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P09172 (DOPO_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 162. 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·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length617 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 vesiclesecretory vesicle lumen. Cytoplasmic vesiclesecretory vesiclechromaffin granule lumen.

Cytoplasmic vesiclesecretory vesicle membrane; Single-pass type II membrane protein. Cytoplasmic vesiclesecretory vesiclechromaffin 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 processCatecholamine biosynthesis
   Cellular componentCytoplasmic vesicle
Membrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   LigandCopper
Metal-binding
PQQ
Vitamin C
   Molecular functionMonooxygenase
Oxidoreductase
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processbehavioral response to ethanol

Inferred from electronic annotation. Source: Ensembl

blood vessel remodeling

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

dopamine catabolic process

Inferred from electronic annotation. Source: Ensembl

fear response

Inferred from electronic annotation. Source: Ensembl

glucose homeostasis

Inferred from electronic annotation. Source: Ensembl

homoiothermy

Inferred from electronic annotation. Source: Ensembl

leukocyte mediated immunity

Inferred from electronic annotation. Source: Ensembl

leukocyte migration

Inferred from electronic annotation. Source: Ensembl

locomotory behavior

Inferred from electronic annotation. Source: Ensembl

maternal behavior

Inferred from electronic annotation. Source: Ensembl

memory

Inferred from electronic annotation. Source: Ensembl

norepinephrine biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-UniPathway

positive regulation of vasoconstriction

Inferred from electronic annotation. Source: Ensembl

regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

regulation of extrinsic apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

response to amphetamine

Inferred from electronic annotation. Source: Ensembl

response to pain

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

synaptic transmission

Traceable author statement PubMed 2880016. Source: ProtInc

visual learning

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentchromaffin granule lumen

Inferred from electronic annotation. Source: UniProtKB-SubCell

chromaffin granule membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Traceable author statement Ref.2. Source: ProtInc

extracellular region

Non-traceable author statement PubMed 14718574. Source: UniProtKB

integral component of 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_functionL-ascorbic acid binding

Inferred from electronic annotation. Source: UniProtKB-KW

catalytic activity

Traceable author statement Ref.2. Source: ProtInc

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 617617Dopamine beta-hydroxylase
PRO_0000006356
Chain40 – 617578Soluble dopamine beta-hydroxylase
PRO_0000308209

Regions

Topological domain1 – 1616Cytoplasmic Potential
Transmembrane17 – 3721Helical; Signal-anchor for type II membrane protein; Potential
Topological domain38 – 617580Intragranular Potential
Domain57 – 173117DOMON

Sites

Active site2301 Potential
Active site4121 Potential
Metal binding2621Copper A By similarity
Metal binding2631Copper A By similarity
Metal binding3331Copper A By similarity
Metal binding4121Copper B By similarity
Metal binding4141Copper B By similarity
Metal binding4871Copper B By similarity

Amino acid modifications

Glycosylation641N-linked (GlcNAc...) Potential
Glycosylation1841N-linked (GlcNAc...) (complex) Ref.6 Ref.7
Disulfide bond154 ↔ 596 By similarity
Disulfide bond232 ↔ 283 By similarity
Disulfide bond269 ↔ 295 By similarity
Disulfide bond390 ↔ 503 By similarity
Disulfide bond394 ↔ 565 By similarity
Disulfide bond466 ↔ 488 By similarity
Disulfide bond528Interchain By similarity
Disulfide bond530Interchain By similarity

Natural variations

Natural variant121G → S.
Corresponds to variant rs5318 [ dbSNP | Ensembl ].
VAR_048838
Natural variant1011V → M in DBH deficiency. Ref.12
VAR_022758
Natural variant1141D → E in DBH deficiency. Ref.12
VAR_022759
Natural variant1811E → Q.
Corresponds to variant rs5319 [ dbSNP | Ensembl ].
VAR_014706
Natural variant2111A → T. Ref.2 Ref.11
Corresponds to variant rs5320 [ dbSNP | Ensembl ].
VAR_013947
Natural variant2391K → N.
Corresponds to variant rs5321 [ dbSNP | Ensembl ].
VAR_014707
Natural variant2501E → Q.
Corresponds to variant rs5323 [ dbSNP | Ensembl ].
VAR_014708
Natural variant2901D → N.
Corresponds to variant rs5324 [ dbSNP | Ensembl ].
VAR_014709
Natural variant3171L → P.
Corresponds to variant rs5325 [ dbSNP | Ensembl ].
VAR_014710
Natural variant3181A → S in allele DBH-B. Ref.8 Ref.9 Ref.11
Corresponds to variant rs4531 [ dbSNP | Ensembl ].
VAR_002196
Natural variant3451D → N in DBH deficiency. Ref.12
VAR_022760
Natural variant5491R → C. Ref.2 Ref.9
Corresponds to variant rs6271 [ dbSNP | Ensembl ].
VAR_013948

Experimental info

Sequence conflict5051S → T in CAA68285. Ref.2
Sequence conflict5051S → T in CAA31631. Ref.4
Sequence conflict5051S → T in CAA31632. Ref.4

Sequences

Sequence LengthMass (Da)Tools
P09172 [UniParc].

Last modified July 24, 2007. Version 3.
Checksum: 4D5586F0E358885D

FASTA61769,065
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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.
Tissue: Plasma.
[7]"A strategy for precise and large scale identification of core fucosylated glycoproteins."
Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.
Mol. Cell. Proteomics 8:913-923(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-184.
[8]"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.
[9]"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.
[10]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)
[11]"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.
[12]"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

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.
CCDSCCDS6977.2.
PIRS03020.
RefSeqNP_000778.3. NM_000787.3.
UniGeneHs.591890.

3D structure databases

ProteinModelPortalP09172.
SMRP09172. Positions 205-502.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107989. 2 interactions.
IntActP09172. 1 interaction.
MINTMINT-2843963.
STRING9606.ENSP00000376776.

Chemistry

BindingDBP09172.
ChEMBLCHEMBL3102.
DrugBankDB00988. Dopamine.
DB00126. Vitamin C.
GuidetoPHARMACOLOGY2486.

PTM databases

PhosphoSiteP09172.

Polymorphism databases

DMDM158517849.

Proteomic databases

PaxDbP09172.
PRIDEP09172.

Protocols and materials databases

DNASU1621.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000393056; ENSP00000376776; ENSG00000123454.
GeneID1621.
KEGGhsa:1621.
UCSCuc004cel.3. human.

Organism-specific databases

CTD1621.
GeneCardsGC09P136501.
GeneReviewsDBH.
H-InvDBHIX0008510.
HGNCHGNC:2689. DBH.
HPAHPA005960.
MIM223360. phenotype.
609312. gene.
neXtProtNX_P09172.
Orphanet230. Dopamine beta-hydroxylase deficiency.
PharmGKBPA136.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG286384.
HOGENOMHOG000063669.
HOVERGENHBG005519.
InParanoidP09172.
KOK00503.
OMASYFGDAW.
OrthoDBEOG78WKR4.
PhylomeDBP09172.
TreeFamTF320698.

Enzyme and pathway databases

BioCycMetaCyc:MONOMER66-381.
ReactomeREACT_111217. Metabolism.
SignaLinkP09172.
UniPathwayUPA00748; UER00735.

Gene expression databases

ArrayExpressP09172.
BgeeP09172.
CleanExHS_DBH.
GenevestigatorP09172.

Family and domain databases

Gene3D2.60.120.230. 1 hit.
2.60.120.310. 1 hit.
InterProIPR014784. Cu2_ascorb_mOase-like_C.
IPR020611. Cu2_ascorb_mOase_CS-1.
IPR014783. Cu2_ascorb_mOase_CS-2.
IPR000323. Cu2_ascorb_mOase_N.
IPR000945. DBH-rel.
IPR005018. DOMON_domain.
IPR008977. PHM/PNGase_F_dom.
IPR028460. Tbh/DBH.
[Graphical view]
PANTHERPTHR10157. PTHR10157. 1 hit.
PTHR10157:SF4. PTHR10157:SF4. 1 hit.
PfamPF01082. Cu2_monooxygen. 1 hit.
PF03351. DOMON. 1 hit.
[Graphical view]
PRINTSPR00767. DBMONOXGNASE.
SMARTSM00664. DoH. 1 hit.
[Graphical view]
SUPFAMSSF49742. SSF49742. 2 hits.
PROSITEPS00084. CU2_MONOOXYGENASE_1. 1 hit.
PS00085. CU2_MONOOXYGENASE_2. 1 hit.
PS50836. DOMON. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiDopamine_beta_hydroxylase.
GenomeRNAi1621.
NextBio6654.
PROP09172.
SOURCESearch...

Entry information

Entry nameDOPO_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 162 of the entry and version 3 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

PATHWAY comments

Index of metabolic and biosynthesis pathways

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 9

Human chromosome 9: entries, gene names and cross-references to MIM