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Protein

Fructose-2,6-bisphosphatase TIGAR

Gene

TIGAR

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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. 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. 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. 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. Plays a role in adult intestinal regeneration; contributes to the growth, proliferation and survival of intestinal crypts following tissue ablation. Plays a neuroprotective role against ischemic brain damage by enhancing PPP flux and preserving mitochondria functions. 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. Involved in intestinal tumor progression.By similarity

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei11 – 111Tele-phosphohistidine intermediateBy similarity
Active sitei89 – 891Proton donor/acceptorBy similarity
Sitei198 – 1981Transition state stabilizerBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Apoptosis, Autophagy

Enzyme and pathway databases

ReactomeiR-BTA-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 phosphataseBy similarity
Gene namesi
Name:TIGARBy similarity
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 5

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity
  • Mitochondrion By similarity

  • 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. 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

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 270270Fructose-2,6-bisphosphatase TIGARPRO_0000363066Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei50 – 501N6-acetyllysineBy similarity

Keywords - PTMi

Acetylation

Proteomic databases

PaxDbiQ1JQA7.

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

STRINGi9913.ENSBTAP00000022146.

Structurei

3D structure databases

ProteinModelPortaliQ1JQA7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the phosphoglycerate mutase family.Curated

Phylogenomic databases

eggNOGiENOG410IUDB. Eukaryota.
COG0406. LUCA.
GeneTreeiENSGT00390000013224.
HOGENOMiHOG000060277.
HOVERGENiHBG108569.
InParanoidiQ1JQA7.
KOiK14634.
OMAiNFEEGRE.
OrthoDBiEOG7CVPZ7.
TreeFamiTF329053.

Family and domain databases

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.

Q1JQA7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTRFALTVVR HGETRLNKEK IIQGQGIDEP LSETGFKQAA AAGIFLKDVK
60 70 80 90 100
FTHVFSSDLT RTKQTVHGIL EKSKFCKDMT VKYDSRLRER KYGVAEGRPL
110 120 130 140 150
SELRAMAKAA GEECPAFTPP GGETLDQLKR RGKDFFEFLC QLILKEAGQN
160 170 180 190 200
EQFSQEAPSS CLESSLAEIF PLGKNCASTF NSDSGTPGLA ASVLVVSHGA
210 220 230 240 250
YIRSLLDYFL TDLKCSFPAT LSRSELTSVS PNTGMTVFIL NFEKGGKGRP
260 270
TAQCVCVNLQ GHLAGVNKTP
Length:270
Mass (Da):29,467
Last modified:June 13, 2006 - v1
Checksum:i2D738CBE454EA6D8
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC116101 mRNA. Translation: AAI16102.1.
RefSeqiNP_001069838.1. NM_001076370.1.
UniGeneiBt.61374.

Genome annotation databases

EnsembliENSBTAT00000022146; ENSBTAP00000022146; ENSBTAG00000016650.
GeneIDi615392.
KEGGibta:615392.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC116101 mRNA. Translation: AAI16102.1.
RefSeqiNP_001069838.1. NM_001076370.1.
UniGeneiBt.61374.

3D structure databases

ProteinModelPortaliQ1JQA7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000022146.

Proteomic databases

PaxDbiQ1JQA7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000022146; ENSBTAP00000022146; ENSBTAG00000016650.
GeneIDi615392.
KEGGibta:615392.

Organism-specific databases

CTDi57103.

Phylogenomic databases

eggNOGiENOG410IUDB. Eukaryota.
COG0406. LUCA.
GeneTreeiENSGT00390000013224.
HOGENOMiHOG000060277.
HOVERGENiHBG108569.
InParanoidiQ1JQA7.
KOiK14634.
OMAiNFEEGRE.
OrthoDBiEOG7CVPZ7.
TreeFamiTF329053.

Enzyme and pathway databases

ReactomeiR-BTA-5628897. TP53 Regulates Metabolic Genes.

Miscellaneous databases

NextBioi20899599.

Family and domain databases

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...

Publicationsi

  1. NIH - Mammalian Gene Collection (MGC) project
    Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Hereford.
    Tissue: Ascending colon.

Entry informationi

Entry nameiTIGAR_BOVIN
AccessioniPrimary (citable) accession number: Q1JQA7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 10, 2009
Last sequence update: June 13, 2006
Last modified: May 11, 2016
This is version 67 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. 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.