AKR1C3

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)
End	5,107,686 bp
Gene location (Mouse)
Chr.	Chromosome 13 (mouse)
End	4,200,653 bp
RNA expression pattern
	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
	; ;
	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
	8644
	105349
	ENSG00000196139
	ENSMUSG00000021214
	P42330
	Q8K023
	NM_003739; NM_001253908; NM_001253909; NM_016253
	NM_134066; NM_001346535
	NP_001240837; NP_001240838; NP_003730
	NP_001333464; NP_598827
	Wikidata
View/Edit Human	View/Edit Mouse

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]

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

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000196139 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000021214 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ ^a ^b ^c EntrezGene 8644 AKR1C3 aldo-keto reductase family 1 member C3 [ Homo sapiens (human) ]
^ 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
^ 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.
^ 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