Fructose-2,6-bisphosphatase TIGAR (EC 3.1.3.46) (TP53-induced glycolysis and apoptosis regulator) (TP53-induced glycolysis regulatory phosphatase)
1_MARFA 6_ LTVVR 11_ HGETR 16_ FNKEK 21_ IIQGQ 26_ GVDEP 31_ LSETG 36_ FKQAA 41_ AAGIF 46_ LNNVK 51_ FTHAF 56_ SSDLM 61_ RTKQT 66_ MHGIL 71_ ERSKF 76_ CKDMT 81_ VKYDS 86_ RLRER 91_ KYGVV 96_ EGKAL 101_ SELRA 106_ MAKAA 111_ REECP 116_ VFTPP 121_ GGETL 126_ DQVKM 131_ RGIDF 136_ FEFLC 141_ QLILK 146_ EADQK 151_ EQFSQ 156_ GSPSN 161_ CLETS 166_ LAEIF 171_ PLGKN 176_ HSSKV 181_ NSDSG 186_ IPGLA 191_ ASVLV 196_ VSHGA 201_ YMRSL 206_ FDYFL 211_ TDLKC 216_ SLPAT 221_ LSRSE 226_ LMSVT 231_ PNTGM 236_ SLFII 241_ NFEEG 246_ REVKP 251_ TVQCI 256_ CMNLQ 261_DHLNG
1: 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:22887998, PubMed:23726973, 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)