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Protein

Fructose-2,6-bisphosphatase TIGAR

Gene

Tigar

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

Caution

Not expected to have any kinase activity.Curated

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

  • bisphosphoglycerate 2-phosphatase activity Source: UniProtKB
  • fructose-2,6-bisphosphate 2-phosphatase activity Source: MGI

GO - Biological processi

Keywordsi

Molecular functionHydrolase
Biological processApoptosis, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:2442752 Tigar

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 Expressed in 222 organ(s), highest expression level in quadriceps femoris
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, 1 hit
InterProiView protein in InterPro
IPR013078 His_Pase_superF_clade-1
IPR029033 His_PPase_superfam
IPR001345 PG/BPGM_mutase_AS
PfamiView protein in Pfam
PF00300 His_Phos_1, 1 hit
SMARTiView protein in SMART
SM00855 PGAM, 1 hit
SUPFAMiSSF53254 SSF53254, 2 hits
PROSITEiView protein in PROSITE
PS00175 PG_MUTASE, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0J9YV11A0A0J9YV11_MOUSE
Fructose-2,6-bisphosphatase TIGAR
Tigar
49Annotation score:

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

Similar proteinsi

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

PROiPR:Q8BZA9
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000038028 Expressed in 222 organ(s), highest expression level in quadriceps femoris
CleanExiMM_9630033F20RIK
ExpressionAtlasiQ8BZA9 baseline and differential
GenevisibleiQ8BZA9 MM

Family and domain databases

CDDicd07067 HP_PGM_like, 1 hit
Gene3Di3.40.50.1240, 1 hit
InterProiView protein in InterPro
IPR013078 His_Pase_superF_clade-1
IPR029033 His_PPase_superfam
IPR001345 PG/BPGM_mutase_AS
PfamiView protein in Pfam
PF00300 His_Phos_1, 1 hit
SMARTiView protein in SMART
SM00855 PGAM, 1 hit
SUPFAMiSSF53254 SSF53254, 2 hits
PROSITEiView protein in PROSITE
PS00175 PG_MUTASE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTIGAR_MOUSE
AccessioniPrimary (citable) accession number: Q8BZA9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: March 1, 2003
Last modified: September 12, 2018
This is version 115 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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