ID   TIGAR_XENTR             Reviewed;         275 AA.
AC   B1WAX6;
DT   10-FEB-2009, integrated into UniProtKB/Swiss-Prot.
DT   20-MAY-2008, sequence version 1.
DT   03-AUG-2022, entry version 57.
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};
GN   Name=tigar {ECO:0000250|UniProtKB:Q9NQ88};
OS   Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX   NCBI_TaxID=8364;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Embryo;
RG   NIH - Xenopus Gene Collection (XGC) project;
RL   Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Fructose-bisphosphatase hydrolyzing fructose-2,6-bisphosphate
CC       as well as fructose-1,6-bisphosphate. Acts as a negative regulator of
CC       glycolysis by lowering intracellular levels of fructose-2,6-
CC       bisphosphate in a p53/TP53-dependent manner, resulting in the pentose
CC       phosphate pathway (PPP) activation and NADPH production. Contributes to
CC       the generation of reduced glutathione to cause a decrease in
CC       intracellular reactive oxygen species (ROS) content, correlating with
CC       its ability to protect cells from oxidative or metabolic stress-induced
CC       cell death. May play a role in mitophagy inhibition.
CC       {ECO:0000250|UniProtKB:Q8BZA9, 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   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8BZA9}. Nucleus
CC       {ECO:0000250|UniProtKB:Q9NQ88}. Mitochondrion
CC       {ECO:0000250|UniProtKB:Q8BZA9}.
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; BC161536; AAI61536.1; -; mRNA.
DR   RefSeq; NP_001120569.1; NM_001127097.1.
DR   AlphaFoldDB; B1WAX6; -.
DR   SMR; B1WAX6; -.
DR   STRING; 8364.ENSXETP00000013129; -.
DR   PaxDb; B1WAX6; -.
DR   GeneID; 100145723; -.
DR   KEGG; xtr:100145723; -.
DR   CTD; 57103; -.
DR   Xenbase; XB-GENE-1008472; tigar.
DR   eggNOG; KOG0235; Eukaryota.
DR   InParanoid; B1WAX6; -.
DR   OrthoDB; 1112626at2759; -.
DR   Reactome; R-XTR-5628897; TP53 Regulates Metabolic Genes.
DR   Proteomes; UP000008143; Chromosome 3.
DR   Proteomes; UP000790000; Unplaced.
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:0004083; F:bisphosphoglycerate 2-phosphatase activity; 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:0030388; P:fructose 1,6-bisphosphate metabolic process; ISS:UniProtKB.
DR   GO; GO:0006003; P:fructose 2,6-bisphosphate metabolic process; 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; IBA:GO_Central.
DR   GO; GO:0045739; P:positive regulation of DNA repair; IBA:GO_Central.
DR   GO; GO:0043456; P:regulation of pentose-phosphate shunt; IBA:GO_Central.
DR   CDD; cd07067; HP_PGM_like; 1.
DR   Gene3D; 3.40.50.1240; -; 1.
DR   InterPro; IPR013078; His_Pase_superF_clade-1.
DR   InterPro; IPR029033; His_PPase_superfam.
DR   InterPro; IPR001345; PG/BPGM_mutase_AS.
DR   Pfam; PF00300; His_Phos_1; 1.
DR   SMART; SM00855; PGAM; 1.
DR   SUPFAM; SSF53254; SSF53254; 1.
DR   PROSITE; PS00175; PG_MUTASE; 1.
PE   2: Evidence at transcript level;
KW   Apoptosis; Autophagy; Cytoplasm; Hydrolase; Mitochondrion; Nucleus;
KW   Reference proteome.
FT   CHAIN           1..275
FT                   /note="Fructose-2,6-bisphosphatase TIGAR"
FT                   /id="PRO_0000363070"
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"
SQ   SEQUENCE   275 AA;  30738 MW;  C98131CCDF93B3FA CRC64;
     MARFALTIVR HGETRYNKEK LLQGQGIDEP LSEIGFKQAD AVGRFLSNVR FTHVFSSDLI
     RAKQTACAIM ENNKISEDIK IIYDRRLRER KYGDAEGRPL SELKVMAKKA GDQCPSYTPP
     GGETLEQVRA RAKDFFEYLC RLVLEESSAK EQSELGASGM GGVTSADLGP FVNHNKEPAE
     LGESRDVTVH ASVLLVSHGA YMRNWIKYLV EDLQFTFPPE LKKSRELPVS PNTGISHFIV
     TVSSATPRKP EIQCVCINLH SHLSDINADT SHYQV