aldo-keto reductase family 1, member C4; 3-alpha-hydroxysteroid dehydrogenase type 1; dihydrodiol dehydrogenase 4; chlordecone reductase; DD4; HAKRA (AKR1C4, CHDR)

Function

• terminates androgen action by converting potent androgen 5-alpha-dihydrotestosterone to less active form 3-alpha-androstanediol
• also has some 20-alpha-hydroxysteroid dehydrogenase activity
• biotransformation of the pesticide chlordecone (kepone) to its corresponding alcohol leads to increased biliary excretion of the pesticide & concomitant reduction of its neurotoxicity since bile is the major excretory route

chlordecone alcohol + NADP+ <--> chlordecone + NADPH

androsterone + NAD+/NADP+
          <-->
5-alpha-androstane-3,17-dione + NADH/NADPH

Structure

• monomer
• N-terminus is blocked
• belongs to the aldo/keto reductase family

Compartment

cytoplasm

Expression

liver specific

Polymorphism

• allele with Cys-145/Val-311 shows a 3-5 fold decrease in catalytic efficiency for xenobiotic & steroidal substrates compared to the Ser-145/Leu-311 allele

More general terms

• 3-alpha-hydroxysteroid dehydrogenase

Database

• UniProt: http://www.uniprot.org/uniprot/P17516.html
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:1109
• OMIM: https://mirror.omim.org/entry/600451
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=1109