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FLASH GENE
Symbol TIGAR contributors: mct/npt/pgu - updated : 03-12-2019
HGNC name chromosome 12 open reading frame 5
HGNC id 1185
Location 12p13.32      Physical location : -
Genatlas name TP53-induced glycolysis and apoptosis regulator
Synonym name transactivated by NS3TP2 protein
Synonym symbol(s) C12orf5, FR2BP
EC.number 3.1.3.46
DNA
TYPE functioning gene
STRUCTURE 38.84 kb     6 Exon(s)
regulatory sequence Promoter
Binding site   cAMP
text structure
  • SP1 participates in regulating TIGAR promoter activity
  • SP1 is indispensable for basal activity of TIGAR promoter
  • the region at -4/+13 contained a cAMP-response element (CRE) in promoter region
  • MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 8237 30 270 - 2009 19015259
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivepancreas exocrine   moderately
     pharynx   predominantly
    Endocrineadrenal gland   moderately
     neuroendocrinepituitary  highly
    Lymphoid/Immunetonsils   highly
    Nervousbrain     Homo sapiens
    Reproductivefemale systembreastmammary gland moderately
    Respiratoryrespiratory tractlarynx  moderately
    Urinarykidney   moderately
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a histidine phosphatase fold that is closest related to the PhoE phosphatase (
  • a conserved catalytic core centred on a histidine which becomes phosphorylated during the course of the reaction
  • HOMOLOGY
    interspecies homolog to highly similar to the zebrafish Tigar (PMID:19015259)
    Homologene
    FAMILY
  • phosphoglycerate mutase family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text under hypoxia, a fraction of TIGAR protein relocalized to mitochondria and formed a complex with hexokinase 2 (HK2), resulting in an increase in HK2 activity
    basic FUNCTION
  • acting as an isomerase
  • functioning by blocking glycolysis and directing the pathway into the pentose phosphate shunt
  • functions as a regulator of glycolysis, and therefore has a relationship with glucose as well as energy
  • TP53-inducible gene that inhibits glycolysis by reducing cellular levels of fructose-2,6-bisphosphate, an activator of glycolysis and inhibitor of gluconeogenesis (
  • protecting cells from DNA damaging reactive oxygen species
  • providing some protection from DNA damage-induced apoptosis
  • involved in down-regulation of glycolysis, reduction of intracellular levels of reactive oxygen species, and protection from apoptosis
  • can modulate ROS in response to nutrient starvation or metabolic stress, and functions to inhibit autophagy
  • inhibits proliferation of cancer cells and increases drug-mediated tumour regression by promoting p53-mediated cell-cycle arrest
  • acts as a fructose-2,6-bisphosphatase, potentially promoting the pentose phosphate pathway to produce NADPH for antioxidant function and ribose-5-phosphate for nucleotide synthesis
  • TIGAR inhibits both apoptosis and autophagy, resulting in a dual impact on tumor cell survival in response to tumor chemotherapy
  • under low ischemic burden, TIGAR activation induces the pentose phosphate pathway and autophagy as a protective mechanism
  • TIGAR expression changes during development and its expression level may be likely correlated with the vulnerability of neurons to ischemic injury
  • inhibits ischemia/reperfusion-induced inflammatory response of astrocytes
  • role for TIGAR in modulating redox homeostasis during oocyte maturation,
  • is a TP53 target protein that plays critical roles in glycolysis and redox balance
  • glycolytic inhibitor, plays vital roles in regulating cellular metabolism and oxidative stress
  • overexpression of mitochondrial-TIGAR enhanced ATP generation, maintained mitochondrial membrane potential and reduced mitochondrial oxidative stress under hypoxia condition
  • promotes metabolic reprogramming and regulates neural stem cells (NSCs) differentiation through an epigenetic mechanism
  • has anti-epileptic, anti-oxidant and anti-apoptotic effects
  • activates the pentose phosphate pathway (PPP), which feeds reduced nicotinamide adenine dinucleotide phosphate (NADPH) to the antioxidant glutathione pathway
  • TIGAR may have an anti-apoptosis effect via up-regulation of autophagy in diabetic neuropathy
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism carbohydrate
    signaling
    tyrosine kinase/TIGAR/NADPH cascade
    a component inhibition of a tyrosine kinase/TIGAR/NADPH cascade may have therapeutic applicability in human cancers
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • TP53 can modulate the metabolic pathways via the proteins SCO2 and TIGAR in human breast cancer
  • CREB1 regulates TIGAR expression via a CRE-binding site at the TIGAR promoter
  • TIGAR potently inhibits NFKB1-dependent gene expression by suppressing the upstream activation of IKBKB phosphorylation and kinase activation
  • TIGAR may promote glioblastoma growth and progression through oxidation resistance and AKT1 activation
  • down-regulation of TFAM increases the sensitivity of tumour cells to radiation via TP53/TIGAR signalling pathway
  • endogenous inhibitor of glycolysis and increases the flux of pentose phosphate pathway (PPP) by regulating glucose 6-phosphate dehydrogenase (G6PD)
  • cell & other
    REGULATION
    induced by TP53, to reduce glycolysis, and induces SCO2 and GLS2 to promote mitochondrial respiration
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    ameliorated the effects of MET kinase inhibition, inhibiting tumor growth (
    tumoral     --over  
    in breast cancer (
    tumoral     --over  
    in colon tumors suggested that deregulated TIGAR supports cancer progression
    tumoral     --over  
    in glioblastomas
    constitutional       loss of function
    loss of TIGAR is a critical pathway mediating the effects of maternal obesity on oocyte quality
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • might be a predictor of poor survival and high incidence of relapse in AML patients
  • Therapy target
    SystemTypeDisorderPubmed
    cancer  
    inhibition of a tyrosine kinase/TIGAR/NADPH cascade may have therapeutic applicability in human cancers
    cancerdigestivecolon
    potential therapeutic target in diseases such as intestinal cancer
    immunologyinflammatory 
    potential therapeutic target in diseases such as ulcerative colitis
    neurologyepilepsy 
    promising therapeutictarget for epilepsy
    cancerhemopathy 
    combination of TIGAR inhibitors with anti-glycolytic agents may be novel therapies for the future clinical use in AML (acute myeloid leukemia) patients
    cancer  
    could serve as a potential target for the development of effective antineoplastic therapies
    ANIMAL & CELL MODELS