AKR1C3

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 PDB Ortholog search: PDBe RCSB List of PDB id codes 1RY0, 1RY8, 1S1P, 1S1R, 1S2A, 1S2C, 1XF0, 1ZQ5, 2F38, 2FGB, 3R43, 3R58, 3R6I, 3R7M, 3R8G, 3R8H, 3R94, 3UFY, 3UG8, 3UGR, 3UWE, 4DBS, 4DBU, 4DBW, 4DZ5, 4FA3, 4FAL, 4FAM, 4H7C, 4HMN, 4WDT, 4WDU, 4WDW, 4WDX, 4WRH, 4XVD, 4XVE, 4ZFC, 4YVX, 4YVV
Identifiers
Aliases	AKR1C3, DD3, DDX, HA1753, HAKRB, HAKRe, HSD17B5, PGFS, hluPGFS, aldo-keto reductase family 1, member C3, aldo-keto reductase family 1 member C3
External IDs	OMIM: 603966; MGI: 2145420; HomoloGene: 128661; GeneCards: AKR1C3; OMA:AKR1C3 - orthologs
EC number	1.3.1.20
Gene location (Human) Chr. Chromosome 10 (human)[1] Band 10p15.1 Start 5,035,354 bp[1] End 5,107,686 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13|13 A1 Start 4,182,614 bp[2] End 4,200,653 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in jejunal mucosa pancreatic ductal cell gallbladder duodenum mucosa of ileum right lobe of liver kidney tubule islet of Langerhans mucosa of transverse colon skin of hip Top expressed in skin of external ear lacrimal gland right kidney lip conjunctival fornix parotid gland proximal tubule gastrula human kidney decidua More reference expression data BioGPS More reference expression data
Gene ontology Molecular function delta4-3-oxosteroid 5beta-reductase activity prostaglandin-F synthase activity trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity alditol:NADP+ 1-oxidoreductase activity retinal dehydrogenase activity geranylgeranyl reductase activity indanol dehydrogenase activity aldo-keto reductase (NADP) activity dihydrotestosterone 17-beta-dehydrogenase activity phenanthrene 9,10-monooxygenase activity ketoreductase activity oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor testosterone dehydrogenase (NAD+) activity NAD-retinol dehydrogenase activity testosterone 17-beta-dehydrogenase (NADP+) activity oxidoreductase activity androsterone dehydrogenase activity 15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity ketosteroid monooxygenase activity NADP-retinol dehydrogenase activity prostaglandin D2 11-ketoreductase activity prostaglandin H2 endoperoxidase reductase activity alcohol dehydrogenase (NADP+) activity steroid dehydrogenase activity Cellular component cytoplasm cytosol intracellular anatomical structure extracellular exosome nucleus Biological process cellular response to calcium ion negative regulation of retinoic acid biosynthetic process prostaglandin metabolic process G protein-coupled receptor signaling pathway cellular response to jasmonic acid stimulus steroid metabolic process positive regulation of protein kinase B signaling male gonad development positive regulation of cell death daunorubicin metabolic process doxorubicin metabolic process response to nutrient regulation of retinoic acid receptor signaling pathway progesterone metabolic process cellular response to starvation regulation of testosterone biosynthetic process cellular response to cadmium ion cellular response to corticosteroid stimulus cyclooxygenase pathway keratinocyte differentiation retinal metabolic process retinoid metabolic process cellular response to reactive oxygen species farnesol catabolic process positive regulation of endothelial cell apoptotic process positive regulation of reactive oxygen species metabolic process cellular response to prostaglandin D stimulus positive regulation of cell population proliferation renal absorption testosterone biosynthetic process cellular response to prostaglandin stimulus retinol metabolic process macromolecule metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8644 105349 Ensembl ENSG00000196139 ENSMUSG00000021214 UniProt P42330 Q8K023 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 Mb Chr 13: 4.18 – 4.2 Mb PubMed search [3] [4]
Wikidata
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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.^[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

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

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

• 3α-Hydroxysteroid dehydrogenase