3α-Hydroxysteroid dehydrogenase

AKR1C4
	Gene ontology
Molecular function	retinal dehydrogenase activity; aldo-keto reductase (NADP) activity; bile acid transmembrane transporter activity; oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor; chlordecone reductase activity; electron transfer activity; oxidoreductase activity; androsterone dehydrogenase activity; alditol:NADP+ 1-oxidoreductase activity; alcohol dehydrogenase (NADP+) activity; steroid dehydrogenase activity; ketosteroid monooxygenase activity;
Cellular component	cytoplasm; cytosol; extracellular exosome;
Biological process	cellular response to jasmonic acid stimulus; steroid metabolic process; daunorubicin metabolic process; doxorubicin metabolic process; androgen metabolic process; retinoid metabolic process; bile acid and bile salt transport; bile acid biosynthetic process; electron transport chain; prostaglandin metabolic process; progesterone metabolic process;
	Sources:Amigo / QuickGO

endogenous neurosteroids allopregnanolone, THDOC, and 3α-androstanediol. It is also known to catalyze the reversible conversion of 3α-androstanediol (5α-androstane-3α,17β-diol) to dihydrotestosterone (DHT, 5α-androstan-17β-ol-3-one) and vice versa.^[11]

Function

This gene encodes a member of the

NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme catalyzes the bioreduction of chlordecone, a toxic organochlorine pesticide, to chlordecone alcohol in liver. This gene shares high sequence identity with three other gene members and is clustered with those three genes at 10p15-p14 on chromosome 10.^[10]

Clinical significance

Various

selective brain steroidogenic stimulants (SBSSs).^[12]^[13]^[14]

Isozymes of aldo-keto reductase family 1 member C


HGNC Gene Symbol	Enzyme Name Aliases^[15]
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: ENSG00000198610 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000021210 – 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.
PMID 31610224
.

PMID 17996986
.

PMID 29928928
.

S2CID 257943362. This article incorporates text from this source, which is available under the CC BY 4.0
license.

PMID 7789999
.

^ ^a ^b EntrezGene 1109 AKR1C4 aldo-keto reductase family 1 member C4 [ Homo sapiens (human) ]

PMID 12810547
.

PMID 10557352
.

PMID 20716970
.

S2CID 21473462
.

PMID 11158055
. human types 1 and 3 3α-HSD, 20α-HSD, and type 5 17β-HSD were named AKR1C4, AKR1C2, AKR1C1, and AKR1C3, respectively

External links

Human AKR1C4 genome location and AKR1C4 gene details page in the UCSC Genome Browser.

Further reading

Binstock JM, Iyer RB, Hamby CV, Fried VA, Schwartz IS, Weinstein BI, Southren AL (September 1992). "Human hepatic 3 alpha-hydroxysteroid dehydrogenase: possible identity with human hepatic chlordecone reductase". Biochemical and Biophysical Research Communications. 187 (2): 760–6.
PMID 1530633
.

Winters CJ, Molowa DT, Guzelian PS (January 1990). "Isolation and characterization of cloned cDNAs encoding human liver chlordecone reductase". Biochemistry. 29 (4): 1080–7.
PMID 2187532
.

Khanna M, Qin KN, Cheng KC (June 1995). "Distribution of 3 alpha-hydroxysteroid dehydrogenase in rat brain and molecular cloning of multiple cDNAs encoding structurally related proteins in humans". The Journal of Steroid Biochemistry and Molecular Biology. 53 (1–6): 41–6.
S2CID 11316547
.

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): 20162–8.
PMID 7650035
.

Deyashiki Y, Ogasawara A, Nakayama T, Nakanishi M, Miyabe Y, Sato K, Hara A (April 1994). "Molecular cloning of two human liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase isoenzymes that are identical with chlordecone reductase and bile-acid binder". The Biochemical Journal. 299 ( Pt 2) (2): 545–52.
PMID 8172617
.

Qin KN, New MI, Cheng KC (December 1993). "Molecular cloning of multiple cDNAs encoding human enzymes structurally related to 3 alpha-hydroxysteroid dehydrogenase". The Journal of Steroid Biochemistry and Molecular Biology. 46 (6): 673–9.
S2CID 36210133
.

Kume T, Iwasa H, Shiraishi H, Yokoi T, Nagashima K, Otsuka M, Terada T, Takagi T, Hara A, Kamataki T (December 1999). "Characterization of a novel variant (S145C/L311V) of 3alpha-hydroxysteroid/dihydrodiol dehydrogenase in human liver". Pharmacogenetics. 9 (6): 763–71.
PMID 10634139
.

Nishizawa M, Nakajima T, Yasuda K, Kanzaki H, Sasaguri Y, Watanabe K, Ito S (February 2000). "Close kinship of human 20alpha-hydroxysteroid dehydrogenase gene with three aldo-keto reductase genes". Genes to Cells. 5 (2): 111–25.
S2CID 25136637
.

Dufort I, Labrie F, Luu-The V (February 2001). "Human types 1 and 3 3 alpha-hydroxysteroid dehydrogenases: differential lability and tissue distribution". The Journal of Clinical Endocrinology and Metabolism. 86 (2): 841–6.
PMID 11158055
.

Ozeki T, Takahashi Y, Kume T, Nakayama K, Yokoi T, Nunoya K, Hara A, Kamataki T (April 2001). "Co-operative regulation of the transcription of human dihydrodiol dehydrogenase (DD)4/aldo-keto reductase (AKR)1C4 gene by hepatocyte nuclear factor (HNF)-4alpha/gamma and HNF-1alpha". The Biochemical Journal. 355 (Pt 2): 537–44.
PMID 11284743
.

Ozeki T, Takahashi Y, Nakayama K, Kamataki T (September 2002). "Hepatocyte nuclear factor (HNF)-4 alpha/gamma, HNF-1 alpha, and vHNF-1 regulate the cell-specific expression of the human dihydrodiol dehydrogenase (DD)4/AKR1C4 gene". Archives of Biochemistry and Biophysics. 405 (2): 185–90.
PMID 12220531
.

Ozeki T, Takahashi Y, Nakayama K, Funayama M, Nagashima K, Kodama T, Kamataki T (January 2003). "Hepatocyte nuclear factor-4 alpha/gamma and hepatocyte nuclear factor-1 alpha as causal factors of interindividual difference in the expression of human dihydrodiol dehydrogenase 4 mRNA in human livers". Pharmacogenetics. 13 (1): 49–53.
PMID 12544512
.

Schüle C, Romeo E, Uzunov DP, Eser D, di Michele F, Baghai TC, Pasini A, Schwarz M, Kempter H, Rupprecht R (March 2006). "Influence of mirtazapine on plasma concentrations of neuroactive steroids in major depression and on 3alpha-hydroxysteroid dehydrogenase activity". Molecular Psychiatry. 11 (3): 261–72.
S2CID 21473462
.

v
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e
PDB gallery

2fvl: Crystal structure of human 3-alpha hydroxysteroid/dihydrodiol dehydrogenase (AKR1C4) complexed with NADP+

v
t
e
Oxidoreductases: alcohol oxidoreductases (EC 1.1)
1.1.1: NAD/NADP acceptor

3-hydroxyacyl-CoA dehydrogenase

3-hydroxybutyryl-CoA dehydrogenase

Alcohol dehydrogenase

Aldo-keto reductase
1A1

1B1

1B10

1C1

1C3

1C4

7A2

Aldose reductase

Beta-Ketoacyl ACP reductase

Carbohydrate dehydrogenases

Carnitine dehydrogenase

D-malate dehydrogenase (decarboxylating)

DXP reductoisomerase

Glucose-6-phosphate dehydrogenase

Glycerol-3-phosphate dehydrogenase

HMG-CoA reductase

IMP dehydrogenase

Isocitrate dehydrogenase

Lactate dehydrogenase

L-threonine dehydrogenase

L-xylulose reductase

Malate dehydrogenase

Malate dehydrogenase (decarboxylating)

Malate dehydrogenase (NADP+)

Malate dehydrogenase (oxaloacetate-decarboxylating)

Malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+)

Phosphogluconate dehydrogenase

Sorbitol dehydrogenase

3β

3β-HSD

NSDHL

11β

11β-HSD1

11β-HSD2

17β

1.1.2: cytochrome acceptor

D-lactate dehydrogenase (cytochrome)

D-lactate dehydrogenase (cytochrome c-553)

Mannitol dehydrogenase (cytochrome)

1.1.3: oxygen acceptor

Glucose oxidase

L-gulonolactone oxidase

Xanthine oxidase

Alcohol oxidase

1.1.4: disulfide as acceptor

Vitamin K epoxide reductase

Vitamin-K-epoxide reductase (warfarin-insensitive)

1.1.5: quinone/similar acceptor

Malate dehydrogenase (quinone)

Quinoprotein glucose dehydrogenase

1.1.99: other acceptors

Choline dehydrogenase

L2HGDH

v
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e
Enzymes
Activity

Active site

Binding site

Catalytic triad

Oxyanion hole

Enzyme promiscuity

Diffusion-limited enzyme

Cofactor

Enzyme catalysis

Regulation

Allosteric regulation

Cooperativity

Enzyme inhibitor

Enzyme activator

Classification

EC number

Enzyme superfamily

Enzyme family

List of enzymes

Kinetics

Enzyme kinetics

Eadie–Hofstee diagram

Hanes–Woolf plot

Lineweaver–Burk plot

Michaelis–Menten kinetics

Types

EC1 Oxidoreductases (list)

EC2 Transferases (list)

EC3 Hydrolases (list)

EC4 Lyases (list)

EC5 Isomerases (list)

EC6 Ligases (list)

EC7 Translocases (list)

Portal:
Biology

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000198610 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000021210 – Ensembl, 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] PMID 31610224
.

[6] PMID 17996986
.

[7] PMID 29928928
.

[wj-8] S2CID 257943362. This article incorporates text from this source, which is available under the CC BY 4.0
license.

[pmid7789999-9] PMID 7789999
.

[entrez-10] EntrezGene 1109 AKR1C4 aldo-keto reductase family 1 member C4 [ Homo sapiens (human) ]

[pmid12810547-11] PMID 12810547
.

[pmid10557352-12] PMID 10557352
.

[pmid20716970-13] PMID 20716970
.

[pmid16344854-14] S2CID 21473462
.

[pmid11158055-15] PMID 11158055
. human types 1 and 3 3α-HSD, 20α-HSD, and type 5 17β-HSD were named AKR1C4, AKR1C2, AKR1C1, and AKR1C3, respectively

[11]

[10]

[12]

[13]

[14]

[15]

Function

Clinical significance

Isozymes of aldo-keto reductase family 1 member C

See also

References

External links

Further reading