Gp_dh_NGlyceraldehyde 3-phosphate dehydrogenase, NAD binding domain
|SMART accession number:||SM00846|
|Description:||GAPDH is a tetrameric NAD-binding enzyme involved in glycolysis and glyconeogenesis. N-terminal domain is a Rossmann NAD(P) binding fold.|
|Interpro abstract (IPR020828):|
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays an important role in glycolysis and gluconeogenesis [(PUBMED:2716055)] by reversibly catalysing the oxidation and phosphorylation of D-glyceraldehyde-3-phosphate to 1,3-diphospho-glycerate. The enzyme exists as a tetramer of identical subunits, each containing 2 conserved functional domains: an NAD-binding domain, and a highly conserved catalytic domain [(PUBMED:6303388)]. The enzyme has been found to bind to actin and tropomyosin, and may thus have a role in cytoskeleton assembly. Alternatively, the cytoskeleton may provide a framework for precise positioning of the glycolytic enzymes, thus permitting efficient passage of metabolites from enzyme to enzyme [(PUBMED:6303388)].
GAPDH displays diverse non-glycolytic functions as well, its role depending upon its subcellular location. For instance, the translocation of GAPDH to the nucleus acts as a signalling mechanism for programmed cell death, or apoptosis [(PUBMED:10740219)]. The accumulation of GAPDH within the nucleus is involved in the induction of apoptosis, where GAPDH functions in the activation of transcription. The presence of GAPDH is associated with the synthesis of pro-apoptotic proteins like BAX, c-JUN and GAPDH itself.
GAPDH has been implicated in certain neurological diseases: GAPDH is able to bind to the gene products from neurodegenerative disorders such as Huntington's disease, Alzheimer's disease, Parkinson's disease and Machado-Joseph disease through stretches encoded by their CAG repeats. Abnormal neuronal apoptosis is associated with these diseases. Propargylamines such as deprenyl increase neuronal survival by interfering with apoptosis signalling pathways via their binding to GAPDH, which decreases the synthesis of pro-apoptotic proteins [(PUBMED:12721812)].
This entry represents the N-terminal domain which is a Rossmann NAD(P) binding fold.
|GO process:||oxidation-reduction process (GO:0055114)|
|GO function:||oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor (GO:0016620)|
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