TIGAR
entrez
57103
canonical
uniprot
Q9NQ88
canonical
ensembl
ENSG00000078237
resolver
ensp
ENSP00000179259
resolver
enst
ENST00000179259
resolver
genesymbol
TIGAR
resolver
genesymbol_syn
C12orf5
resolver
hgnc
HGNC:1185
resolver
uniprot
B2R840
resolver
uniprot_entry
TIGAR_HUMAN
resolver
uniprot_sec
B2R840
resolver
amino_acid_sequence
MARFALTVVRHGETRFNKEKIIQGQGVDEPLSETGFKQAAAAGIFLNNVKFTHAFSSDLMRTKQTMHGILERSKFCKDMTVKYDSRLRERKYGVVEGKALSELRAMAKAAREECPVFTPPGGETLDQVKMRGIDFFEFLCQLILKEADQKEQFSQGSPSNCLETSLAEIFPLGKNHSSKVNSDSGIPGLAASVLVVSHGAYMRSLFDYFLTDLKCSLPATLSRSELMSVTPNTGMSLFIINFEEGREVKPTVQCICMNLQDHLNGLTETR
uniprot
proteins
ec_number
3.1.3.46
uniprot
proteins
function
FUNCTION: 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). {ECO:0000250|UniProtKB:Q8BZA9, ECO:0000269|PubMed:16839880, ECO:0000269|PubMed:19015259, ECO:0000269|PubMed:19713938, ECO:0000269|PubMed:22887998, ECO:0000269|PubMed:23185017, ECO:0000269|PubMed:23726973, ECO:0000269|PubMed:23817040, ECO:0000269|PubMed:25928429}.
uniprot
proteins
mass_dalton
30063
uniprot
proteins
mutagenesis
MUTAGEN 11; /note="H->A: Abolishes the ability to lower cellular fructose-2,6-bisphosphate levels, to inhibit the glycolytic activity, to reduce levels of ROS, to increase oxygen consumption and to protect toward hypoxic cell death; when associated with A-11 and A-102. Retains the ability to interact and enhance HK2 activity, to localize to the mitochondria, to limit mitochondrial ROS level increase during hypoxia and to rescued partially crypt growth; when associated with A-102 and A-198. Loss of the ability to protect against cell death during hypoxia; when associated with A-102; A-198 and 258-N--D-261 Del."; /evidence="ECO:0000269|PubMed:16839880, ECO:0000269|PubMed:22887998, ECO:0000269|PubMed:23185017, ECO:0000269|PubMed:23726973"; MUTAGEN 102; /note="E->A: Abolishes the ability to lower cellular fructose-2,6-bisphosphate levels, to inhibit the glycolytic activity, to reduce levels of ROS, to increase oxygen consumption and to protect toward hypoxic cell death; when associated with A-11 and A-198. Retains the ability to interact and enhance HK2 activity, to localize to the mitochondria, to limit mitochondrial ROS level increase during hypoxia and to rescued partially crypt growth; when associated with A-11 and A-198. Loss of the ability to protect against cell death during hypoxia; when associated with A-11; A-198 and 258-N--D-261 Del."; /evidence="ECO:0000269|PubMed:16839880, ECO:0000269|PubMed:22887998, ECO:0000269|PubMed:23185017, ECO:0000269|PubMed:23726973"; MUTAGEN 198; /note="H->A: Abolishes the ability to lower cellular fructose-2,6-bisphosphate levels, to inhibit the glycolytic activity, to reduce levels of ROS, to increase oxygen consumption and to protect toward hypoxic cell death; when associated with A-11 and A-102. Retains the ability to interact and enhance HK2 activity, to localize to the mitochondria, to limit mitochondrial ROS level increase during hypoxia and to rescued partially crypt growth; when associated with A-11 and A-102. Loss of the ability to protect against cell death during hypoxia; when associated with A-11; A-102 and 258-N--D-261 Del."; /evidence="ECO:0000269|PubMed:16839880, ECO:0000269|PubMed:22887998, ECO:0000269|PubMed:23185017, ECO:0000269|PubMed:23726973"; MUTAGEN 258..261; /note="Missing: Inhibits the ability to interact and enhance HK2 activity, to localize to the mitochondria, to protect against the decrease of mitochondrial membrane potential and to limit mitochondrial ROS level increase during hypoxia. Does not abolish the ability to lower cellular fructose-2,6-bisphosphate levels during hypoxia. Loss of the ability to protect against cell death during hypoxia; when associated with A-11; A-102 and A-198."; /evidence="ECO:0000269|PubMed:23185017
uniprot
proteins
protein_family
Phosphoglycerate mutase family
uniprot
proteins
pubmed
11062477
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16140933
uniprot
proteins
pubmed
16839880
uniprot
proteins
pubmed
17525332
uniprot
proteins
pubmed
19015259
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19713938
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21820150
uniprot
proteins
pubmed
22887998
uniprot
proteins
pubmed
23185017
uniprot
proteins
pubmed
23726973
uniprot
proteins
pubmed
23817040
uniprot
proteins
pubmed
25928429
uniprot
proteins
sequence_length
270
uniprot
proteins
subcellular_location
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}.
uniprot
proteins