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Aliases for TIGAR Gene

Aliases for TIGAR Gene

  • TP53 Induced Glycolysis Regulatory Phosphatase 2 3 5
  • TP53-Induced Glycolysis And Apoptosis Regulator 2 3 4
  • TP53-Induced Glycolysis Regulatory Phosphatase 3 4
  • C12orf5 3 4
  • Probable Fructose-2,6-Bisphosphatase TIGAR 3
  • Fructose-2,6-Bisphosphate 2-Phosphatase 3
  • Chromosome 12 Open Reading Frame 5 2
  • Transactivated By NS3TP2 Protein 3
  • EC 3.1.3.46 4
  • FR2BP 3

External Ids for TIGAR Gene

Previous HGNC Symbols for TIGAR Gene

  • C12orf5

Previous GeneCards Identifiers for TIGAR Gene

  • GC12P004323
  • GC12P004588

Summaries for TIGAR Gene

Entrez Gene Summary for TIGAR Gene

  • 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]

GeneCards Summary for TIGAR Gene

TIGAR (TP53 Induced Glycolysis Regulatory Phosphatase) is a Protein Coding gene. Diseases associated with TIGAR include hypoxia. Among its related pathways are Central carbon metabolism in cancer and Fructose and mannose metabolism. GO annotations related to this gene include phosphatase activity and fructose-2,6-bisphosphate 2-phosphatase activity.

UniProtKB/Swiss-Prot for TIGAR Gene

  • 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).

Gene Wiki entry for TIGAR Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for TIGAR Gene

Genomics for TIGAR Gene

Regulatory Elements for TIGAR Gene

Enhancers for TIGAR Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around TIGAR on UCSC Golden Path with GeneCards custom track

Promoters for TIGAR Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around TIGAR on UCSC Golden Path with GeneCards custom track

Genomic Location for TIGAR Gene

Chromosome:
12
Start:
4,307,763 bp from pter
End:
4,360,028 bp from pter
Size:
52,266 bases
Orientation:
Plus strand

Genomic View for TIGAR Gene

Genes around TIGAR on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TIGAR Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TIGAR Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TIGAR Gene

Proteins for TIGAR Gene

  • Protein details for TIGAR Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NQ88-TIGAR_HUMAN
    Recommended name:
    Fructose-2,6-bisphosphatase TIGAR
    Protein Accession:
    Q9NQ88
    Secondary Accessions:
    • B2R840

    Protein attributes for TIGAR Gene

    Size:
    270 amino acids
    Molecular mass:
    30063 Da
    Quaternary structure:
    • Interacts with HK2; the interaction increases hexokinase HK2 activity in a hypoxia- and HIF1A-dependent manner, resulting in the regulation of mitochondrial membrane potential, thus increasing NADPH production and decreasing intracellular ROS levels (PubMed:23185017).

    Three dimensional structures from OCA and Proteopedia for TIGAR Gene

neXtProt entry for TIGAR Gene

Proteomics data for TIGAR Gene at MOPED

Post-translational modifications for TIGAR Gene

  • Ubiquitination at Lys 37
  • Modification sites at PhosphoSitePlus

Other Protein References for TIGAR Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • R&D Systems Antibodies for TIGAR (TIGAR/C12orf5)
  • Cell Signaling Technology (CST) Antibodies for TIGAR (TIGAR)

No data available for DME Specific Peptides for TIGAR Gene

Domains & Families for TIGAR Gene

Gene Families for TIGAR Gene

Suggested Antigen Peptide Sequences for TIGAR Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q9NQ88

UniProtKB/Swiss-Prot:

TIGAR_HUMAN :
  • Belongs to the phosphoglycerate mutase family.
Family:
  • Belongs to the phosphoglycerate mutase family.
genes like me logo Genes that share domains with TIGAR: view

Function for TIGAR Gene

Molecular function for TIGAR Gene

UniProtKB/Swiss-Prot CatalyticActivity:
Beta-D-fructose 2,6-bisphosphate + H(2)O = D-fructose 6-phosphate + phosphate.
UniProtKB/Swiss-Prot 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: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).
UniProtKB/Swiss-Prot Induction:
Up-regulated by p53/TP53 (at protein level) (PubMed:16839880). Rapidly up-regulated by p53/TP53 (PubMed:16140933, PubMed:16839880, PubMed:19713938). Up-regulated in glioma cell line in a p53/TP53-independent manner (PubMed:22887998).

Enzyme Numbers (IUBMB) for TIGAR Gene

genes like me logo Genes that share phenotypes with TIGAR: view

Animal Models for TIGAR Gene

MGI Knock Outs for TIGAR:

Animal Model Products

miRNA for TIGAR Gene

miRTarBase miRNAs that target TIGAR

No data available for Gene Ontology (GO) - Molecular Function , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for TIGAR Gene

Localization for TIGAR Gene

Subcellular locations from UniProtKB/Swiss-Prot for TIGAR Gene

Cytoplasm. Nucleus. Mitochondrion. 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}.

Gene Ontology (GO) - Cellular Components for TIGAR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005741 mitochondrial outer membrane IDA 23185017
genes like me logo Genes that share ontologies with TIGAR: view

No data available for Subcellular locations from COMPARTMENTS for TIGAR Gene

Pathways & Interactions for TIGAR Gene

genes like me logo Genes that share pathways with TIGAR: view

Pathways by source for TIGAR Gene

1 R&D Systems pathway for TIGAR Gene

Interacting Proteins for TIGAR Gene

Gene Ontology (GO) - Biological Process for TIGAR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002931 response to ischemia ISS --
GO:0006003 fructose 2,6-bisphosphate metabolic process IEA,IDA 19015259
GO:0006914 autophagy IEA --
GO:0006915 apoptotic process IEA --
GO:0006974 cellular response to DNA damage stimulus IDA 25928429
genes like me logo Genes that share ontologies with TIGAR: view

No data available for SIGNOR curated interactions for TIGAR Gene

Drugs & Compounds for TIGAR Gene

(5) Additional Compounds for TIGAR Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Beta-D-Fructose 6-phosphate
  • beta-D-Fructose 6-phosphate
D-Fructose 2,6-bisphosphate
  • b-D-Fructose 2,6-bisphosphate
  • beta-D-Fructose 2,6-bisphosphate
  • D-Fructose 2,6-bisphosphate
  • Fru 2,6-P2, Fructose 2,6-diphosphate
  • Fructose 2,6-bisphosphate
Fructose 6-phosphate
  • D-Fructose 6-phosphate
  • D-Fructose 6-phosphorate
  • D-Fructose 6-phosphoric acid
  • D-Fructose-6-P
  • D-Fructose-6-phosphate
643-13-0
phosphoric acid
  • Acide phosphorique (FRENCH)
  • Acido fosforico [Italian]
  • Acidum phosphoricum
  • Diphosphate tetrasodium
  • Fosforzuuroplossingen [Dutch]
7664-38-2
Water
  • Dihydrogen oxide
  • Steam
7732-18-5
genes like me logo Genes that share compounds with TIGAR: view

Transcripts for TIGAR Gene

Alternative Splicing Database (ASD) splice patterns (SP) for TIGAR Gene

No ASD Table

Relevant External Links for TIGAR Gene

GeneLoc Exon Structure for
TIGAR
ECgene alternative splicing isoforms for
TIGAR

Expression for TIGAR Gene

mRNA expression in normal human tissues for TIGAR Gene

Protein differential expression in normal tissues from HIPED for TIGAR Gene

This gene is overexpressed in Heart (18.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for TIGAR Gene



mRNA Expression by UniProt/SwissProt for TIGAR Gene

Q9NQ88-TIGAR_HUMAN
Tissue specificity: Expressed in the brain (PubMed:22887998). Expressed in breast tumors (PubMed:21820150). Expressed in glioblastomas (PubMed:22887998).
genes like me logo Genes that share expression patterns with TIGAR: view

Protein tissue co-expression partners for TIGAR Gene

In Situ Assay Products

No data available for mRNA differential expression in normal tissues for TIGAR Gene

Orthologs for TIGAR Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for TIGAR Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia C5H12orf5 35
  • 83.4 (n)
  • 81.78 (a)
TIGAR 36
  • 81 (a)
OneToOne
dog
(Canis familiaris)
Mammalia C27H12orf5 35
  • 86.86 (n)
  • 84.76 (a)
C12orf5 36
  • 84 (a)
OneToOne
mouse
(Mus musculus)
Mammalia 9630033F20Rik 35
  • 75.56 (n)
  • 73.31 (a)
Tigar 16
9630033F20Rik 36
  • 72 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia C12H12orf5 35
  • 99.51 (n)
  • 98.89 (a)
C12orf5 36
  • 99 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia RGD1308005 35
  • 75.17 (n)
  • 73.71 (a)
oppossum
(Monodelphis domestica)
Mammalia C12orf5 36
  • 67 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia C12orf5 36
  • 52 (a)
OneToOne
chicken
(Gallus gallus)
Aves C1H12ORF5 35
  • 67.18 (n)
  • 60.15 (a)
C12orf5 36
  • 55 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia c12orf5 35
  • 58.77 (n)
  • 53.38 (a)
zebrafish
(Danio rerio)
Actinopterygii C25H12orf5 (2 of 2) 36
  • 38 (a)
OneToMany
C4H12orf5 (1 of 2) 36
  • 39 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes -- 36
  • 27 (a)
OneToOne
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 32 (a)
OneToOne
Species with no ortholog for TIGAR:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for TIGAR Gene

ENSEMBL:
Gene Tree for TIGAR (if available)
TreeFam:
Gene Tree for TIGAR (if available)

Paralogs for TIGAR Gene

No data available for Paralogs for TIGAR Gene

Variants for TIGAR Gene

Sequence variations from dbSNP and Humsavar for TIGAR Gene

SNP ID Clin Chr 12 pos Sequence Context AA Info Type
rs7133330 -- 4,352,319(+) GAAGC(A/G)GATCA reference, synonymous-codon
rs7134591 -- 4,340,088(+) GAAAG(A/G)AATAA intron-variant
rs7135386 -- 4,339,979(+) AGAAA(C/G)TGAAA intron-variant
rs7135796 -- 4,340,326(+) AAATA(A/C)TCAGG intron-variant
rs7296130 -- 4,353,866(+) GTTGG(G/T)GGGGA utr-variant-3-prime

Variation tolerance for TIGAR Gene

Residual Variation Intolerance Score: 51.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.95; 19.65% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for TIGAR Gene

HapMap Linkage Disequilibrium report
TIGAR

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Structural Variations from Database of Genomic Variants (DGV) for TIGAR Gene

Disorders for TIGAR Gene

MalaCards: The human disease database

(1) MalaCards diseases for TIGAR Gene - From: GeneCards

Disorder Aliases PubMed IDs
hypoxia
- elite association - COSMIC cancer census association via MalaCards
Search TIGAR in MalaCards View complete list of genes associated with diseases

Relevant External Links for TIGAR

Atlas of Genetics and Cytogenetics in Oncology and Haematology:
TIGAR
genes like me logo Genes that share disorders with TIGAR: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TIGAR Gene

Publications for TIGAR Gene

  1. Modulation of intracellular ROS levels by TIGAR controls autophagy. (PMID: 19713938) Bensaad K. … Vousden K.H. (EMBO J. 2009) 2 3 4 67
  2. Identification of TIGAR in the equilibrative nucleoside transporter 2-mediated response to fludarabine in chronic lymphocytic leukemia cells. (PMID: 18945750) LA^pez-Guerra M. … Pastor-Anglada M. (Haematologica 2008) 2 3
  3. Chemotherapy of metastatic seminoma: the Southeastern Cancer Study Group experience. (PMID: 2442317) Loehrer P.J. … Einhorn L.H. (J. Clin. Oncol. 1987) 2 3
  4. MiR-144 inhibits proliferation and induces apoptosis and autophagy in lung cancer cells by targeting TIGAR. (PMID: 25660220) Chen S. … Zhang G. (Cell. Physiol. Biochem. 2015) 3
  5. TIGAR regulates DNA damage and repair through pentosephosphate pathway and Cdk5-ATM pathway. (PMID: 25928429) Yu H.P. … Qin Z.H. (Sci. Rep. 2015) 3

Products for TIGAR Gene

Sources for TIGAR Gene

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