Protein: Fructose-2,6-bisphosphatase TIGAR (EC 3.1.3.46) (TP53-induced glycolysis and apoptosis regulator) (TP53-induced glycolysis regulatory phosphatase) (Q9NQ88)
Organism: Homo sapiens (Human)
Function: 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 (By similarity). 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 (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. 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.
Subcellular location: Cytoplasm {ECO:0000269|PubMed:23185017, ECO:0000269|PubMed:25928429}. Nucleus {ECO:0000269|PubMed:25928429}. Mitochondrion {ECO:0000269|PubMed:23185017}. Note=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). {ECO:0000250|UniProtKB:Q8BZA9, ECO:0000269|PubMed:23185017, ECO:0000269|PubMed:25928429}.
Interaction partners:
- Cellular tumor antigen p53
- ATP-dependent 6-phosphofructokinase, muscle type
- Hexokinase-2
- 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3
- 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2
- 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4
- 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 1
- Fructose-1,6-bisphosphatase isozyme 2
- ATP-dependent 6-phosphofructokinase, platelet type
- ATP-dependent 6-phosphofructokinase, liver type
Sequence:
MARFALTVVRHGETRFNKEKIIQGQGVDEPLSETGFKQAAAAGIFLNNVKFTHAFSSDLMRTKQTMHGILERSKFCKDMTVKYDSRLRERKYGVVEGKALSELRAMAKAAREECPVFTPPGGETLDQVKMRGIDFFEFLCQLILKEADQKEQFSQGSPSNCLETSLAEIFPLGKNHSSKVNSDSGIPGLAASVLVVSHGAYMRSLFDYFLTDLKCSLPATLSRSELMSVTPNTGMSLFIINFEEGREVKPTVQCICMNLQDHLNGLTETR