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Protein

Dopamine beta-hydroxylase

Gene

DBH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Conversion of dopamine to noradrenaline.4 Publications

Catalytic activityi

3,4-dihydroxyphenethylamine + ascorbate + O2 = noradrenaline + dehydroascorbate + H2O.3 Publications

Cofactori

Cu2+1 Publication1 PublicationNote: Binds 2 copper ions per subunit.1 Publication

Kineticsi

  1. KM=1.8 mM for tyramine1 Publication

    pH dependencei

    Optimum pH is 5.2.1 Publication

    Pathwayi: (R)-noradrenaline biosynthesis

    This protein is involved in step 1 of the subpathway that synthesizes (R)-noradrenaline from dopamine.3 Publications
    Proteins known to be involved in this subpathway in this organism are:
    1. Dopamine beta-hydroxylase (DBH)
    This subpathway is part of the pathway (R)-noradrenaline biosynthesis, which is itself part of Catecholamine biosynthesis.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes (R)-noradrenaline from dopamine, the pathway (R)-noradrenaline biosynthesis and in Catecholamine biosynthesis.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei230Sequence analysis1
    Metal bindingi262Copper ABy similarity1
    Metal bindingi263Copper ABy similarity1
    Metal bindingi333Copper ABy similarity1
    Active sitei412Sequence analysis1
    Metal bindingi412Copper BCombined sources1 Publication1
    Metal bindingi414Copper BCombined sources1 Publication1
    Metal bindingi487Copper BCombined sources1 Publication1

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Molecular functionMonooxygenase, Oxidoreductase
    Biological processCatecholamine biosynthesis
    LigandCopper, Metal-binding, Vitamin C

    Enzyme and pathway databases

    BioCyciMetaCyc:MONOMER66-381
    BRENDAi1.14.17.1 2681
    ReactomeiR-HSA-209905 Catecholamine biosynthesis
    SignaLinkiP09172
    SIGNORiP09172
    UniPathwayi
    UPA00748;UER00735

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Dopamine beta-hydroxylase (EC:1.14.17.13 Publications)
    Alternative name(s):
    Dopamine beta-monooxygenase
    Cleaved into the following chain:
    Gene namesi
    Name:DBH
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 9

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000123454.10
    HGNCiHGNC:2689 DBH
    MIMi609312 gene
    neXtProtiNX_P09172

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Topological domaini1 – 16CytoplasmicSequence analysisAdd BLAST16
    Transmembranei17 – 37Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
    Topological domaini38 – 617IntragranularSequence analysisAdd BLAST580

    Keywords - Cellular componenti

    Cytoplasmic vesicle, Membrane, Secreted

    Pathology & Biotechi

    Involvement in diseasei

    Dopamine beta-hydroxylase deficiency (DBH deficiency)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionCharacterized by profound deficits in autonomic and cardiovascular function, but apparently only subtle signs, if any, of central nervous system dysfunction.
    See also OMIM:223360
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_022758101V → M in DBH deficiency. 1 PublicationCorresponds to variant dbSNP:rs267606760EnsemblClinVar.1
    Natural variantiVAR_022759114D → E in DBH deficiency. 1 PublicationCorresponds to variant dbSNP:rs77576840EnsemblClinVar.1
    Natural variantiVAR_022760345D → N in DBH deficiency. 1 PublicationCorresponds to variant dbSNP:rs267606761EnsemblClinVar.1

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    DisGeNETi1621
    GeneReviewsiDBH
    MalaCardsiDBH
    MIMi223360 phenotype
    OpenTargetsiENSG00000123454
    Orphaneti230 Dopamine beta-hydroxylase deficiency
    PharmGKBiPA136

    Chemistry databases

    ChEMBLiCHEMBL3102
    DrugBankiDB06774 Capsaicin
    DB05394 corticotropin-releasing factor
    DB00822 Disulfiram
    DB00988 Dopamine
    DB00550 Propylthiouracil
    DB00126 Vitamin C
    GuidetoPHARMACOLOGYi2486

    Polymorphism and mutation databases

    BioMutaiDBH
    DMDMi158517849

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000063561 – 617Dopamine beta-hydroxylaseAdd BLAST617
    ChainiPRO_000030820940 – 617Soluble dopamine beta-hydroxylaseAdd BLAST578

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Glycosylationi64N-linked (GlcNAc...) asparagineSequence analysisCombined sources1 Publication1
    Disulfide bondi154 ↔ 596Combined sources1 Publication
    Glycosylationi184N-linked (GlcNAc...) (complex) asparagineCombined sources3 Publications1
    Disulfide bondi232 ↔ 283Combined sources1 Publication
    Disulfide bondi269 ↔ 295Combined sources1 Publication
    Disulfide bondi390 ↔ 503Combined sources1 Publication
    Disulfide bondi394 ↔ 565Combined sources1 Publication
    Disulfide bondi466 ↔ 488Combined sources1 Publication
    Disulfide bondi528Interchain (with C-530)Combined sources1 Publication
    Disulfide bondi530Interchain (with C-528)Combined sources1 Publication
    Glycosylationi566N-linked (GlcNAc...) asparagineCombined sources1 Publication1

    Post-translational modificationi

    N-glycosylated.2 Publications
    Proteolytic cleavage after the membrane-anchor leads to the release of the soluble form.By similarity

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sitei39 – 40CleavageBy similarity2

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiP09172
    PeptideAtlasiP09172
    PRIDEiP09172
    ProteomicsDBi52205

    PTM databases

    iPTMnetiP09172
    PhosphoSitePlusiP09172

    Expressioni

    Inductioni

    Activity is enhanced by nerve growth factor (in superior cervical ganglia and adrenal medulla). Trans-synaptic stimulation with reserpine, acetylcholine and glucocorticoids.

    Gene expression databases

    BgeeiENSG00000123454 Expressed in 77 organ(s), highest expression level in right adrenal gland
    CleanExiHS_DBH
    ExpressionAtlasiP09172 baseline and differential
    GenevisibleiP09172 HS

    Organism-specific databases

    HPAiHPA002130
    HPA005960
    HPA070789

    Interactioni

    Subunit structurei

    Homotetramer; composed of two disulfide-linked dimers.1 Publication

    Protein-protein interaction databases

    BioGridi107989, 6 interactors
    IntActiP09172, 2 interactors
    MINTiP09172
    STRINGi9606.ENSP00000376776

    Chemistry databases

    BindingDBiP09172

    Structurei

    Secondary structure

    1617
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliP09172
    SMRiP09172
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini57 – 173DOMONPROSITE-ProRule annotationAdd BLAST117

    Sequence similaritiesi

    Keywords - Domaini

    Signal-anchor, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG3568 Eukaryota
    ENOG410XR89 LUCA
    GeneTreeiENSGT00530000063085
    HOGENOMiHOG000063669
    HOVERGENiHBG005519
    InParanoidiP09172
    KOiK00503
    OMAiMYEPIVT
    OrthoDBiEOG091G03XS
    PhylomeDBiP09172
    TreeFamiTF320698

    Family and domain databases

    Gene3Di2.60.120.230, 1 hit
    2.60.120.310, 1 hit
    InterProiView protein in InterPro
    IPR014784 Cu2_ascorb_mOase-like_C
    IPR020611 Cu2_ascorb_mOase_CS-1
    IPR014783 Cu2_ascorb_mOase_CS-2
    IPR000323 Cu2_ascorb_mOase_N
    IPR036939 Cu2_ascorb_mOase_N_sf
    IPR024548 Cu2_monoox_C
    IPR005018 DOMON_domain
    IPR008977 PHM/PNGase_F_dom_sf
    IPR028460 Tbh/DBH
    PfamiView protein in Pfam
    PF03712 Cu2_monoox_C, 1 hit
    PF01082 Cu2_monooxygen, 1 hit
    PF03351 DOMON, 1 hit
    PRINTSiPR00767 DBMONOXGNASE
    SMARTiView protein in SMART
    SM00664 DoH, 1 hit
    SUPFAMiSSF49742 SSF49742, 2 hits
    PROSITEiView protein in PROSITE
    PS00084 CU2_MONOOXYGENASE_1, 1 hit
    PS00085 CU2_MONOOXYGENASE_2, 1 hit
    PS50836 DOMON, 1 hit

    Sequence (1+)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

    P09172-1 [UniParc]FASTAAdd to basket
    « Hide
            10         20         30         40         50
    MPALSRWASL PGPSMREAAF MYSTAVAIFL VILVAALQGS APRESPLPYH
    60 70 80 90 100
    IPLDPEGSLE LSWNVSYTQE AIHFQLLVRR LKAGVLFGMS DRGELENADL
    110 120 130 140 150
    VVLWTDGDTA YFADAWSDQK GQIHLDPQQD YQLLQVQRTP EGLTLLFKRP
    160 170 180 190 200
    FGTCDPKDYL IEDGTVHLVY GILEEPFRSL EAINGSGLQM GLQRVQLLKP
    210 220 230 240 250
    NIPEPELPSD ACTMEVQAPN IQIPSQETTY WCYIKELPKG FSRHHIIKYE
    260 270 280 290 300
    PIVTKGNEAL VHHMEVFQCA PEMDSVPHFS GPCDSKMKPD RLNYCRHVLA
    310 320 330 340 350
    AWALGAKAFY YPEEAGLAFG GPGSSRYLRL EVHYHNPLVI EGRNDSSGIR
    360 370 380 390 400
    LYYTAKLRRF NAGIMELGLV YTPVMAIPPR ETAFILTGYC TDKCTQLALP
    410 420 430 440 450
    PSGIHIFASQ LHTHLTGRKV VTVLVRDGRE WEIVNQDNHY SPHFQEIRML
    460 470 480 490 500
    KKVVSVHPGD VLITSCTYNT EDRELATVGG FGILEEMCVN YVHYYPQTQL
    510 520 530 540 550
    ELCKSAVDAG FLQKYFHLIN RFNNEDVCTC PQASVSQQFT SVPWNSFNRD
    560 570 580 590 600
    VLKALYSFAP ISMHCNKSSA VRFQGEWNLQ PLPKVISTLE EPTPQCPTSQ
    610
    GRSPAGPTVV SIGGGKG
    Length:617
    Mass (Da):69,065
    Last modified:July 24, 2007 - v3
    Checksum:i4D5586F0E358885D
    GO

    Computationally mapped potential isoform sequencesi

    There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    Q5T382Q5T382_HUMAN
    Dopamine beta-hydroxylase
    DBH
    244Annotation score:

    Sequence cautioni

    The sequence AAH17174 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
    The sequence CAA31631 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
    The sequence CAA31632 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
    The sequence CAA68285 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti505S → T in CAA68285 (PubMed:3443096).Curated1
    Sequence conflicti505S → T in CAA31631 (PubMed:2922261).Curated1
    Sequence conflicti505S → T in CAA31632 (PubMed:2922261).Curated1

    Polymorphismi

    There are two main alleles of DBH: DBH-A with Ala-318 and DBH-B with Ser-318 (PubMed:10490716, PubMed:10391209, PubMed:10391210).3 Publications

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_04883812G → S. Corresponds to variant dbSNP:rs5318Ensembl.1
    Natural variantiVAR_022758101V → M in DBH deficiency. 1 PublicationCorresponds to variant dbSNP:rs267606760EnsemblClinVar.1
    Natural variantiVAR_022759114D → E in DBH deficiency. 1 PublicationCorresponds to variant dbSNP:rs77576840EnsemblClinVar.1
    Natural variantiVAR_014706181E → Q. Corresponds to variant dbSNP:rs5319Ensembl.1
    Natural variantiVAR_013947211A → T2 PublicationsCorresponds to variant dbSNP:rs5320EnsemblClinVar.1
    Natural variantiVAR_014707239K → N. Corresponds to variant dbSNP:rs5321Ensembl.1
    Natural variantiVAR_014708250E → Q. Corresponds to variant dbSNP:rs5323Ensembl.1
    Natural variantiVAR_014709290D → N. Corresponds to variant dbSNP:rs5324EnsemblClinVar.1
    Natural variantiVAR_014710317L → P. Corresponds to variant dbSNP:rs5325Ensembl.1
    Natural variantiVAR_002196318A → S in allele DBH-B. 3 PublicationsCorresponds to variant dbSNP:rs4531EnsemblClinVar.1
    Natural variantiVAR_022760345D → N in DBH deficiency. 1 PublicationCorresponds to variant dbSNP:rs267606761EnsemblClinVar.1
    Natural variantiVAR_013948549R → C2 PublicationsCorresponds to variant dbSNP:rs6271EnsemblClinVar.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AL365494 Genomic DNA No translation available.
    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.
    CCDSiCCDS6977.2
    PIRiS03020
    RefSeqiNP_000778.3, NM_000787.3
    UniGeneiHs.591890

    Genome annotation databases

    EnsembliENST00000393056; ENSP00000376776; ENSG00000123454
    GeneIDi1621
    KEGGihsa:1621
    UCSCiuc004cel.4 human

    Keywords - Coding sequence diversityi

    Polymorphism

    Similar proteinsi

    Cross-referencesi

    Web resourcesi

    Wikipedia

    Dopamine beta hydroxylase entry

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AL365494 Genomic DNA No translation available.
    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.
    CCDSiCCDS6977.2
    PIRiS03020
    RefSeqiNP_000778.3, NM_000787.3
    UniGeneiHs.591890

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    4ZELX-ray2.90A/B40-617[»]
    ProteinModelPortaliP09172
    SMRiP09172
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi107989, 6 interactors
    IntActiP09172, 2 interactors
    MINTiP09172
    STRINGi9606.ENSP00000376776

    Chemistry databases

    BindingDBiP09172
    ChEMBLiCHEMBL3102
    DrugBankiDB06774 Capsaicin
    DB05394 corticotropin-releasing factor
    DB00822 Disulfiram
    DB00988 Dopamine
    DB00550 Propylthiouracil
    DB00126 Vitamin C
    GuidetoPHARMACOLOGYi2486

    PTM databases

    iPTMnetiP09172
    PhosphoSitePlusiP09172

    Polymorphism and mutation databases

    BioMutaiDBH
    DMDMi158517849

    Proteomic databases

    PaxDbiP09172
    PeptideAtlasiP09172
    PRIDEiP09172
    ProteomicsDBi52205

    Protocols and materials databases

    DNASUi1621
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000393056; ENSP00000376776; ENSG00000123454
    GeneIDi1621
    KEGGihsa:1621
    UCSCiuc004cel.4 human

    Organism-specific databases

    CTDi1621
    DisGeNETi1621
    EuPathDBiHostDB:ENSG00000123454.10
    GeneCardsiDBH
    GeneReviewsiDBH
    H-InvDBiHIX0008510
    HGNCiHGNC:2689 DBH
    HPAiHPA002130
    HPA005960
    HPA070789
    MalaCardsiDBH
    MIMi223360 phenotype
    609312 gene
    neXtProtiNX_P09172
    OpenTargetsiENSG00000123454
    Orphaneti230 Dopamine beta-hydroxylase deficiency
    PharmGKBiPA136
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG3568 Eukaryota
    ENOG410XR89 LUCA
    GeneTreeiENSGT00530000063085
    HOGENOMiHOG000063669
    HOVERGENiHBG005519
    InParanoidiP09172
    KOiK00503
    OMAiMYEPIVT
    OrthoDBiEOG091G03XS
    PhylomeDBiP09172
    TreeFamiTF320698

    Enzyme and pathway databases

    UniPathwayi
    UPA00748;UER00735

    BioCyciMetaCyc:MONOMER66-381
    BRENDAi1.14.17.1 2681
    ReactomeiR-HSA-209905 Catecholamine biosynthesis
    SignaLinkiP09172
    SIGNORiP09172

    Miscellaneous databases

    GeneWikiiDopamine_beta_hydroxylase
    GenomeRNAii1621
    PROiPR:P09172
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000123454 Expressed in 77 organ(s), highest expression level in right adrenal gland
    CleanExiHS_DBH
    ExpressionAtlasiP09172 baseline and differential
    GenevisibleiP09172 HS

    Family and domain databases

    Gene3Di2.60.120.230, 1 hit
    2.60.120.310, 1 hit
    InterProiView protein in InterPro
    IPR014784 Cu2_ascorb_mOase-like_C
    IPR020611 Cu2_ascorb_mOase_CS-1
    IPR014783 Cu2_ascorb_mOase_CS-2
    IPR000323 Cu2_ascorb_mOase_N
    IPR036939 Cu2_ascorb_mOase_N_sf
    IPR024548 Cu2_monoox_C
    IPR005018 DOMON_domain
    IPR008977 PHM/PNGase_F_dom_sf
    IPR028460 Tbh/DBH
    PfamiView protein in Pfam
    PF03712 Cu2_monoox_C, 1 hit
    PF01082 Cu2_monooxygen, 1 hit
    PF03351 DOMON, 1 hit
    PRINTSiPR00767 DBMONOXGNASE
    SMARTiView protein in SMART
    SM00664 DoH, 1 hit
    SUPFAMiSSF49742 SSF49742, 2 hits
    PROSITEiView protein in PROSITE
    PS00084 CU2_MONOOXYGENASE_1, 1 hit
    PS00085 CU2_MONOOXYGENASE_2, 1 hit
    PS50836 DOMON, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiDOPO_HUMAN
    AccessioniPrimary (citable) accession number: P09172
    Secondary accession number(s): Q5T381, Q96AG2
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
    Last sequence update: July 24, 2007
    Last modified: November 7, 2018
    This is version 197 of the entry and version 3 of the sequence. See complete history.
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. Human chromosome 9
      Human chromosome 9: entries, gene names and cross-references to MIM
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