TIGAR

This gene is regulated as part of the p53 tumor suppressor pathway and encodes a protein with sequence similarity to the bisphosphate domain of the glycolytic enzyme that degrades fructose-2,6-bisphosphate. The protein functions by blocking glycolysis and directing the pathway into the pentose phosphate shunt. Expression of this protein also protects cells from DNA damaging reactive oxygen species and provides some protection from DNA damage-induced apoptosis. The 12p13.32 region that includes this gene is paralogous to the 11q13.3 region. [provided by RefSeq, Jul 2008]

TIGAR Gene(Protein Coding) TP53 Induced Glycolysis Regulatory Phosphatase

Fructose-bisphosphatase hydrolyzing fructose-2,6-bisphosphate as well as fructose-1,6-bisphosphate (PubMed:19015259).
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 (PubMed:16839880, PubMed:22887998).
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 (PubMed:16839880, PubMed:19713938, PubMed:23726973, PubMed:22887998, PubMed:23817040).
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 (PubMed:23185017).
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 (By similarity).
Plays a role in adult intestinal regeneration; contributes to the growth, proliferation and survival of intestinal crypts following tissue ablation (PubMed:23726973).
Plays a neuroprotective role against ischemic brain damage by enhancing PPP flux and preserving mitochondria functions (By similarity).
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 (PubMed:22887998).
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 (PubMed:25928429).
Involved in intestinal tumor progression (PubMed:23726973).

Biological Process cardiac muscle cell apoptotic processSource:Ensembl
Biological Process cellular response to cobalt ionSource:UniProtKB1 Publication
Biological Process cellular response to DNA damage stimulusSource:UniProtKB1 Publication
Biological Process cellular response to hypoxiaSource:UniProtKB1 Publication
Biological Process fructose 1,6-bisphosphate metabolic processSource:UniProtKB1 Publication
Biological Process fructose 2,6-bisphosphate metabolic processSource:UniProtKB1 Publication
Biological Process glucose catabolic process to lactate via pyruvateSource:Ensembl
Biological Process glycolytic processSource:Ensembl
Biological Process intestinal epithelial cell developmentSource:Ensembl
Biological Process mitophagySource:Ensembl
Biological Process negative regulation of glucose catabolic process to lactate via pyruvateSource:Ensembl
Biological Process negative regulation of glycolytic processSource:GO_Central1 Publication
Biological Process negative regulation of mitophagySource:Ensembl
Biological Process negative regulation of neuron deathSource:Ensembl
Biological Process negative regulation of programmed cell deathSource:UniProtKB1 Publication
Biological Process negative regulation of reactive oxygen species metabolic processSource:Ensembl
Biological Process positive regulation of cardiac muscle cell apoptotic processSource:Ensembl
Biological Process positive regulation of DNA repairSource:UniProtKB1 Publication
Biological Process positive regulation of hexokinase activitySource:UniProtKB1 Publication
Biological Process reactive oxygen species metabolic processSource:Ensembl
Biological Process regulation of pentose-phosphate shuntSource:UniProtKB1 Publication
Biological Process regulation of response to DNA damage checkpoint signalingSource:UniProtKB1 Publication
Biological Process response to gamma radiationSource:Ensembl
Biological Process response to ischemiaSource:UniProtKB
Biological Process response to xenobiotic stimulusSource:Ensembl

Cytoplasm
Nucleus
Mitochondrion
Translocated to the mitochondria during hypoxia in a HIF1A-dependent manner (PubMed:23185017).
Colocalizes with HK2 in the mitochondria during hypoxia (PubMed:23185017).
Translocated to the nucleus during hypoxia and/or genome stress-induced DNA damage responses in cancer cells (PubMed:25928429).
Translocation to the mitochondria is enhanced in ischemic cortex after reperfusion and/or during oxygen and glucose deprivation (OGD)/reoxygenation insult in primary neurons (By similarity).