ID   TIGAR_XENLA             Reviewed;         275 AA.
AC   Q4V7R0;
DT   10-FEB-2009, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2005, sequence version 1.
DT   03-AUG-2022, entry version 59.
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 laevis (African clawed frog).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX   NCBI_TaxID=8355;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Egg;
RG   NIH - Xenopus Gene Collection (XGC) project;
RL   Submitted (JUN-2005) 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; BC097765; AAH97765.1; -; mRNA.
DR   RefSeq; NP_001089513.1; NM_001096044.1.
DR   AlphaFoldDB; Q4V7R0; -.
DR   SMR; Q4V7R0; -.
DR   MaxQB; Q4V7R0; -.
DR   PRIDE; Q4V7R0; -.
DR   DNASU; 734566; -.
DR   GeneID; 734566; -.
DR   KEGG; xla:734566; -.
DR   CTD; 734566; -.
DR   Xenbase; XB-GENE-1008476; tigar.S.
DR   OrthoDB; 1112626at2759; -.
DR   Proteomes; UP000186698; Chromosome 3S.
DR   Bgee; 734566; Expressed in testis and 19 other tissues.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
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   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_0000363069"
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;  30658 MW;  95DF4520AEF1C924 CRC64;
     MARFALTIVR HGETRYNKEK LLQGQGIDEP LSEMGFKQAD AAGRFLSNVR FTHVFSSDLI
     RAKQTACAIM RNNQLSEDIK IMYDPRLRER KYGDAEGRPL SELKVMAKKA GGQCPSYTPP
     GGETLEQVRA CAKDFFEYLC QLVMAESSVK EKSELGASGM VGIMSTDLAP FVNHNKEPTI
     FGESRDVTLD ASVLLVSHGA YMRNWIKYFV EDLQFTFPPE LKKSRELSVS PNTGISHFIV
     TVGSGATRKP EIQCVCINLH GHLSDIDADT SHYQV