DOPO_HUMAN
ID DOPO_HUMAN Reviewed; 617 AA.
AC P09172; Q5T381; Q96AG2;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 24-JUL-2007, sequence version 3.
DT 03-AUG-2022, entry version 222.
DE RecName: Full=Dopamine beta-hydroxylase;
DE EC=1.14.17.1 {ECO:0000269|PubMed:3443096, ECO:0000269|PubMed:7961964, ECO:0000269|PubMed:8546710};
DE AltName: Full=Dopamine beta-monooxygenase;
DE Contains:
DE RecName: Full=Soluble dopamine beta-hydroxylase;
GN Name=DBH;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-617, PARTIAL PROTEIN SEQUENCE, VARIANTS
RP THR-211 AND CYS-549, CATALYTIC ACTIVITY, FUNCTION, AND PATHWAY.
RX PubMed=3443096; DOI=10.1002/j.1460-2075.1987.tb02734.x;
RA Lamouroux A., Vigny A., Faucon Biguet N., Darmon M.C., Franck R.,
RA Henry J.-P., Mallet J.;
RT "The primary structure of human dopamine-beta-hydroxylase: insights into
RT the relationship between the soluble and the membrane-bound forms of the
RT enzyme.";
RL EMBO J. 6:3931-3937(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3-617.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 5-617.
RX PubMed=2922261; DOI=10.1093/nar/17.3.1089;
RA Kobayashi K., Kurosawa Y., Fukita K., Nagatsu T.;
RT "Human dopamine beta-hydroxylase gene: two mRNA types having different 3'-
RT terminal regions are produced through alternative polyadenylation.";
RL Nucleic Acids Res. 17:1089-1102(1989).
RN [5]
RP PROTEIN SEQUENCE OF 40-48, CATALYTIC ACTIVITY, FUNCTION, PATHWAY,
RP SUBCELLULAR LOCATION, GLYCOSYLATION, COFACTOR, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=8546710; DOI=10.1042/bj3130057;
RA Li B., Tsing S., Kosaka A.H., Nguyen B., Osen E.G., Bach C., Chan H.,
RA Barnett J.;
RT "Expression of human dopamine beta-hydroxylase in Drosophila Schneider 2
RT cells.";
RL Biochem. J. 313:57-64(1996).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=7961964; DOI=10.1016/s0021-9258(18)43941-5;
RA Kobayashi K., Morita S., Mizuguchi T., Sawada H., Yamada K., Nagatsu I.,
RA Fujita K., Nagatsu T.;
RT "Functional and high level expression of human dopamine beta-hydroxylase in
RT transgenic mice.";
RL J. Biol. Chem. 269:29725-29731(1994).
RN [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-184.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [8]
RP GLYCOSYLATION AT ASN-184.
RX PubMed=19139490; DOI=10.1074/mcp.m800504-mcp200;
RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B.,
RA Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L.,
RA Ying W.T., He S.M., Qian X.H.;
RT "A strategy for precise and large scale identification of core fucosylated
RT glycoproteins.";
RL Mol. Cell. Proteomics 8:913-923(2009).
RN [9]
RP FUNCTION, AND PATHWAY.
RX PubMed=27148966; DOI=10.1371/journal.pone.0154864;
RA Cubells J.F., Schroeder J.P., Barrie E.S., Manvich D.F., Sadee W., Berg T.,
RA Mercer K., Stowe T.A., Liles L.C., Squires K.E., Mezher A., Curtin P.,
RA Perdomo D.L., Szot P., Weinshenker D.;
RT "Human bacterial artificial chromosome (BAC) transgenesis fully rescues
RT noradrenergic function in dopamine beta-hydroxylase knockout mice.";
RL PLoS ONE 11:E0154864-E0154864(2016).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 40-617 IN COMPLEX WITH COPPER
RP IONS, SUBUNIT, DISULFIDE BONDS, GLYCOSYLATION AT ASN-64; ASN-184 AND
RP ASN-566, AND COFACTOR.
RX PubMed=27152332; DOI=10.1126/sciadv.1500980;
RA Vendelboe T.V., Harris P., Zhao Y., Walter T.S., Harlos K., El Omari K.,
RA Christensen H.E.;
RT "The crystal structure of human dopamine beta-hydroxylase at 2.9 A
RT resolution.";
RL Sci. Adv. 2:E1500980-E1500980(2016).
RN [11]
RP VARIANT SER-318.
RX PubMed=10490716;
RX DOI=10.1002/(sici)1096-8628(19991015)88:5<557::aid-ajmg22>3.0.co;2-f;
RA Williams H.J., Bray N., Murphy K.C., Cardno A.G., Jones L.A., Owen M.J.;
RT "No evidence for allelic association between schizophrenia and a functional
RT variant of the human dopamine beta-hydroxylase gene (DBH).";
RL Am. J. Med. Genet. 88:557-559(1999).
RN [12]
RP VARIANTS SER-318 AND CYS-549.
RX PubMed=10391209; DOI=10.1038/10290;
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RT "Characterization of single-nucleotide polymorphisms in coding regions of
RT human genes.";
RL Nat. Genet. 22:231-238(1999).
RN [13]
RP ERRATUM OF PUBMED:10391209.
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RL Nat. Genet. 23:373-373(1999).
RN [14]
RP VARIANTS THR-211 AND SER-318.
RX PubMed=10391210; DOI=10.1038/10297;
RA Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A.,
RA Cooper R., Lipshutz R., Chakravarti A.;
RT "Patterns of single-nucleotide polymorphisms in candidate genes for blood-
RT pressure homeostasis.";
RL Nat. Genet. 22:239-247(1999).
RN [15]
RP VARIANTS ORTHYP1 MET-101; GLU-114 AND ASN-345.
RX PubMed=11857564; DOI=10.1002/ajmg.10196.abs;
RA Kim C.-H., Zabetian C.P., Cubells J.F., Cho S., Biaggioni I., Cohen B.M.,
RA Robertson D., Kim K.-S.;
RT "Mutations in the dopamine beta-hydroxylase gene are associated with human
RT norepinephrine deficiency.";
RL Am. J. Med. Genet. 108:140-147(2002).
CC -!- FUNCTION: Conversion of dopamine to noradrenaline.
CC {ECO:0000269|PubMed:27148966, ECO:0000269|PubMed:3443096,
CC ECO:0000269|PubMed:7961964, ECO:0000269|PubMed:8546710}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dopamine + 2 L-ascorbate + O2 = (R)-noradrenaline + H2O + 2
CC monodehydro-L-ascorbate radical; Xref=Rhea:RHEA:19117,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:38290,
CC ChEBI:CHEBI:59513, ChEBI:CHEBI:59905, ChEBI:CHEBI:72587;
CC EC=1.14.17.1; Evidence={ECO:0000269|PubMed:3443096,
CC ECO:0000269|PubMed:7961964, ECO:0000269|PubMed:8546710};
CC -!- COFACTOR:
CC Name=Cu(2+); Xref=ChEBI:CHEBI:29036;
CC Evidence={ECO:0000269|PubMed:8546710, ECO:0000305|PubMed:27152332};
CC Note=Binds 2 copper ions per subunit. {ECO:0000305|PubMed:27152332};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.8 mM for tyramine {ECO:0000269|PubMed:8546710};
CC pH dependence:
CC Optimum pH is 5.2. {ECO:0000269|PubMed:8546710};
CC -!- PATHWAY: Catecholamine biosynthesis; (R)-noradrenaline biosynthesis;
CC (R)-noradrenaline from dopamine: step 1/1.
CC {ECO:0000269|PubMed:27148966, ECO:0000269|PubMed:3443096,
CC ECO:0000269|PubMed:8546710}.
CC -!- SUBUNIT: Homotetramer; composed of two disulfide-linked dimers.
CC {ECO:0000269|PubMed:27152332}.
CC -!- INTERACTION:
CC P09172; P00352: ALDH1A1; NbExp=3; IntAct=EBI-8589586, EBI-752170;
CC P09172; P63010-2: AP2B1; NbExp=3; IntAct=EBI-8589586, EBI-11529439;
CC P09172; Q04656: ATP7A; NbExp=2; IntAct=EBI-8589586, EBI-7706409;
CC P09172; Q8WUW1: BRK1; NbExp=3; IntAct=EBI-8589586, EBI-2837444;
CC P09172; Q9UNS2: COPS3; NbExp=3; IntAct=EBI-8589586, EBI-350590;
CC P09172; Q71DI3: H3C15; NbExp=3; IntAct=EBI-8589586, EBI-750650;
CC P09172; P61978: HNRNPK; NbExp=3; IntAct=EBI-8589586, EBI-304185;
CC P09172; Q9Y2M5: KLHL20; NbExp=3; IntAct=EBI-8589586, EBI-714379;
CC P09172; Q92876: KLK6; NbExp=3; IntAct=EBI-8589586, EBI-2432309;
CC P09172; P08727: KRT19; NbExp=3; IntAct=EBI-8589586, EBI-742756;
CC P09172; Q14693: LPIN1; NbExp=3; IntAct=EBI-8589586, EBI-5278370;
CC P09172; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-8589586, EBI-22310682;
CC P09172; Q6GQQ9-2: OTUD7B; NbExp=3; IntAct=EBI-8589586, EBI-25830200;
CC P09172; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-8589586, EBI-9090282;
CC P09172; Q9ULX5: RNF112; NbExp=3; IntAct=EBI-8589586, EBI-25829984;
CC P09172; Q96D59: RNF183; NbExp=3; IntAct=EBI-8589586, EBI-743938;
CC P09172; Q8N6K7-2: SAMD3; NbExp=3; IntAct=EBI-8589586, EBI-11528848;
CC P09172; Q8IUW3: SPATA2L; NbExp=3; IntAct=EBI-8589586, EBI-2510414;
CC P09172; Q86WT6-2: TRIM69; NbExp=3; IntAct=EBI-8589586, EBI-11525489;
CC P09172; Q9GZS3: WDR61; NbExp=3; IntAct=EBI-8589586, EBI-358545;
CC -!- SUBCELLULAR LOCATION: [Soluble dopamine beta-hydroxylase]: Cytoplasmic
CC vesicle, secretory vesicle lumen {ECO:0000269|PubMed:7961964}.
CC Cytoplasmic vesicle, secretory vesicle, chromaffin granule lumen
CC {ECO:0000269|PubMed:7961964}. Secreted {ECO:0000269|PubMed:7961964,
CC ECO:0000269|PubMed:8546710}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle membrane
CC {ECO:0000269|PubMed:7961964}; Single-pass type II membrane protein
CC {ECO:0000305}. Cytoplasmic vesicle, secretory vesicle, chromaffin
CC granule membrane {ECO:0000269|PubMed:7961964}; Single-pass type II
CC membrane protein {ECO:0000305}.
CC -!- INDUCTION: Activity is enhanced by nerve growth factor (in superior
CC cervical ganglia and adrenal medulla). Trans-synaptic stimulation with
CC reserpine, acetylcholine and glucocorticoids.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:27152332,
CC ECO:0000269|PubMed:8546710}.
CC -!- PTM: Proteolytic cleavage after the membrane-anchor leads to the
CC release of the soluble form. {ECO:0000250|UniProtKB:P15101}.
CC -!- POLYMORPHISM: There are two main alleles of DBH: DBH-A with Ala-318 and
CC DBH-B with Ser-318 (PubMed:10490716, PubMed:10391209, PubMed:10391210).
CC {ECO:0000269|PubMed:10391209, ECO:0000269|PubMed:10391210,
CC ECO:0000269|PubMed:10490716}.
CC -!- DISEASE: Orthostatic hypotension 1 (ORTHYP1) [MIM:223360]: A form of
CC orthostatic hypotension due to congenital dopamine beta-hydroxylase
CC deficiency. Orthostatic hypotension, also known as postural
CC hypotension, is a finding defined as a 20-mm Hg decrease in systolic
CC pressure or a 10-mm Hg decrease in diastolic pressure occurring 3
CC minutes after a person has risen from supine to standing. Symptoms
CC include dizziness, blurred vision, and sometimes syncope. ORTHYP1 is an
CC autosomal recessive condition apparent from infancy or early childhood
CC and characterized by low plasma and urinary levels of norepinephrine
CC and epinephrine, and episodic hypoglycemia.
CC {ECO:0000269|PubMed:11857564}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the copper type II ascorbate-dependent
CC monooxygenase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH17174.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA31631.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA31632.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA68285.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Dopamine beta hydroxylase entry;
CC URL="https://en.wikipedia.org/wiki/Dopamine_beta_hydroxylase";
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DR EMBL; AL365494; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Y00096; CAA68285.1; ALT_INIT; mRNA.
DR EMBL; BC017174; AAH17174.1; ALT_INIT; mRNA.
DR EMBL; X13255; CAA31631.1; ALT_INIT; mRNA.
DR EMBL; X13256; CAA31632.1; ALT_INIT; mRNA.
DR CCDS; CCDS6977.2; -.
DR PIR; S03020; S03020.
DR RefSeq; NP_000778.3; NM_000787.3.
DR PDB; 4ZEL; X-ray; 2.90 A; A/B=40-617.
DR PDBsum; 4ZEL; -.
DR AlphaFoldDB; P09172; -.
DR SMR; P09172; -.
DR BioGRID; 107989; 19.
DR IntAct; P09172; 23.
DR MINT; P09172; -.
DR STRING; 9606.ENSP00000376776; -.
DR BindingDB; P09172; -.
DR ChEMBL; CHEMBL3102; -.
DR DrugBank; DB00126; Ascorbic acid.
DR DrugBank; DB06774; Capsaicin.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB05394; Corticorelin.
DR DrugBank; DB00822; Disulfiram.
DR DrugBank; DB00988; Dopamine.
DR DrugBank; DB00968; Methyldopa.
DR DrugBank; DB00550; Propylthiouracil.
DR DrugCentral; P09172; -.
DR GuidetoPHARMACOLOGY; 2486; -.
DR GlyConnect; 1933; 9 N-Linked glycans (1 site).
DR GlyGen; P09172; 4 sites, 9 N-linked glycans (1 site).
DR iPTMnet; P09172; -.
DR PhosphoSitePlus; P09172; -.
DR BioMuta; DBH; -.
DR DMDM; 158517849; -.
DR MassIVE; P09172; -.
DR PaxDb; P09172; -.
DR PeptideAtlas; P09172; -.
DR PRIDE; P09172; -.
DR ProteomicsDB; 52205; -.
DR Antibodypedia; 881; 540 antibodies from 47 providers.
DR DNASU; 1621; -.
DR Ensembl; ENST00000393056.8; ENSP00000376776.2; ENSG00000123454.12.
DR GeneID; 1621; -.
DR KEGG; hsa:1621; -.
DR MANE-Select; ENST00000393056.8; ENSP00000376776.2; NM_000787.4; NP_000778.3.
DR UCSC; uc004cel.4; human.
DR CTD; 1621; -.
DR DisGeNET; 1621; -.
DR GeneCards; DBH; -.
DR GeneReviews; DBH; -.
DR HGNC; HGNC:2689; DBH.
DR HPA; ENSG00000123454; Group enriched (adrenal gland, brain).
DR MalaCards; DBH; -.
DR MIM; 223360; phenotype.
DR MIM; 609312; gene.
DR neXtProt; NX_P09172; -.
DR OpenTargets; ENSG00000123454; -.
DR Orphanet; 230; Dopamine beta-hydroxylase deficiency.
DR PharmGKB; PA136; -.
DR VEuPathDB; HostDB:ENSG00000123454; -.
DR eggNOG; KOG3568; Eukaryota.
DR GeneTree; ENSGT00530000063085; -.
DR HOGENOM; CLU_017939_3_0_1; -.
DR InParanoid; P09172; -.
DR OMA; CAPEMDN; -.
DR OrthoDB; 1472750at2759; -.
DR PhylomeDB; P09172; -.
DR TreeFam; TF320698; -.
DR BioCyc; MetaCyc:MON66-381; -.
DR BRENDA; 1.14.17.1; 2681.
DR PathwayCommons; P09172; -.
DR Reactome; R-HSA-209905; Catecholamine biosynthesis.
DR SignaLink; P09172; -.
DR SIGNOR; P09172; -.
DR UniPathway; UPA00748; UER00735.
DR BioGRID-ORCS; 1621; 7 hits in 1069 CRISPR screens.
DR ChiTaRS; DBH; human.
DR GeneWiki; Dopamine_beta_hydroxylase; -.
DR GenomeRNAi; 1621; -.
DR Pharos; P09172; Tchem.
DR PRO; PR:P09172; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; P09172; protein.
DR Bgee; ENSG00000123454; Expressed in right lobe of liver and 103 other tissues.
DR ExpressionAtlas; P09172; baseline and differential.
DR Genevisible; P09172; HS.
DR GO; GO:0034451; C:centriolar satellite; IDA:HPA.
DR GO; GO:0034466; C:chromaffin granule lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0042584; C:chromaffin granule membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005576; C:extracellular region; NAS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0034774; C:secretory granule lumen; IDA:UniProtKB.
DR GO; GO:0030667; C:secretory granule membrane; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003824; F:catalytic activity; TAS:ProtInc.
DR GO; GO:0005507; F:copper ion binding; IDA:UniProtKB.
DR GO; GO:0004500; F:dopamine beta-monooxygenase activity; IDA:UniProtKB.
DR GO; GO:0031418; F:L-ascorbic acid binding; IEA:UniProtKB-KW.
DR GO; GO:0048149; P:behavioral response to ethanol; IEA:Ensembl.
DR GO; GO:0001974; P:blood vessel remodeling; IEA:Ensembl.
DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR GO; GO:0042420; P:dopamine catabolic process; IDA:UniProtKB.
DR GO; GO:0042596; P:fear response; IEA:Ensembl.
DR GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
DR GO; GO:0042309; P:homoiothermy; IEA:Ensembl.
DR GO; GO:0002443; P:leukocyte mediated immunity; IEA:Ensembl.
DR GO; GO:0050900; P:leukocyte migration; IEA:Ensembl.
DR GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
DR GO; GO:0042711; P:maternal behavior; IEA:Ensembl.
DR GO; GO:0007613; P:memory; IEA:Ensembl.
DR GO; GO:0042421; P:norepinephrine biosynthetic process; IMP:UniProtKB.
DR GO; GO:0006589; P:octopamine biosynthetic process; IBA:GO_Central.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; IEA:Ensembl.
DR GO; GO:2001236; P:regulation of extrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:1904705; P:regulation of vascular associated smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:1905562; P:regulation of vascular endothelial cell proliferation; IEA:Ensembl.
DR GO; GO:0001975; P:response to amphetamine; IEA:Ensembl.
DR GO; GO:0048265; P:response to pain; IEA:Ensembl.
DR GO; GO:0042310; P:vasoconstriction; IEA:Ensembl.
DR GO; GO:0008542; P:visual learning; IEA:Ensembl.
DR CDD; cd09631; DOMON_DOH; 1.
DR Gene3D; 2.60.120.230; -; 1.
DR Gene3D; 2.60.120.310; -; 1.
DR InterPro; IPR014784; Cu2_ascorb_mOase-like_C.
DR InterPro; IPR020611; Cu2_ascorb_mOase_CS-1.
DR InterPro; IPR014783; Cu2_ascorb_mOase_CS-2.
DR InterPro; IPR000323; Cu2_ascorb_mOase_N.
DR InterPro; IPR036939; Cu2_ascorb_mOase_N_sf.
DR InterPro; IPR024548; Cu2_monoox_C.
DR InterPro; IPR000945; DBH-like.
DR InterPro; IPR045266; DOH_DOMON.
DR InterPro; IPR005018; DOMON_domain.
DR InterPro; IPR008977; PHM/PNGase_F_dom_sf.
DR InterPro; IPR028460; Tbh/DBH.
DR PANTHER; PTHR10157; PTHR10157; 1.
DR Pfam; PF03712; Cu2_monoox_C; 1.
DR Pfam; PF01082; Cu2_monooxygen; 1.
DR PRINTS; PR00767; DBMONOXGNASE.
DR SMART; SM00664; DoH; 1.
DR SUPFAM; SSF49742; SSF49742; 2.
DR PROSITE; PS00084; CU2_MONOOXYGENASE_1; 1.
DR PROSITE; PS00085; CU2_MONOOXYGENASE_2; 1.
DR PROSITE; PS50836; DOMON; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Catecholamine biosynthesis; Copper; Cytoplasmic vesicle;
KW Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein;
KW Membrane; Metal-binding; Monooxygenase; Oxidoreductase; Reference proteome;
KW Secreted; Signal-anchor; Transmembrane; Transmembrane helix; Vitamin C.
FT CHAIN 1..617
FT /note="Dopamine beta-hydroxylase"
FT /id="PRO_0000006356"
FT CHAIN 40..617
FT /note="Soluble dopamine beta-hydroxylase"
FT /id="PRO_0000308209"
FT TOPO_DOM 1..16
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 17..37
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 38..617
FT /note="Intragranular"
FT /evidence="ECO:0000255"
FT DOMAIN 57..173
FT /note="DOMON"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00246"
FT REGION 590..617
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 591..606
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 230
FT /evidence="ECO:0000255"
FT ACT_SITE 412
FT /evidence="ECO:0000255"
FT BINDING 262
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A"
FT /evidence="ECO:0000250"
FT BINDING 263
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A"
FT /evidence="ECO:0000250"
FT BINDING 333
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A"
FT /evidence="ECO:0000250"
FT BINDING 412
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="B"
FT /evidence="ECO:0000305|PubMed:27152332,
FT ECO:0007744|PDB:4ZEL"
FT BINDING 414
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="B"
FT /evidence="ECO:0000305|PubMed:27152332,
FT ECO:0007744|PDB:4ZEL"
FT BINDING 487
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="B"
FT /evidence="ECO:0000305|PubMed:27152332,
FT ECO:0007744|PDB:4ZEL"
FT SITE 39..40
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:P15101"
FT CARBOHYD 64
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:27152332,
FT ECO:0007744|PDB:4ZEL"
FT CARBOHYD 184
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:27152332,
FT ECO:0007744|PDB:4ZEL"
FT CARBOHYD 566
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:27152332,
FT ECO:0007744|PDB:4ZEL"
FT DISULFID 154..596
FT /evidence="ECO:0000269|PubMed:27152332,
FT ECO:0007744|PDB:4ZEL"
FT DISULFID 232..283
FT /evidence="ECO:0000269|PubMed:27152332,
FT ECO:0007744|PDB:4ZEL"
FT DISULFID 269..295
FT /evidence="ECO:0000269|PubMed:27152332,
FT ECO:0007744|PDB:4ZEL"
FT DISULFID 390..503
FT /evidence="ECO:0000269|PubMed:27152332,
FT ECO:0007744|PDB:4ZEL"
FT DISULFID 394..565
FT /evidence="ECO:0000269|PubMed:27152332,
FT ECO:0007744|PDB:4ZEL"
FT DISULFID 466..488
FT /evidence="ECO:0000269|PubMed:27152332,
FT ECO:0007744|PDB:4ZEL"
FT DISULFID 528
FT /note="Interchain (with C-530)"
FT /evidence="ECO:0000269|PubMed:27152332,
FT ECO:0007744|PDB:4ZEL"
FT DISULFID 530
FT /note="Interchain (with C-528)"
FT /evidence="ECO:0000269|PubMed:27152332,
FT ECO:0007744|PDB:4ZEL"
FT VARIANT 12
FT /note="G -> S (in dbSNP:rs5318)"
FT /id="VAR_048838"
FT VARIANT 101
FT /note="V -> M (in ORTHYP1; dbSNP:rs267606760)"
FT /evidence="ECO:0000269|PubMed:11857564"
FT /id="VAR_022758"
FT VARIANT 114
FT /note="D -> E (in ORTHYP1; dbSNP:rs77576840)"
FT /evidence="ECO:0000269|PubMed:11857564"
FT /id="VAR_022759"
FT VARIANT 181
FT /note="E -> Q (in dbSNP:rs5319)"
FT /id="VAR_014706"
FT VARIANT 211
FT /note="A -> T (in dbSNP:rs5320)"
FT /evidence="ECO:0000269|PubMed:10391210,
FT ECO:0000269|PubMed:3443096"
FT /id="VAR_013947"
FT VARIANT 239
FT /note="K -> N (in dbSNP:rs5321)"
FT /id="VAR_014707"
FT VARIANT 250
FT /note="E -> Q (in dbSNP:rs5323)"
FT /id="VAR_014708"
FT VARIANT 290
FT /note="D -> N (in dbSNP:rs5324)"
FT /id="VAR_014709"
FT VARIANT 317
FT /note="L -> P (in dbSNP:rs5325)"
FT /id="VAR_014710"
FT VARIANT 318
FT /note="A -> S (in allele DBH-B; dbSNP:rs4531)"
FT /evidence="ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:10391210, ECO:0000269|PubMed:10490716"
FT /id="VAR_002196"
FT VARIANT 345
FT /note="D -> N (in ORTHYP1; dbSNP:rs267606761)"
FT /evidence="ECO:0000269|PubMed:11857564"
FT /id="VAR_022760"
FT VARIANT 549
FT /note="R -> C (in dbSNP:rs6271)"
FT /evidence="ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:3443096"
FT /id="VAR_013948"
FT CONFLICT 505
FT /note="S -> T (in Ref. 2; CAA68285 and 4; CAA31631/
FT CAA31632)"
FT /evidence="ECO:0000305"
FT STRAND 48..52
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 58..66
FT /evidence="ECO:0007829|PDB:4ZEL"
FT TURN 67..70
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 71..80
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 83..93
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 98..104
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 111..117
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 130..138
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 143..151
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 166..173
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 191..195
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 212..217
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 220..222
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 225..236
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 244..252
FT /evidence="ECO:0007829|PDB:4ZEL"
FT TURN 255..260
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 261..268
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 279..284
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 286..288
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 290..294
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 297..303
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 313..319
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 327..335
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 348..356
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 359..361
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 363..369
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 375..377
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 382..390
FT /evidence="ECO:0007829|PDB:4ZEL"
FT HELIX 392..398
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 404..412
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 417..426
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 429..439
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 448..456
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 461..468
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 477..482
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 489..496
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 499..507
FT /evidence="ECO:0007829|PDB:4ZEL"
FT HELIX 509..522
FT /evidence="ECO:0007829|PDB:4ZEL"
FT HELIX 535..539
FT /evidence="ECO:0007829|PDB:4ZEL"
FT HELIX 546..558
FT /evidence="ECO:0007829|PDB:4ZEL"
FT STRAND 561..567
FT /evidence="ECO:0007829|PDB:4ZEL"
SQ SEQUENCE 617 AA; 69065 MW; 4D5586F0E358885D CRC64;
MPALSRWASL PGPSMREAAF MYSTAVAIFL VILVAALQGS APRESPLPYH IPLDPEGSLE
LSWNVSYTQE AIHFQLLVRR LKAGVLFGMS DRGELENADL VVLWTDGDTA YFADAWSDQK
GQIHLDPQQD YQLLQVQRTP EGLTLLFKRP FGTCDPKDYL IEDGTVHLVY GILEEPFRSL
EAINGSGLQM GLQRVQLLKP NIPEPELPSD ACTMEVQAPN IQIPSQETTY WCYIKELPKG
FSRHHIIKYE PIVTKGNEAL VHHMEVFQCA PEMDSVPHFS GPCDSKMKPD RLNYCRHVLA
AWALGAKAFY YPEEAGLAFG GPGSSRYLRL EVHYHNPLVI EGRNDSSGIR LYYTAKLRRF
NAGIMELGLV YTPVMAIPPR ETAFILTGYC TDKCTQLALP PSGIHIFASQ LHTHLTGRKV
VTVLVRDGRE WEIVNQDNHY SPHFQEIRML KKVVSVHPGD VLITSCTYNT EDRELATVGG
FGILEEMCVN YVHYYPQTQL ELCKSAVDAG FLQKYFHLIN RFNNEDVCTC PQASVSQQFT
SVPWNSFNRD VLKALYSFAP ISMHCNKSSA VRFQGEWNLQ PLPKVISTLE EPTPQCPTSQ
GRSPAGPTVV SIGGGKG
