Q9QYY9 · ADH4_MOUSE

  • Protein
    All-trans-retinol dehydrogenase [NAD(+)] ADH4
  • Gene
    Adh4
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Catalyzes the NAD-dependent oxidation of either all-trans-retinol or 9-cis-retinol (PubMed:17279314).
Also oxidizes long chain omega-hydroxy fatty acids, such as 20-HETE, producing both the intermediate aldehyde, 20-oxoarachidonate and the end product, a dicarboxylic acid, (5Z,8Z,11Z,14Z)-eicosatetraenedioate (PubMed:16081420).
Also catalyzes the reduction of benzoquinones (By similarity).

Caution

Has a much lower NAD-retinol dehydrogenase activity compared to the human ortholog.

Catalytic activity

  • all-trans-retinol + NAD+ = all-trans-retinal + H+ + NADH
    This reaction proceeds in the forward direction.
    EC:1.1.1.105 (UniProtKB | ENZYME | Rhea)
  • 9-cis-retinol + NAD+ = 9-cis-retinal + H+ + NADH
    This reaction proceeds in the forward direction.
  • 20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + NAD+ = 20-oxo-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H+ + NADH
    This reaction proceeds in the forward direction.
  • 20-oxo-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H2O + NAD+ = (5Z,8Z,11Z,14Z)-eicosatetraenedioate + 2 H+ + NADH
    This reaction proceeds in the forward direction.
  • 1,4-benzoquinone + H+ + NADH = hydroquinone + NAD+
    This reaction proceeds in the forward direction.

Cofactor

Zn2+ (UniProtKB | Rhea| CHEBI:29105 )
Note: Binds 2 Zn2+ ions per subunit.

Activity regulation

Oxidation of 20-HETE is inhibited by low concentrations of N-heptylformamide (PubMed:16081420).
Oxidation of 20-HETE is a decreased by 55-65% by either all-trans-retinol or all-trans-retinoic acid (PubMed:16081420).
Strongly inhibited by omega-hydroxy fatty acids (PubMed:10514444).

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
35 μM20-HETE
0.24 mM1,4-benzoquinone

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site47Zn2+ 1 (UniProtKB | ChEBI); catalytic
Binding site49NAD+ (UniProtKB | ChEBI)
Binding site68Zn2+ 1 (UniProtKB | ChEBI); catalytic
Binding site98Zn2+ 2 (UniProtKB | ChEBI)
Binding site101Zn2+ 2 (UniProtKB | ChEBI)
Binding site104Zn2+ 2 (UniProtKB | ChEBI)
Binding site112Zn2+ 2 (UniProtKB | ChEBI)
Binding site179Zn2+ 1 (UniProtKB | ChEBI); catalytic
Binding site204-209NAD+ (UniProtKB | ChEBI)
Binding site228NAD+ (UniProtKB | ChEBI)
Binding site233NAD+ (UniProtKB | ChEBI)
Binding site297-299NAD+ (UniProtKB | ChEBI)
Binding site320-322NAD+ (UniProtKB | ChEBI)
Binding site372NAD+ (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentcytosol
Cellular Componentnucleoplasm
Molecular Functionalcohol dehydrogenase (NAD+) activity
Molecular Functionalcohol dehydrogenase (NAD+) activity, zinc-dependent
Molecular Functionaldose reductase (NADPH) activity
Molecular Functionall-trans retinal binding
Molecular Functionall-trans-retinol dehydrogenase (NAD+) activity
Molecular Functionbenzaldehyde dehydrogenase [NAD(P)+] activity
Molecular Functionethanol binding
Molecular FunctionNAD binding
Molecular FunctionNADPH:quinone reductase activity
Molecular Functionretinol binding
Molecular FunctionS-(hydroxymethyl)glutathione dehydrogenase (NAD(P)+) activity
Molecular Functionzinc ion binding
Biological Processalcohol catabolic process
Biological Processcellular aldehyde metabolic process
Biological Processethanol metabolic process
Biological Processfatty acid omega-oxidation
Biological Processformaldehyde catabolic process
Biological Processquinone metabolic process
Biological Processretinol metabolic process

Keywords

Enzyme and pathway databases

Chemistry

Names & Taxonomy

Protein names

  • Recommended name
    All-trans-retinol dehydrogenase [NAD(+)] ADH4
  • EC number
  • Alternative names
    • ADH2
    • Alcohol dehydrogenase 2
    • Alcohol dehydrogenase 4
    • Alcohol dehydrogenase class II (Alcohol dehydrogenase II)

Gene names

    • Name
      Adh4
    • Synonyms
      Adh2

Organism names

  • Taxonomic identifier
  • Strain
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q9QYY9
  • Secondary accessions
    • Q3V0P5

Proteomes

Organism-specific databases

Subcellular Location

Keywords

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis48Strongly increases NAD-retinol dehydrogenase activity.
Mutagenesis52No effect.
Mutagenesis183Strongly increases activity towards ethanol, increases KM for benzoquinone 10-fold.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 28 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00001606821-377All-trans-retinol dehydrogenase [NAD+] ADH4

Proteomic databases

PTM databases

Expression

Tissue specificity

Liver specific.

Gene expression databases

Interaction

Subunit

Dimer.

Protein-protein interaction databases

Miscellaneous

Family & Domains

Sequence similarities

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    377
  • Mass (Da)
    40,211
  • Last updated
    2011-06-28 v4
  • Checksum
    5B527E48BB745E14
MGTQGKVIKCKAAIAWKTGSPLCIEEIEVSPPKACEVRIQVIATCVCPTDINATDPKKKALFPVVLGHECAGIVESVGPGVTNFKPGDKVIPFFAPQCKRCKLCLSPLTNLCGKLRNFKYPTIDQELMEDRTSRFTCKGRSIYHFMGVSSFSQYTVVSEANLARVDDEANLERVCLIGCGFSSGYGAAINTAKVTPSSTCAVFGLGCVGLSAIIGCKIAGASRIIAIDINGEKFPKAKALGATDCLNPRELDKPVQDVITELTAGGVDYSLDCAGTAQTLKAAVDCTVLGWGSCTVVGAKVDKMTIPTVDVILGRSINGTFFGGWKSVDSVPNLVSDYKNKKFDLDLLVTHALPFESINDAIDLMKEGKSIRTILTF

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
E0CYI4E0CYI4_MOUSEAdh4216

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict197in Ref. 1; CAB57455
Sequence conflict303in Ref. 1; CAB57455

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AJ245750
EMBL· GenBank· DDBJ
CAB57455.1
EMBL· GenBank· DDBJ
mRNA
AK132994
EMBL· GenBank· DDBJ
BAE21459.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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