AKR1C3

{{Short description|Protein-coding gene in the species Homo sapiens}}

Aldo-keto reductase family 1 member C3 (AKR1C3), also known as 17β-hydroxysteroid dehydrogenase type 5 (17β-HSD5, HSD17B5) or 3α-hydroxysteroid dehydrogenase type 2 (3α-HSD2){{cite journal | vauthors = Zhang B, Zhu DW, Hu XJ, Zhou M, Shang P, Lin SX | title = Human 3-alpha hydroxysteroid dehydrogenase type 3 (3α-HSD3): the V54L mutation restricting the steroid alternative binding and enhancing the 20α-HSD activity | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 141 | pages = 135–143 | date = May 2014 | pmid = 24434280 | doi = 10.1016/j.jsbmb.2014.01.003 }}{{cite journal | vauthors = Li T, Zhang W, Lin SX | title = Steroid enzyme and receptor expression and regulations in breast tumor samples - A statistical evaluation of public data | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 196 | pages = 105494 | date = February 2020 | pmid = 31610224 | doi = 10.1016/j.jsbmb.2019.105494 }}{{cite journal |doi=10.15347/WJM/2023.003 |doi-access=free |title=Alternative androgen pathways |date=3 April 2023 | vauthors = Masiutin MM, Yadav MK |journal=WikiJournal of Medicine |volume=10 |pages=29 |s2cid=257943362 |url=https://upload.wikimedia.org/wikiversity/en/a/a7/Alternative_androgens_pathways.pdf}}{{Creative Commons text attribution notice|cc=by4|from this source=yes}} is a steroidogenic enzyme that in humans is encoded by the AKR1C3 gene.{{cite journal | vauthors = Khanna M, Qin KN, Wang RW, Cheng KC | title = Substrate specificity, gene structure, and tissue-specific distribution of multiple human 3 alpha-hydroxysteroid dehydrogenases | journal = The Journal of Biological Chemistry | volume = 270 | issue = 34 | pages = 20162–20168 | date = August 1995 | pmid = 7650035 | doi = 10.1074/jbc.270.34.20162 | doi-access = free }}{{cite journal | vauthors = Matsuura K, Shiraishi H, Hara A, Sato K, Deyashiki Y, Ninomiya M, Sakai S | title = Identification of a principal mRNA species for human 3alpha-hydroxysteroid dehydrogenase isoform (AKR1C3) that exhibits high prostaglandin D2 11-ketoreductase activity | journal = Journal of Biochemistry | volume = 124 | issue = 5 | pages = 940–946 | date = November 1998 | pmid = 9792917 | doi = 10.1093/oxfordjournals.jbchem.a022211 }}{{EntrezGene|8644}} AKR1C3 aldo-keto reductase family 1 member C3 [ Homo sapiens (human) ]

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.{{cite journal | vauthors = Theisen JG, Sundaram V, Filchak MS, Chorich LP, Sullivan ME, Knight J, Kim HG, Layman LC | title = The Use of Whole Exome Sequencing in a Cohort of Transgender Individuals to Identify Rare Genetic Variants | journal = Scientific Reports | volume = 9 | issue = 1 | pages = 20099 | date = December 2019 | pmid = 31882810 | pmc = 6934803 | doi = 10.1038/s41598-019-53500-y | bibcode = 2019NatSR...920099T | quote = Table 4 | doi-access = free }}

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.{{cite journal | vauthors = Tian Y, Zhao L, Zhang H, Liu X, Zhao L, Zhao X, Li Y, Li J | title = AKR1C3 overexpression may serve as a promising biomarker for prostate cancer progression | journal = Diagnostic Pathology | volume = 9 | issue = 1 | pages = 42 | date = February 2014 | pmid = 24571686 | pmc = 3939640 | doi = 10.1186/1746-1596-9-42 | doi-access = free }}

Isozymes of aldo-keto reductase family 1 member C

References

External links

{{UCSC gene info|AKR1C3}}

{{cite journal | vauthors = Lin SX, Shi R, Qiu W, Azzi A, Zhu DW, Dabbagh HA, Zhou M | title = Structural basis of the multispecificity demonstrated by 17beta-hydroxysteroid dehydrogenase types 1 and 5 | journal = Molecular and Cellular Endocrinology | volume = 248 | issue = 1–2 | pages = 38–46 | date = March 2006 | pmid = 16480815 | doi = 10.1016/j.mce.2005.11.035 | s2cid = 19087697 }}
{{cite journal | vauthors = Khanna M, Qin KN, Cheng KC | title = Distribution of 3 alpha-hydroxysteroid dehydrogenase in rat brain and molecular cloning of multiple cDNAs encoding structurally related proteins in humans | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 53 | issue = 1–6 | pages = 41–46 | date = June 1995 | pmid = 7626489 | doi = 10.1016/0960-0760(95)00019-V | s2cid = 11316547 | doi-access = free }}
{{cite journal | vauthors = Nagase T, Miyajima N, Tanaka A, Sazuka T, Seki N, Sato S, Tabata S, Ishikawa K, Kawarabayasi Y, Kotani H | title = 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 | journal = DNA Research | volume = 2 | issue = 1 | pages = 37–43 | year = 1995 | pmid = 7788527 | doi = 10.1093/dnares/2.1.37 | doi-access = free }}
{{cite journal | vauthors = Khanna M, Qin KN, Klisak I, Belkin S, Sparkes RS, Cheng KC | title = 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 | journal = Genomics | volume = 25 | issue = 2 | pages = 588–590 | date = January 1995 | pmid = 7789999 | doi = 10.1016/0888-7543(95)80066-U | doi-access = free }}
{{cite journal | vauthors = Qin KN, New MI, Cheng KC | title = Molecular cloning of multiple cDNAs encoding human enzymes structurally related to 3 alpha-hydroxysteroid dehydrogenase | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 46 | issue = 6 | pages = 673–679 | date = December 1993 | pmid = 8274401 | doi = 10.1016/0960-0760(93)90308-J | s2cid = 36210133 }}
{{cite journal | vauthors = Bennett MJ, Schlegel BP, Jez JM, Penning TM, Lewis M | title = Structure of 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase complexed with NADP+ | journal = Biochemistry | volume = 35 | issue = 33 | pages = 10702–10711 | date = August 1996 | pmid = 8718859 | doi = 10.1021/bi9604688 }}
{{cite journal | vauthors = Lin HK, Jez JM, Schlegel BP, Peehl DM, Pachter JA, Penning TM | title = 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 | journal = Molecular Endocrinology | volume = 11 | issue = 13 | pages = 1971–1984 | date = December 1997 | pmid = 9415401 | doi = 10.1210/mend.11.13.0026 }}
{{cite journal | vauthors = Mills KI, Gilkes AF, Sweeney M, Choudhry MA, Woodgate LJ, Bunce CM, Brown G, Burnett AK | title = Identification of a retinoic acid responsive aldoketoreductase expressed in HL60 leukaemic cells | journal = FEBS Letters | volume = 440 | issue = 1–2 | pages = 158–162 | date = November 1998 | pmid = 9862446 | doi = 10.1016/S0014-5793(98)01435-5 | s2cid = 21355070 | doi-access = free | bibcode = 1998FEBSL.440..158M }}
{{cite journal | vauthors = Dufort I, Rheault P, Huang XF, Soucy P, Luu-The V | title = Characteristics of a highly labile human type 5 17beta-hydroxysteroid dehydrogenase | journal = Endocrinology | volume = 140 | issue = 2 | pages = 568–574 | date = February 1999 | pmid = 9927279 | doi = 10.1210/endo.140.2.6531 | doi-access = free }}
{{cite journal | vauthors = Rheault P, Dufort I, Soucy P, Luu-The V | title = 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 | journal = Cytogenetics and Cell Genetics | volume = 84 | issue = 3–4 | pages = 241–242 | year = 1999 | pmid = 10393440 | doi = 10.1159/000015267 | s2cid = 5792836 }}
{{cite journal | vauthors = Griffin LD, Mellon SH | title = Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 23 | pages = 13512–13517 | date = November 1999 | pmid = 10557352 | pmc = 23979 | doi = 10.1073/pnas.96.23.13512 | doi-access = free | bibcode = 1999PNAS...9613512G }}
{{cite journal | vauthors = Suzuki-Yamamoto T, Nishizawa M, Fukui M, Okuda-Ashitaka E, Nakajima T, Ito S, Watanabe K | title = cDNA cloning, expression and characterization of human prostaglandin F synthase | journal = FEBS Letters | volume = 462 | issue = 3 | pages = 335–340 | date = December 1999 | pmid = 10622721 | doi = 10.1016/S0014-5793(99)01551-3 | s2cid = 19812463 | doi-access = free }}
{{cite journal | vauthors = Nishizawa M, Nakajima T, Yasuda K, Kanzaki H, Sasaguri Y, Watanabe K, Ito S | title = Close kinship of human 20alpha-hydroxysteroid dehydrogenase gene with three aldo-keto reductase genes | journal = Genes to Cells | volume = 5 | issue = 2 | pages = 111–125 | date = February 2000 | pmid = 10672042 | doi = 10.1046/j.1365-2443.2000.00310.x | s2cid = 25136637 | doi-access = free }}
{{cite journal | vauthors = Penning TM, Burczynski ME, Jez JM, Hung CF, Lin HK, Ma H, Moore M, Palackal N, Ratnam K | title = 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 | journal = The Biochemical Journal | volume = 351 | issue = Pt 1 | pages = 67–77 | date = October 2000 | pmid = 10998348 | pmc = 1221336 | doi = 10.1042/bj3510067 }}
{{cite journal | vauthors = Hartley JL, Temple GF, Brasch MA | title = DNA cloning using in vitro site-specific recombination | journal = Genome Research | volume = 10 | issue = 11 | pages = 1788–1795 | date = November 2000 | pmid = 11076863 | pmc = 310948 | doi = 10.1101/gr.143000 }}
{{cite journal | vauthors = Penning TM, Burczynski ME, Jez JM, Lin HK, Ma H, Moore M, Ratnam K, Palackal N | title = Structure-function aspects and inhibitor design of type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3) | journal = Molecular and Cellular Endocrinology | volume = 171 | issue = 1–2 | pages = 137–149 | date = January 2001 | pmid = 11165022 | doi = 10.1016/S0303-7207(00)00426-3 | s2cid = 11599113 }}
{{cite journal | vauthors = Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S | title = Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing | journal = EMBO Reports | volume = 1 | issue = 3 | pages = 287–292 | date = September 2000 | pmid = 11256614 | pmc = 1083732 | doi = 10.1093/embo-reports/kvd058 }}

Category:EC 1.1.1