Hmdb loader
Identification
HMDB Protein ID HMDBP00507
Secondary Accession Numbers
  • 5754
  • HMDBP04364
Name Alcohol dehydrogenase [NADP(+)]
Synonyms
  1. Aldehyde reductase
  2. Aldo-keto reductase family 1 member A1
Gene Name AKR1A1
Protein Type Enzyme
Biological Properties
General Function Involved in oxidoreductase activity
Specific Function Catalyzes the NADPH-dependent reduction of a variety of aromatic and aliphatic aldehydes to their corresponding alcohols. Catalyzes the reduction of mevaldate to mevalonic acid and of glyceraldehyde to glycerol. Has broad substrate specificity. In vitro substrates include succinic semialdehyde, 4-nitrobenzaldehyde, 1,2-naphthoquinone, methylglyoxal, and D-glucuronic acid. Plays a role in the activation of procarcinogens, such as polycyclic aromatic hydrocarbon trans-dihydrodiols, and in the metabolism of various xenobiotics and drugs, including the anthracyclines doxorubicin (DOX) and daunorubicin (DAUN).
Pathways
  • Doxorubicin Metabolism Pathway
  • Glycerolipid metabolism
  • Glycolysis / Gluconeogenesis
Reactions
An alcohol + NADP → an aldehyde + NADPH details
Ethanol + NADP → Acetaldehyde + NADPH + Hydrogen Ion details
Glycerol + NADP → Glyceraldehyde + NADPH + Hydrogen Ion details
6-Hydroxyhexanoic acid + NADP → Adipate semialdehyde + NADPH + Hydrogen Ion details
GO Classification
Biological Process
cellular aldehyde metabolic process
aldehyde catabolic process
D-glucuronate catabolic process
glucose metabolic process
L-ascorbic acid biosynthetic process
Cellular Component
cytosol
apical plasma membrane
Function
catalytic activity
oxidoreductase activity
Molecular Function
electron carrier activity
alditol:NADP+ 1-oxidoreductase activity
L-glucuronate reductase activity
Process
metabolic process
oxidation reduction
Cellular Location Not Available
Gene Properties
Chromosome Location 1
Locus 1p33-p32
SNPs AKR1A1
Gene Sequence
>978 bp
ATGGCGGCTTCCTGTGTTCTACTGCACACTGGGCAGAAGATGCCTCTGATTGGTCTGGGT
ACCTGGAAGAGTGAGCCTGGTCAGGTAAAAGCAGCTGTTAAGTATGCCCTTAGCGTAGGC
TACCGCCACATTGATTGTGCTGCTATCTACGGCAATGAGCCTGAGATTGGGGAGGCCCTG
AAGGAGGACGTGGGACCAGGCAAGGCGGTGCCTCGGGAGGAGCTGTTTGTGACATCCAAG
CTGTGGAACACCAAGCACCACCCCGAGGATGTGGAGCCTGCCCTCCGGAAGACTCTGGCT
GACCTCCAGCTGGAGTATCTGGACCTGTACCTGATGCACTGGCCTTATGCCTTTGAGCGG
GGAGACAACCCCTTCCCCAAGAATGCTGATGGGACTATATGCTACGACTCCACCCACTAC
AAGGAGACTTGGAAGGCTCTGGAGGCACTGGTGGCTAAGGGGCTGGTGCAGGCGCTGGGC
CTGTCCAACTTCAACAGTCGGCAGATTGATGACATACTCAGTGTGGCCTCCGTGCGTCCA
GCTGTCTTGCAGGTGGAATGCCACCCATACTTGGCTCAAAATGAGCTAATTGCCCACTGC
CAAGCACGTGGCTTGGAGGTAACTGCTTATAGCCCTTTGGGCTCCTCTGATCGTGCATGG
CGTGATCCTGATGAGCCTGTCCTGCTGGAGGAACCAGTAGTCCTGGCATTGGCTGAAAAG
TATGGCCGATCTCCAGCTCAGATCTTGCTCAGGTGGCAGGTCCAGCGGAAAGTGATCTGC
ATCCCCAAAAGTATCACTCCTTCTCGAATCCTTCAGAACATCAAGGTGTTTGACTTCACC
TTTAGCCCAGAAGAGATGAAGCAGCTAAATGCCCTGAACAAAAATTGGAGATATATTGTG
CCTATGCTTACGGTGGATGGGAAGAGAGTCCCAAGGGATGCAGGGCATCCTCTGTACCCC
TTTAATGACCCGTACTGA
Protein Properties
Number of Residues 325
Molecular Weight 36572.71
Theoretical pI 6.793
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Alcohol dehydrogenase [NADP+]
MAASCVLLHTGQKMPLIGLGTWKSEPGQVKAAVKYALSVGYRHIDCAAIYGNEPEIGEAL
KEDVGPGKAVPREELFVTSKLWNTKHHPEDVEPALRKTLADLQLEYLDLYLMHWPYAFER
GDNPFPKNADGTICYDSTHYKETWKALEALVAKGLVQALGLSNFNSRQIDDILSVASVRP
AVLQVECHPYLAQNELIAHCQARGLEVTAYSPLGSSDRAWRDPDEPVLLEEPVVLALAEK
YGRSPAQILLRWQVQRKVICIPKSITPSRILQNIKVFDFTFSPEEMKQLNALNKNWRYIV
PMLTVDGKRVPRDAGHPLYPFNDPY
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P14550
UniProtKB/Swiss-Prot Entry Name AK1A1_HUMAN
PDB IDs
GenBank Gene ID J04794
GeneCard ID AKR1A1
GenAtlas ID AKR1A1
HGNC ID HGNC:380
References
General References
  1. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  2. 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 ]
  3. Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E: The DNA sequence and biological annotation of human chromosome 1. Nature. 2006 May 18;441(7091):315-21. [PubMed:16710414 ]
  4. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330 ]
  5. Bohren KM, Bullock B, Wermuth B, Gabbay KH: The aldo-keto reductase superfamily. cDNAs and deduced amino acid sequences of human aldehyde and aldose reductases. J Biol Chem. 1989 Jun 5;264(16):9547-51. [PubMed:2498333 ]
  6. Fujii J, Hamaoka R, Matsumoto A, Fujii T, Yamaguchi Y, Egashira M, Miyoshi O, Niikawa N, Taniguchi N: The structural organization of the human aldehyde reductase gene, AKR1A1, and mapping to chromosome 1p33-->p32. Cytogenet Cell Genet. 1999;84(3-4):230-2. [PubMed:10393438 ]
  7. Barski OA, Gabbay KH, Bohren KM: Characterization of the human aldehyde reductase gene and promoter. Genomics. 1999 Sep 1;60(2):188-98. [PubMed:10486210 ]
  8. Wermuth B, Omar A, Forster A, di Francesco C, Wolf M, von Wartburg JP, Bullock B, Gabbay KH: Primary structure of aldehyde reductase from human liver. Prog Clin Biol Res. 1987;232:297-307. [PubMed:3615425 ]
  9. Barski OA, Gabbay KH, Grimshaw CE, Bohren KM: Mechanism of human aldehyde reductase: characterization of the active site pocket. Biochemistry. 1995 Sep 5;34(35):11264-75. [PubMed:7669785 ]
  10. O'connor T, Ireland LS, Harrison DJ, Hayes JD: 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. Biochem J. 1999 Oct 15;343 Pt 2:487-504. [PubMed:10510318 ]
  11. Palackal NT, Burczynski ME, Harvey RG, Penning TM: Metabolic activation of polycyclic aromatic hydrocarbon trans-dihydrodiols by ubiquitously expressed aldehyde reductase (AKR1A1). Chem Biol Interact. 2001 Jan 30;130-132(1-3):815-24. [PubMed:11306097 ]
  12. Bains OS, Takahashi RH, Pfeifer TA, Grigliatti TA, Reid RE, Riggs KW: Two allelic variants of aldo-keto reductase 1A1 exhibit reduced in vitro metabolism of daunorubicin. Drug Metab Dispos. 2008 May;36(5):904-10. doi: 10.1124/dmd.107.018895. Epub 2008 Feb 14. [PubMed:18276838 ]
  13. El-Kabbani O, Green NC, Lin G, Carson M, Narayana SV, Moore KM, Flynn TG, DeLucas LJ: Structures of human and porcine aldehyde reductase: an enzyme implicated in diabetic complications. Acta Crystallogr D Biol Crystallogr. 1994 Nov 1;50(Pt 6):859-68. [PubMed:15299353 ]