GAPDH Active Protein

This gene encodes a member of the glyceraldehyde-3-phosphate dehydrogenase protein family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. The encoded protein was originally identified as a key glycolytic enzyme that converts D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate. Subsequent studies have assigned a variety of additional functions to the protein including nitrosylation of nuclear proteins, the regulation of mRNA stability, and acting as a transferrin receptor on the cell surface of macrophage. Alternative splicing results in multiple transcript variants. Many pseudogenes similar to this locus are found throughout the mouse genome. [provided by RefSeq, Jan 2014]

GAPDH: a multifunctional enzyme with both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities. A key glycolytic enzyme that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate. An important enzyme for energy metabolism, and the production of ATP and pyruvate through anaerobic glycolysis in the cytoplasm. Additionally, it participates in apoptosis, membrane trafficking, iron metabolism, nuclear activities and receptor mediated cell signaling. Its subcellular localization changes reflecting its multiple activities. Is cytosolic, but is also localized in the membrane, the nucleus, polysomes, the ER and the Golgi. Participates in transcription, RNA transport, DNA replication and apoptosis. S-nitrosylation on Cys-152 following apoptotic stimulates its interaction with SIAH2, which in turn moderates its translocation into the nucleus. Mediates cysteine S-nitrosylation of nuclear target proteins including SIRT1, HDAC2 and DNA-PK. Deregulated in lung cancer, renal cancer, breast cancer, gastric cancer, glioma, liver cancer, colorectal cancer, melanoma, prostatic cancer, pancreatic cancer and bladder cancer. Its increased expression and enzymatic activity is associated with cell proliferation and tumorigenesis, Oxidative stress impairs GAPDH catalytic activity and leads to cellular aging and apoptosis. In experimental animal models, injection of GAPDH antagonists induces apoptosis and blocks Hep3B tumor progression, suggesting a therapeutic potential of targeting GAPDH in human hepatocellular carcinoma

Protein type: Carbohydrate Metabolism - glycolysis and gluconeogenesis; EC 1.2.1.12; Oxidoreductase

Chromosomal Location of Human Ortholog: 6 F2|6 59.32 cM

Cellular Component: cytoplasm; cytosol; extracellular matrix; intracellular membrane-bound organelle; lipid particle; membrane; microtubule cytoskeleton; mitochondrion; myelin sheath; nuclear membrane; nucleus; plasma membrane; ribonucleoprotein complex; vesicle

Molecular Function: aspartic-type endopeptidase inhibitor activity; enzyme binding; glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) activity; identical protein binding; microtubule binding; protein binding

Biological Process: apoptosis; carbohydrate metabolic process; defense response to fungus; gluconeogenesis; glycolysis; killing by host of symbiont cells; killing of cells of another organism; microtubule cytoskeleton organization and biogenesis; multicellular organismal development; negative regulation of translation; neuron apoptosis; positive regulation by organism of apoptosis in other organism during symbiotic interaction; positive regulation of cytokine secretion; protein stabilization