Catalyzes the NADPH-dependent reduction of succinic semialdehyde to gamma-hydroxybutyrate. May have an important role in producing the neuromodulator gamma-hydroxybutyrate (GHB). Has broad substrate specificity. Has NADPH-dependent aldehyde reductase activity towards 2-carboxybenzaldehyde, 2-nitrobenzaldehyde and pyridine-2-aldehyde (in vitro). Can reduce 1,2-naphthoquinone and 9,10-phenanthrenequinone (in vitro). Can reduce the dialdehyde protein-binding form of aflatoxin B1 (AFB1) to the non-binding AFB1 dialcohol. May be involved in protection of liver against the toxic and carcinogenic effects of AFB1, a potent hepatocarcinogen. The protein encoded by this gene belongs to the aldo/keto reductase (AKR) superfamily and AKR7 family, which are involved in the detoxification of aldehydes and ketones. The AKR7 family consists of 3 genes that are present in a cluster on the p arm of chromosome 1. This protein, thought to be localized in the golgi, catalyzes the NADPH-dependent reduction of succinic semialdehyde to the endogenous neuromodulator, gamma-hydroxybutyrate. It may also function as a detoxication enzyme in the reduction of aflatoxin B1 and 2-carboxybenzaldehyde. Alternative splicing results in multiple transcript variants.
Background References
1. "Novel homodimeric and heterodimeric rat gamma-hydroxybutyrate synthases that associate with the Golgi apparatus define a distinct subclass of aldo-keto reductase 7 family proteins." Kelly V.P., Sherratt P.J., Crouch D.H., Hayes J.D. Biochem. J. 366:847-861(2002)
2. "Synthesis and catabolism of gamma-hydroxybutyrate in SH-SY5Y human neuroblastoma cells: role of the aldo-keto reductase AKR7A2." Lyon R.C., Johnston S.M., Watson D.G., McGarvie G., Ellis E.M. J. Biol. Chem. 282:25986-25992(2007)
3. "Genetic variation of aflatoxin B1 aldehyde reductase genes (AFAR) in human tumour cells." Praml C., Schulz W., Claas A., Mollenhauer J., Poustka A., Ackermann R., Schwab M., Henrich K.-O.Cancer Lett. 272:160-166(2008)
Sequence Similarity
Belongs to the aldo/keto reductase family. Aldo/keto reductase 2 subfamily.
Tissue Specificity
Detected in brain, liver, small intestine and testis, and at lower levels in heart, prostate, skeletal muscle and spleen. Detected in kidney proximal and distal tubules, endothelial cells lining the Bowman's capsules and some cysts. Detected at low levels in lung and pancreas (at protein level). Widely expressed.
Western blot analysis of AKR7A2 on different lysates with Rabbit anti-AKR7A2 antibody (R1408-3) at 1/1,000 dilution.
Lane 1: 293T cell lysate Lane 2: A431 cell lysate Lane 3: Jurkat cell lysate Lane 4: Mouse liver tissue lysate Lane 5: Rat liver tissue lysate Lane 6: Human liver tissue lysate
Predicted band size: 40 kDa Observed band size: 40 kDa
ICC staining AKR7A2 in Hela cells (green). Cells were fixed in paraformaldehyde, permeabilised with 0.25% Triton X100/PBS and counterstained with DAPI in order to highlight the nucleus (blue).
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