This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. These enzymes catalyze the conversion of aldehydes and ketones to their corresponding alcohols by utilizing NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme catalyzes the bioreduction of chlordecone, a toxic organochlorine pesticide, to chlordecone alcohol in liver. This gene shares high sequence identity with three other gene members and is clustered with those three genes at 10p15-p14 on chromosome 10.[10]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Li, Tang; Zhang, Wenfa; Lin, Sheng-Xiang (February 2020). "Steroid enzyme and receptor expression and regulations in breast tumor samples – A statistical evaluation of public data". The Journal of Steroid Biochemistry and Molecular Biology. 196: 105494. doi:10.1016/j.jsbmb.2019.105494. PMID31610224.
^Longone, Patrizia; Rupprecht, Rainer; Manieri, Gaia A.; Bernardi, Giorgio; Romeo, Elena; Pasini, Augusto (March 2008). "The complex roles of neurosteroids in depression and anxiety disorders". Neurochemistry International. 52 (4–5): 596–601. doi:10.1016/j.neuint.2007.10.001. PMID17996986.
^Savchuk, I.; Morvan, M.L.; Antignac, J.P.; Gemzell-Danielsson, K.; Le Bizec, B.; Söder, O.; Svechnikov, K. (December 2018). "The human genital tubercle is steroidogenic organ at early pregnancy". Molecular and Cellular Endocrinology. 477: 148–155. doi:10.1016/j.mce.2018.06.012. PMID29928928.
^Schüle C, Romeo E, Uzunov DP, Eser D, di Michele F, Baghai TC, Pasini A, Schwarz M, Kempter H, Rupprecht R (March 2006). "Influence of mirtazapine on plasma concentrations of neuroactive steroids in major depression and on 3alpha-hydroxysteroid dehydrogenase activity". Molecular Psychiatry. 11 (3): 261–72. doi:10.1038/sj.mp.4001782. PMID16344854. S2CID21473462.
Binstock JM, Iyer RB, Hamby CV, Fried VA, Schwartz IS, Weinstein BI, Southren AL (September 1992). "Human hepatic 3 alpha-hydroxysteroid dehydrogenase: possible identity with human hepatic chlordecone reductase". Biochemical and Biophysical Research Communications. 187 (2): 760–6. doi:10.1016/0006-291X(92)91260-W. PMID1530633.
Winters CJ, Molowa DT, Guzelian PS (January 1990). "Isolation and characterization of cloned cDNAs encoding human liver chlordecone reductase". Biochemistry. 29 (4): 1080–7. doi:10.1021/bi00456a034. PMID2187532.
Qin KN, New MI, Cheng KC (December 1993). "Molecular cloning of multiple cDNAs encoding human enzymes structurally related to 3 alpha-hydroxysteroid dehydrogenase". The Journal of Steroid Biochemistry and Molecular Biology. 46 (6): 673–9. doi:10.1016/0960-0760(93)90308-J. PMID8274401. S2CID36210133.
Kume T, Iwasa H, Shiraishi H, Yokoi T, Nagashima K, Otsuka M, Terada T, Takagi T, Hara A, Kamataki T (December 1999). "Characterization of a novel variant (S145C/L311V) of 3alpha-hydroxysteroid/dihydrodiol dehydrogenase in human liver". Pharmacogenetics. 9 (6): 763–71. doi:10.1097/00008571-199912000-00011. PMID10634139.
Ozeki T, Takahashi Y, Nakayama K, Kamataki T (September 2002). "Hepatocyte nuclear factor (HNF)-4 alpha/gamma, HNF-1 alpha, and vHNF-1 regulate the cell-specific expression of the human dihydrodiol dehydrogenase (DD)4/AKR1C4 gene". Archives of Biochemistry and Biophysics. 405 (2): 185–90. doi:10.1016/S0003-9861(02)00384-3. PMID12220531.
Ozeki T, Takahashi Y, Nakayama K, Funayama M, Nagashima K, Kodama T, Kamataki T (January 2003). "Hepatocyte nuclear factor-4 alpha/gamma and hepatocyte nuclear factor-1 alpha as causal factors of interindividual difference in the expression of human dihydrodiol dehydrogenase 4 mRNA in human livers". Pharmacogenetics. 13 (1): 49–53. doi:10.1097/00008571-200301000-00007. PMID12544512.
Schüle C, Romeo E, Uzunov DP, Eser D, di Michele F, Baghai TC, Pasini A, Schwarz M, Kempter H, Rupprecht R (March 2006). "Influence of mirtazapine on plasma concentrations of neuroactive steroids in major depression and on 3alpha-hydroxysteroid dehydrogenase activity". Molecular Psychiatry. 11 (3): 261–72. doi:10.1038/sj.mp.4001782. PMID16344854. S2CID21473462.
PDB gallery
2fvl: Crystal structure of human 3-alpha hydroxysteroid/dihydrodiol dehydrogenase (AKR1C4) complexed with NADP+