Aldo-keto reductase family 1 member A1

Details

Name
Aldo-keto reductase family 1 member A1
Kind
protein
Synonyms
  • 1.1.1.2
  • 1.1.1.372
  • 1.1.1.54
  • Alcohol dehydrogenase [NADP(+)]
  • Aldehyde reductase
  • ALDR1
  • ALR
  • Glucuronate reductase
  • Glucuronolactone reductase
  • S-nitroso-CoA reductase
  • ScorR
Gene Name
AKR1A1
UniProtKB Entry
P14550Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0017416|Aldo-keto reductase family 1 member A1
MAASCVLLHTGQKMPLIGLGTWKSEPGQVKAAVKYALSVGYRHIDCAAIYGNEPEIGEAL
KEDVGPGKAVPREELFVTSKLWNTKHHPEDVEPALRKTLADLQLEYLDLYLMHWPYAFER
GDNPFPKNADGTICYDSTHYKETWKALEALVAKGLVQALGLSNFNSRQIDDILSVASVRP
AVLQVECHPYLAQNELIAHCQARGLEVTAYSPLGSSDRAWRDPDEPVLLEEPVVLALAEK
YGRSPAQILLRWQVQRKVICIPKSITPSRILQNIKVFDFTFSPEEMKQLNALNKNWRYIV
PMLTVDGKRVPRDAGHPLYPFNDPY
Number of residues
325
Molecular Weight
36572.71
Theoretical pI
6.79
GO Classification
Functions
L-glucuronate reductase activity
Processes
aldehyde catabolic process / D-glucuronate catabolic process / glucuronate catabolic process to xylulose 5-phosphate / glutathione derivative biosynthetic process / L-ascorbic acid biosynthetic process
Components
apical plasma membrane / cytosol / extracellular exosome / extracellular space
General Function
Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols (PubMed:10510318, PubMed:30538128). Displays enzymatic activity towards endogenous metabolites such as aromatic and aliphatic aldehydes, ketones, monosaccharides and bile acids, with a preference for negatively charged substrates, such as glucuronate and succinic semialdehyde (PubMed:10510318, PubMed:30538128). Functions as a detoxifiying enzyme by reducing a range of toxic aldehydes (By similarity). Reduces methylglyoxal and 3-deoxyglucosone, which are present at elevated levels under hyperglycemic conditions and are cytotoxic (By similarity). Involved also in the detoxification of lipid-derived aldehydes like acrolein (By similarity). 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) (PubMed:11306097, PubMed:18276838). Also acts as an inhibitor of protein S-nitrosylation by mediating degradation of S-nitroso-coenzyme A (S-nitroso-CoA), a cofactor required to S-nitrosylate proteins (PubMed:30538128). S-nitroso-CoA reductase activity is involved in reprogramming intermediary metabolism in renal proximal tubules, notably by inhibiting protein S-nitrosylation of isoform 2 of PKM (PKM2) (By similarity). Also acts as a S-nitroso-glutathione reductase by catalyzing the NADPH-dependent reduction of S-nitrosoglutathione (PubMed:31649033). Displays no reductase activity towards retinoids (By similarity)
Specific Function
aldo-keto reductase (NADPH) activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm, cytosol
Gene sequence
>lcl|BSEQ0017417|Alcohol dehydrogenase [NADP(+)] (AKR1A1)
ATGGCGGCTTCCTGTGTTCTACTGCACACTGGGCAGAAGATGCCTCTGATTGGTCTGGGT
ACCTGGAAGAGTGAGCCTGGTCAGGTAAAAGCAGCTGTTAAGTATGCCCTTAGCGTAGGC
TACCGCCACATTGATTGTGCTGCTATCTACGGCAATGAGCCTGAGATTGGGGAGGCCCTG
AAGGAGGACGTGGGACCAGGCAAGGCGGTGCCTCGGGAGGAGCTGTTTGTGACATCCAAG
CTGTGGAACACCAAGCACCACCCCGAGGATGTGGAGCCTGCCCTCCGGAAGACTCTGGCT
GACCTCCAGCTGGAGTATCTGGACCTGTACCTGATGCACTGGCCTTATGCCTTTGAGCGG
GGAGACAACCCCTTCCCCAAGAATGCTGATGGGACTATATGCTACGACTCCACCCACTAC
AAGGAGACTTGGAAGGCTCTGGAGGCACTGGTGGCTAAGGGGCTGGTGCAGGCGCTGGGC
CTGTCCAACTTCAACAGTCGGCAGATTGATGACATACTCAGTGTGGCCTCCGTGCGTCCA
GCTGTCTTGCAGGTGGAATGCCACCCATACTTGGCTCAAAATGAGCTAATTGCCCACTGC
CAAGCACGTGGCCTGGAGGTAACTGCTTATAGCCCTTTGGGCTCCTCTGATCGTGCATGG
CGTGATCCTGATGAGCCTGTCCTGCTGGAGGAACCAGTAGTCCTGGCATTGGCTGAAAAG
TATGGCCGATCTCCAGCTCAGATCTTGCTCAGGTGGCAGGTCCAGCGGAAAGTGATCTGC
ATCCCCAAAAGTATCACTCCTTCTCGAATCCTTCAGAACATCAAGGTGTTTGACTTCACC
TTTAGCCCAGAAGAGATGAAGCAGCTAAATGCCCTGAACAAAAATTGGAGATATATTGTG
CCTATGCTTACGGTGGATGGGAAGAGAGTCCCAAGGGATGCAGGGCATCCTCTGTACCCC
TTTAATGACCCGTACTGA
Chromosome Location
1
Locus
1p34.1
External Identifiers
ResourceLink
UniProtKB IDP14550
UniProtKB Entry NameAK1A1_HUMAN
GenBank Protein ID178481
GenBank Gene IDJ04794
GeneCard IDAKR1A1
HGNC IDHGNC:380
PDB ID(s)2ALR
KEGG IDhsa:10327
NCBI Gene ID10327
General References
  1. 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. [Article]
  2. 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. [Article]
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Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Nicotinamide adenine dinucleotide phosphateexperimentalunknowntargetDetails
TolrestatwithdrawnunknowntargetDetails
NADHapproved, nutraceuticalunknownenzymesubstrateDetails
Doxorubicinapproved, investigationalnoenzymesubstrateDetails
EthanolapprovedunknownenzymesubstrateDetails
Copperapproved, investigationalunknowntargetDetails
Certolizumab pegolapprovednoenzymesubstrateDetails
SilodosinapprovedunknownenzymesubstrateDetails