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)[5][6][7] is a steroidogenic enzyme that in humans is encoded by the AKR1C3 gene.[8][9][10]

AKR1C3
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesAKR1C3, DD3, DDX, HA1753, HAKRB, HAKRe, HSD17B5, PGFS, hluPGFS, aldo-keto reductase family 1, member C3, aldo-keto reductase family 1 member C3
External IDsOMIM: 603966; MGI: 2145420; HomoloGene: 128661; GeneCards: AKR1C3; OMA:AKR1C3 - orthologs
EC number1.3.1.20
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003739
NM_001253908
NM_001253909
NM_016253

NM_134066
NM_001346535

RefSeq (protein)

NP_001240837
NP_001240838
NP_003730

NP_001333464
NP_598827

Location (UCSC)Chr 10: 5.04 – 5.11 MbChr 13: 4.18 – 4.2 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

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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 to prostaglandin D2.[10] It is also capable of metabolizing estrogen and progesterone.[11]

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.[10]

Pathology

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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.[12]

Isozymes of aldo-keto reductase family 1 member C

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HGNC Gene Symbol Enzyme Name Aliases[13]
AKR1C1 aldo-keto reductase family 1 member C1; 20α-hydroxysteroid dehydrogenase
AKR1C2 aldo-keto reductase family 1 member C2; 3α-hydroxysteroid dehydrogenase type 3
AKR1C3 aldo-keto reductase family 1 member C3; 3α-hydroxysteroid dehydrogenase type 2; 17β-hydroxysteroid dehydrogenase type 5; HSD17B5
AKR1C4 aldo-keto reductase family 1 member C4; 3α-hydroxysteroid dehydrogenase type 1

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000196139Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021214Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Zhang B, Zhu DW, Hu XJ, Zhou M, Shang P, Lin SX (May 2014). "Human 3-alpha hydroxysteroid dehydrogenase type 3 (3α-HSD3): the V54L mutation restricting the steroid alternative binding and enhancing the 20α-HSD activity". The Journal of Steroid Biochemistry and Molecular Biology. 141: 135–143. doi:10.1016/j.jsbmb.2014.01.003. PMID 24434280.
  6. ^ Li T, Zhang W, Lin SX (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. PMID 31610224.
  7. ^ Masiutin MM, Yadav MK (3 April 2023). "Alternative androgen pathways" (PDF). WikiJournal of Medicine. 10: 29. doi:10.15347/WJM/2023.003. S2CID 257943362.  This article incorporates text from this source, which is available under the CC BY 4.0 license.
  8. ^ Khanna M, Qin KN, Wang RW, Cheng KC (August 1995). "Substrate specificity, gene structure, and tissue-specific distribution of multiple human 3 alpha-hydroxysteroid dehydrogenases". The Journal of Biological Chemistry. 270 (34): 20162–20168. doi:10.1074/jbc.270.34.20162. PMID 7650035.
  9. ^ Matsuura K, Shiraishi H, Hara A, Sato K, Deyashiki Y, Ninomiya M, et al. (November 1998). "Identification of a principal mRNA species for human 3alpha-hydroxysteroid dehydrogenase isoform (AKR1C3) that exhibits high prostaglandin D2 11-ketoreductase activity". Journal of Biochemistry. 124 (5): 940–946. doi:10.1093/oxfordjournals.jbchem.a022211. PMID 9792917.
  10. ^ a b c EntrezGene 8644 AKR1C3 aldo-keto reductase family 1 member C3 [ Homo sapiens (human) ]
  11. ^ Theisen JG, Sundaram V, Filchak MS, Chorich LP, Sullivan ME, Knight J, et al. (December 2019). "The Use of Whole Exome Sequencing in a Cohort of Transgender Individuals to Identify Rare Genetic Variants". Scientific Reports. 9 (1): 20099. Bibcode:2019NatSR...920099T. doi:10.1038/s41598-019-53500-y. PMC 6934803. PMID 31882810. Table 4
  12. ^ Tian Y, Zhao L, Zhang H, Liu X, Zhao L, Zhao X, et al. (February 2014). "AKR1C3 overexpression may serve as a promising biomarker for prostate cancer progression". Diagnostic Pathology. 9 (1): 42. doi:10.1186/1746-1596-9-42. PMC 3939640. PMID 24571686.
  13. ^ Dufort I, Labrie F, Luu-The V (February 2001). "Human types 1 and 3 3 alpha-hydroxysteroid dehydrogenases: differential lability and tissue distribution". J Clin Endocrinol Metab. 86 (2): 841–6. doi:10.1210/jcem.86.2.7216. PMID 11158055. human types 1 and 3 3α-HSD, 20α-HSD, and type 5 17β-HSD were named AKR1C4, AKR1C2, AKR1C1, and AKR1C3, respectively
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Further reading

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