AKR1C1 explained
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 AKR1C1 gene.[1] [2]
Superfamily of enzymes
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 specific enzyme, AKR1C1, among other reactions, catalyzes the reduction of progesterone to the inactive form 20-alpha-hydroxy-progesterone. The AKR1C1 gene shares high sequence identity with three other gene members, and is clustered with those three genes at chromosome 10p15-p14.[2]
See also
Further reading
- Ciaccio PJ, Jaiswal AK, Tew KD . Regulation of human dihydrodiol dehydrogenase by Michael acceptor xenobiotics . The Journal of Biological Chemistry . 269 . 22 . 15558–62 . Jun 1994 . 10.1016/S0021-9258(17)40716-2 . 7515059 . free .
- Khanna M, Qin KN, Cheng KC . 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 . Jun 1995 . 7626489 . 10.1016/0960-0760(95)00019-V . 11316547 . free .
- Khanna M, Qin KN, Klisak I, Belkin S, Sparkes RS, Cheng KC . 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 . Jan 1995 . 7789999 . 10.1016/0888-7543(95)80066-U . free .
- Lou H, Hammond L, Sharma V, Sparkes RS, Lusis AJ, Stolz A . 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 . Mar 1994 . 10.1016/S0021-9258(17)37210-1 . 8132567 . free .
- Deyashiki Y, Ogasawara A, Nakayama T, Nakanishi M, Miyabe Y, Sato K, Hara A . Molecular cloning of two human liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase isoenzymes that are identical with chlordecone reductase and bile-acid binder . The Biochemical Journal . 299 . 2 . 545–52 . Apr 1994 . 8172617 . 1138306 . 10.1042/bj2990545.
- Qin KN, New MI, Cheng KC . 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 . Dec 1993 . 8274401 . 10.1016/0960-0760(93)90308-J . 36210133 .
- Stolz A, Hammond L, Lou H, Takikawa H, Ronk M, Shively JE . 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 . May 1993 . 10.1016/S0021-9258(18)82220-7 . 8486699 . free .
- Hara A, Matsuura K, Tamada Y, Sato K, Miyabe Y, Deyashiki Y, Ishida N . Relationship of human liver dihydrodiol dehydrogenases to hepatic bile-acid-binding protein and an oxidoreductase of human colon cells . The Biochemical Journal . 313 . 2 . 373–6 . Jan 1996 . 8573067 . 1216918 . 10.1042/bj3130373.
- O'connor T, Ireland LS, Harrison DJ, Hayes JD . Major differences exist in the function and tissue-specific expression of human aflatoxin B1 aldehyde reductase and the principal human aldo-keto reductase AKR1 family members . The Biochemical Journal . 343 . 2 . 487–504 . Oct 1999 . 10510318 . 1220579 . 10.1042/bj3430487 .
- Nishizawa M, Nakajima T, Yasuda K, Kanzaki H, Sasaguri Y, Watanabe K, Ito S . Close kinship of human 20alpha-hydroxysteroid dehydrogenase gene with three aldo-keto reductase genes . Genes to Cells . 5 . 2 . 111–25 . Feb 2000 . 10672042 . 10.1046/j.1365-2443.2000.00310.x . 25136637 . free .
- Zhang Y, Dufort I, Rheault P, Luu-The V . Characterization of a human 20alpha-hydroxysteroid dehydrogenase . Journal of Molecular Endocrinology . 25 . 2 . 221–8 . Oct 2000 . 11013348 . 10.1677/jme.0.0250221 . free .
- Nahoum V, Gangloff A, Legrand P, Zhu DW, Cantin L, Zhorov BS, Luu-The V, Labrie F, Breton R, Lin SX . 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 . Nov 2001 . 11514561 . 10.1074/jbc.M105610200 . free .
- Chen CY, Hsu CP, Hsu NY, Shih CS, Lin TY, Chow KC . Expression of dihydrodiol dehydrogenase in the resected stage I non-small cell lung cancer . Oncology Reports . 9 . 3 . 515–9 . 2002 . 11956619 . 10.3892/or.9.3.515 .
- Yang MD, Wu CC, Chiou SH, Chiu CF, Lin TY, Chiang IP, Chow KC . Reduction of dihydrodiol dehydrogenase expression in resected hepatocellular carcinoma . Oncology Reports . 10 . 2 . 271–6 . 2003 . 12579257 . 10.3892/or.10.2.271 .
- Nakajima T, Yasuda K, Nishizawa M, Okada H, Yoshimura T, Ito S, Kanzaki H . Expression of 20alpha-hydroxysteroid dehydrogenase mRNA in human endometrium and decidua . Endocrine Journal . 50 . 1 . 105–11 . Feb 2003 . 12733716 . 10.1507/endocrj.50.105 . free .
- Couture JF, Legrand P, Cantin L, Luu-The V, Labrie F, Breton R . 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 . Aug 2003 . 12899831 . 10.1016/S0022-2836(03)00762-9 .
- Agapova OA, Yang P, Wang WH, Lane DA, Clark AF, Weinstein BI, Hernandez MR . Altered expression of 3 alpha-hydroxysteroid dehydrogenases in human glaucomatous optic nerve head astrocytes . Neurobiology of Disease . 14 . 1 . 63–73 . Oct 2003 . 13678667 . 10.1016/S0969-9961(03)00101-3 . 21159141 .
Notes and References
- Ciaccio PJ, Tew KD . cDNA and deduced amino acid sequences of a human colon dihydrodiol dehydrogenase . Biochimica et Biophysica Acta (BBA) - Bioenergetics . 1186 . 1–2 . 129–32 . Jun 1994 . 8011662 . 10.1016/0005-2728(94)90144-9 .
- Web site: Entrez Gene: AKR1C1 aldo-keto reductase family 1, member C1 (dihydrodiol dehydrogenase 1; 20-alpha (3-alpha)-hydroxysteroid dehydrogenase).