DHRS4
Domain
The C-terminus peroxisomal targeting signal tripeptide is important for peroxisomal import. Once in the peroxisome, it is involved in intersubunit interactions.
Three specific residues, Ser-176, Phe-179 and Thr-195 are conserved between primates whereas the respective residues are phenylalanine, leucine, and asparagine in the other mammal enzymes (PubMed:18571493, PubMed:19056333). The two residues at positions 176 and 179 are molecular determinants responsible for the stereoselective reduction of 3-ketosteroids and benzil (PubMed:19056333). The presence of an asparagine at position 195 is important for the maintenance of the quaternary structure and stability at cold temperature (PubMed:18571493, PubMed:19056333). The absence of an asparagine at position 195 destabilizes the quaternary structure, thereby affecting catalytic efficiency toward some substrates and decreasing stability at cold temperature (PubMed:18571493, PubMed:19056333).
Function
NADPH-dependent oxidoreductase which catalyzes the reduction of a variety of compounds bearing carbonyl groups including ketosteroids, alpha-dicarbonyl compounds, aldehydes, aromatic ketones and quinones (PubMed:18571493, PubMed:19056333). Reduces 3-ketosteroids and benzil into 3beta-hydroxysteroids and R-benzoin, respectively, in contrast to the stereoselectivity of non-primate DHRS4s which produce 3alpha-hydroxysteroids and S-benzoin (PubMed:19056333). Diplays low activity toward all-trans-retinal and no activity toward 9-cis-retinal as compared to non-primate mammals (PubMed:18571493, PubMed:19056333). In the reverse reaction, catalyze the NAD-dependent oxidation of 3beta-hydroxysteroids and alcohol, but with much lower efficiency (PubMed:18571493, PubMed:19056333). Involved in the metabolism of 3beta-hydroxysteroids, isatin and xenobiotic carbonyl compounds (PubMed:18571493, PubMed:19056333).
Isoform 7
No detected catalytic activity in vitro, possibly due to the lack of catalytic site.
Isoform 8
NADPH-dependent oxidoreductase which catalyzes the reduction of a variety of compounds bearing carbonyl groups including ketosteroids, alpha-dicarbonyl compounds, aldehydes, aromatic ketones and quinones. Involved in the metabolism of 3beta-hydroxysteroids, isatin and xenobiotic carbonyl compounds. Has a higher catalytic activity for xenobiotic alpha-dicarbonyl compounds, sucha as benzil, than isoform 1 and is involved in benzil detoxification.
Sequence Similarities
Belongs to the short-chain dehydrogenases/reductases (SDR) family.
Tissue Specificity
Isoform 1
Predominantly expressed in normal cervix (at protein level).
Isoform 4
Expressed in some neoplastic cervical tissues, but not in normal cervix (at protein level).
Isoform 5
Expressed in a few neoplastic cervical tissues.
Isoform 6
Expressed in a few neoplastic cervical tissues.
Isoform 8
High expression in liver.
Cellular localization
- Isoform 1
- Peroxisome
- Isoform 4 is not peroxisomal.
- Isoform 7
- Nucleus
Alternative names
SDR25C2, UNQ851/PRO1800, DHRS4, Dehydrogenase/reductase SDR family member 4, NADPH-dependent carbonyl reductase, NADPH-dependent retinol dehydrogenase/reductase, Peroxisomal short-chain alcohol dehydrogenase, SCAD-SRL, Short chain dehydrogenase/reductase family 25C member 2, Short-chain dehydrogenase/reductase family member 4, CR, NRDR, humNRDR, PSCD, Protein SDR25C2