Protein: Fructose-2,6-bisphosphatase TIGAR (EC 3.1.3.46) (TP53-induced glycolysis and apoptosis regulator) (TP53-induced glycolysis regulatory phosphatase) (Q8BZA9)
Organism: Mus musculus (Mouse)
Function: Fructose-bisphosphatase hydrolyzing fructose-2,6-bisphosphate as well as fructose-1,6-bisphosphate (By similarity). 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 (By similarity). 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 (By similarity). Involved in intestinal tumor progression.
Subcellular location: Cytoplasm {ECO:0000269|PubMed:24872551}. Nucleus {ECO:0000250|UniProtKB:Q9NQ88}. Mitochondrion {ECO:0000269|PubMed:24872551}. Note=Translocated to the mitochondria during hypoxia in a HIF1A-dependent manner. Colocalizes with HK2 in the mitochondria during hypoxia. Translocated to the nucleus during hypoxia and/or genome stress-induced DNA damage responses in cancer cells (By similarity). Translocation to the mitochondria is enhanced in ischemic cortex after reperfusion and/or during oxygen and glucose deprivation (OGD)/reoxygenation insult in primary neurons (PubMed:24872551). {ECO:0000250|UniProtKB:Q9NQ88, ECO:0000269|PubMed:24872551}.
Interaction partners:
- Hexokinase-2
- Cellular tumor antigen p53
- Fructose-1,6-bisphosphatase isozyme 2
- 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 1
- 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2
- 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 splice variant 2
- Fructose-1,6-bisphosphatase 1
- ATP-dependent 6-phosphofructokinase, platelet type
- ATP-dependent 6-phosphofructokinase, liver type
- ATP-dependent 6-phosphofructokinase, muscle type
Sequence:
MPRFALTVIRHGETRLNKEKIIQGQGVDAPLSETGFRQAAAAGQFLSNVQFTHAFSSDLTRTKQTIHGILEKSRFCKDMAVKYDSRLRERMYGVAEGKPLSELRAMAKAAGEECPMFTPPGGETVEQVKMRGKDFFDFICQLILGKAGQRESVLPGAPGSGLESSLAEVFPVGKHGSLGANPKGGTLGLAASILVVSHGAYMRSLFGYFLSDLRCSLPGARDKLELSSITPNTGISVFIIDCEEARQPSIQCVCMNLQEHLNGVTEKQH