal binding	262	1	Copper A By similarity
	Metal binding	263	1	Copper A By similarity
	Metal binding	333	1	Copper A By similarity
	Metal binding	412	1	Copper B By similarity
	Metal binding	414	1	Copper B By similarity
	Metal binding	487	1	Copper B By similarity
Amino acid modifications
	Glycosylation	64	1	N-linked (GlcNAc...) Potential
	Glycosylation	184	1	N-linked (GlcNAc...) Ref.6
	Disulfide bond	154 ↔ 596		By similarity
	Disulfide bond	232 ↔ 283		By similarity
	Disulfide bond	269 ↔ 295		By similarity
	Disulfide bond	390 ↔ 503		By similarity
	Disulfide bond	394 ↔ 565		By similarity
	Disulfide bond	466 ↔ 488		By similarity
	Disulfide bond	528		Interchain By similarity
	Disulfide bond	530		Interchain By similarity
Natural variations
	Natural variant	12	1	G → S: dbSNP rs5318.		VAR_048838
	Natural variant	101	1	V → M in DBH deficiency.		VAR_022758
	Natural variant	114	1	D → E in DBH deficiency.		VAR_022759
	Natural variant	181	1	E → Q: dbSNP rs5319.		VAR_014706
	Natural variant	211	1	A → T: dbSNP rs5320. Ref.2 Ref.10		VAR_013947
	Natural variant	239	1	K → N: dbSNP rs5321.		VAR_014707
	Natural variant	250	1	E → Q: dbSNP rs5323.		VAR_014708
	Natural variant	290	1	D → N: dbSNP rs5324.		VAR_014709
	Natural variant	317	1	L → P: dbSNP rs5325.		VAR_014710
	Natural variant	318	1	A → S in allele DBH-B. dbSNP rs4531. Ref.10 Ref.7 Ref.8		VAR_002196
	Natural variant	345	1	D → N in DBH deficiency.		VAR_022760
	Natural variant	549	1	R → C: dbSNP rs6271. Ref.2 Ref.8		VAR_013948
Experimental info
	Sequence conflict	505	1	S → T in CAA68285. Ref.2
	Sequence conflict	505	1	S → T in CAA31631. Ref.4
	Sequence conflict	505	1	S → T in CAA31632. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P09172-1 [UniParc]. Last modified July 24, 2007. Version 3. Checksum: 4D5586F0E358885D	FASTA	617	69,065
	10 20 30 40 50 60 MPALSRWASL PGPSMREAAF MYSTAVAIFL VILVAALQGS APRESPLPYH IPLDPEGSLE 70 80 90 100 110 120 LSWNVSYTQE AIHFQLLVRR LKAGVLFGMS DRGELENADL VVLWTDGDTA YFADAWSDQK 130 140 150 160 170 180 GQIHLDPQQD YQLLQVQRTP EGLTLLFKRP FGTCDPKDYL IEDGTVHLVY GILEEPFRSL 190 200 210 220 230 240 EAINGSGLQM GLQRVQLLKP NIPEPELPSD ACTMEVQAPN IQIPSQETTY WCYIKELPKG 250 260 270 280 290 300 FSRHHIIKYE PIVTKGNEAL VHHMEVFQCA PEMDSVPHFS GPCDSKMKPD RLNYCRHVLA 310 320 330 340 350 360 AWALGAKAFY YPEEAGLAFG GPGSSRYLRL EVHYHNPLVI EGRNDSSGIR LYYTAKLRRF 370 380 390 400 410 420 NAGIMELGLV YTPVMAIPPR ETAFILTGYC TDKCTQLALP PSGIHIFASQ LHTHLTGRKV 430 440 450 460 470 480 VTVLVRDGRE WEIVNQDNHY SPHFQEIRML KKVVSVHPGD VLITSCTYNT EDRELATVGG 490 500 510 520 530 540 FGILEEMCVN YVHYYPQTQL ELCKSAVDAG FLQKYFHLIN RFNNEDVCTC PQASVSQQFT 550 560 570 580 590 600 SVPWNSFNRD VLKALYSFAP ISMHCNKSSA VRFQGEWNLQ PLPKVISTLE EPTPQCPTSQ 610 GRSPAGPTVV SIGGGKG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	"The primary structure of human dopamine-beta-hydroxylase: insights into the relationship between the soluble and the membrane-bound forms of the enzyme." Lamouroux A., Vigny A., Faucon Biguet N., Darmon M.C., Franck R., Henry J.-P., Mallet J. EMBO J. 6:3931-3937(1987) [PubMed: 3443096] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2-617, PARTIAL PROTEIN SEQUENCE, VARIANTS THR-211 AND CYS-549.
[3]	"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] OF 3-617. Tissue: Brain.
[4]	"Human dopamine beta-hydroxylase gene: two mRNA types having different 3'-terminal regions are produced through alternative polyadenylation." Kobayashi K., Kurosawa Y., Fukita K., Nagatsu T. Nucleic Acids Res. 17:1089-1102(1989) [PubMed: 2922261] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 5-617.
[5]	"Expression of human dopamine beta-hydroxylase in Drosophila Schneider 2 cells." Li B., Tsing S., Kosaka A.H., Nguyen B., Osen E.G., Bach C., Chan H., Barnett J. Biochem. J. 313:57-64(1996) [PubMed: 8546710] [Abstract] Cited for: PROTEIN SEQUENCE OF 40-48.
[6]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-184, MASS SPECTROMETRY. Tissue: Plasma.
[7]	"No evidence for allelic association between schizophrenia and a functional variant of the human dopamine beta-hydroxylase gene (DBH)." Williams H.J., Bray N., Murphy K.C., Cardno A.G., Jones L.A., Owen M.J. Am. J. Med. Genet. 88:557-559(1999) [PubMed: 10490716] [Abstract] Cited for: VARIANT SER-318.
[8]	"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: VARIANTS SER-318 AND CYS-549.
[9]	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)
[10]	"Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis." Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A., Cooper R., Lipshutz R., Chakravarti A. Nat. Genet. 22:239-247(1999) [PubMed: 10391210] [Abstract] Cited for: VARIANTS THR-211 AND SER-318.
[11]	"Mutations in the dopamine beta-hydroxylase gene are associated with human norepinephrine deficiency." Kim C.-H., Zabetian C.P., Cubells J.F., Cho S., Biaggioni I., Cohen B.M., Robertson D., Kim K.-S. Am. J. Med. Genet. 108:140-147(2002) [PubMed: 11857564] [Abstract] Cited for: VARIANTS DBH DEFICIENCY MET-101; GLU-114 AND ASN-345.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

Dopamine beta hydroxylase entry

Cross-references

Sequence databases
EMBLGenBankDDBJ	AL365494 Genomic DNA. Translation: CAI13354.2. Y00096 mRNA. Translation: CAA68285.1. Different initiation. BC017174 mRNA. Translation: AAH17174.1. Different initiation. X13255 mRNA. Translation: CAA31631.1. Different initiation. X13256 mRNA. Translation: CAA31632.1. Different initiation.
IPI	IPI00171678.
PIR	S03020.
RefSeq	NP_000778.3.
UniGene	Hs.591890
3D structure databases
ModBase	Search...
Proteomic databases
PRIDE	P09172.
Genome annotation databases
Ensembl	ENSG00000123454. Homo sapiens. [Contig view]
GeneID	1621.
KEGG	hsa:1621.
Organism-specific databases
GeneCards	GC09P135491.
H-InvDB	HIX0008510.
HGNC	HGNC:2689. DBH.
HPA	HPA005960.
MIM	223360. phenotype. 609312. gene.
Orphanet	230. Dopamine beta-hydroxylase deficiency.
PharmGKB	PA136.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P09172.
HOVERGEN	P09172.
OMA	P09172. LDSQQDY.
Enzyme and pathway databases
BRENDA	1.14.17.1. 247.
Gene expression databases
ArrayExpress	P09172.
Bgee	P09172.
CleanEx	HS_DBH.
GermOnline	ENSG00000123454. Homo sapiens.
Family and domain databases
InterPro	IPR014783. Cu2_ascorb_mOase_C. IPR000323. Cu2_ascorb_mOase_N. IPR013050. DOMON. IPR005018. DOMON_rel. IPR000945. Dopamine_b_mOase. [Graphical view]
PANTHER	PTHR10157. Dopamine_b_mOase. 1 hit.
Pfam	PF03712. Cu2_monoox_C. 1 hit. PF01082. Cu2_monooxygen. 1 hit. PF03351. DOMON. 1 hit. [Graphical view]
PRINTS	PR00767. DBMONOXGNASE.
SMART	SM00664. DoH. 1 hit. [Graphical view]
PROSITE	PS00084. CU2_MONOOXYGENASE_1. 1 hit. PS00085. CU2_MONOOXYGENASE_2. 1 hit. PS50836. DOMON. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00988. Dopamine. DB00126. Vitamin C.
NextBio	6654.
SOURCE	Search...

Entry information

Entry name

DOPO_HUMAN

Accession

Primary (citable) accession number: P09172
Secondary accession number(s): Q5T381, Q96AG2

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 24, 2007
Last modified:	June 16, 2009
This is version 107 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)