TIGAR

TP53 induced glycolysis regulatory phosphatase
General Information
Name TP53 induced glycolysis regulatory phosphatase
Alias
  • fructose-2,6-bisphosphatase TIGAR
  • TP53-induced glycolysis and apoptosis regulator
  • fructose-2,6-bisphosphate 2-phosphatase
  • probable fructose-2,6-bisphosphatase TIGAR
  • transactivated by NS3TP2 protein
Synonyms C12orf5 FR2BP
Gene_family Sugar phosphatases
organism Homo sapiens
entrez_id 57103
location 12p13.32
transcript_count 1
exon_count 6
Cross References
Location
by NCBI GRCh38.p14
    Summary
      Entrez 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]
      nextProt 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).
    Interactions
    NCBI
    A A.Source B B.DB B.Source Description PubMed
    TIGAR BioGRID PPIA GeneID BioGRID Proximity Label-MS
    TIGAR BioGRID NFE2L2 GeneID BioGRID Affinity Capture-Western; Reconstituted Complex
    TIGAR BioGRID RPA3 GeneID BioGRID Proximity Label-MS
    TIGAR BioGRID RPA2 GeneID BioGRID Proximity Label-MS
    TIGAR BioGRID RPA1 GeneID BioGRID Proximity Label-MS
    TIGAR BioGRID TRIM67 GeneID BioGRID Affinity Capture-MS
    TIGAR BioGRID TIPARP GeneID BioGRID Affinity Capture-MS
    TIGAR BioGRID PRKN GeneID BioGRID Affinity Capture-MS
    TIGAR BioGRID HMGCL GeneID BioGRID Co-fractionation
    TIGAR BioGRID ETFA GeneID BioGRID Co-fractionation
    TIGAR BioGRID AKR1C2 GeneID BioGRID Co-fractionation
    TIGAR BioGRID ABAT GeneID BioGRID Co-fractionation
    TIGAR BioGRID NANP GeneID BioGRID Co-fractionation
    TIGAR BioGRID GLTP GeneID BioGRID Co-fractionation
    TIGAR BioGRID GSTO1 GeneID BioGRID Co-fractionation
    TIGAR BioGRID NDUFV1 GeneID BioGRID Co-fractionation
    TIGAR BioGRID TRIM35 GeneID BioGRID Affinity Capture-Western
    TIGAR BioGRID NUP35 GeneID BioGRID Proximity Label-MS
    TIGAR BioGRID TRIM31 GeneID BioGRID Affinity Capture-Western
    TIGAR BioGRID GSX1 GeneID BioGRID Affinity Capture-MS
    TIGAR BioGRID MTPN GeneID BioGRID Affinity Capture-MS
    TIGAR BioGRID ALG8 GeneID BioGRID Affinity Capture-MS
    TIGAR BioGRID PIGT GeneID BioGRID Affinity Capture-MS
    TIGAR BioGRID PHF11 GeneID BioGRID Affinity Capture-MS
    TIGAR BioGRID NEUROG3 GeneID BioGRID Affinity Capture-MS
    TIGAR BioGRID KLK13 GeneID BioGRID Affinity Capture-MS
    TIGAR BioGRID NTNG1 GeneID BioGRID Affinity Capture-MS
    TIGAR BioGRID AGPAT1 GeneID BioGRID Affinity Capture-MS
    TIGAR BioGRID NMI GeneID BioGRID Affinity Capture-MS
    TIGAR BioGRID PNPLA4 GeneID BioGRID Affinity Capture-MS
    TIGAR BioGRID TWF1 GeneID BioGRID Affinity Capture-MS
    TIGAR BioGRID IGHG2 GeneID BioGRID Affinity Capture-MS
    TIGAR BioGRID CCR1 GeneID BioGRID Affinity Capture-MS
    TIGAR BioGRID FAM184A GeneID BioGRID Proximity Label-MS
    TIGAR BioGRID DNAJB4 GeneID BioGRID Proximity Label-MS
    TIGAR BioGRID HSPA5 GeneID BioGRID Proximity Label-MS
    TIGAR BioGRID HSCB GeneID BioGRID Affinity Capture-MS
    TIGAR BioGRID BCAR1 GeneID BioGRID Affinity Capture-MS
    TIGAR BioGRID WWP2 GeneID BioGRID Affinity Capture-MS
    TIGAR BioGRID MSRB3 GeneID BioGRID Co-fractionation
    TIGAR BioGRID LYRM2 GeneID BioGRID Co-fractionation
    TIGAR BioGRID TXN2 GeneID BioGRID Co-fractionation
    TIGAR BioGRID TBCA GeneID BioGRID Co-fractionation
    TIGAR BioGRID HINT1 GeneID BioGRID Co-fractionation
    TIGAR BioGRID GUK1 GeneID BioGRID Co-fractionation
    TIGAR BioGRID ANXA1 GeneID BioGRID Co-fractionation
    TIGAR BioGRID HK2 GeneID BioGRID Affinity Capture-Western
    TIGAR BioGRID SHARPIN GeneID BioGRID Affinity Capture-MS
    TIGAR BioGRID RNF31 GeneID BioGRID Affinity Capture-Western
    TIGAR BioGRID PIH1D1 GeneID BioGRID Affinity Capture-MS
    TIGAR BioGRID TP53 GeneID BioGRID Co-localization
    TIGAR BioGRID SET GeneID BioGRID Co-localization
    TIGAR BioGRID HNRNPL GeneID BioGRID Affinity Capture-RNA
    TIGAR BioGRID OFD1 GeneID BioGRID Proximity Label-MS
    TIGAR BioGRID TKT GeneID BioGRID Co-fractionation
    TIGAR BioGRID PCBP1 GeneID BioGRID Co-fractionation
    TIGAR BioGRID RPL11 GeneID BioGRID Two-hybrid
    TIGAR BioGRID UBE2L3 GeneID BioGRID Co-fractionation
    TIGAR BioGRID TSC2 GeneID BioGRID Co-fractionation
    TIGAR BioGRID APP GeneID BioGRID Reconstituted Complex
    StringDB
    A B experiments database textmining combined score hadb nhadb
    C12orf5 ATG4A 0 0 163 181 2 1
    C12orf5 RAB8B 0 0 0 317 2 1
    C12orf5 RPTOR 0 0 211 211 2 1
    C12orf5 PRKAB1 0 0 282 282 2 1
    C12orf5 CASP8 0 0 150 168 2 1
    C12orf5 PGK1 0 0 233 694 2 1
    C12orf5 SIRT3 0 0 260 292 2 1
    C12orf5 KEAP1 0 0 241 240 2 1
    C12orf5 GABARAPL1 0 0 181 198 2 1
    C12orf5 HSPA8 0 0 102 196 2 1
    C12orf5 FUNDC1 0 0 157 167 2 1
    C12orf5 EI24 0 0 209 209 2 1
    C12orf5 ULK2 0 0 218 337 2 1
    C12orf5 BCL2L1 0 0 242 241 2 1
    C12orf5 GABARAPL2 0 0 160 178 2 1
    C12orf5 RAB12 0 0 0 317 2 1
    C12orf5 HIF1A 0 0 493 504 2 1
    C12orf5 STAT3 0 0 193 204 2 1
    C12orf5 MYC 0 0 457 457 2 1
    C12orf5 PIK3CA 0 0 138 175 2 1
    C12orf5 UBQLN2 0 0 0 151 2 1
    C12orf5 MAP1LC3B 0 0 181 215 2 1
    C12orf5 ULK1 0 0 184 235 2 1
    C12orf5 KAT5 0 0 194 213 2 1
    C12orf5 AMBRA1 0 0 155 154 2 1
    C12orf5 CASP3 0 0 260 276 2 1
    C12orf5 ATG16L1 0 0 134 164 2 1
    C12orf5 CDKN2A 0 0 203 203 2 1
    C12orf5 LPIN1 0 0 325 396 2 1
    C12orf5 BECN1 0 0 335 346 2 1
    C12orf5 AKT1 0 0 458 458 2 1
    C12orf5 ERBB2 0 0 184 183 2 1
    C12orf5 RAB25 0 0 113 155 2 1
    C12orf5 EIF2S1 0 0 74 190 2 1
    C12orf5 BNIP3L 0 0 298 298 2 1
    C12orf5 TSC2 271 0 381 529 2 1
    C12orf5 SESN1 0 0 558 561 2 1
    C12orf5 RPS6KB1 0 0 234 234 2 1
    C12orf5 DRAM1 0 0 518 518 2 1
    C12orf5 UVRAG 0 0 161 164 2 1
    C12orf5 FIS1 0 0 124 156 2 1
    C12orf5 SESN2 0 0 520 539 2 1
    C12orf5 CDK5 0 0 134 159 2 1
    C12orf5 DRAM2 0 0 57 220 2 1
    C12orf5 ATG13 0 0 118 158 2 1
    C12orf5 SQSTM1 0 0 213 213 2 1
    C12orf5 BNIP3 0 0 408 408 2 1
    C12orf5 HSP90AA1 0 0 123 207 2 1
    C12orf5 TP73 0 0 66 231 2 1
    C12orf5 ATG9A 0 0 141 175 2 1
    C12orf5 CDKN1A 0 0 325 329 2 1
    C12orf5 BAX 0 0 150 173 2 1
    C12orf5 ARNT 0 0 261 261 2 1
    C12orf5 GAPDH 0 0 321 580 2 1
    C12orf5 SIRT2 0 0 228 261 2 1
    C12orf5 MTOR 0 0 390 399 2 1
    C12orf5 PIK3C3 0 0 145 180 2 1
    C12orf5 MFN2 0 0 180 197 2 1
    C12orf5 RAB8A 0 0 0 317 2 1
    C12orf5 TP53 273 900 703 977 2 1
    C12orf5 RB1CC1 0 0 218 218 2 1
    C12orf5 STK11 0 0 367 404 2 1
    C12orf5 RAB13 0 0 0 317 2 1
    C12orf5 SIRT1 0 0 369 396 2 1
    C12orf5 MCL1 0 0 217 217 2 1
    C12orf5 ATG5 0 0 295 295 2 1
    C12orf5 ATG10 0 0 152 187 2 1
    C12orf5 ATG7 0 0 274 293 2 1
    C12orf5 DNM1L 0 0 151 194 2 1
    C12orf5 PTEN 0 0 451 463 2 1
    C12orf5 SREBF1 0 0 233 244 2 1
    C12orf5 ATG12 0 0 204 204 2 1
    C12orf5 HSPA5 0 0 106 168 2 1
    C12orf5 FOXO1 0 0 161 161 2 1
    C12orf5 LRRK2 270 0 42 286 2 1
    C12orf5 PINK1 0 0 195 195 2 1
    C12orf5 UBQLN1 0 0 0 173 2 1
    C12orf5 FOXO3 0 0 247 246 2 1
    C12orf5 TP53INP1 0 0 322 321 2 1
    C12orf5 ATG3 0 0 134 186 2 1
    C12orf5 VDAC1 0 0 263 279 2 1
    C12orf5 RHEB 0 0 223 246 2 1
    C12orf5 TP53INP2 0 0 123 161 2 1
    C12orf5 PRKAA1 0 0 180 321 2 1
    Ontologies
    ID Category Term Effect Evidence PubMed
    GO:0004331 Molecular Function fructose-2,6-bisphosphate 2-phosphatase activity enables EXP
    GO:0004331 Molecular Function fructose-2,6-bisphosphate 2-phosphatase activity enables IBA
    GO:0004331 Molecular Function fructose-2,6-bisphosphate 2-phosphatase activity enables IDA
    GO:0005515 Molecular Function protein binding enables IPI
    GO:0006974 Biological Process DNA damage response involved_in IDA
    GO:0010659 Biological Process cardiac muscle cell apoptotic process involved_in IEA
    GO:0071279 Biological Process cellular response to cobalt ion involved_in IDA
    GO:0071456 Biological Process cellular response to hypoxia involved_in IDA
    GO:0006003 Biological Process fructose 2,6-bisphosphate metabolic process involved_in IEA
    GO:0019661 Biological Process glucose catabolic process to lactate via pyruvate involved_in IEA
    GO:0006096 Biological Process glycolytic process involved_in IEA
    GO:0060576 Biological Process intestinal epithelial cell development involved_in IEA
    GO:0000423 Biological Process mitophagy involved_in IEA
    GO:1904024 Biological Process negative regulation of glucose catabolic process to lactate via pyruvate involved_in IEA
    GO:0045820 Biological Process negative regulation of glycolytic process involved_in IBA
    GO:1901525 Biological Process negative regulation of mitophagy involved_in IEA
    GO:0043069 Biological Process negative regulation of programmed cell death involved_in IDA
    GO:2000378 Biological Process negative regulation of reactive oxygen species metabolic process involved_in IEA
    GO:0045739 Biological Process positive regulation of DNA repair involved_in IMP
    GO:0010666 Biological Process positive regulation of cardiac muscle cell apoptotic process involved_in IEA
    GO:1903301 Biological Process positive regulation of hexokinase activity involved_in IDA
    GO:1905857 Biological Process positive regulation of pentose-phosphate shunt involved_in IEA
    GO:0072593 Biological Process reactive oxygen species metabolic process involved_in IEA
    GO:0043456 Biological Process regulation of pentose-phosphate shunt involved_in IBA
    GO:0043456 Biological Process regulation of pentose-phosphate shunt involved_in IMP
    GO:1902153 Biological Process regulation of response to DNA damage checkpoint signaling involved_in IMP
    GO:0010332 Biological Process response to gamma radiation involved_in IEA
    GO:0002931 Biological Process response to ischemia involved_in ISS
    GO:0009410 Biological Process response to xenobiotic stimulus involved_in IEA
    GO:0005737 Cellular Component cytoplasm located_in IDA
    GO:0005829 Cellular Component cytosol is_active_in IBA
    GO:0005829 Cellular Component cytosol located_in IDA
    GO:0005829 Cellular Component cytosol located_in TAS
    GO:0005741 Cellular Component mitochondrial outer membrane located_in IDA
    GO:0005634 Cellular Component nucleus located_in IDA
    Pathways
    Name DB ID
    Generic Transcription Pathway Reactome R-HSA-212436
    Transcriptional Regulation by TP53 Reactome R-HSA-3700989
    TP53 Regulates Metabolic Genes Reactome R-HSA-5628897
    RNA Polymerase II Transcription Reactome R-HSA-73857
    Gene expression (Transcription) Reactome R-HSA-74160
    p53 transcriptional gene network (WP4963) WikiPathways WP4963_r122690
    Metabolic reprogramming in colon cancer (WP4290) WikiPathways WP4290_r118611
    Transcripts
    Accession Version MolecularType Name NCBI Comments
    NM_020375 3 mRNA None NC_000012 Reference