Aldo-keto reductase family 1 member C4

Details

Name
Aldo-keto reductase family 1 member C4
Synonyms
  • 1.1.1.-
  • 3-alpha-HSD1
  • 3-alpha-hydroxysteroid dehydrogenase type I
  • CDR
  • CHDR
  • Chlordecone reductase
  • DD-4
  • DD4
  • Dihydrodiol dehydrogenase 4
  • HAKRA
Gene Name
AKR1C4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0037019|Aldo-keto reductase family 1 member C4
MDPKYQRVELNDGHFMPVLGFGTYAPPEVPRNRAVEVTKLAIEAGFRHIDSAYLYNNEEQ
VGLAIRSKIADGSVKREDIFYTSKLWCTFFQPQMVQPALESSLKKLQLDYVDLYLLHFPM
ALKPGETPLPKDENGKVIFDTVDLSATWEVMEKCKDAGLAKSIGVSNFNCRQLEMILNKP
GLKYKPVCNQVECHPYLNQSKLLDFCKSKDIVLVAHSALGTQRHKLWVDPNSPVLLEDPV
LCALAKKHKQTPALIALRYQLQRGVVVLAKSYNEQRIRENIQVFEFQLTSEDMKVLDGLN
RNYRYVVMDFLMDHPDYPFSDEY
Number of residues
323
Molecular Weight
37066.52
Theoretical pI
7.19
GO Classification
Functions
aldo-keto reductase (NADP) activity / androsterone dehydrogenase activity / bile acid transmembrane transporter activity / chlordecone reductase activity / electron carrier activity / oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor / retinal dehydrogenase activity
Processes
androgen metabolic process / bile acid and bile salt transport / bile acid biosynthetic process / bile acid metabolic process / cellular response to jasmonic acid stimulus / daunorubicin metabolic process / doxorubicin metabolic process / phototransduction, visible light / retinoid metabolic process / small molecule metabolic process / steroid metabolic process
Components
cytoplasm / cytosol / extracellular exosome
General Function
Retinal dehydrogenase activity
Specific Function
Catalyzes the transformation of the potent androgen dihydrotestosterone (DHT) into the less active form, 5-alpha-androstan-3-alpha,17-beta-diol (3-alpha-diol). Also has some 20-alpha-hydroxysteroid dehydrogenase activity. The biotransformation of the pesticide chlordecone (kepone) to its corresponding alcohol leads to increased biliary excretion of the pesticide and concomitant reduction of its neurotoxicity since bile is the major excretory route.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0016094|Aldo-keto reductase family 1 member C4 (AKR1C4)
ATGGATCCCAAATATCAGCGTGTAGAGCTAAATGATGGTCACTTCATGCCCGTATTGGGA
TTTGGCACCTATGCACCTCCAGAGGTTCCGAGGAACAGAGCTGTAGAGGTCACCAAATTA
GCAATAGAAGCTGGCTTCCGCCATATTGATTCTGCTTATTTATACAATAATGAGGAGCAG
GTTGGACTGGCCATCCGAAGCAAGATTGCAGATGGCAGTGTGAAGAGAGAAGACATATTC
TACACTTCAAAGCTTTGGTGCACTTTCTTTCAACCACAGATGGTCCAACCAGCCTTGGAA
AGCTCACTGAAAAAACTTCAACTGGACTATGTTGACCTCTATCTTCTTCATTTCCCAATG
GCTCTCAAGCCAGGTGAGACGCCACTACCAAAAGATGAAAATGGAAAAGTAATATTCGAC
ACAGTGGATCTCTCTGCCACATGGGAGGTCATGGAGAAGTGTAAGGATGCAGGATTGGCC
AAGTCCATCGGGGTGTCAAACTTCAACTGCAGGCAGCTGGAGATGATCCTCAACAAGCCA
GGACTCAAGTACAAGCCTGTCTGCAACCAGGTAGAATGTCATCCTTACCTCAACCAGAGC
AAACTGCTGGATTTCTGCAAGTCAAAAGACATTGTTCTGGTTGCCCACAGTGCTCTGGGA
ACCCAACGACATAAACTATGGGTGGACCCAAACTCCCCAGTTCTTTTGGAGGACCCAGTT
CTTTGTGCCTTAGCAAAGAAACACAAACGAACCCCAGCCCTGATTGCCCTGCGCTACCAG
CTGCAGCGTGGGGTTGTGGTCCTGGCCAAGAGCTACAATGAGCAGCGGATCAGAGAGAAC
ATCCAGGTTTTTGAATTCCAGTTGACATCAGAGGATATGAAAGTTCTAGATGGTCTAAAC
AGAAATTATCGATATGTTGTCATGGATTTTCTTATGGACCATCCTGATTATCCATTTTCA
GATGAATATTAG
Chromosome Location
10
Locus
10p15-p14
External Identifiers
ResourceLink
UniProtKB IDP17516
UniProtKB Entry NameAK1C4_HUMAN
GenBank Protein ID4261710
GenBank Gene IDS68287
GenAtlas IDAKR1C4
HGNC IDHGNC:387
General References
  1. 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]
  2. Khanna M, Qin KN, Wang RW, Cheng KC: Substrate specificity, gene structure, and tissue-specific distribution of multiple human 3 alpha-hydroxysteroid dehydrogenases. J Biol Chem. 1995 Aug 25;270(34):20162-8. [PubMed:7650035]
  3. Khanna M, Qin KN, Cheng KC: Distribution of 3 alpha-hydroxysteroid dehydrogenase in rat brain and molecular cloning of multiple cDNAs encoding structurally related proteins in humans. J Steroid Biochem Mol Biol. 1995 Jun;53(1-6):41-6. [PubMed:7626489]
  4. Kume T, Iwasa H, Shiraishi H, Yokoi T, Nagashima K, Otsuka M, Terada T, Takagi T, Hara A, Kamataki T: Characterization of a novel variant (S145C/L311V) of 3alpha-hydroxysteroid/dihydrodiol dehydrogenase in human liver. Pharmacogenetics. 1999 Dec;9(6):763-71. [PubMed:10634139]
  5. 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]
  6. Dufort I, Labrie F, Luu-The V: Human types 1 and 3 3 alpha-hydroxysteroid dehydrogenases: differential lability and tissue distribution. J Clin Endocrinol Metab. 2001 Feb;86(2):841-6. [PubMed:11158055]
  7. Deloukas P, Earthrowl ME, Grafham DV, Rubenfield M, French L, Steward CA, Sims SK, Jones MC, Searle S, Scott C, Howe K, Hunt SE, Andrews TD, Gilbert JG, Swarbreck D, Ashurst JL, Taylor A, Battles J, Bird CP, Ainscough R, Almeida JP, Ashwell RI, Ambrose KD, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Bates K, Beasley H, Bray-Allen S, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Cahill P, Camire D, Carter NP, Chapman JC, Clark SY, Clarke G, Clee CM, Clegg S, Corby N, Coulson A, Dhami P, Dutta I, Dunn M, Faulkner L, Frankish A, Frankland JA, Garner P, Garnett J, Gribble S, Griffiths C, Grocock R, Gustafson E, Hammond S, Harley JL, Hart E, Heath PD, Ho TP, Hopkins B, Horne J, Howden PJ, Huckle E, Hynds C, Johnson C, Johnson D, Kana A, Kay M, Kimberley AM, Kershaw JK, Kokkinaki M, Laird GK, Lawlor S, Lee HM, Leongamornlert DA, Laird G, Lloyd C, Lloyd DM, Loveland J, Lovell J, McLaren S, McLay KE, McMurray A, Mashreghi-Mohammadi M, Matthews L, Milne S, Nickerson T, Nguyen M, Overton-Larty E, Palmer SA, Pearce AV, Peck AI, Pelan S, Phillimore B, Porter K, Rice CM, Rogosin A, Ross MT, Sarafidou T, Sehra HK, Shownkeen R, Skuce CD, Smith M, Standring L, Sycamore N, Tester J, Thorpe A, Torcasso W, Tracey A, Tromans A, Tsolas J, Wall M, Walsh J, Wang H, Weinstock K, West AP, Willey DL, Whitehead SL, Wilming L, Wray PW, Young L, Chen Y, Lovering RC, Moschonas NK, Siebert R, Fechtel K, Bentley D, Durbin R, Hubbard T, Doucette-Stamm L, Beck S, Smith DR, Rogers J: The DNA sequence and comparative analysis of human chromosome 10. Nature. 2004 May 27;429(6990):375-81. [PubMed:15164054]
  8. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  9. Winters CJ, Molowa DT, Guzelian PS: Isolation and characterization of cloned cDNAs encoding human liver chlordecone reductase. Biochemistry. 1990 Jan 30;29(4):1080-7. [PubMed:2187532]
  10. Deyashiki Y, Ogasawara A, Nakayama T, Nakanishi M, Miyabe Y, Sato K, Hara A: Molecular cloning of two human liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase isoenzymes that are identical with chlordecone reductase and bile-acid binder. Biochem J. 1994 Apr 15;299 ( Pt 2):545-52. [PubMed:8172617]
  11. Binstock JM, Iyer RB, Hamby CV, Fried VA, Schwartz IS, Weinstein BI, Southren AL: Human hepatic 3 alpha-hydroxysteroid dehydrogenase: possible identity with human hepatic chlordecone reductase. Biochem Biophys Res Commun. 1992 Sep 16;187(2):760-6. [PubMed:1530633]
  12. Fluck CE, Meyer-Boni M, Pandey AV, Kempna P, Miller WL, Schoenle EJ, Biason-Lauber A: Why boys will be boys: two pathways of fetal testicular androgen biosynthesis are needed for male sexual differentiation. Am J Hum Genet. 2011 Aug 12;89(2):201-18. doi: 10.1016/j.ajhg.2011.06.009. Epub 2011 Jul 28. [PubMed:21802064]
  13. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [PubMed:24275569]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00157NADHapproved, nutraceuticalunknownDetails
DB13751Glycyrrhizic acidapproved, experimentalnosubstrateDetails
DB00461NabumetoneapprovedunknownDetails