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TIGAR
Fructose-bisphosphatase hydrolyzing fructose-2,6-bisphosphate as well as fructose-1,6-bisphosphate. Acts as a negative regulator of glycolysis by lowering intracellular levels of fructose-2,6-bisphosphate in a p53/TP53-dependent manner, resulting in the pentose phosphate pathway (PPP) activation and NADPH production. Contributes to the generation of reduced glutathione to cause a decrease in intracellular reactive oxygen species (ROS) content, correlating with its ability to protect cells from oxidative or metabolic stress-induced cell death. Plays a role in promoting protection against cell death during hypoxia by decreasing mitochondria ROS levels in a HK2-dependent manner through a mechanism that is independent of its fructose-bisphosphatase activity. In response to cardiac damage stress, mediates p53-induced inhibition of myocyte mitophagy through ROS levels reduction and the subsequent inactivation of BNIP3. Reduced mitophagy results in an enhanced apoptotic myocyte cell death, and exacerbates cardiac damage. Plays a role in adult intestinal regeneration; contributes to the growth, proliferation and survival of intestinal crypts following tissue ablation. Plays a neuroprotective role against ischemic brain damage by enhancing PPP flux and preserving mitochondria functions. Protects glioma cells from hypoxia- and ROS-induced cell death by inhibiting glycolysis and activating mitochondrial energy metabolism and oxygen consumption in a TKTL1-dependent and p53/TP53-independent manner. Plays a role in cancer cell survival by promoting DNA repair through activating PPP flux in a CDK5-ATM-dependent signaling pathway during hypoxia and/or genome stress-induced DNA damage responses. Involved in intestinal tumor progression. Belongs to the phosphoglycerate mutase family. Expressed in the brain (PubMed:22887998). Expressed in breast tumors (PubMed:21820150). Expressed in glioblastomas (PubMed:22887998). Note: This description may include information from UniProtKB.
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| Protein type: EC 3.1.3.46; Phosphatase (non-protein) |
| Chromosomal Location of mouse Ortholog: 6|6 F3 |
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Cellular Component:
cytoplasm; cytosol; mitochondrial outer membrane; mitochondrion; nucleus
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Molecular Function:
catalytic activity; fructose-2,6-bisphosphate 2-phosphatase activity; hydrolase activity
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Biological Process:
apoptotic process; autophagy; cardiac muscle cell apoptotic process; cellular response to cobalt ion; cellular response to hypoxia; DNA damage response; fructose 2,6-bisphosphate metabolic process; glucose catabolic process to lactate via pyruvate; glycolytic process; intestinal epithelial cell development; mitophagy; negative regulation of glucose catabolic process to lactate via pyruvate; negative regulation of glycolytic process; negative regulation of kinase activity; negative regulation of mitophagy; negative regulation of programmed cell death; negative regulation of reactive oxygen species metabolic process; positive regulation of cardiac muscle cell apoptotic process; positive regulation of DNA repair; positive regulation of hexokinase activity; positive regulation of pentose-phosphate shunt; reactive oxygen species metabolic process; regulation of pentose-phosphate shunt; regulation of response to DNA damage checkpoint signaling; response to gamma radiation; response to ischemia; response to xenobiotic stimulus
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Reference #:
Q8BZA9
(UniProtKB)
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Alt. Names/Synonyms: 9630033F20Rik; AA793651; AI595337; C79710; C85509; Fructose-2,6-bisphosphatase TIGAR; OTTMUSP00000028647; Probable fructose-2,6-bisphosphatase TIGAR; RIKEN cDNA 9630033F20 gene; Tigar; TP53-induced glycolysis and apoptosis regulator; TP53-induced glycolysis regulatory phosphatase; Trp53 induced glycolysis regulatory phosphatase; Trp53 induced glycolysis repulatory phosphatase
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Gene Symbols: Tigar
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Molecular weight:
29,191 Da
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Basal Isoelectric point:
8.45
Predict pI for various phosphorylation states
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CST Pathways:
Warburg Effect
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