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Identification
HMDB Protein ID HMDBP00387
Secondary Accession Numbers
  • 5624
Name Aldo-keto reductase family 1 member C2
Synonyms
  1. 3-alpha-HSD3
  2. Chlordecone reductase homolog HAKRD
  3. DD-2
  4. DD/BABP
  5. DD2
  6. Dihydrodiol dehydrogenase 2
  7. Dihydrodiol dehydrogenase/bile acid-binding protein
  8. Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase
  9. Type III 3-alpha-hydroxysteroid dehydrogenase
Gene Name AKR1C2
Protein Type Unknown
Biological Properties
General Function Involved in oxidoreductase activity
Specific Function Works in concert with the 5-alpha/5-beta-steroid reductases to convert steroid hormones into the 3-alpha/5-alpha and 3-alpha/5-beta-tetrahydrosteroids. Catalyzes the inactivation of the most potent androgen 5-alpha-dihydrotestosterone (5-alpha-DHT) to 5-alpha-androstane-3-alpha,17-beta-diol (3-alpha-diol). Has a high bile-binding ability.
Pathways
  • Chemical carcinogenesis - DNA adducts
  • Metabolism of xenobiotics by cytochrome P450
  • Steroid hormone biosynthesis
Reactions
trans-1,2-Dihydrobenzene-1,2-diol + NADP → Pyrocatechol + NADPH details
A 3-alpha-hydroxysteroid + NAD(P)(+) → a 3-oxosteroid + NAD(P)H details
5alpha-Dihydrodeoxycorticosterone + NADPH + Hydrogen Ion → Tetrahydrodeoxycorticosterone + NADP details
5a-Pregnane-3,20-dione + NADPH + Hydrogen Ion → Allopregnanolone + NADP details
5alpha-Pregnan-20alpha-ol-3-one + NADPH + Hydrogen Ion → 5alpha-Pregnane-3alpha,20alpha-diol + NADP details
GO Classification
Biological Process
positive regulation of cell proliferation
prostaglandin metabolic process
daunorubicin metabolic process
digestion
doxorubicin metabolic process
cellular response to jasmonic acid stimulus
progesterone metabolic process
positive regulation of protein kinase B signaling cascade
response to prostaglandin stimulus
Cellular Component
cytoplasm
Function
catalytic activity
oxidoreductase activity
Molecular Function
alditol:NADP+ 1-oxidoreductase activity
bile acid binding
ketosteroid monooxygenase activity
oxidoreductase activity, acting on NADH or NADPH, quinone or similar compound as acceptor
phenanthrene 9,10-monooxygenase activity
trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
androsterone dehydrogenase (A-specific) activity
prostaglandin F receptor activity
Process
metabolic process
oxidation reduction
Cellular Location
  1. Cytoplasm (Potential)
Gene Properties
Chromosome Location 10
Locus 10p15-p14
SNPs AKR1C2
Gene Sequence
>972 bp
ATGGATTCGAAATACCAGTGTGTGAAGCTGAATGATGGTCACTTCATGCCTGTCCTGGGA
TTTGGCACCTATGCGCCTGCAGAGGTTCCTAAAAGTAAAGCTCTAGAGGCCGTCAAATTG
GCAATAGAAGCCGGGTTCCACCATATTGATTCTGCACATGTTTACAATAATGAGGAGCAG
GTTGGACTGGCCATCCGAAGCAAGATTGCAGATGGCAGTGTGAAGAGAGAAGACATATTC
TACACTTCAAAGCTTTGGAGCAATTCCCATCGACCAGAGTTGGTCCGACCAGCCTTGGAA
AGGTCACTGAAAAATCTTCAATTGGACTATGTTGACCTCTATCTTATTCATTTTCCAGTG
TCTGTAAAGCCAGGTGAGGAAGTGATCCCAAAAGATGAAAATGGAAAAATACTATTTGAC
ACAGTGGATCTCTGTGCCACATGGGAGGCCATGGAGAAGTGTAAAGATGCAGGATTGGCC
AAGTCCATCGGGGTGTCCAACTTCAACCACAGGCTGCTGGAGATGATCCTCAACAAGCCA
GGGCTCAAGTACAAGCCTGTCTGCAACCAGGTGGAATGTCATCCTTACTTCAACCAGAGA
AAACTGCTGGATTTCTGCAAGTCAAAAGACATTGTTCTGGTTGCCTATAGTGCTCTGGGA
TCCCATCGAGAAGAACCATGGGTGGACCCGAACTCCCCGGTGCTCTTGGAGGACCCAGTC
CTTTGTGCCTTGGCAAAAAAGCACAAGCGAACCCCAGCCCTGATTGCCCTGCGCTACCAG
CTGCAGCGTGGGGTTGTGGTCCTGGCCAAGAGCTACAATGAGCAGCGCATCAGACAGAAC
GTGCAGGTGTTTGAATTCCAGTTGACTTCAGAGGAGATGAAAGCCATAGATGGCCTAAAC
AGAAATGTGCGATATTTGACCCTTGATATTTTTGCTGGCCCCCCTAATTATCCATTTTCT
GATGAATATTAA
Protein Properties
Number of Residues 323
Molecular Weight 15747.91
Theoretical pI 8.148
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Aldo-keto reductase family 1 member C2
MDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEAVKLAIEAGFHHIDSAHVYNNEEQ
VGLAIRSKIADGSVKREDIFYTSKLWSNSHRPELVRPALERSLKNLQLDYVDLYLIHFPV
SVKPGEEVIPKDENGKILFDTVDLCATWEAMEKCKDAGLAKSIGVSNFNHRLLEMILNKP
GLKYKPVCNQVECHPYFNQRKLLDFCKSKDIVLVAYSALGSHREEPWVDPNSPVLLEDPV
LCALAKKHKRTPALIALRYQLQRGVVVLAKSYNEQRIRQNVQVFEFQLTSEEMKAIDGLN
RNVRYLTLDIFAGPPNYPFSDEY
GenBank ID Protein 4062863
UniProtKB/Swiss-Prot ID P52895
UniProtKB/Swiss-Prot Entry Name AK1C2_HUMAN
PDB IDs
GenBank Gene ID AB021654
GeneCard ID AKR1C2
GenAtlas ID AKR1C2
HGNC ID HGNC:385
References
General References
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  3. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
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  5. Qin KN, New MI, Cheng KC: Molecular cloning of multiple cDNAs encoding human enzymes structurally related to 3 alpha-hydroxysteroid dehydrogenase. J Steroid Biochem Mol Biol. 1993 Dec;46(6):673-9. [PubMed:8274401 ]
  6. Nishizawa M, Nakajima T, Yasuda K, Kanzaki H, Sasaguri Y, Watanabe K, Ito S: Close kinship of human 20alpha-hydroxysteroid dehydrogenase gene with three aldo-keto reductase genes. Genes Cells. 2000 Feb;5(2):111-25. [PubMed:10672042 ]
  7. Stolz A, Hammond L, Lou H, Takikawa H, Ronk M, Shively JE: cDNA cloning and expression of the human hepatic bile acid-binding protein. A member of the monomeric reductase gene family. J Biol Chem. 1993 May 15;268(14):10448-57. [PubMed:8486699 ]
  8. Hara A, Matsuura K, Tamada Y, Sato K, Miyabe Y, Deyashiki Y, Ishida N: Relationship of human liver dihydrodiol dehydrogenases to hepatic bile-acid-binding protein and an oxidoreductase of human colon cells. Biochem J. 1996 Jan 15;313 ( Pt 2):373-6. [PubMed:8573067 ]
  9. Ciaccio PJ, Tew KD: cDNA and deduced amino acid sequences of a human colon dihydrodiol dehydrogenase. Biochim Biophys Acta. 1994 Jun 28;1186(1-2):129-32. [PubMed:8011662 ]
  10. Qin KN, Khanna M, Cheng KC: Structure of a gene coding for human dihydrodiol dehydrogenase/bile acid-binding protein. Gene. 1994 Nov 18;149(2):357-61. [PubMed:7959017 ]
  11. Dufort I, Soucy P, Labrie F, Luu-The V: Molecular cloning of human type 3 3 alpha-hydroxysteroid dehydrogenase that differs from 20 alpha-hydroxysteroid dehydrogenase by seven amino acids. Biochem Biophys Res Commun. 1996 Nov 12;228(2):474-9. [PubMed:8920937 ]
  12. Shiraishi H, Ishikura S, Matsuura K, Deyashiki Y, Ninomiya M, Sakai S, Hara A: Sequence of the cDNA of a human dihydrodiol dehydrogenase isoform (AKR1C2) and tissue distribution of its mRNA. Biochem J. 1998 Sep 1;334 ( Pt 2):399-405. [PubMed:9716498 ]
  13. Jin Y, Stayrook SE, Albert RH, Palackal NT, Penning TM, Lewis M: Crystal structure of human type III 3alpha-hydroxysteroid dehydrogenase/bile acid binding protein complexed with NADP(+) and ursodeoxycholate. Biochemistry. 2001 Aug 28;40(34):10161-8. [PubMed:11513593 ]
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