DOPO_BOVIN
ID DOPO_BOVIN Reviewed; 610 AA.
AC P15101; Q0V8A8; Q28094; Q9TVD1;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 02-OCT-2007, sequence version 2.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Dopamine beta-hydroxylase;
DE EC=1.14.17.1 {ECO:0000269|PubMed:2620060, ECO:0000269|PubMed:4525162};
DE AltName: Full=Dopamine beta-monooxygenase;
DE Contains:
DE RecName: Full=Soluble dopamine beta-hydroxylase;
GN Name=DBH;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF N-TERMINUS OF SOLUBLE AND
RP MEMBRANE-BOUND FORM, CLEAVAGE SITE, SUBCELLULAR LOCATION, CATALYTIC
RP ACTIVITY, FUNCTION, COFACTOR, PATHWAY, AND TISSUE SPECIFICITY.
RX PubMed=2620060; DOI=10.1021/bi00452a026;
RA Taljanidisz J., Stewart L., Smith A.J., Klinman J.P.;
RT "Structure of bovine adrenal dopamine beta-monooxygenase, as deduced from
RT cDNA and protein sequencing: evidence that the membrane-bound form of the
RT enzyme is anchored by an uncleaved signal peptide.";
RL Biochemistry 28:10054-10061(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1688549; DOI=10.1016/s0021-9258(19)40153-1;
RA Lewis E.J., Allison S., Fader D., Claflin V., Baizer L.;
RT "Bovine dopamine beta-hydroxylase cDNA. Complete coding sequence and
RT expression in mammalian cells with vaccinia virus vector.";
RL J. Biol. Chem. 265:1021-1028(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4-610.
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 14-610, AND GLYCOSYLATION.
RC TISSUE=Adrenal medulla;
RX PubMed=1693949; DOI=10.1111/j.1471-4159.1990.tb08826.x;
RA Wu H.J., Parmer R.J., Koop A.H., Rozansky D.J., O'Connor D.T.;
RT "Molecular cloning, structure, and expression of dopamine-beta-hydroxylase
RT from bovine adrenal medulla.";
RL J. Neurochem. 55:97-105(1990).
RN [5]
RP PROTEIN SEQUENCE OF 33-610, AND GLYCOSYLATION.
RX PubMed=2295597; DOI=10.1016/s0021-9258(19)40154-3;
RA Robertson J.G., Desai P.R., Kumar A., Farrington G.K., Fitzpatrick P.F.,
RA Villafranca J.J.;
RT "Primary amino acid sequence of bovine dopamine beta-hydroxylase.";
RL J. Biol. Chem. 265:1029-1035(1990).
RN [6]
RP PROTEIN SEQUENCE OF 33-50, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC TISSUE=Adrenal medulla;
RX PubMed=843373; DOI=10.1016/0006-291x(77)90609-x;
RA Skotland T., Ljones T., Flatmark T., Sletten K.;
RT "NH2-terminal sequence of dopamine beta-hydroxylase from bovine adrenal
RT medulla.";
RL Biochem. Biophys. Res. Commun. 74:1483-1489(1977).
RN [7]
RP PROTEIN SEQUENCE OF 33-37.
RX PubMed=2909511; DOI=10.1016/s0021-9258(17)31216-4;
RA Taylor C.S., Kent U.M., Fleming P.J.;
RT "The membrane-binding segment of dopamine beta-hydroxylase is not an
RT uncleaved signal sequence.";
RL J. Biol. Chem. 264:14-16(1989).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 39-566, GLYCOSYLATION AT ASN-177 AND ASN-559,
RP AND LACK OF PYRROLOQUINOLINE QUINONE BINDING.
RX PubMed=2207088; DOI=10.1021/bi00479a019;
RA Wang N., Southan C., DeWolf W.E. Jr., Wells T.N., Kruse L.I.,
RA Leatherbarrow R.J.;
RT "Bovine dopamine beta-hydroxylase, primary structure determined by cDNA
RT cloning and amino acid sequencing.";
RL Biochemistry 29:6466-6474(1990).
RN [9]
RP SUBUNIT, GLYCOSYLATION, TISSUE SPECIFICITY, COFACTOR, AND CATALYTIC
RP ACTIVITY.
RX PubMed=4525162; DOI=10.1073/pnas.70.8.2253;
RA Wallace E.F., Krantz M.J., Lovenberg W.;
RT "Dopamine-beta-hydroxylase: a tetrameric glycoprotein.";
RL Proc. Natl. Acad. Sci. U.S.A. 70:2253-2255(1973).
RN [10]
RP LACK OF PYRROLOQUINOLINE QUINONE BINDING.
RX PubMed=2555337; DOI=10.1016/s0021-9258(19)47198-6;
RA Robertson J.G., Kumar A., Mancewicz J.A., Villafranca J.J.;
RT "Spectral studies of bovine dopamine beta-hydroxylase. Absence of
RT covalently bound pyrroloquinoline quinone.";
RL J. Biol. Chem. 264:19916-19921(1989).
RN [11]
RP DISULFIDE BONDS.
RX PubMed=7918370; DOI=10.1021/bi00204a019;
RA Robertson J.G., Adams G.W., Medzihradszky K.F., Burlingame A.L.,
RA Villafranca J.J.;
RT "Complete assignment of disulfide bonds in bovine dopamine beta-
RT hydroxylase.";
RL Biochemistry 33:11563-11575(1994).
CC -!- FUNCTION: Conversion of dopamine to noradrenaline.
CC {ECO:0000269|PubMed:2620060}.
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:2620060,
CC ECO:0000269|PubMed:4525162};
CC -!- COFACTOR:
CC Name=Cu(2+); Xref=ChEBI:CHEBI:29036;
CC Evidence={ECO:0000269|PubMed:2620060, ECO:0000269|PubMed:4525162};
CC Note=Binds 2 copper ions per subunit. {ECO:0000269|PubMed:4525162};
CC -!- PATHWAY: Catecholamine biosynthesis; (R)-noradrenaline biosynthesis;
CC (R)-noradrenaline from dopamine: step 1/1.
CC {ECO:0000269|PubMed:2620060}.
CC -!- SUBUNIT: Homotetramer; composed of two disulfide-linked dimers.
CC {ECO:0000269|PubMed:4525162, ECO:0000269|PubMed:7918370}.
CC -!- SUBCELLULAR LOCATION: [Soluble dopamine beta-hydroxylase]: Cytoplasmic
CC vesicle, secretory vesicle lumen. Cytoplasmic vesicle, secretory
CC vesicle, chromaffin granule lumen {ECO:0000269|PubMed:843373,
CC ECO:0000305|PubMed:2620060}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle membrane;
CC Single-pass type II membrane protein. Cytoplasmic vesicle, secretory
CC vesicle, chromaffin granule membrane {ECO:0000269|PubMed:2620060};
CC Single-pass type II membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Detected in chromaffin granules in the adrenal
CC medulla (at protein level) (PubMed:2620060, PubMed:843373,
CC PubMed:4525162). Detected in adrenal medulla (PubMed:2620060).
CC {ECO:0000269|PubMed:2620060, ECO:0000269|PubMed:4525162,
CC ECO:0000269|PubMed:843373}.
CC -!- PTM: Proteolytic cleavage after the membrane-anchor leads to the
CC release of the soluble form. {ECO:0000269|PubMed:2620060}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:1693949,
CC ECO:0000269|PubMed:2295597, ECO:0000269|PubMed:4525162}.
CC -!- SIMILARITY: Belongs to the copper type II ascorbate-dependent
CC monooxygenase family. {ECO:0000305}.
CC -!- CAUTION: Contrary to earlier results, does not contain a
CC pyrroloquinoline quinone (PQQ) cofactor. {ECO:0000269|PubMed:2207088,
CC ECO:0000269|PubMed:2555337}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA30490.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; J02890; AAA30356.1; -; mRNA.
DR EMBL; J05160; AAA30490.1; ALT_INIT; mRNA.
DR EMBL; BT026311; ABG81467.1; -; mRNA.
DR EMBL; AF118638; AAD09829.1; -; mRNA.
DR EMBL; J02909; AAA30491.1; -; mRNA.
DR PIR; A33650; A33650.
DR RefSeq; NP_851338.1; NM_180995.2.
DR AlphaFoldDB; P15101; -.
DR SMR; P15101; -.
DR BioGRID; 158157; 1.
DR STRING; 9913.ENSBTAP00000005924; -.
DR BindingDB; P15101; -.
DR ChEMBL; CHEMBL4702; -.
DR DrugCentral; P15101; -.
DR iPTMnet; P15101; -.
DR PaxDb; P15101; -.
DR PRIDE; P15101; -.
DR GeneID; 280758; -.
DR KEGG; bta:280758; -.
DR CTD; 1621; -.
DR eggNOG; KOG3568; Eukaryota.
DR InParanoid; P15101; -.
DR OrthoDB; 1472750at2759; -.
DR TreeFam; TF320698; -.
DR SABIO-RK; P15101; -.
DR UniPathway; UPA00748; UER00735.
DR PRO; PR:P15101; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0034466; C:chromaffin granule lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0042584; C:chromaffin granule membrane; IDA: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:0034774; C:secretory granule lumen; ISS:UniProtKB.
DR GO; GO:0030667; C:secretory granule membrane; IBA:GO_Central.
DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell.
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:0042420; P:dopamine catabolic process; IDA:UniProtKB.
DR GO; GO:0042421; P:norepinephrine biosynthetic process; ISS:UniProtKB.
DR GO; GO:0006589; P:octopamine biosynthetic process; IBA:GO_Central.
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 Catecholamine biosynthesis; Copper; Cytoplasmic vesicle;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Membrane;
KW Metal-binding; Monooxygenase; Oxidoreductase; Reference proteome;
KW Signal-anchor; Transmembrane; Transmembrane helix; Vitamin C.
FT CHAIN 1..610
FT /note="Dopamine beta-hydroxylase"
FT /id="PRO_0000006355"
FT CHAIN 33..610
FT /note="Soluble dopamine beta-hydroxylase"
FT /evidence="ECO:0000269|PubMed:2295597"
FT /id="PRO_0000308206"
FT TOPO_DOM 1..9
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 10..30
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 31..610
FT /note="Intragranular"
FT /evidence="ECO:0000255"
FT DOMAIN 50..166
FT /note="DOMON"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00246"
FT REGION 585..610
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 223
FT /evidence="ECO:0000255"
FT ACT_SITE 405
FT /evidence="ECO:0000255"
FT BINDING 255
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A"
FT /evidence="ECO:0000250"
FT BINDING 256
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A"
FT /evidence="ECO:0000250"
FT BINDING 326
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A"
FT /evidence="ECO:0000250"
FT BINDING 405
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="B"
FT /evidence="ECO:0000250|UniProtKB:P09172"
FT BINDING 407
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="B"
FT /evidence="ECO:0000250|UniProtKB:P09172"
FT BINDING 480
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="B"
FT /evidence="ECO:0000250|UniProtKB:P09172"
FT SITE 32..33
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:2295597,
FT ECO:0000269|PubMed:2620060, ECO:0000269|PubMed:843373"
FT CARBOHYD 177
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:2207088"
FT CARBOHYD 559
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:2207088"
FT DISULFID 147..589
FT /evidence="ECO:0000269|PubMed:7918370"
FT DISULFID 225..276
FT /evidence="ECO:0000269|PubMed:7918370"
FT DISULFID 262..288
FT /evidence="ECO:0000269|PubMed:7918370"
FT DISULFID 383..496
FT /evidence="ECO:0000269|PubMed:7918370"
FT DISULFID 387..558
FT /evidence="ECO:0000269|PubMed:7918370"
FT DISULFID 459..481
FT /evidence="ECO:0000269|PubMed:7918370"
FT DISULFID 521
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:7918370"
FT DISULFID 523
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:7918370"
FT CONFLICT 35
FT /note="P -> T (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 40
FT /note="F -> S (in Ref. 4; AAD09829)"
FT /evidence="ECO:0000305"
FT CONFLICT 48
FT /note="P -> T (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 55..57
FT /note="SWN -> RYV (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 74
FT /note="L -> F (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 104
FT /note="Y -> D (in Ref. 4; AAD09829)"
FT /evidence="ECO:0000305"
FT CONFLICT 205
FT /note="R -> C (in Ref. 1; AAA30356)"
FT /evidence="ECO:0000305"
FT CONFLICT 215
FT /note="L -> F (in Ref. 3; ABG81467)"
FT /evidence="ECO:0000305"
FT CONFLICT 267..269
FT /note="ETI -> RDH (in Ref. 1; AAA30356)"
FT /evidence="ECO:0000305"
FT CONFLICT 349
FT /note="A -> R (in Ref. 8; AAA30491)"
FT /evidence="ECO:0000305"
FT CONFLICT 376
FT /note="A -> P (in Ref. 4; AAD09829)"
FT /evidence="ECO:0000305"
FT CONFLICT 560
FT /note="R -> C (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 566..567
FT /note="FQ -> LE (in Ref. 4; AAD09829)"
FT /evidence="ECO:0000305"
FT CONFLICT 588
FT /note="H -> Q (in Ref. 1; AAA30356)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 610 AA; 68141 MW; 709D23860617CD3A CRC64;
MQVPSPSVRE AASMYGTAVA VFLVILVAAL QGSAPAESPF PFHIPLDPEG TLELSWNISY
AQETIYFQLL VRELKAGVLF GMSDRGELEN ADLVVLWTDR DGAYFGDAWS DQKGQVHLDS
QQDYQLLRAQ RTPEGLYLLF KRPFGTCDPN DYLIEDGTVH LVYGFLEEPL RSLESINTSG
LHTGLQRVQL LKPSIPKPAL PADTRTMEIR APDVLIPGQQ TTYWCYVTEL PDGFPRHHIV
MYEPIVTEGN EALVHHMEVF QCAAEFETIP HFSGPCDSKM KPQRLNFCRH VLAAWALGAK
AFYYPEEAGL AFGGPGSSRF LRLEVHYHNP LVITGRRDSS GIRLYYTAAL RRFDAGIMEL
GLAYTPVMAI PPQETAFVLT GYCTDKCTQL ALPASGIHIF ASQLHTHLTG RKVVTVLARD
GRETEIVNRD NHYSPHFQEI RMLKKVVSVQ PGDVLITSCT YNTEDRRLAT VGGFGILEEM
CVNYVHYYPQ TQLELCKSAV DPGFLHKYFR LVNRFNSEEV CTCPQASVPE QFASVPWNSF
NREVLKALYG FAPISMHCNR SSAVRFQGEW NRQPLPEIVS RLEEPTPHCP ASQAQSPAGP
TVLNISGGKG
