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dopamine beta-hydroxylase (DBH)
Function:
- conversion of dopamine to noradrenaline
- catecholamine biosynthesis
3,4-dihydroxyphenethylamine + ascorbate + O2
noradrenaline + dehydroascorbate + H2O
Cofactor:
- binds 1 PQQ per subunit
- binds 2 copper ions per subunit
Structure:
- homotetramer composed of two non-covalently bound disulfide-linked dimers
- belongs to the copper type 2 ascorbate-dependent monooxygenase family
- contains 1 DOMON domain
Compartment:
- soluble dopamine beta-hydroxylase: cytoplasmic vesicle, secretory vesicle lumen, chromaffin granule lumen
- secretory vesicle membrane
- chromaffin granule membrane
Expression:
- activity is enhanced by nerve growth factor (in superior cervical ganglia & adrenal medulla)
- trans-synaptic stimulation with reserpine, acetylcholine & glucocorticoids
Polymorphism:
- 2 main alleles of DBH:
a) DBH-A with Ala- 318
b) DBH-B with Ser-318
Pathology:
- defects in DBH are the cause of dopamine-beta hydroxylase deficiency
Interactions
molecular events
General
glycoprotein
hydroxylase; monooxygenase
membrane protein
Properties
SIZE: entity length = 617 aa
MW = 69 kD
COMPARTMENT: cytoplasm
cellular membrane
MOTIF: transmembrane domain {17-37}
Intragranular {38-617}
MOTIF: DOMON {57-173}
N-glycosylation site {N64}
cysteine residue {C154}
MODIFICATION: cysteine residue {C596}
N-glycosylation site {N184}
tyrosine residue {Y230}
cysteine residue {C232}
MODIFICATION: cysteine residue {C283}
copper [Cu]-binding site
SITE: 262-262
MOTIF: histidine residue (3)
copper [Cu]-binding site
SITE: 263-263
MOTIF: histidine residue (3)
cysteine residue {C269}
MODIFICATION: cysteine residue {C295}
cysteine residue {C283}
MODIFICATION: cysteine residue {C232}
cysteine residue {C295}
MODIFICATION: cysteine residue {C269}
copper [Cu]-binding site
SITE: 333-333
MOTIF: histidine residue (3)
cysteine residue {C390}
MODIFICATION: cysteine residue {C503}
cysteine residue {C394}
MODIFICATION: cysteine residue {C565}
histidine residue {H412}
copper [Cu]-binding site
SITE: 412-412
MOTIF: histidine residue (3)
copper [Cu]-binding site
SITE: 414-414
MOTIF: histidine residue (3)
cysteine residue {C466}
MODIFICATION: cysteine residue {C488}
copper [Cu]-binding site
SITE: 487-487
MOTIF: histidine residue (3)
cysteine residue {C488}
MODIFICATION: cysteine residue {C466}
cysteine residue {C503}
MODIFICATION: cysteine residue {C390}
cysteine residue {C528}
MODIFICATION: cysteine residue {C-INTERCHAIN}
cysteine residue {C530}
MODIFICATION: cysteine residue {C-INTERCHAIN }
cysteine residue {C565}
MODIFICATION: cysteine residue {C394}
cysteine residue {C596}
MODIFICATION: cysteine residue {C154}
Database Correlations
OMIM 223360
UniProt P09172
PFAM correlations
Kegg hsa:1621
ENZYME 1.14.17.1
References
- UniProt :accession P09172
- GeneReviews
https://www.genecards.org/cgi-bin/carddisp.pl?gene=DBH
- Wikipedia, dopamine beta hydroxylase entry
http://en.wikipedia.org/wiki/dopamine_beta_hydroxylase