P09172 (DOPO_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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. Soluble dopamine beta-hydroxylase

Gene names

Name:

DBH

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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; (R)-noradrenaline biosynthesis; (R)-noradrenaline 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	Dopamine beta-hydroxylase deficiency (DBH deficiency) [MIM:223360]: Characterized by profound deficits in autonomic and cardiovascular function, but apparently only subtle signs, if any, of central nervous system dysfunction. Note: The disease is caused by mutations affecting the gene represented in this entry.
Sequence similarities	Belongs to the copper type II ascorbate-dependent monooxygenase family. Contains 1 DOMON domain.
Sequence caution	The sequence AAH17174.1 differs from that shown. Reason: Erroneous initiation. The sequence CAA31631.1 differs from that shown. Reason: Erroneous initiation. The sequence CAA31632.1 differs from that shown. Reason: Erroneous initiation. The sequence CAA68285.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Catecholamine biosynthesis
Cellular component	Cytoplasmic vesicle Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal-anchor Transmembrane Transmembrane helix
Ligand	Copper Metal-binding PQQ Vitamin C
Molecular function	Monooxygenase Oxidoreductase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	behavioral response to ethanol Inferred from electronic annotation. Source: Compara blood vessel remodeling Inferred from electronic annotation. Source: Compara catecholamine biosynthetic process Traceable author statement. Source: Reactome cellular nitrogen compound metabolic process Traceable author statement. Source: Reactome cytokine production Inferred from electronic annotation. Source: Compara dopamine catabolic process Inferred from electronic annotation. Source: Compara fear response Inferred from electronic annotation. Source: Compara glucose homeostasis Inferred from electronic annotation. Source: Compara homoiothermy Inferred from electronic annotation. Source: Compara leukocyte mediated immunity Inferred from electronic annotation. Source: Compara leukocyte migration Inferred from electronic annotation. Source: Compara locomotory behavior Inferred from electronic annotation. Source: Compara maternal behavior Inferred from electronic annotation. Source: Compara memory Inferred from electronic annotation. Source: Compara norepinephrine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway positive regulation of vasoconstriction Inferred from electronic annotation. Source: Compara regulation of apoptotic process Inferred from electronic annotation. Source: Compara regulation of cell proliferation Inferred from electronic annotation. Source: Compara response to amphetamine Inferred from electronic annotation. Source: Compara response to pain Inferred from electronic annotation. Source: Compara synaptic transmission Traceable author statement PubMed 2880016. Source: ProtInc visual learning Inferred from electronic annotation. Source: Compara
Cellular_component	chromaffin granule Non-traceable author statement. Source: UniProtKB 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 PubMed 14718574. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW membrane Traceable author statement Ref.2. Source: ProtInc secretory granule lumen Traceable author statement. Source: Reactome transport vesicle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	L-ascorbic acid binding Inferred from electronic annotation. Source: UniProtKB-KW copper ion binding Inferred from electronic annotation. Source: InterPro dopamine beta-monooxygenase activity Traceable author statement. Source: Reactome
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	Helical; Signal-anchor for type II membrane protein; 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. Corresponds to variant rs5318 [ dbSNP | Ensembl ].		VAR_048838
	Natural variant	101	1	V → M in DBH deficiency. Ref.11		VAR_022758
	Natural variant	114	1	D → E in DBH deficiency. Ref.11		VAR_022759
	Natural variant	181	1	E → Q. Corresponds to variant rs5319 [ dbSNP | Ensembl ].		VAR_014706
	Natural variant	211	1	A → T. Ref.2 Ref.10 Corresponds to variant rs5320 [ dbSNP | Ensembl ].		VAR_013947
	Natural variant	239	1	K → N. Corresponds to variant rs5321 [ dbSNP | Ensembl ].		VAR_014707
	Natural variant	250	1	E → Q. Corresponds to variant rs5323 [ dbSNP | Ensembl ].		VAR_014708
	Natural variant	290	1	D → N. Corresponds to variant rs5324 [ dbSNP | Ensembl ].		VAR_014709
	Natural variant	317	1	L → P. Corresponds to variant rs5325 [ dbSNP | Ensembl ].		VAR_014710
	Natural variant	318	1	A → S in allele DBH-B. Ref.7 Ref.8 Ref.10 Corresponds to variant rs4531 [ dbSNP | Ensembl ].		VAR_002196
	Natural variant	345	1	D → N in DBH deficiency. Ref.11		VAR_022760
	Natural variant	549	1	R → C. Ref.2 Ref.8 Corresponds to variant rs6271 [ dbSNP | Ensembl ].		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 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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
EMBL GenBank DDBJ	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. NM_000787.3.
UniGene	Hs.591890.
3D structure databases
ProteinModelPortal	P09172.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-2843963.
STRING	9606.ENSP00000376776.
PTM databases
PhosphoSite	P09172.
Polymorphism databases
DMDM	158517849.
Proteomic databases
PaxDb	P09172.
PRIDE	P09172.
Protocols and materials databases
DNASU	1621.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000393056; ENSP00000376776; ENSG00000123454.
GeneID	1621.
KEGG	hsa:1621.
UCSC	uc004cel.3. human.
Organism-specific databases
CTD	1621.
GeneCards	GC09P136501.
H-InvDB	HIX0008510.
HGNC	HGNC:2689. DBH.
HPA	HPA005960.
MIM	223360. phenotype. 609312. gene.
neXtProt	NX_P09172.
Orphanet	230. Dopamine beta-hydroxylase deficiency.
PharmGKB	PA136.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG286384.
HOGENOM	HOG000063669.
HOVERGEN	HBG005519.
InParanoid	P09172.
KO	K00503.
OMA	GAKAFYY.
OrthoDB	EOG4SN1ND.
Enzyme and pathway databases
BioCyc	MetaCyc:MONOMER66-381.
Reactome	REACT_111217. Metabolism.
SignaLink	P09172.
UniPathway	UPA00748; UER00735.
Gene expression databases
ArrayExpress	P09172.
Bgee	P09172.
CleanEx	HS_DBH.
Genevestigator	P09172.
GermOnline	ENSG00000123454. Homo sapiens.
Family and domain databases
Gene3D	2.60.120.230. 1 hit. 2.60.120.310. 1 hit.
InterPro	IPR014784. Cu2_ascorb_mOase-like_C. IPR020611. Cu2_ascorb_mOase_CS-1. IPR014783. Cu2_ascorb_mOase_CS-2. IPR000323. Cu2_ascorb_mOase_N. IPR005018. DOMON_domain. IPR000945. Dopamine_b_mOase. IPR008977. PHM/PNGase_F_dom. [Graphical view]
PANTHER	PTHR10157. PTHR10157. 1 hit.
Pfam	PF01082. Cu2_monooxygen. 1 hit. PF03351. DOMON. 1 hit. [Graphical view]
PRINTS	PR00767. DBMONOXGNASE.
SMART	SM00664. DoH. 1 hit. [Graphical view]
SUPFAM	SSF49742. PHM_PNGase_F. 2 hits.
PROSITE	PS00084. CU2_MONOOXYGENASE_1. 1 hit. PS00085. CU2_MONOOXYGENASE_2. 1 hit. PS50836. DOMON. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P09172.
ChEMBL	CHEMBL3102.
DrugBank	DB00988. Dopamine. DB00126. Vitamin C.
GenomeRNAi	1621.
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:	May 29, 2013
This is version 151 of the entry and version 3 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.