AKR1C1

Available structures

Ortholog search: PDBe RCSB

List of PDB id codes
1MRQ, 3C3U, 3GUG, 3NTY, 4YVP

Identifiers

Aliases

AKR1C1, 2-ALPHA-HSD, 20-ALPHA-HSD, C9, DD1, DD1/DD2, DDH, DDH1, H-37, HAKRC, HBAB, MBAB, aldo-keto reductase family 1, member C1, aldo-keto reductase family 1 member C1

External IDs

OMIM: 600449 MGI: 1924587 HomoloGene: 134114 GeneCards: AKR1C1

EC number

1.1.1.112

Gene location (Human)

Chr.	Chromosome 10 (human)^[1]

Band	10p15.1	Start	4,963,253 bp^[1]
Band	10p15.1	End	4,983,283 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 13 (mouse)^[2]

Band	13\|13 A1	Start	4,624,074 bp^[2]
Band	13\|13 A1	End	4,636,540 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

islet of Langerhans

gastric mucosa

right lobe of liver

body of stomach

left coronary artery

ascending aorta

gallbladder

right lobe of thyroid gland

tibial nerve

minor salivary gland

Top expressed in

kidney

proximal tubule

morula

secondary oocyte

blastocyst

spermatid

adrenal gland

liver

jejunum

submandibular gland

More reference expression data

BioGPS


More reference expression data

Gene ontology
Molecular function	trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity alditol:NADP+ 1-oxidoreductase activity indanol dehydrogenase activity aldo-keto reductase (NADP) activity 17-alpha,20-alpha-dihydroxypregn-4-en-3-one dehydrogenase activity androsterone dehydrogenase (B-specific) activity phenanthrene 9,10-monooxygenase activity oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor bile acid binding protein binding carboxylic acid binding oxidoreductase activity ketosteroid monooxygenase activity alcohol dehydrogenase (NADP+) activity steroid dehydrogenase activity
Cellular component	cytoplasm cytosol extracellular exosome
Biological process	cellular response to jasmonic acid stimulus epithelial cell differentiation daunorubicin metabolic process doxorubicin metabolic process progesterone metabolic process bile acid metabolic process digestion retinal metabolic process retinoid metabolic process response to organophosphorus bile acid and bile salt transport intestinal cholesterol absorption xenobiotic metabolic process cholesterol homeostasis protein homooligomerization steroid metabolic process
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


1645


77337

Ensembl


ENSG00000187134


ENSMUSG00000021207

UniProt


Q04828


Q91WR5

RefSeq (mRNA)


NM_001353


NM_029901

RefSeq (protein)


NP_001344


NP_084177

Location (UCSC)

Chr 10: 4.96 – 4.98 Mb

Chr 13: 4.62 – 4.64 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Aldo-keto reductase family 1 member C1 also known as 20α-hydroxysteroid dehydrogenase, 3α-hydroxysteroid dehydrogenase, and dihydrodiol dehydrogenase 1/2 is an enzyme that in humans is encoded by the AKR1C1 gene.^[5]^[6]

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 progesterone to the inactive form 20-alpha-hydroxy-progesterone. This gene shares high sequence identity with three other gene members, and is clustered with those three genes at chromosome 10p15-p14.^[6]

References

External links

Ciaccio PJ, Jaiswal AK, Tew KD (Jun 1994). "Regulation of human dihydrodiol dehydrogenase by Michael acceptor xenobiotics". The Journal of Biological Chemistry. 269 (22): 15558–62. doi:10.1016/S0021-9258(17)40716-2. PMID 7515059.
Khanna M, Qin KN, Cheng KC (Jun 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. doi:10.1016/0960-0760(95)00019-V. PMID 7626489. S2CID 11316547.
Khanna M, Qin KN, Klisak I, Belkin S, Sparkes RS, Cheng KC (Jan 1995). "Localization of multiple human dihydrodiol dehydrogenase (DDH1 and DDH2) and chlordecone reductase (CHDR) genes in chromosome 10 by the polymerase chain reaction and fluorescence in situ hybridization". Genomics. 25 (2): 588–90. doi:10.1016/0888-7543(95)80066-U. PMID 7789999.
Lou H, Hammond L, Sharma V, Sparkes RS, Lusis AJ, Stolz A (Mar 1994). "Genomic organization and chromosomal localization of a novel human hepatic dihydrodiol dehydrogenase with high affinity bile acid binding". The Journal of Biological Chemistry. 269 (11): 8416–22. doi:10.1016/S0021-9258(17)37210-1. PMID 8132567.
Deyashiki Y, Ogasawara A, Nakayama T, Nakanishi M, Miyabe Y, Sato K, Hara A (Apr 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 (2): 545–52. doi:10.1042/bj2990545. PMC 1138306. PMID 8172617.
Qin KN, New MI, Cheng KC (Dec 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. doi:10.1016/0960-0760(93)90308-J. PMID 8274401. S2CID 36210133.
Stolz A, Hammond L, Lou H, Takikawa H, Ronk M, Shively JE (May 1993). "cDNA cloning and expression of the human hepatic bile acid-binding protein. A member of the monomeric reductase gene family". The Journal of Biological Chemistry. 268 (14): 10448–57. doi:10.1016/S0021-9258(18)82220-7. PMID 8486699.
Hara A, Matsuura K, Tamada Y, Sato K, Miyabe Y, Deyashiki Y, Ishida N (Jan 1996). "Relationship of human liver dihydrodiol dehydrogenases to hepatic bile-acid-binding protein and an oxidoreductase of human colon cells". The Biochemical Journal. 313 (2): 373–6. doi:10.1042/bj3130373. PMC 1216918. PMID 8573067.
O'connor T, Ireland LS, Harrison DJ, Hayes JD (Oct 1999). "Major differences exist in the function and tissue-specific expression of human aflatoxin B1 aldehyde reductase and the principal human aldo-keto reductase AKR1 family members". The Biochemical Journal. 343 (2): 487–504. doi:10.1042/bj3430487. PMC 1220579. PMID 10510318.
Nishizawa M, Nakajima T, Yasuda K, Kanzaki H, Sasaguri Y, Watanabe K, Ito S (Feb 2000). "Close kinship of human 20alpha-hydroxysteroid dehydrogenase gene with three aldo-keto reductase genes". Genes to Cells. 5 (2): 111–25. doi:10.1046/j.1365-2443.2000.00310.x. PMID 10672042. S2CID 25136637.
Zhang Y, Dufort I, Rheault P, Luu-The V (Oct 2000). "Characterization of a human 20alpha-hydroxysteroid dehydrogenase". Journal of Molecular Endocrinology. 25 (2): 221–8. doi:10.1677/jme.0.0250221. PMID 11013348.
Nahoum V, Gangloff A, Legrand P, Zhu DW, Cantin L, Zhorov BS, Luu-The V, Labrie F, Breton R, Lin SX (Nov 2001). "Structure of the human 3alpha-hydroxysteroid dehydrogenase type 3 in complex with testosterone and NADP at 1.25-A resolution". The Journal of Biological Chemistry. 276 (45): 42091–8. doi:10.1074/jbc.M105610200. PMID 11514561.
Chen CY, Hsu CP, Hsu NY, Shih CS, Lin TY, Chow KC (2002). "Expression of dihydrodiol dehydrogenase in the resected stage I non-small cell lung cancer". Oncology Reports. 9 (3): 515–9. doi:10.3892/or.9.3.515. PMID 11956619.
Yang MD, Wu CC, Chiou SH, Chiu CF, Lin TY, Chiang IP, Chow KC (2003). "Reduction of dihydrodiol dehydrogenase expression in resected hepatocellular carcinoma". Oncology Reports. 10 (2): 271–6. doi:10.3892/or.10.2.271. PMID 12579257.
Nakajima T, Yasuda K, Nishizawa M, Okada H, Yoshimura T, Ito S, Kanzaki H (Feb 2003). "Expression of 20alpha-hydroxysteroid dehydrogenase mRNA in human endometrium and decidua". Endocrine Journal. 50 (1): 105–11. doi:10.1507/endocrj.50.105. PMID 12733716.
Couture JF, Legrand P, Cantin L, Luu-The V, Labrie F, Breton R (Aug 2003). "Human 20alpha-hydroxysteroid dehydrogenase: crystallographic and site-directed mutagenesis studies lead to the identification of an alternative binding site for C21-steroids". Journal of Molecular Biology. 331 (3): 593–604. doi:10.1016/S0022-2836(03)00762-9. PMID 12899831.
Agapova OA, Yang P, Wang WH, Lane DA, Clark AF, Weinstein BI, Hernandez MR (Oct 2003). "Altered expression of 3 alpha-hydroxysteroid dehydrogenases in human glaucomatous optic nerve head astrocytes". Neurobiology of Disease. 14 (1): 63–73. doi:10.1016/S0969-9961(03)00101-3. PMID 13678667. S2CID 21159141.

PDB gallery

1ihi: Crystal Structure of Human Type III 3-alpha-Hydroxysteroid Dehydrogenase/Bile Acid Binding Protein (AKR1C2) Complexed with NADP+ and Ursodeoxycholate
1j96: Human 3alpha-HSD type 3 in Ternary Complex with NADP and Testosterone
1mrq: Crystal structure of human 20alpha-HSD in ternary complex with NADP and 20alpha-hydroxy-progesterone
1xjb: Crystal structure of human type 3 3alpha-hydroxysteroid dehydrogenase in complex with NADP(H), citrate and acetate molecules
2hdj: Crystal structure of human type 3 3alpha-hydroxysteroid dehydrogenase in complex with NADP(H)

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 Hydroxysteroid 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 t 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)

References

External links

Further reading