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Protein

Fructose-2,6-bisphosphatase TIGAR

Gene

Tigar

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Fructose-bisphosphatase hydrolyzing fructose-2,6-bisphosphate as well as fructose-1,6-bisphosphate (By similarity). 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:23726973). 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:23726973). 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 (By similarity). In response to cardiac damage stress, mediates p53-induced inhibition of myocyte mitophagy through ROS levels reduction and the subsequent inactivation of BNIP3 (PubMed:22044588). Reduced mitophagy results in an enhanced apoptotic myocyte cell death, and exacerbates cardiac damage (PubMed:22044588). 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 (PubMed:24872551). 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. 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 (By similarity). Involved in intestinal tumor progression (PubMed:23726973).By similarity3 Publications

Catalytic activityi

Beta-D-fructose 2,6-bisphosphate + H2O = D-fructose 6-phosphate + phosphate.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei11Tele-phosphohistidine intermediateBy similarity1
Active sitei89Proton donor/acceptorBy similarity1
Sitei198Transition state stabilizerBy similarity1

GO - Molecular functioni

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • autophagy Source: UniProtKB-KW
  • cellular response to cobalt ion Source: MGI
  • cellular response to DNA damage stimulus Source: UniProtKB
  • cellular response to hypoxia Source: UniProtKB
  • fructose 1,6-bisphosphate metabolic process Source: UniProtKB
  • fructose 2,6-bisphosphate metabolic process Source: UniProtKB
  • intestinal epithelial cell development Source: MGI
  • negative regulation of glucose catabolic process to lactate via pyruvate Source: MGI
  • negative regulation of glycolytic process Source: MGI
  • negative regulation of kinase activity Source: MGI
  • negative regulation of macromitophagy Source: MGI
  • negative regulation of neuron death Source: UniProtKB
  • negative regulation of programmed cell death Source: UniProtKB
  • negative regulation of reactive oxygen species metabolic process Source: MGI
  • positive regulation of cardiac muscle cell apoptotic process Source: MGI
  • positive regulation of DNA repair Source: UniProtKB
  • positive regulation of hexokinase activity Source: UniProtKB
  • regulation of pentose-phosphate shunt Source: UniProtKB
  • regulation of response to DNA damage checkpoint signaling Source: UniProtKB
  • response to gamma radiation Source: MGI
  • response to ischemia Source: UniProtKB
  • response to xenobiotic stimulus Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Apoptosis, Autophagy

Enzyme and pathway databases

ReactomeiR-MMU-5628897. TP53 Regulates Metabolic Genes.

Names & Taxonomyi

Protein namesi
Recommended name:
Fructose-2,6-bisphosphatase TIGARCurated (EC:3.1.3.46By similarity)
Alternative name(s):
TP53-induced glycolysis and apoptosis regulatorBy similarity
TP53-induced glycolysis regulatory phosphataseImported
Gene namesi
Name:TigarImported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:2442752. Tigar.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Nucleus By similarity
  • Mitochondrion 1 Publication

  • Note: Translocated to the mitochondria during hypoxia in a HIF1A-dependent manner. Colocalizes with HK2 in the mitochondria during hypoxia. Translocated to the nucleus during hypoxia and/or genome stress-induced DNA damage responses in cancer cells (By similarity). Translocation to the mitochondria is enhanced in ischemic cortex after reperfusion and/or during oxygen and glucose deprivation (OGD)/reoxygenation insult in primary neurons (PubMed:24872551).By similarity1 Publication

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: GO_Central
  • intracellular Source: MGI
  • mitochondrial outer membrane Source: UniProtKB
  • mitochondrion Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice are viable and fertile and show no obvious developmental defects (PubMed:23726973). Following intestine ablation by gamma irradiation, adult mice display a reduction in the size and number of proliferating intestinal crypts and an increase in cell death (PubMed:23726973). Mice display reduced intestinal tumor progression compared to wild-type mice (PubMed:23726973). In response to ischemic myocardium injury, display an increase in the ability to stimulate myocyte mitophagy in ischemic border zones through a ROS-induced and BNIP3 activation dependent manner leading to a reduction of defective mitochondria and myocyte cell death, and hence a better recovery of cardiac function (PubMed:22044588).2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001799581 – 269Fructose-2,6-bisphosphatase TIGARAdd BLAST269

Proteomic databases

EPDiQ8BZA9.
MaxQBiQ8BZA9.
PaxDbiQ8BZA9.
PRIDEiQ8BZA9.

PTM databases

iPTMnetiQ8BZA9.
PhosphoSitePlusiQ8BZA9.

Expressioni

Tissue specificityi

Expressed in olfactory bulb, cerebellum, and cortex (PubMed:24872551). Expressed in neurons and astrocytes (PubMed:24872551) (at protein level). Expressed in intestinal crypt (PubMed:23726973).2 Publications

Inductioni

Up-regulated by hypoxia in cardiac myocytes in a p53/TP53-dependent manner (PubMed:20935145). Up-regulated in ischemic cortex after reperfusion in a p53/TP5-independent manner (PubMed:24872551). Up-regulated in primary neurons by oxygen and glucose deprivation (OGD)/reoxygenation insult in a p53/TP5-independent manner (at protein level) (PubMed:24872551). Up-regulated in ischemic myocardium in a p53/TP5-dependent manner (PubMed:22044588). Up-regulated in small intestine after gamma irradiation damage (PubMed:23726973).4 Publications

Gene expression databases

BgeeiENSMUSG00000038028.
CleanExiMM_9630033F20RIK.
ExpressionAtlasiQ8BZA9. baseline and differential.
GenevisibleiQ8BZA9. MM.

Interactioni

Subunit structurei

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.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000048643.

Structurei

3D structure databases

ProteinModelPortaliQ8BZA9.
SMRiQ8BZA9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the phosphoglycerate mutase family.Curated

Phylogenomic databases

eggNOGiENOG410IUDB. Eukaryota.
COG0406. LUCA.
GeneTreeiENSGT00390000013224.
HOGENOMiHOG000060277.
HOVERGENiHBG108569.
InParanoidiQ8BZA9.
KOiK14634.
OMAiNFEEGRE.
OrthoDBiEOG091G0W1L.
PhylomeDBiQ8BZA9.
TreeFamiTF329053.

Family and domain databases

CDDicd07067. HP_PGM_like. 1 hit.
Gene3Di3.40.50.1240. 2 hits.
InterProiIPR013078. His_Pase_superF_clade-1.
IPR029033. His_PPase_superfam.
IPR001345. PG/BPGM_mutase_AS.
[Graphical view]
PfamiPF00300. His_Phos_1. 1 hit.
[Graphical view]
SMARTiSM00855. PGAM. 1 hit.
[Graphical view]
SUPFAMiSSF53254. SSF53254. 2 hits.
PROSITEiPS00175. PG_MUTASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8BZA9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPRFALTVIR HGETRLNKEK IIQGQGVDAP LSETGFRQAA AAGQFLSNVQ
60 70 80 90 100
FTHAFSSDLT RTKQTIHGIL EKSRFCKDMA VKYDSRLRER MYGVAEGKPL
110 120 130 140 150
SELRAMAKAA GEECPMFTPP GGETVEQVKM RGKDFFDFIC QLILGKAGQR
160 170 180 190 200
ESVLPGAPGS GLESSLAEVF PVGKHGSLGA NPKGGTLGLA ASILVVSHGA
210 220 230 240 250
YMRSLFGYFL SDLRCSLPGA RDKLELSSIT PNTGISVFII DCEEARQPSI
260
QCVCMNLQEH LNGVTEKQH
Length:269
Mass (Da):29,191
Last modified:March 1, 2003 - v1
Checksum:iD029B6E34226FE0E
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK036082 mRNA. Translation: BAC29298.1.
AK145896 mRNA. Translation: BAE26732.1.
AK163290 mRNA. Translation: BAE37278.1.
CCDSiCCDS20563.1.
RefSeqiNP_795977.1. NM_177003.5.
UniGeneiMm.101836.

Genome annotation databases

EnsembliENSMUST00000039913; ENSMUSP00000048643; ENSMUSG00000038028.
GeneIDi319801.
KEGGimmu:319801.
UCSCiuc009dvq.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK036082 mRNA. Translation: BAC29298.1.
AK145896 mRNA. Translation: BAE26732.1.
AK163290 mRNA. Translation: BAE37278.1.
CCDSiCCDS20563.1.
RefSeqiNP_795977.1. NM_177003.5.
UniGeneiMm.101836.

3D structure databases

ProteinModelPortaliQ8BZA9.
SMRiQ8BZA9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000048643.

PTM databases

iPTMnetiQ8BZA9.
PhosphoSitePlusiQ8BZA9.

Proteomic databases

EPDiQ8BZA9.
MaxQBiQ8BZA9.
PaxDbiQ8BZA9.
PRIDEiQ8BZA9.

Protocols and materials databases

DNASUi319801.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000039913; ENSMUSP00000048643; ENSMUSG00000038028.
GeneIDi319801.
KEGGimmu:319801.
UCSCiuc009dvq.2. mouse.

Organism-specific databases

CTDi57103.
MGIiMGI:2442752. Tigar.

Phylogenomic databases

eggNOGiENOG410IUDB. Eukaryota.
COG0406. LUCA.
GeneTreeiENSGT00390000013224.
HOGENOMiHOG000060277.
HOVERGENiHBG108569.
InParanoidiQ8BZA9.
KOiK14634.
OMAiNFEEGRE.
OrthoDBiEOG091G0W1L.
PhylomeDBiQ8BZA9.
TreeFamiTF329053.

Enzyme and pathway databases

ReactomeiR-MMU-5628897. TP53 Regulates Metabolic Genes.

Miscellaneous databases

PROiQ8BZA9.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000038028.
CleanExiMM_9630033F20RIK.
ExpressionAtlasiQ8BZA9. baseline and differential.
GenevisibleiQ8BZA9. MM.

Family and domain databases

CDDicd07067. HP_PGM_like. 1 hit.
Gene3Di3.40.50.1240. 2 hits.
InterProiIPR013078. His_Pase_superF_clade-1.
IPR029033. His_PPase_superfam.
IPR001345. PG/BPGM_mutase_AS.
[Graphical view]
PfamiPF00300. His_Phos_1. 1 hit.
[Graphical view]
SMARTiSM00855. PGAM. 1 hit.
[Graphical view]
SUPFAMiSSF53254. SSF53254. 2 hits.
PROSITEiPS00175. PG_MUTASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTIGAR_MOUSE
AccessioniPrimary (citable) accession number: Q8BZA9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: March 1, 2003
Last modified: November 2, 2016
This is version 108 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

Not expected to have any kinase activity.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.