AKR1C3 (aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II))

Identity

Other names	DD3
	HA1753
	HAKRB
	HAKRe
	HSD17B5
	KIAA0119
	hluPGFS
HGNC	AKR1C3
Location	10p15.1
Location_base_pair	Starts at 5126568 and ends at 5139878 bp from pter ( according to hg18-Mar_2006).

DNA/RNA

Transcription

1170 bp mRNA; transcript has been detected in brain, lung, liver, small intestine, mammary gland, uterus, prostate, testis.

Protein

Description	323 amino acids, molecular weight 37 kDa.
Expression	Activated macrophage, malignant prostate epithelium, normal mammary epithelium, mature blood vessel.
Localisation	Mainly in cytoplasm.
Function	AKR1C3 metabolizes various androgen metabolites including 5a-dihydrotestosterone to 5a-androstane-3a,17b-diol, Delta4-androstene-3,17-dione to testosterone, androstanedione to 5a-dihydrotestosterone, androsterone to 5a-androstane-3a,17b-diol. AKR1C3 is also involved in estrogen metabolism converting estrone to 17b-estradiol as well as progesterone metabolism converting prostaglandin D2 to 9a,11b-prostaglandin F2a. AKR1C3 has the capability of regulating the trans-activation of various nuclear receptors including androgen receptor, estrogen receptor, and peroxisome proliferator activated receptor (PPARG) by regulating the ligand availability for the nuclear receptors.
Homology	A member of the of AKR1C family proteins; AKR1C1, AKR1C2, AKR1C3, AKR1C4 in human, and AKR1C9 in rat.

Mutations

Note	Mutation of AKR1C3 has not been identified.

Implicated in

Entity	Various cancers
Note	Elevated levels of AKR1C3 expression are implicated in leukemia cell differentiation, prostate cancer (in both androgen-dependent and androgen-independent prostate cancer), and endometrial cancer. Expression of AKR1C3 was detected in a patient with myelodysplastic syndrome (MDS, refractory anemia) with progression to acute myelogenous leukemia. Overexpression of AKR1C3 in a human promyelocytic leukemia cell line, HL-60, rendered cells more resistant to all-trans retinoic acid (ATRA) and 1a,25-dihydroxyvitamin D3 induced cell differentiation.
Entity	Prostate cancer
Disease	Immunohistochemical staining of human prostate tissues detected negative or low levels of AKR1C3 expression in normal prostate epithelial cells. Strong positive AKR1C3 immunoreactivity was demonstrated in primary and androgen-independent prostate cancers. Variable increases in AKR1C3 expression were also demonstrated in non-neoplastic changes in the prostate including chronic inflammation, atrophy, and urothelial cell metaplasia.
Entity	Endometrial cancer
Disease	Quantitative transcriptosome analysis using real-time polymerase chain reaction, AKR1C3 mRNA expression was shown to be elevated in endometrial cancer versus adjacent normal endometrium.
Entity	Breast tumor
Disease	Expression of AKR1C3 mRNA was reduced in breast tumor as compared to adjacent normal breast tissue. Immunohistochemstry revealed that the ductal epithelial cells and stromal cells of the breast express AKR1C3. In myoepithelial cells of the breast, immunoreactive AKR1C3 was absent in normal tissues, whereas strong AKR1C3 staining was apparent in cells surrounding the neoplastic epithelium of ductal carcinoma in situ.

External links

	Nomenclature
HGNC	AKR1C3   386
Entrez_Gene	AKR1C3  8644  aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II)
	Cards
Atlas	AKR1C3ID612ch10p15
GeneCards	AKR1C3
Ensembl	ENSG00000196139 [Gene_View]  AKR1C3 [Vega]
Genatlas	AKR1C3
	Genomic and cartography
GoldenPath	AKR1C3  -  10p15.1   chr10:5126568-5139878 +  10p15-p14   [Description]    (hg18-Mar_2006)
Ensembl	AKR1C3 - 10p15-p14 [CytoView]
NCBI	Mapview
OMIM	603966 Disease map [OMIM]
HomoloGene	AKR1C3
	Gene and transcription
Genbank	AB018580 [ ENTREZ ]
Genbank	AF149416 [ ENTREZ ]
Genbank	AK290365 [ ENTREZ ]
Genbank	AK296829 [ ENTREZ ]
Genbank	AK310940 [ ENTREZ ]
RefSeq	NM_003739 [ SRS ]    NM_003739 [ ENTREZ ]
RefSeq	AC_000053 [ SRS ]    AC_000053 [ ENTREZ ]
RefSeq	AC_000142 [ SRS ]    AC_000142 [ ENTREZ ]
RefSeq	NC_000010 [ SRS ]    NC_000010 [ ENTREZ ]
RefSeq	NT_077567 [ SRS ]    NT_077567 [ ENTREZ ]
RefSeq	NW_001837930 [ SRS ]    NW_001837930 [ ENTREZ ]
RefSeq	NW_924584 [ SRS ]    NW_924584 [ ENTREZ ]
CCDS	AKR1C3 CCDS - NCBI
AceView	AKR1C3 AceView - NCBI
Unigene	Hs.78183 [ SRS ]    Hs.78183 [ NCBI ]
Fast-db	720 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P42330 [ SRS]    P42330 [ EXPASY ]     P42330 [ INTERPRO ]     P42330 [ UNIPROT ] P42330 [ VarSplice FASTA ]
Prosite	PS00798 ALDOKETO_REDUCTASE_1 [ SRS ]    PS00798 ALDOKETO_REDUCTASE_1 [ Expasy ]
Prosite	PS00062 ALDOKETO_REDUCTASE_2 [ SRS ]    PS00062 ALDOKETO_REDUCTASE_2 [ Expasy ]
Prosite	PS00063 ALDOKETO_REDUCTASE_3 [ SRS ]    PS00063 ALDOKETO_REDUCTASE_3 [ Expasy ]
Interpro	IPR001395 Aldo/ket_red [ SRS ]    IPR001395 Aldo/ket_red [ EBI ]
CluSTr	P42330
Pfam	PF00248 Aldo_ket_red [ SRS ]    PF00248 Aldo_ket_red [ Sanger ]    pfam00248 [ NCBI-CDD ]
Prodom	PD000288 Aldo/ket_red[INRA-Toulouse]
Prodom	P42330 AK1C3_HUMAN [ Domain structure ]   P42330 AK1C3_HUMAN  [ sequences sharing at least 1 domain ]
Blocks	P42330
PDB	1RY0 [ SRS ]    1RY0 [ PdbSum ],   1RY0 [ IMB ]   1RY0 [ RSDB ]
PDB	1RY8 [ SRS ]    1RY8 [ PdbSum ],   1RY8 [ IMB ]   1RY8 [ RSDB ]
PDB	1S1P [ SRS ]    1S1P [ PdbSum ],   1S1P [ IMB ]   1S1P [ RSDB ]
PDB	1S1R [ SRS ]    1S1R [ PdbSum ],   1S1R [ IMB ]   1S1R [ RSDB ]
PDB	1S2A [ SRS ]    1S2A [ PdbSum ],   1S2A [ IMB ]   1S2A [ RSDB ]
PDB	1S2C [ SRS ]    1S2C [ PdbSum ],   1S2C [ IMB ]   1S2C [ RSDB ]
PDB	1XF0 [ SRS ]    1XF0 [ PdbSum ],   1XF0 [ IMB ]   1XF0 [ RSDB ]
PDB	1ZQ5 [ SRS ]    1ZQ5 [ PdbSum ],   1ZQ5 [ IMB ]   1ZQ5 [ RSDB ]
PDB	2F38 [ SRS ]    2F38 [ PdbSum ],   2F38 [ IMB ]   2F38 [ RSDB ]
PDB	2FGB [ SRS ]    2FGB [ PdbSum ],   2FGB [ IMB ]   2FGB [ RSDB ]
HPRD	04911
	Protein Interaction databases
DIP	P42330
IntAct	P42330
	Polymorphism : SNP, mutations, diseases
OMIM	603966    [ map ]
GENETests	603966
SNP	AKR1C3 [dbSNP-NCBI]
SNP	NM_003739 [SNP-NCI]
SNP	AKR1C3 [GeneSNPs - Utah]  AKR1C3] [HGBASE - SRS]
HAPMAP	AKR1C3 [HAPMAP]
HGMD	AKR1C3
Genetic Association	AKR1C3
CDC HuGE	AKR1C3
	General knowledge
Family Browser	AKR1C3 [UCSC Family Browser]
SOURCE	NM_003739
SMD	Hs.78183
SAGE	Hs.78183
Enzyme	1.-.-.- [ Enzyme-Expasy ]   1.-.-.- [ Enzyme-SRS ]   1.-.-.- [ IntEnz-EBI ]   1.-.-.- [ BRENDA ]   1.-.-.- [ KEGG ]
GO	aldo-keto reductase activity [Amigo]  aldo-keto reductase activity
GO	intracellular [Amigo]  intracellular
GO	cytoplasm [Amigo]  cytoplasm
GO	prostaglandin metabolic process [Amigo]  prostaglandin metabolic process
GO	oxidoreductase activity [Amigo]  oxidoreductase activity
GO	prostaglandin-F synthase activity [Amigo]  prostaglandin-F synthase activity
GO	3-alpha-hydroxysteroid dehydrogenase (A-specific) activity [Amigo]  3-alpha-hydroxysteroid dehydrogenase (A-specific) activity
GO	testosterone 17-beta-dehydrogenase (NADP+) activity [Amigo]  testosterone 17-beta-dehydrogenase (NADP+) activity
GO	trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity [Amigo]  trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
GO	testosterone 17-beta-dehydrogenase activity [Amigo]  testosterone 17-beta-dehydrogenase activity
GO	oxidation reduction [Amigo]  oxidation reduction
KEGG	Arachidonic acid metabolism
KEGG	Metabolism of xenobiotics by cytochrome P450
PubGene	AKR1C3
TreeFam	AKR1C3
CTD	8644 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	AKR1C3 Related clones (RZPD - Berlin)
	PubMed
PubMed	55 Pubmed reference(s) in Entrez

Bibliography

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.

Lin HK, Jez JM, Schlegel BP, Peehl DM, Pachter JA, Penning TM

Molecular endocrinology (Baltimore, Md.). 1997 ; 11 (13) : 1971-1984.

PMID 9415401

Localization of type 5 17beta-hydroxysteroid dehydrogenase, 3beta-hydroxysteroid dehydrogenase, and androgen receptor in the human prostate by in situ hybridization and immunocytochemistry.

El-Alfy M, Luu-The V, Huang XF, Berger L, Labrie F, Pelletier G

Endocrinology. 1999 ; 140 (3) : 1481-1491.

PMID 10067877

Immunoelectron microscopic localization of 3beta-hydroxysteroid dehydrogenase and type 5 17beta-hydroxysteroid dehydrogenase in the human prostate and mammary gland.

Pelletier G, Luu-The V, El-Alfy M, Li S, Labrie F

Journal of molecular endocrinology. 2001 ; 26 (1) : 11-19.

PMID 11174850

The aldo-keto reductase AKR1C3 is a novel suppressor of cell differentiation that provides a plausible target for the non-cyclooxygenase-dependent antineoplastic actions of nonsteroidal anti-inflammatory drugs.

Desmond JC, Mountford JC, Drayson MT, Walker EA, Hewison M, Ride JP, Luong QT, Hayden RE, Vanin EF, Bunce CM

Cancer research. 2003 ; 63 (2) : 505-512.

PMID 12543809

Selective loss of AKR1C1 and AKR1C2 in breast cancer and their potential effect on progesterone signaling.

Ji Q, Aoyama C, Nien YD, Liu PI, Chen PK, Chang L, Stanczyk FZ, Stolz A

Cancer research. 2004 ; 64 (20) : 7610-7617.

PMID 15492289

Expression of progesterone metabolizing enzyme genes (AKR1C1, AKR1C2, AKR1C3, SRD5A1, SRD5A2) is altered in human breast carcinoma.

Lewis MJ, Wiebe JP, Heathcote JG

BMC cancer. 2004 ; 4 : page 27.

PMID 15212687

In situ androgen producing enzymes in human prostate cancer.

Nakamura Y, Suzuki T, Nakabayashi M, Endoh M, Sakamoto K, Mikami Y, Moriya T, Ito A, Takahashi S, Yamada S, Arai Y, Sasano H

Endocrine-related cancer. 2005 ; 12 (1) : 101-107.

PMID 15788642

Paracrine-stimulated gene expression profile favors estradiol production in breast tumors.

Amin SA, Huang CC, Reierstad S, Lin Z, Arbieva Z, Wiley E, Saborian H, Haynes B, Cotterill H, Dowsett M, Bulun SE

Molecular and cellular endocrinology. 2006 ; 253 (1-2) : 44-55.

PMID 16735089

Increased expression of type 2 3alpha-hydroxysteroid dehydrogenase/type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3) and its relationship with androgen receptor in prostate carcinoma.

Fung KM, Samara EN, Wong C, Metwalli A, Krlin R, Bane B, Liu CZ, Yang JT, Pitha JV, Culkin DJ, Kropp BP, Penning TM, Lin HK

Endocrine-related cancer. 2006 ; 13 (1) : 169-180.

PMID 16601286

Transcriptosome and serum cytokine profiling of an atypical case of myelodysplastic syndrome with progression to acute myelogenous leukemia.

Mahadevan D, DiMento J, Croce KD, Riley C, George B, Fuchs D, Mathews T, Wilson C, Lobell M

American journal of hematology. 2006 ; 81 (10) : 779-786.

PMID 16838325

Aldo-keto reductase (AKR) 1C3: role in prostate disease and the development of specific inhibitors.

Penning TM, Steckelbroeck S, Bauman DR, Miller MW, Jin Y, Peehl DM, Fung KM, Lin HK

Molecular and cellular endocrinology. 2006 ; 248 (1-2) : 182-191.

PMID 16417966

AKR1C1 and AKR1C3 may determine progesterone and estrogen ratios in endometrial cancer.

Rizner TL, Smuc T, Rupreht R, Sinkovec J, Penning TM

Molecular and cellular endocrinology. 2006 ; 248 (1-2) : 126-135.

PMID 16338060

Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer.

Stanbrough M, Bubley GJ, Ross K, Golub TR, Rubin MA, Penning TM, Febbo PG, Balk SP

Cancer research. 2006 ; 66 (5) : 2815-2825.

PMID 16510604

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Contributor(s)

Written	11-2007	Hsueh Kung Lin
		Department of Urology, University of Oklahoma Health Sciences Center, 920 Stanton L Young Blvd, WP3150, Oklahoma City, Oklahoma 73104, USA

Citation

This paper should be referenced as such :

Lin HK . AKR1C3 (aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II)). Atlas Genet Cytogenet Oncol Haematol. November 2007 . URL : http://AtlasGeneticsOncology.org/Genes/AKR1C3ID612ch10p15.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Sat Dec 6 17:53:39 2008