Biology:AKR1C3

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

Aldo-keto reductase family 1 member C3 (AKR1C3), also known as 17β-hydroxysteroid dehydrogenase type 5 (17β-HSD5, HSD17B5) is a key steroidogenic enzyme that in humans is encoded by the AKR1C3 gene.

Function

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 prostaglandin D₂, prostaglandin H₂, and phenanthrenequinone, and the oxidation of prostaglandin F_2α to prostaglandin D₂. It is also capable of metabolizing estrogen and progesterone.

AKR1C3 may play an important role in the development of allergic diseases such as asthma, and may also have a role in controlling cell growth and/or differentiation. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14.

Pathology

AKR1C3 is overexpressed in prostate cancer (PCa) and is associated with the development of castration-resistant prostate cancer (CRPC). In addition, AKR1C3 overexpression may serve as a promising biomarker for prostate cancer progression.

External links

• Human AKR1C3 genome location and AKR1C3 gene details page in the UCSC Genome Browser.

Further reading

• "Structural basis of the multispecificity demonstrated by 17beta-hydroxysteroid dehydrogenase types 1 and 5". Molecular and Cellular Endocrinology 248 (1–2): 38–46. Mar 2006. doi:10.1016/j.mce.2005.11.035. PMID 16480815. 
• "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. doi:10.1016/0960-0760(95)00019-V. PMID 7626489. 
• "Prediction of the coding sequences of unidentified human genes. III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of cDNA clones from human cell line KG-1". DNA Research 2 (1): 37–43. 1995. doi:10.1093/dnares/2.1.37. PMID 7788527. 
• "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. doi:10.1016/0888-7543(95)80066-U. PMID 7789999. 
• "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. doi:10.1016/0960-0760(93)90308-J. PMID 8274401. 
• "Structure of 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase complexed with NADP+". Biochemistry 35 (33): 10702–11. Aug 1996. doi:10.1021/bi9604688. PMID 8718859. 
• "Expression and characterization of recombinant type 2 3 alpha-hydroxysteroid dehydrogenase (HSD) from human prostate: demonstration of bifunctional 3 alpha/17 beta-HSD activity and cellular distribution". Molecular Endocrinology 11 (13): 1971–84. Dec 1997. doi:10.1210/mend.11.13.0026. PMID 9415401. 
• "Identification of a retinoic acid responsive aldoketoreductase expressed in HL60 leukaemic cells". FEBS Letters 440 (1–2): 158–62. Nov 1998. doi:10.1016/S0014-5793(98)01435-5. PMID 9862446. 
• "Characteristics of a highly labile human type 5 17beta-hydroxysteroid dehydrogenase". Endocrinology 140 (2): 568–74. Feb 1999. doi:10.1210/endo.140.2.6531. PMID 9927279. 
• "Assignment of HSD17B5 encoding type 5 17 beta-hydroxysteroid dehydrogenase to human chromosome bands 10p15-->p14 and mouse chromosome 13 region A2 by in situ hybridization: identification of a new syntenic relationship". Cytogenetics and Cell Genetics 84 (3–4): 241–2. 1999. doi:10.1159/000015267. PMID 10393440. 
• "Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes". Proceedings of the National Academy of Sciences of the United States of America 96 (23): 13512–7. Nov 1999. doi:10.1073/pnas.96.23.13512. PMID 10557352. Bibcode: 1999PNAS...9613512G. 
• "cDNA cloning, expression and characterization of human prostaglandin F synthase". FEBS Letters 462 (3): 335–40. Dec 1999. doi:10.1016/S0014-5793(99)01551-3. PMID 10622721. 
• "Close kinship of human 20alpha-hydroxysteroid dehydrogenase gene with three aldo-keto reductase genes". Genes to Cells 5 (2): 111–25. Feb 2000. doi:10.1046/j.1365-2443.2000.00310.x. PMID 10672042. 
• "Human 3alpha-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the aldo-keto reductase superfamily: functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones". The Biochemical Journal 351 (Pt 1): 67–77. Oct 2000. doi:10.1042/bj3510067. PMID 10998348. 
• "DNA cloning using in vitro site-specific recombination". Genome Research 10 (11): 1788–95. Nov 2000. doi:10.1101/gr.143000. PMID 11076863. 
• "Structure-function aspects and inhibitor design of type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3)". Molecular and Cellular Endocrinology 171 (1–2): 137–49. Jan 2001. doi:10.1016/S0303-7207(00)00426-3. PMID 11165022. 
• "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Reports 1 (3): 287–92. Sep 2000. doi:10.1093/embo-reports/kvd058. PMID 11256614.