Aldo-keto reductase family 1 member C1

NameAldo-keto reductase family 1 member C1
Synonyms1.1.1.- 20-alpha-HSD 20-alpha-hydroxysteroid dehydrogenase Chlordecone reductase homolog HAKRC DD1/DD2 DDH DDH1 Dihydrodiol dehydrogenase 1/2 HBAB High-affinity hepatic bile acid-binding protein Indanol dehydrogenase Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase
Gene NameAKR1C1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0016017|Aldo-keto reductase family 1 member C1
MDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEATKLAIEAGFRHIDSAHLYNNEEQ
VGLAIRSKIADGSVKREDIFYTSKLWCNSHRPELVRPALERSLKNLQLDYVDLYLIHFPV
SVKPGEEVIPKDENGKILFDTVDLCATWEAVEKCKDAGLAKSIGVSNFNRRQLEMILNKP
GLKYKPVCNQVECHPYFNQRKLLDFCKSKDIVLVAYSALGSHREEPWVDPNSPVLLEDPV
LCALAKKHKRTPALIALRYQLQRGVVVLAKSYNEQRIRQNVQVFEFQLTSEEMKAIDGLN
RNVRYLTLDIFAGPPNYPFSDEY
Number of residues323
Molecular Weight36788.02
Theoretical pI7.99
GO Classification
Functions
    bile acid binding
aldo-keto reductase (NADP) activity
oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor
carboxylic acid binding
androsterone dehydrogenase (B-specific) activity
ketosteroid monooxygenase activity
indanol dehydrogenase activity
phenanthrene 9,10-monooxygenase activity
trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
17-alpha,20-alpha-dihydroxypregn-4-en-3-one dehydrogenase activity
alditol
Processes
    epithelial cell differentiation
bile acid metabolic process
progesterone metabolic process
bile acid and bile salt transport
intestinal cholesterol absorption
oxidation-reduction process
retinal metabolic process
phototransduction, visible light
cholesterol homeostasis
xenobiotic metabolic process
retinoid metabolic process
cellular response to jasmonic acid stimulus
digestion
protein homooligomerization
daunorubicin metabolic process
doxorubicin metabolic process
response to organophosphorus
Components
    extracellular exosome
cytosol
General FunctionTrans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
Specific FunctionConverts progesterone to its inactive form, 20-alpha-dihydroxyprogesterone (20-alpha-OHP). In the liver and intestine, may have a role in the transport of bile. May have a role in monitoring the intrahepatic bile acid concentration. Has a low bile-binding ability. May play a role in myelin formation.
Transmembrane Regions
GenBank Protein ID181549
UniProtKB IDQ04828
UniProtKB Entry NameAK1C1_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0016018|Aldo-keto reductase family 1 member C1 (AKR1C1)
ATGGATTCGAAATATCAGTGTGTGAAGCTGAATGATGGTCACTTCATGCCTGTCCTGGGA
TTTGGCACCTATGCGCCTGCAGAGGTTCCTAAAAGTAAAGCTTTAGAGGCCACCAAATTG
GCAATTGAAGCTGGCTTCCGCCATATTGATTCTGCTCATTTATACAATAATGAGGAGCAG
GTTGGACTGGCCATCCGAAGCAAGATTGCAGATGGCAGTGTGAAGAGAGAAGACATATTC
TACACTTCAAAGCTTTGGTGCAATTCCCATCGACCAGAGTTGGTCCGACCAGCCTTGGAA
AGGTCACTGAAAAATCTTCAATTGGATTATGTTGACCTCTACCTTATTCATTTTCCAGTG
TCTGTAAAGCCAGGTGAGGAAGTGATCCCAAAAGATGAAAATGGAAAAATACTATTTGAC
ACAGTGGATCTCTGTGCCACATGGGAGGCCGTGGAGAAGTGTAAAGATGCAGGATTGGCC
AAGTCCATCGGGGTGTCCAACTTCAACCGCAGGCAGCTGGAGATGATCCTCAACAAGCCA
GGGCTCAAGTACAAGCCTGTCTGCAACCAGGTGGAATGTCATCCTTACTTCAACCAGAGA
AAACTGCTGGATTTCTGCAAGTCAAAAGACATTGTTCTGGTTGCCTATAGTGCTCTGGGA
TCCCACCGAGAAGAACCATGGGTGGACCCGAACTCCCCGGTGCTCTTGGAGGACCCAGTC
CTTTGTGCCTTGGCAAAAAAGCACAAGCGAACCCCAGCCCTGATTGCCCTGCGCTACCAG
CTACAGCGTGGGGTTGTGGTCCTGGCCAAGAGCTACAATGAGCAGCGCATCAGACAGAAC
GTGCAGGTGTTTGAATTCCAGTTGACTTCAGAGGAGATGAAAGCCATAGATGGCCTAAAC
AGAAATGTGCGATATTTGACCCTTGATATTTTTGCTGGCCCCCCTAATTATCCATTTTCT
GATGAATATTAA
GenBank Gene IDM86609
GeneCard IDNone
GenAtlas IDAKR1C1
HGNC IDHGNC:384
Chromosome Location10
Locus10p15-p14
References
  1. 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.[15164054 ]
  2. 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.[8486699 ]
  3. Lou H, Hammond L, Sharma V, Sparkes RS, Lusis AJ, Stolz A: Genomic organization and chromosomal localization of a novel human hepatic dihydrodiol dehydrogenase with high affinity bile acid binding. J Biol Chem. 1994 Mar 18;269(11):8416-22.[8132567 ]
  4. Ciaccio PJ, Jaiswal AK, Tew KD: Regulation of human dihydrodiol dehydrogenase by Michael acceptor xenobiotics. J Biol Chem. 1994 Jun 3;269(22):15558-62.[7515059 ]
  5. 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.[7626489 ]
  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.[10672042 ]
  7. Zhang Y, Dufort I, Rheault P, Luu-The V: Characterization of a human 20alpha-hydroxysteroid dehydrogenase. J Mol Endocrinol. 2000 Oct;25(2):221-8.[11013348 ]
  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.[15489334 ]
  9. 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.[8274401 ]
  10. 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.[8573067 ]
  11. 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.[8172617 ]
  12. Couture JF, Legrand P, Cantin L, Luu-The V, Labrie F, Breton R: Human 20alpha-hydroxysteroid dehydrogenase: crystallographic and site-directed mutagenesis studies lead to the identification of an alternative binding site for C21-steroids. J Mol Biol. 2003 Aug 15;331(3):593-604.[12899831 ]
  13. El-Kabbani O, Dhagat U, Soda M, Endo S, Matsunaga T, Hara A: Probing the inhibitor selectivity pocket of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1) with X-ray crystallography and site-directed mutagenesis. Bioorg Med Chem Lett. 2011 Apr 15;21(8):2564-7. doi: 10.1016/j.bmcl.2011.01.076. Epub 2011 Jan 22.[21414777 ]

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