Aldo-keto reductase family 1 member C1 also known as 20α-hydroxysteroid dehydrogenase, 3α-hydroxysteroid dehydrogenase, and dihydrodiol dehydrogenase 1/2 is an enzyme that in humans is encoded by the AKR1C1gene.[1][2]
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 reduction of progesterone to the inactive form 20-alpha-hydroxy-progesterone. This gene shares high sequence identity with three other gene members, and is clustered with those three genes at chromosome 10p15-p14.[2]
References
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Khanna M, Qin KN, Cheng KC (Jun 1995). "Distribution of 3 alpha-hydroxysteroid dehydrogenase in rat brain and molecular cloning of multiple cDNAs encoding structurally related proteins in humans". The Journal of Steroid Biochemistry and Molecular Biology. 53 (1–6): 41–6. doi:10.1016/0960-0760(95)00019-V. PMID7626489.
Khanna M, Qin KN, Klisak I, Belkin S, Sparkes RS, Cheng KC (Jan 1995). "Localization of multiple human dihydrodiol dehydrogenase (DDH1 and DDH2) and chlordecone reductase (CHDR) genes in chromosome 10 by the polymerase chain reaction and fluorescence in situ hybridization". Genomics. 25 (2): 588–90. doi:10.1016/0888-7543(95)80066-U. PMID7789999.
Lou H, Hammond L, Sharma V, Sparkes RS, Lusis AJ, Stolz A (Mar 1994). "Genomic organization and chromosomal localization of a novel human hepatic dihydrodiol dehydrogenase with high affinity bile acid binding". The Journal of Biological Chemistry. 269 (11): 8416–22. PMID8132567.
Qin KN, New MI, Cheng KC (Dec 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.
Stolz A, Hammond L, Lou H, Takikawa H, Ronk M, Shively JE (May 1993). "cDNA cloning and expression of the human hepatic bile acid-binding protein. A member of the monomeric reductase gene family". The Journal of Biological Chemistry. 268 (14): 10448–57. PMID8486699.
Nishizawa M, Nakajima T, Yasuda K, Kanzaki H, Sasaguri Y, Watanabe K, Ito S (Feb 2000). "Close kinship of human 20alpha-hydroxysteroid dehydrogenase gene with three aldo-keto reductase genes". Genes to Cells. 5 (2): 111–25. doi:10.1046/j.1365-2443.2000.00310.x. PMID10672042.
Zhang Y, Dufort I, Rheault P, Luu-The V (Oct 2000). "Characterization of a human 20alpha-hydroxysteroid dehydrogenase". Journal of Molecular Endocrinology. 25 (2): 221–8. doi:10.1677/jme.0.0250221. PMID11013348.
Nahoum V, Gangloff A, Legrand P, Zhu DW, Cantin L, Zhorov BS, Luu-The V, Labrie F, Breton R, Lin SX (Nov 2001). "Structure of the human 3alpha-hydroxysteroid dehydrogenase type 3 in complex with testosterone and NADP at 1.25-A resolution". The Journal of Biological Chemistry. 276 (45): 42091–8. doi:10.1074/jbc.M105610200. PMID11514561.
Chen CY, Hsu CP, Hsu NY, Shih CS, Lin TY, Chow KC (2002). "Expression of dihydrodiol dehydrogenase in the resected stage I non-small cell lung cancer". Oncology Reports. 9 (3): 515–9. doi:10.3892/or.9.3.515. PMID11956619.
Yang MD, Wu CC, Chiou SH, Chiu CF, Lin TY, Chiang IP, Chow KC (2003). "Reduction of dihydrodiol dehydrogenase expression in resected hepatocellular carcinoma". Oncology Reports. 10 (2): 271–6. doi:10.3892/or.10.2.271. PMID12579257.
Nakajima T, Yasuda K, Nishizawa M, Okada H, Yoshimura T, Ito S, Kanzaki H (Feb 2003). "Expression of 20alpha-hydroxysteroid dehydrogenase mRNA in human endometrium and decidua". Endocrine Journal. 50 (1): 105–11. doi:10.1507/endocrj.50.105. PMID12733716.
Couture JF, Legrand P, Cantin L, Luu-The V, Labrie F, Breton R (Aug 2003). "Human 20alpha-hydroxysteroid dehydrogenase: crystallographic and site-directed mutagenesis studies lead to the identification of an alternative binding site for C21-steroids". Journal of Molecular Biology. 331 (3): 593–604. doi:10.1016/S0022-2836(03)00762-9. PMID12899831.
Agapova OA, Yang P, Wang WH, Lane DA, Clark AF, Weinstein BI, Hernandez MR (Oct 2003). "Altered expression of 3 alpha-hydroxysteroid dehydrogenases in human glaucomatous optic nerve head astrocytes". Neurobiology of Disease. 14 (1): 63–73. doi:10.1016/S0969-9961(03)00101-3. PMID13678667.
1ihi: Crystal Structure of Human Type III 3-alpha-Hydroxysteroid Dehydrogenase/Bile Acid Binding Protein (AKR1C2) Complexed with NADP+ and Ursodeoxycholate