Aldose reductase


NameAldose reductase
Synonyms1.1.1.21 Aldehyde reductase Aldo-keto reductase family 1 member B1 ALDR1 AR
Gene NameAKR1B1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0016194|Aldose reductase
MASRLLLNNGAKMPILGLGTWKSPPGQVTEAVKVAIDVGYRHIDCAHVYQNENEVGVAIQ
EKLREQVVKREELFIVSKLWCTYHEKGLVKGACQKTLSDLKLDYLDLYLIHWPTGFKPGK
EFFPLDESGNVVPSDTNILDTWAAMEELVDEGLVKAIGISNFNHLQVEMILNKPGLKYKP
AVNQIECHPYLTQEKLIQYCQSKGIVVTAYSPLGSPDRPWAKPEDPSLLEDPRIKAIAAK
HNKTTAQVLIRFPMQRNLVVIPKSVTPERIAENFKVFDFELSSQDMTTLLSYNRNWRVCA
LLSCTSHKDYPFHEEF
Number of residues316
Molecular Weight35853.125
Theoretical pI6.99
GO Classification
Functions
    alditol
    glyceraldehyde oxidoreductase activity
    aldo-keto reductase (NADP) activity
    electron carrier activity
Processes
    response to water deprivation
    sorbitol biosynthetic process
    fructose metabolic process
    response to thyroid hormone
    stress-activated protein kinase signaling cascade
    carbohydrate metabolic process
    C21-steroid hormone biosynthetic process
    daunorubicin metabolic process
    steroid metabolic process
    doxorubicin metabolic process
    positive regulation of smooth muscle cell proliferation
    cellular response to methylglyoxal
    tissue homeostasis
    norepinephrine metabolic process
    response to stress
    cellular response to peptide
    cellular response to hydrogen peroxide
    positive regulation of JAK-STAT cascade
    inner medullary collecting duct development
    maternal process involved in female pregnancy
    small molecule metabolic process
    naphthalene metabolic process
    fructose biosynthetic process
Components
    cytosol
    extracellular exosome
    paranodal junction
    nucleoplasm
    mast cell granule
    cell projection cytoplasm
    perinuclear region of cytoplasm
    Schwann cell microvillus
    cytoplasm
    extracellular space
    Schmidt-Lanterman incisure
General FunctionGlyceraldehyde oxidoreductase activity
Specific FunctionCatalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies.
Transmembrane Regions
GenBank Protein ID178487
UniProtKB IDP15121
UniProtKB Entry NameALDR_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0016195|Aldose reductase (AKR1B1)
ATGGCAAGCCGTCTCCTGCTCAACAACGGCGCCAAGATGCCCATCCTGGGGTTGGGTACC
TGGAAGTCCCCTCCAGGGCAGGTGACTGAGGCCGTGAAGGTGGCCATTGACGTCGGGTAC
CGCCACATCGACTGTGCCCATGTGTACCAGAATGAGAATGAGGTGGGGGTGGCCATTCAG
GAGAAGCTCAGGGAGCAGGTGGTGAAGCGTGAGGAGCTCTTCATCGTCAGCAAGCTGTGG
TGCACGTACCATGAGAAGGGCCTGGTGAAAGGAGCCTGCCAGAAGACACTCAGCGACCTG
AAGCTGGACTACCTGGACCTCTACCTTATTCACTGGCCGACTGGCTTTAAGCCTGGGAAG
GAATTTTTCCCATTGGATGAGTCGGGCAATGTGGTTCCCAGTGACACCAACATTCTGGAC
ACGTGGGCGGCCATGGAAGAGCTGGTGGATGAAGGGCTGGTGAAAGCTATTGGCATCTCC
AACTTCAACCATCTCCAGGTGGAGATGATCTTAAACAAACCTGGCTTGAAGTATAAGCCT
GCAGTTAACCAGATTGAGTGCCACCCATATCTCACTCAGGAGAAGTTAATCCAGTACTGC
CAGTCCAAAGGCATCGTGGTGACCGCCTACAGCCCCCTCGGCTCTCCTGACAGGCCCTGG
GCCAAGCCCGAGGACCCTTCTCTCCTGGAGGATCCCAGGATCAAGGCGATCGCAGCCAAG
CACAATAAAACTACAGCCCAGGTCCTGATCCGGTTCCCCATGCAGAGGAACTTGGTGGTG
ATCCCCAAGTCTGTGACACCAGAACGCATTGCTGAGAACTTTAAGGTCTTTGACTTTGAA
CTGAGCAGCCAGGATATGACCACCTTACTCAGCTACAACAGGAACTGGAGGGTCTGTGCC
TTGTTGAGCTGTACCTCCCACAAGGATTACCCCTTCCATGAAGAGTTTTGA
GenBank Gene IDJ04795
GeneCard IDNone
GenAtlas IDAKR1B1
HGNC IDHGNC:381
Chromosome Location7
Locus7q35
References
  1. Borhani DW, Harter TM, Petrash JM: The crystal structure of the aldose reductase.NADPH binary complex. J Biol Chem. 1992 Dec 5;267(34):24841-7.[1447221 ]
  2. Wilson DK, Bohren KM, Gabbay KH, Quiocho FA: An unlikely sugar substrate site in the 1.65 A structure of the human aldose reductase holoenzyme implicated in diabetic complications. Science. 1992 Jul 3;257(5066):81-4.[1621098 ]
  3. 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.[2498333 ]
  4. Chung S, LaMendola J: Cloning and sequence determination of human placental aldose reductase gene. J Biol Chem. 1989 Sep 5;264(25):14775-7.[2504709 ]
  5. Graham A, Hedge PJ, Powell SJ, Riley J, Brown L, Gammack A, Carey F, Markham AF: Nucleotide sequence of cDNA for human aldose reductase. Nucleic Acids Res. 1989 Oct 25;17(20):8368.[2510130 ]
  6. Grundmann U, Bohn H, Obermeier R, Amann E: Cloning and prokaryotic expression of a biologically active human placental aldose reductase. DNA Cell Biol. 1990 Apr;9(3):149-57.[2111143 ]
  7. Nishimura C, Matsuura Y, Kokai Y, Akera T, Carper D, Morjana N, Lyons C, Flynn TG: Cloning and expression of human aldose reductase. J Biol Chem. 1990 Jun 15;265(17):9788-92.[2112546 ]
  8. Graham A, Brown L, Hedge PJ, Gammack AJ, Markham AF: Structure of the human aldose reductase gene. J Biol Chem. 1991 Apr 15;266(11):6872-7.[1901857 ]
  9. Ko BC, Ruepp B, Bohren KM, Gabbay KH, Chung SS: Identification and characterization of multiple osmotic response sequences in the human aldose reductase gene. J Biol Chem. 1997 Jun 27;272(26):16431-7.[9195951 ]
  10. Hartmann TB, Thiel D, Dummer R, Schadendorf D, Eichmuller S: SEREX identification of new tumour-associated antigens in cutaneous T-cell lymphoma. Br J Dermatol. 2004 Feb;150(2):252-8.[14996095 ]
  11. Howard EI, Sanishvili R, Cachau RE, Mitschler A, Chevrier B, Barth P, Lamour V, Van Zandt M, Sibley E, Bon C, Moras D, Schneider TR, Joachimiak A, Podjarny A: Ultrahigh resolution drug design I: details of interactions in human aldose reductase-inhibitor complex at 0.66 A. Proteins. 2004 Jun 1;55(4):792-804.[15146478 ]
  12. Steuber H, Zentgraf M, Podjarny A, Heine A, Klebe G: High-resolution crystal structure of aldose reductase complexed with the novel sulfonyl-pyridazinone inhibitor exhibiting an alternative active site anchoring group. J Mol Biol. 2006 Feb 10;356(1):45-56. Epub 2005 Nov 10.[16337231 ]
  13. Biadene M, Hazemann I, Cousido A, Ginell S, Joachimiak A, Sheldrick GM, Podjarny A, Schneider TR: The atomic resolution structure of human aldose reductase reveals that rearrangement of a bound ligand allows the opening of the safety-belt loop. Acta Crystallogr D Biol Crystallogr. 2007 Jun;63(Pt 6):665-72. Epub 2007 May 15.[17505104 ]
  14. Steuber H, Zentgraf M, La Motta C, Sartini S, Heine A, Klebe G: Evidence for a novel binding site conformer of aldose reductase in ligand-bound state. J Mol Biol. 2007 May 25;369(1):186-97. Epub 2007 Mar 15.[17418233 ]
  15. Scherer SW, Cheung J, MacDonald JR, Osborne LR, Nakabayashi K, Herbrick JA, Carson AR, Parker-Katiraee L, Skaug J, Khaja R, Zhang J, Hudek AK, Li M, Haddad M, Duggan GE, Fernandez BA, Kanematsu E, Gentles S, Christopoulos CC, Choufani S, Kwasnicka D, Zheng XH, Lai Z, Nusskern D, Zhang Q, Gu Z, Lu F, Zeesman S, Nowaczyk MJ, Teshima I, Chitayat D, Shuman C, Weksberg R, Zackai EH, Grebe TA, Cox SR, Kirkpatrick SJ, Rahman N, Friedman JM, Heng HH, Pelicci PG, Lo-Coco F, Belloni E, Shaffer LG, Pober B, Morton CC, Gusella JF, Bruns GA, Korf BR, Quade BJ, Ligon AH, Ferguson H, Higgins AW, Leach NT, Herrick SR, Lemyre E, Farra CG, Kim HG, Summers AM, Gripp KW, Roberts W, Szatmari P, Winsor EJ, Grzeschik KH, Teebi A, Minassian BA, Kere J, Armengol L, Pujana MA, Estivill X, Wilson MD, Koop BF, Tosi S, Moore GE, Boright AP, Zlotorynski E, Kerem B, Kroisel PM, Petek E, Oscier DG, Mould SJ, Dohner H, Dohner K, Rommens JM, Vincent JB, Venter JC, Li PW, Mural RJ, Adams MD, Tsui LC: Human chromosome 7: DNA sequence and biology. Science. 2003 May 2;300(5620):767-72. Epub 2003 Apr 10.[12690205 ]
  16. Ferraretto A, Negri A, Giuliani A, De Grada L, Fuhrman Conti AM, Ronchi S: Aldose reductase is involved in long-term adaptation of EUE cells to hyperosmotic stress. Biochim Biophys Acta. 1993 Feb 17;1175(3):283-8.[8435445 ]
  17. Morjana NA, Lyons C, Flynn TG: Aldose reductase from human psoas muscle. Affinity labeling of an active site lysine by pyridoxal 5'-phosphate and pyridoxal 5'-diphospho-5'-adenosine. J Biol Chem. 1989 Feb 15;264(5):2912-9.[2492527 ]
  18. Liu SQ, Bhatnagar A, Ansari NH, Srivastava SK: Identification of the reactive cysteine residue in human placenta aldose reductase. Biochim Biophys Acta. 1993 Aug 7;1164(3):268-72.[8343525 ]
  19. Jaquinod M, Potier N, Klarskov K, Reymann JM, Sorokine O, Kieffer S, Barth P, Andriantomanga V, Biellmann JF, Van Dorsselaer A: Sequence of pig lens aldose reductase and electrospray mass spectrometry of non-covalent and covalent complexes. Eur J Biochem. 1993 Dec 15;218(3):893-903.[8281941 ]
  20. Tarle I, Borhani DW, Wilson DK, Quiocho FA, Petrash JM: Probing the active site of human aldose reductase. Site-directed mutagenesis of Asp-43, Tyr-48, Lys-77, and His-110. J Biol Chem. 1993 Dec 5;268(34):25687-93.[8245005 ]
  21. 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.[19413330 ]
  22. 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.[19608861 ]
  23. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17.[21269460 ]
  24. Wilson DK, Tarle I, Petrash JM, Quiocho FA: Refined 1.8 A structure of human aldose reductase complexed with the potent inhibitor zopolrestat. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9847-51.[8234324 ]
  25. Harrison DH, Bohren KM, Petsko GA, Ringe D, Gabbay KH: The alrestatin double-decker: binding of two inhibitor molecules to human aldose reductase reveals a new specificity determinant. Biochemistry. 1997 Dec 23;36(51):16134-40.[9405046 ]
  26. Ruiz F, Hazemann I, Mitschler A, Joachimiak A, Schneider T, Karplus M, Podjarny A: The crystallographic structure of the aldose reductase-IDD552 complex shows direct proton donation from tyrosine 48. Acta Crystallogr D Biol Crystallogr. 2004 Aug;60(Pt 8):1347-54. Epub 2004 Jul 21.[15272156 ]
  27. 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.[14702039 ]
  28. 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 ]
  29. Steuber H, Heine A, Klebe G: Structural and thermodynamic study on aldose reductase: nitro-substituted inhibitors with strong enthalpic binding contribution. J Mol Biol. 2007 May 4;368(3):618-38. Epub 2006 Dec 15.[17368668 ]

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