Canmetcon
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Identification
HMDB Protein ID HMDBP00088
Secondary Accession Numbers
  • 5320
  • HMDBP04365
Name Aldose reductase
Synonyms
  1. AR
  2. Aldehyde reductase
  3. Aldo-keto reductase family 1 member B1
Gene Name AKR1B1
Protein Type Unknown
Biological Properties
General Function Involved in oxidoreductase activity
Specific Function Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies.
Pathways
  • D-glyceric acidura
  • Dopa-responsive dystonia
  • Familial lipoprotein lipase deficiency
  • Fructose and Mannose Degradation
  • Fructose and mannose metabolism
  • Fructose intolerance, hereditary
  • Fructosuria
  • Galactose metabolism
  • Galactose Metabolism
  • Galactosemia
  • Glycerol Kinase Deficiency
  • Glycerolipid metabolism
  • Glycerolipid Metabolism
  • Hyperphenylalaniemia due to guanosine triphosphate cyclohydrolase deficiency
  • Hyperphenylalaninemia due to 6-pyruvoyltetrahydropterin synthase deficiency (ptps)
  • Hyperphenylalaninemia due to dhpr-deficiency
  • Leigh Syndrome
  • Pentose and glucuronate interconversions
  • Primary hyperoxaluria II, PH2
  • Pterine Biosynthesis
  • Pyruvate Decarboxylase E1 Component Deficiency (PDHE1 Deficiency)
  • Pyruvate Dehydrogenase Complex Deficiency
  • Pyruvate kinase deficiency
  • Pyruvate Metabolism
  • Pyruvate metabolism
  • Segawa syndrome
  • Sepiapterin reductase deficiency
Reactions
Glycerol + NAD(P)(+) → Glyceraldehyde + NAD(P)H details
Glycerol + NAD → Glyceraldehyde + NADH + Hydrogen Ion details
Glycerol + NADP → Glyceraldehyde + NADPH + Hydrogen Ion details
Beta-D-Galactose + NADH + Hydrogen Ion → Galactitol + NAD details
Beta-D-Galactose + NADPH + Hydrogen Ion → Galactitol + NADP details
D-Xylitol + NADP → D-Xylose + NADPH + Hydrogen Ion details
L-Arabitol + NAD → L-Arabinose + NADH + Hydrogen Ion details
L-Arabitol + NADP → L-Arabinose + NADPH + Hydrogen Ion details
Sorbitol + NADP → Alpha-D-Glucose + NADPH + Hydrogen Ion details
Lactaldehyde + NAD → Pyruvaldehyde + NADH + Hydrogen Ion details
Propylene glycol + NADP → Lactaldehyde + NADPH + Hydrogen Ion details
GO Classification
Biological Process
small molecule metabolic process
C21-steroid hormone biosynthetic process
response to stress
daunorubicin metabolic process
doxorubicin metabolic process
carbohydrate metabolic process
Cellular Component
cytosol
nucleus
extracellular space
Function
catalytic activity
oxidoreductase activity
Molecular Function
electron carrier activity
alditol:NADP+ 1-oxidoreductase activity
glyceraldehyde oxidoreductase activity
Process
metabolic process
oxidation reduction
Cellular Location
  1. Cytoplasm
Gene Properties
Chromosome Location 7
Locus 7q35
SNPs AKR1B1
Gene Sequence
>951 bp
ATGGCAAGCCGTCTCCTGCTCAACAACGGCGCCAAGATGCCCATCCTGGGGTTGGGTACC
TGGAAGTCCCCTCCAGGGCAGGTGACTGAGGCCGTGAAGGTGGCCATTGACGTCGGGTAC
CGCCACATCGACTGTGCCCATGTGTACCAGAATGAGAATGAGGTGGGGGTGGCCATTCAG
GAGAAGCTCAGGGAGCAGGTGGTGAAGCGTGAGGAGCTCTTCATCGTCAGCAAGCTGTGG
TGCACGTACCATGAGAAGGGCCTGGTGAAAGGAGCCTGCCAGAAGACACTCAGCGACCTG
AAGCTGGACTACCTGGACCTCTACCTTATTCACTGGCCGACTGGCTTTAAGCCTGGGAAG
GAATTTTTCCCATTGGATGAGTCGGGCAATGTGGTTCCCAGTGACACCAACATTCTGGAC
ACGTGGGCGGCCATGGAAGAGCTGGTGGATGAAGGGCTGGTGAAAGCTATTGGCATCTCC
AACTTCAACCATCTCCAGGTGGAGATGATCTTAAACAAACCTGGCTTGAAGTATAAGCCT
GCAGTTAACCAGATTGAGTGCCACCCATATCTCACTCAGGAGAAGTTAATCCAGTACTGC
CAGTCCAAAGGCATCGTGGTGACCGCCTACAGCCCCCTCGGCTCTCCTGACAGGCCCTGG
GCCAAGCCCGAGGACCCTTCTCTCCTGGAGGATCCCAGGATCAAGGCGATCGCAGCCAAG
CACAATAAAACTACAGCCCAGGTCCTGATCCGGTTCCCCATGCAGAGGAACTTGGTGGTG
ATCCCCAAGTCTGTGACACCAGAACGCATTGCTGAGAACTTTAAGGTCTTTGACTTTGAA
CTGAGCAGCCAGGATATGACCACCTTACTCAGCTACAACAGGAACTGGAGGGTCTGTGCC
TTGTTGAGCTGTACCTCCCACAAGGATTACCCCTTCCATGAAGAGTTTTGA
Protein Properties
Number of Residues 316
Molecular Weight 35853.125
Theoretical pI 6.982
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Aldose reductase
MASRLLLNNGAKMPILGLGTWKSPPGQVTEAVKVAIDVGYRHIDCAHVYQNENEVGVAIQ
EKLREQVVKREELFIVSKLWCTYHEKGLVKGACQKTLSDLKLDYLDLYLIHWPTGFKPGK
EFFPLDESGNVVPSDTNILDTWAAMEELVDEGLVKAIGISNFNHLQVEMILNKPGLKYKP
AVNQIECHPYLTQEKLIQYCQSKGIVVTAYSPLGSPDRPWAKPEDPSLLEDPRIKAIAAK
HNKTTAQVLIRFPMQRNLVVIPKSVTPERIAENFKVFDFELSSQDMTTLLSYNRNWRVCA
LLSCTSHKDYPFHEEF
GenBank ID Protein 2687578
UniProtKB/Swiss-Prot ID P15121
UniProtKB/Swiss-Prot Entry Name ALDR_HUMAN
PDB IDs
GenBank Gene ID AF032455
GeneCard ID AKR1B1
GenAtlas ID AKR1B1
HGNC ID HGNC:381
References
General References
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  5. 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 ]
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  7. 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 ]
  8. Chung S, LaMendola J: Cloning and sequence determination of human placental aldose reductase gene. J Biol Chem. 1989 Sep 5;264(25):14775-7. [PubMed:2504709 ]
  9. 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. [PubMed:2510130 ]
  10. 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. [PubMed:2111143 ]
  11. 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. [PubMed:2112546 ]
  12. 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. [PubMed:1901857 ]
  13. 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. [PubMed:9195951 ]
  14. 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. [PubMed:14996095 ]
  15. 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. [PubMed:8435445 ]
  16. 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. [PubMed:2492527 ]
  17. 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. [PubMed:8343525 ]
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  19. 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. [PubMed:8245005 ]
  20. 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. [PubMed:1621098 ]
  21. 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. [PubMed:1447221 ]
  22. 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. [PubMed:8234324 ]
  23. 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. [PubMed:9405046 ]
  24. 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. [PubMed:15272156 ]
  25. 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. [PubMed:15146478 ]
  26. 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. [PubMed:16337231 ]
  27. 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. [PubMed:17505104 ]
  28. 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. [PubMed:17418233 ]
  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. [PubMed:17368668 ]