DOPO_RAT
ID DOPO_RAT Reviewed; 620 AA.
AC Q05754;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Dopamine beta-hydroxylase;
DE EC=1.14.17.1 {ECO:0000250|UniProtKB:P09172};
DE AltName: Full=Dopamine beta-monooxygenase;
DE Contains:
DE RecName: Full=Soluble dopamine beta-hydroxylase;
GN Name=Dbh;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2325165; DOI=10.1002/jnr.490250317;
RA McMahon A., Geertman R., Sabban E.L.;
RT "Rat dopamine beta-hydroxylase: molecular cloning and characterization of
RT the cDNA and regulation of the mRNA by reserpine.";
RL J. Neurosci. Res. 25:395-404(1990).
RN [2]
RP SUBCELLULAR LOCATION.
RX PubMed=11418593; DOI=10.1074/jbc.m101088200;
RA Oyarce A.M., Steveson T.C., Jin L., Eipper B.A.;
RT "Dopamine beta-monooxygenase signal/anchor sequence alters trafficking of
RT peptidylglycine alpha-hydroxylating monooxygenase.";
RL J. Biol. Chem. 276:33265-33272(2001).
CC -!- FUNCTION: Conversion of dopamine to noradrenaline.
CC {ECO:0000250|UniProtKB:P09172}.
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:0000250|UniProtKB:P09172};
CC -!- COFACTOR:
CC Name=Cu(2+); Xref=ChEBI:CHEBI:29036;
CC Evidence={ECO:0000250|UniProtKB:P09172};
CC Note=Binds 2 copper ions per subunit. {ECO:0000250|UniProtKB:P09172};
CC -!- PATHWAY: Catecholamine biosynthesis; (R)-noradrenaline biosynthesis;
CC (R)-noradrenaline from dopamine: step 1/1.
CC {ECO:0000250|UniProtKB:P09172}.
CC -!- SUBUNIT: Homotetramer; composed of two disulfide-linked dimers.
CC {ECO:0000250|UniProtKB:P09172}.
CC -!- SUBCELLULAR LOCATION: [Soluble dopamine beta-hydroxylase]: Cytoplasmic
CC vesicle, secretory vesicle lumen {ECO:0000250|UniProtKB:P09172}.
CC Cytoplasmic vesicle, secretory vesicle, chromaffin granule lumen
CC {ECO:0000250|UniProtKB:P09172}. Secreted
CC {ECO:0000250|UniProtKB:P09172}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle membrane
CC {ECO:0000250|UniProtKB:P09172}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:P09172}. Cytoplasmic vesicle, secretory vesicle,
CC chromaffin granule membrane {ECO:0000305|PubMed:11418593}; Single-pass
CC type II membrane protein {ECO:0000250|UniProtKB:P09172}.
CC -!- TISSUE SPECIFICITY: Chromaffin granules of the adrenal medulla and
CC synaptic vesicles of the sympathetic nervous system.
CC -!- PTM: Proteolytic cleavage after the membrane-anchor leads to the
CC release of the soluble form. {ECO:0000250|UniProtKB:P15101}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P09172}.
CC -!- SIMILARITY: Belongs to the copper type II ascorbate-dependent
CC monooxygenase family. {ECO:0000305}.
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DR EMBL; L12407; AAA41091.1; -; mRNA.
DR PIR; A61086; A61086.
DR RefSeq; NP_037290.2; NM_013158.2.
DR PDB; 1ZHB; X-ray; 2.70 A; C/F/I/L=556-564.
DR PDBsum; 1ZHB; -.
DR AlphaFoldDB; Q05754; -.
DR SMR; Q05754; -.
DR STRING; 10116.ENSRNOP00000057915; -.
DR BindingDB; Q05754; -.
DR ChEMBL; CHEMBL2992; -.
DR GlyGen; Q05754; 6 sites.
DR PhosphoSitePlus; Q05754; -.
DR PaxDb; Q05754; -.
DR PRIDE; Q05754; -.
DR GeneID; 25699; -.
DR KEGG; rno:25699; -.
DR UCSC; RGD:2489; rat.
DR CTD; 1621; -.
DR RGD; 2489; Dbh.
DR eggNOG; KOG3568; Eukaryota.
DR InParanoid; Q05754; -.
DR OrthoDB; 1472750at2759; -.
DR PhylomeDB; Q05754; -.
DR BRENDA; 1.14.17.1; 5301.
DR Reactome; R-RNO-209905; Catecholamine biosynthesis.
DR UniPathway; UPA00748; UER00735.
DR EvolutionaryTrace; Q05754; -.
DR PRO; PR:Q05754; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0045177; C:apical part of cell; IDA:RGD.
DR GO; GO:0030424; C:axon; IDA:RGD.
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; IDA:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0034774; C:secretory granule lumen; ISS:UniProtKB.
DR GO; GO:0030667; C:secretory granule membrane; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; IDA:RGD.
DR GO; GO:0043195; C:terminal bouton; IDA:RGD.
DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043196; C:varicosity; IDA:RGD.
DR GO; GO:0005507; F:copper ion binding; IMP:RGD.
DR GO; GO:0004500; F:dopamine beta-monooxygenase activity; IDA:RGD.
DR GO; GO:0031418; F:L-ascorbic acid binding; IEA:UniProtKB-KW.
DR GO; GO:0008306; P:associative learning; ISO:RGD.
DR GO; GO:0048149; P:behavioral response to ethanol; ISO:RGD.
DR GO; GO:0001974; P:blood vessel remodeling; ISO:RGD.
DR GO; GO:0060348; P:bone development; IEP:RGD.
DR GO; GO:0006584; P:catecholamine metabolic process; IC:RGD.
DR GO; GO:0071287; P:cellular response to manganese ion; IEP:RGD.
DR GO; GO:0071316; P:cellular response to nicotine; IEP:RGD.
DR GO; GO:0042420; P:dopamine catabolic process; ISS:UniProtKB.
DR GO; GO:0042596; P:fear response; ISO:RGD.
DR GO; GO:0042593; P:glucose homeostasis; IMP:RGD.
DR GO; GO:0042309; P:homoiothermy; ISO:RGD.
DR GO; GO:0002443; P:leukocyte mediated immunity; ISO:RGD.
DR GO; GO:0050900; P:leukocyte migration; ISO:RGD.
DR GO; GO:0007626; P:locomotory behavior; ISO:RGD.
DR GO; GO:0042711; P:maternal behavior; ISO:RGD.
DR GO; GO:0007613; P:memory; ISO:RGD.
DR GO; GO:0010259; P:multicellular organism aging; IEP:RGD.
DR GO; GO:0042421; P:norepinephrine biosynthetic process; IMP:RGD.
DR GO; GO:0006589; P:octopamine biosynthetic process; IBA:GO_Central.
DR GO; GO:0046333; P:octopamine metabolic process; IMP:RGD.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; ISO:RGD.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISO:RGD.
DR GO; GO:2001236; P:regulation of extrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0001975; P:response to amphetamine; ISO:RGD.
DR GO; GO:0046688; P:response to copper ion; IEP:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0035902; P:response to immobilization stress; IEP:RGD.
DR GO; GO:0010039; P:response to iron ion; IEP:RGD.
DR GO; GO:0035900; P:response to isolation stress; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0010193; P:response to ozone; IEP:RGD.
DR GO; GO:0048265; P:response to pain; ISO:RGD.
DR GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0050909; P:sensory perception of taste; IEP:RGD.
DR GO; GO:0035176; P:social behavior; IEP:RGD.
DR GO; GO:0008542; P:visual learning; ISO:RGD.
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; 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; PS50836; DOMON; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Catecholamine biosynthesis; Copper; Cytoplasmic vesicle;
KW Disulfide bond; Glycoprotein; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Phosphoprotein; Reference proteome; Secreted;
KW Signal-anchor; Transmembrane; Transmembrane helix; Vitamin C.
FT CHAIN 1..620
FT /note="Dopamine beta-hydroxylase"
FT /id="PRO_0000006358"
FT CHAIN 43..620
FT /note="Soluble dopamine beta-hydroxylase"
FT /evidence="ECO:0000255"
FT /id="PRO_0000308211"
FT TOPO_DOM 1..19
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 20..40
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 41..620
FT /note="Intragranular"
FT /evidence="ECO:0000255"
FT DOMAIN 60..176
FT /note="DOMON"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00246"
FT ACT_SITE 233
FT /evidence="ECO:0000255"
FT ACT_SITE 415
FT /evidence="ECO:0000255"
FT BINDING 265
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A"
FT /evidence="ECO:0000250"
FT BINDING 266
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A"
FT /evidence="ECO:0000250"
FT BINDING 336
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A"
FT /evidence="ECO:0000250"
FT BINDING 415
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="B"
FT /evidence="ECO:0000250|UniProtKB:P09172"
FT BINDING 417
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="B"
FT /evidence="ECO:0000250|UniProtKB:P09172"
FT BINDING 490
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="B"
FT /evidence="ECO:0000250|UniProtKB:P09172"
FT SITE 42..43
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:P15101"
FT MOD_RES 349
FT /note="Phosphoserine; by CaMK"
FT /evidence="ECO:0000255"
FT CARBOHYD 67
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 187
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 274
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 475
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 569
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 587
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 157..599
FT /evidence="ECO:0000250|UniProtKB:P09172"
FT DISULFID 235..286
FT /evidence="ECO:0000250|UniProtKB:P09172"
FT DISULFID 272..298
FT /evidence="ECO:0000250|UniProtKB:P09172"
FT DISULFID 393..506
FT /evidence="ECO:0000250|UniProtKB:P09172"
FT DISULFID 397..568
FT /evidence="ECO:0000250|UniProtKB:P09172"
FT DISULFID 469..491
FT /evidence="ECO:0000250|UniProtKB:P09172"
FT DISULFID 531
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P09172"
FT DISULFID 533
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P09172"
SQ SEQUENCE 620 AA; 69875 MW; FFBE26C8A4ED5776 CRC64;
MQPHLSHQPC WSLPSPSVRE AASMYGTAVA IFLVILVAAL QGSEPPESPF PYHIPLDPEG
TLELSWNVSY DQEIIHFQLQ VQGPRAGVLF GMSDRGEMEN ADLVMLWTDG DRTYFADAWS
DQKGQIHLDT HQDYQLLQAQ RVSNSLSLLF KRPFVTCDPK DYVIEDDTVH LVYGILEEPF
QSLEAINTSG LHTGLQQVQL LKPEVSTPAM PADVQTMDIR APDVLIPSTE TTYWCYITEL
PLHFPRHHII MYEAIVTEGN EALVHHMEVF QCTNESEAFP MFNGPCDSKM KPDRLNYCRH
VLAAWALGAK AFYYPEEAGV PLGSSGSSRF LRLEVHYHNP RNIQGRRDSS GIRLHYTASL
RPNEAGIMEL GLVYTPLMAI PPQETTFVLT GYCTDRCTQM ALPKSGIRIF ASQLHTHLTG
RKVITVLARD GQQREVVNRD NHYSPHFQEI RMLKNAVTVH QGDVLITSCT YNTENRTMAT
VGGFGILEEM CVNYVHYYPK TELELCKSAV DDGFLQKYFH IVNRFGNEEV CTCPQASVPQ
QFASVPWNSF NRDMLKALYN YAPISVHCNK TSAVRFPGNW NLQPLPNITS AVEEPDPRCP
IRQTRGPAGP FVVITHGGRH
