ID TIGAR_BOVIN Reviewed; 270 AA.
AC Q1JQA7;
DT 10-FEB-2009, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2006, sequence version 1.
DT 27-MAR-2024, entry version 97.
DE RecName: Full=Fructose-2,6-bisphosphatase TIGAR {ECO:0000305};
DE EC=3.1.3.46 {ECO:0000250|UniProtKB:Q9NQ88};
DE AltName: Full=TP53-induced glycolysis and apoptosis regulator {ECO:0000250|UniProtKB:Q9NQ88};
DE AltName: Full=TP53-induced glycolysis regulatory phosphatase {ECO:0000250|UniProtKB:Q9NQ88};
GN Name=TIGAR {ECO:0000250|UniProtKB:Q9NQ88};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Ascending colon;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Fructose-bisphosphatase hydrolyzing fructose-2,6-bisphosphate
CC as well as fructose-1,6-bisphosphate (By similarity). Acts as a
CC negative regulator of glycolysis by lowering intracellular levels of
CC fructose-2,6-bisphosphate in a p53/TP53-dependent manner, resulting in
CC the pentose phosphate pathway (PPP) activation and NADPH production.
CC Contributes to the generation of reduced glutathione to cause a
CC decrease in intracellular reactive oxygen species (ROS) content,
CC correlating with its ability to protect cells from oxidative or
CC metabolic stress-induced cell death. Plays a role in promoting
CC protection against cell death during hypoxia by decreasing mitochondria
CC ROS levels in a HK2-dependent manner through a mechanism that is
CC independent of its fructose-bisphosphatase activity. In response to
CC cardiac damage stress, mediates p53-induced inhibition of myocyte
CC mitophagy through ROS levels reduction and the subsequent inactivation
CC of BNIP3. Reduced mitophagy results in an enhanced apoptotic myocyte
CC cell death, and exacerbates cardiac damage. Plays a role in adult
CC intestinal regeneration; contributes to the growth, proliferation and
CC survival of intestinal crypts following tissue ablation. Plays a
CC neuroprotective role against ischemic brain damage by enhancing PPP
CC flux and preserving mitochondria functions. Protects glioma cells from
CC hypoxia- and ROS-induced cell death by inhibiting glycolysis and
CC activating mitochondrial energy metabolism and oxygen consumption in a
CC TKTL1-dependent and p53/TP53-independent manner. Plays a role in cancer
CC cell survival by promoting DNA repair through activating PPP flux in a
CC CDK5-ATM-dependent signaling pathway during hypoxia and/or genome
CC stress-induced DNA damage responses. Involved in intestinal tumor
CC progression. {ECO:0000250|UniProtKB:Q8BZA9,
CC ECO:0000250|UniProtKB:Q9NQ88}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-fructose 2,6-bisphosphate + H2O = beta-D-fructose 6-
CC phosphate + phosphate; Xref=Rhea:RHEA:17289, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57634, ChEBI:CHEBI:58579; EC=3.1.3.46;
CC Evidence={ECO:0000250|UniProtKB:Q9NQ88};
CC -!- SUBUNIT: Interacts with HK2; the interaction increases hexokinase HK2
CC activity in a hypoxia- and HIF1A-dependent manner, resulting in the
CC regulation of mitochondrial membrane potential, thus increasing NADPH
CC production and decreasing intracellular ROS levels.
CC {ECO:0000250|UniProtKB:Q9NQ88}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8BZA9}. Nucleus
CC {ECO:0000250|UniProtKB:Q9NQ88}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q8BZA9}. Note=Translocated to the mitochondria
CC during hypoxia in a HIF1A-dependent manner. Colocalizes with HK2 in the
CC mitochondria during hypoxia. Translocated to the nucleus during hypoxia
CC and/or genome stress-induced DNA damage responses in cancer cells.
CC Translocation to the mitochondria is enhanced in ischemic cortex after
CC reperfusion and/or during oxygen and glucose deprivation
CC (OGD)/reoxygenation insult in primary neurons.
CC {ECO:0000250|UniProtKB:Q8BZA9, ECO:0000250|UniProtKB:Q9NQ88}.
CC -!- SIMILARITY: Belongs to the phosphoglycerate mutase family.
CC {ECO:0000305}.
CC -!- CAUTION: Not expected to have any kinase activity. {ECO:0000305}.
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DR EMBL; BC116101; AAI16102.1; -; mRNA.
DR RefSeq; NP_001069838.1; NM_001076370.1.
DR AlphaFoldDB; Q1JQA7; -.
DR SMR; Q1JQA7; -.
DR STRING; 9913.ENSBTAP00000022146; -.
DR PaxDb; 9913-ENSBTAP00000022146; -.
DR Ensembl; ENSBTAT00000022146.4; ENSBTAP00000022146.3; ENSBTAG00000016650.4.
DR GeneID; 615392; -.
DR KEGG; bta:615392; -.
DR CTD; 57103; -.
DR VEuPathDB; HostDB:ENSBTAG00000016650; -.
DR VGNC; VGNC:35863; TIGAR.
DR eggNOG; KOG0235; Eukaryota.
DR GeneTree; ENSGT00390000013224; -.
DR HOGENOM; CLU_033323_16_0_1; -.
DR InParanoid; Q1JQA7; -.
DR OMA; PTIQCVC; -.
DR OrthoDB; 88851at2759; -.
DR TreeFam; TF329053; -.
DR Reactome; R-BTA-5628897; TP53 Regulates Metabolic Genes.
DR Proteomes; UP000009136; Chromosome 5.
DR Bgee; ENSBTAG00000016650; Expressed in oocyte and 105 other cell types or tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0004331; F:fructose-2,6-bisphosphate 2-phosphatase activity; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0071456; P:cellular response to hypoxia; ISS:UniProtKB.
DR GO; GO:0006974; P:DNA damage response; ISS:UniProtKB.
DR GO; GO:0045820; P:negative regulation of glycolytic process; IBA:GO_Central.
DR GO; GO:0043069; P:negative regulation of programmed cell death; ISS:UniProtKB.
DR GO; GO:0045739; P:positive regulation of DNA repair; ISS:UniProtKB.
DR GO; GO:1903301; P:positive regulation of hexokinase activity; ISS:UniProtKB.
DR GO; GO:1905857; P:positive regulation of pentose-phosphate shunt; ISS:UniProtKB.
DR GO; GO:0043456; P:regulation of pentose-phosphate shunt; ISS:UniProtKB.
DR GO; GO:1902153; P:regulation of response to DNA damage checkpoint signaling; ISS:UniProtKB.
DR GO; GO:0002931; P:response to ischemia; ISS:UniProtKB.
DR CDD; cd07067; HP_PGM_like; 1.
DR Gene3D; 3.40.50.1240; Phosphoglycerate mutase-like; 1.
DR InterPro; IPR013078; His_Pase_superF_clade-1.
DR InterPro; IPR029033; His_PPase_superfam.
DR InterPro; IPR001345; PG/BPGM_mutase_AS.
DR PANTHER; PTHR46517; FRUCTOSE-2,6-BISPHOSPHATASE TIGAR; 1.
DR PANTHER; PTHR46517:SF1; FRUCTOSE-2,6-BISPHOSPHATASE TIGAR; 1.
DR Pfam; PF00300; His_Phos_1; 1.
DR SMART; SM00855; PGAM; 1.
DR SUPFAM; SSF53254; Phosphoglycerate mutase-like; 1.
DR PROSITE; PS00175; PG_MUTASE; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Apoptosis; Autophagy; Cytoplasm; Hydrolase; Mitochondrion;
KW Nucleus; Reference proteome.
FT CHAIN 1..270
FT /note="Fructose-2,6-bisphosphatase TIGAR"
FT /id="PRO_0000363066"
FT ACT_SITE 11
FT /note="Tele-phosphohistidine intermediate"
FT /evidence="ECO:0000250|UniProtKB:Q7ZVE3"
FT ACT_SITE 89
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q7ZVE3"
FT SITE 198
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:Q7ZVE3"
FT MOD_RES 50
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9NQ88"
SQ SEQUENCE 270 AA; 29467 MW; 2D738CBE454EA6D8 CRC64;
MTRFALTVVR HGETRLNKEK IIQGQGIDEP LSETGFKQAA AAGIFLKDVK FTHVFSSDLT
RTKQTVHGIL EKSKFCKDMT VKYDSRLRER KYGVAEGRPL SELRAMAKAA GEECPAFTPP
GGETLDQLKR RGKDFFEFLC QLILKEAGQN EQFSQEAPSS CLESSLAEIF PLGKNCASTF
NSDSGTPGLA ASVLVVSHGA YIRSLLDYFL TDLKCSFPAT LSRSELTSVS PNTGMTVFIL
NFEKGGKGRP TAQCVCVNLQ GHLAGVNKTP
//
