TIGAR_HUMAN
ID TIGAR_HUMAN Reviewed; 270 AA.
AC Q9NQ88; B2R840;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Fructose-2,6-bisphosphatase TIGAR {ECO:0000305};
DE EC=3.1.3.46 {ECO:0000269|PubMed:19015259};
DE AltName: Full=TP53-induced glycolysis and apoptosis regulator {ECO:0000303|PubMed:16839880};
DE AltName: Full=TP53-induced glycolysis regulatory phosphatase {ECO:0000312|HGNC:HGNC:1185};
GN Name=TIGAR {ECO:0000303|PubMed:16839880}; Synonyms=C12orf5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11062477; DOI=10.1038/81664;
RA White K.E., Evans W.E., O'Riordan J.L.H., Speer M.C., Econs M.J.,
RA Lorenz-Depiereux B., Grabowski M., Meitinger T., Strom T.M.;
RT "Autosomal dominant hypophosphataemic rickets is associated with mutations
RT in FGF23.";
RL Nat. Genet. 26:345-348(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Cheng J., Dang X., Wang J., Ji D., Wang C., Yang Q., Liu Y.;
RT "Screening and cloning of the target genes transactivated by human gene 2
RT transactivated by nonstructural protein 3 of Hepatitis C virus using
RT suppression subtractive hybridization technique.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=B-cell;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INDUCTION.
RX PubMed=16140933; DOI=10.1158/0008-5472.can-05-1039;
RA Jen K.Y., Cheung V.G.;
RT "Identification of novel p53 target genes in ionizing radiation response.";
RL Cancer Res. 65:7666-7673(2005).
RN [7]
RP FUNCTION, MUTAGENESIS OF HIS-11; GLU-102 AND HIS-198, AND INDUCTION.
RX PubMed=16839880; DOI=10.1016/j.cell.2006.05.036;
RA Bensaad K., Tsuruta A., Selak M.A., Vidal M.N., Nakano K., Bartrons R.,
RA Gottlieb E., Vousden K.H.;
RT "TIGAR, a p53-inducible regulator of glycolysis and apoptosis.";
RL Cell 126:107-120(2006).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [9]
RP FUNCTION, AND INDUCTION.
RX PubMed=19713938; DOI=10.1038/emboj.2009.242;
RA Bensaad K., Cheung E.C., Vousden K.H.;
RT "Modulation of intracellular ROS levels by TIGAR controls autophagy.";
RL EMBO J. 28:3015-3026(2009).
RN [10]
RP CATALYTIC ACTIVITY.
RX PubMed=19015259; DOI=10.1074/jbc.m807821200;
RA Li H., Jogl G.;
RT "Structural and biochemical studies of TIGAR (TP53-induced glycolysis and
RT apoptosis regulator).";
RL J. Biol. Chem. 284:1748-1754(2009).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-50, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP TISSUE SPECIFICITY.
RX PubMed=21820150; DOI=10.1016/j.humpath.2011.04.021;
RA Won K.Y., Lim S.J., Kim G.Y., Kim Y.W., Han S.A., Song J.Y., Lee D.K.;
RT "Regulatory role of p53 in cancer metabolism via SCO2 and TIGAR in human
RT breast cancer.";
RL Hum. Pathol. 43:221-228(2012).
RN [14]
RP FUNCTION, INDUCTION, TISSUE SPECIFICITY, AND MUTAGENESIS OF HIS-11; GLU-102
RP AND HIS-198.
RX PubMed=22887998; DOI=10.1074/jbc.m112.384578;
RA Wanka C., Steinbach J.P., Rieger J.;
RT "Tp53-induced glycolysis and apoptosis regulator (TIGAR) protects glioma
RT cells from starvation-induced cell death by up-regulating respiration and
RT improving cellular redox homeostasis.";
RL J. Biol. Chem. 287:33436-33446(2012).
RN [15]
RP FUNCTION, INTERACTION WITH HK2, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP HIS-11; GLU-102; HIS-198 AND 258-ASN--ASP-261.
RX PubMed=23185017; DOI=10.1073/pnas.1206530109;
RA Cheung E.C., Ludwig R.L., Vousden K.H.;
RT "Mitochondrial localization of TIGAR under hypoxia stimulates HK2 and
RT lowers ROS and cell death.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:20491-20496(2012).
RN [16]
RP FUNCTION.
RX PubMed=23817040; DOI=10.1016/j.bbrc.2013.06.072;
RA Ye L., Zhao X., Lu J., Qian G., Zheng J.C., Ge S.;
RT "Knockdown of TIGAR by RNA interference induces apoptosis and autophagy in
RT HepG2 hepatocellular carcinoma cells.";
RL Biochem. Biophys. Res. Commun. 437:300-306(2013).
RN [17]
RP FUNCTION, AND MUTAGENESIS OF HIS-11; GLU-102 AND HIS-198.
RX PubMed=23726973; DOI=10.1016/j.devcel.2013.05.001;
RA Cheung E.C., Athineos D., Lee P., Ridgway R.A., Lambie W., Nixon C.,
RA Strathdee D., Blyth K., Sansom O.J., Vousden K.H.;
RT "TIGAR is required for efficient intestinal regeneration and
RT tumorigenesis.";
RL Dev. Cell 25:463-477(2013).
RN [18]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25928429; DOI=10.1038/srep09853;
RA Yu H.P., Xie J.M., Li B., Sun Y.H., Gao Q.G., Ding Z.H., Wu H.R., Qin Z.H.;
RT "TIGAR regulates DNA damage and repair through pentosephosphate pathway and
RT Cdk5-ATM pathway.";
RL Sci. Rep. 5:9853-9853(2015).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 2-270.
RG Center for eukaryotic structural genomics (CESG);
RT "Crystal structure a TP53-induced glycolysis and apoptosis regulator
RT protein from Homo sapiens.";
RL Submitted (FEB-2009) to the PDB data bank.
CC -!- FUNCTION: Fructose-bisphosphatase hydrolyzing fructose-2,6-bisphosphate
CC as well as fructose-1,6-bisphosphate (PubMed:19015259). 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 (PubMed:16839880, PubMed:22887998). Contributes to the generation of
CC reduced glutathione to cause a decrease in intracellular reactive
CC oxygen species (ROS) content, correlating with its ability to protect
CC cells from oxidative or metabolic stress-induced cell death
CC (PubMed:16839880, PubMed:19713938, PubMed:23726973, PubMed:22887998,
CC PubMed:23817040). Plays a role in promoting protection against cell
CC death during hypoxia by decreasing mitochondria ROS levels in a HK2-
CC dependent manner through a mechanism that is independent of its
CC fructose-bisphosphatase activity (PubMed:23185017). 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 (By similarity). Plays a
CC role in adult intestinal regeneration; contributes to the growth,
CC proliferation and survival of intestinal crypts following tissue
CC ablation (PubMed:23726973). Plays a neuroprotective role against
CC ischemic brain damage by enhancing PPP flux and preserving mitochondria
CC functions (By similarity). Protects glioma cells from hypoxia- and ROS-
CC induced cell death by inhibiting glycolysis and activating
CC mitochondrial energy metabolism and oxygen consumption in a TKTL1-
CC dependent and p53/TP53-independent manner (PubMed:22887998). Plays a
CC role in cancer cell survival by promoting DNA repair through activating
CC PPP flux in a CDK5-ATM-dependent signaling pathway during hypoxia
CC and/or genome stress-induced DNA damage responses (PubMed:25928429).
CC Involved in intestinal tumor progression (PubMed:23726973).
CC {ECO:0000250|UniProtKB:Q8BZA9, ECO:0000269|PubMed:16839880,
CC ECO:0000269|PubMed:19015259, ECO:0000269|PubMed:19713938,
CC ECO:0000269|PubMed:22887998, ECO:0000269|PubMed:23185017,
CC ECO:0000269|PubMed:23726973, ECO:0000269|PubMed:23817040,
CC ECO:0000269|PubMed:25928429}.
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:0000269|PubMed:19015259};
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 (PubMed:23185017).
CC {ECO:0000269|PubMed:23185017}.
CC -!- INTERACTION:
CC Q9NQ88; P55212: CASP6; NbExp=3; IntAct=EBI-3920747, EBI-718729;
CC Q9NQ88; O00291: HIP1; NbExp=3; IntAct=EBI-3920747, EBI-473886;
CC Q9NQ88; P52789: HK2; NbExp=3; IntAct=EBI-3920747, EBI-741469;
CC Q9NQ88; P13473-2: LAMP2; NbExp=3; IntAct=EBI-3920747, EBI-21591415;
CC Q9NQ88; Q9Y371: SH3GLB1; NbExp=3; IntAct=EBI-3920747, EBI-2623095;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23185017,
CC ECO:0000269|PubMed:25928429}. Nucleus {ECO:0000269|PubMed:25928429}.
CC Mitochondrion {ECO:0000269|PubMed:23185017}. Note=Translocated to the
CC mitochondria during hypoxia in a HIF1A-dependent manner
CC (PubMed:23185017). Colocalizes with HK2 in the mitochondria during
CC hypoxia (PubMed:23185017). Translocated to the nucleus during hypoxia
CC and/or genome stress-induced DNA damage responses in cancer cells
CC (PubMed:25928429). Translocation to the mitochondria is enhanced in
CC ischemic cortex after reperfusion and/or during oxygen and glucose
CC deprivation (OGD)/reoxygenation insult in primary neurons (By
CC similarity). {ECO:0000250|UniProtKB:Q8BZA9,
CC ECO:0000269|PubMed:23185017, ECO:0000269|PubMed:25928429}.
CC -!- TISSUE SPECIFICITY: Expressed in the brain (PubMed:22887998). Expressed
CC in breast tumors (PubMed:21820150). Expressed in glioblastomas
CC (PubMed:22887998). {ECO:0000269|PubMed:21820150,
CC ECO:0000269|PubMed:22887998}.
CC -!- INDUCTION: Up-regulated by p53/TP53 (at protein level)
CC (PubMed:16839880). Rapidly up-regulated by p53/TP53 (PubMed:16140933,
CC PubMed:16839880, PubMed:19713938). Up-regulated in glioma cell line in
CC a p53/TP53-independent manner (PubMed:22887998).
CC {ECO:0000269|PubMed:16140933, ECO:0000269|PubMed:16839880,
CC ECO:0000269|PubMed:19713938, ECO:0000269|PubMed:22887998}.
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; AJ272206; CAC01127.1; -; mRNA.
DR EMBL; AY425618; AAQ98969.1; -; mRNA.
DR EMBL; AK313226; BAG36037.1; -; mRNA.
DR EMBL; CH471116; EAW88849.1; -; Genomic_DNA.
DR EMBL; BC012340; AAH12340.1; -; mRNA.
DR CCDS; CCDS8525.1; -.
DR RefSeq; NP_065108.1; NM_020375.2.
DR PDB; 3DCY; X-ray; 1.75 A; A=2-270.
DR PDBsum; 3DCY; -.
DR AlphaFoldDB; Q9NQ88; -.
DR SMR; Q9NQ88; -.
DR BioGRID; 121369; 51.
DR DIP; DIP-60093N; -.
DR IntAct; Q9NQ88; 11.
DR STRING; 9606.ENSP00000179259; -.
DR ChEMBL; CHEMBL4295958; -.
DR DEPOD; TIGAR; -.
DR GlyGen; Q9NQ88; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NQ88; -.
DR PhosphoSitePlus; Q9NQ88; -.
DR BioMuta; TIGAR; -.
DR DMDM; 74734311; -.
DR EPD; Q9NQ88; -.
DR jPOST; Q9NQ88; -.
DR MassIVE; Q9NQ88; -.
DR MaxQB; Q9NQ88; -.
DR PaxDb; Q9NQ88; -.
DR PeptideAtlas; Q9NQ88; -.
DR PRIDE; Q9NQ88; -.
DR ProteomicsDB; 82106; -.
DR Antibodypedia; 22261; 394 antibodies from 37 providers.
DR DNASU; 57103; -.
DR Ensembl; ENST00000179259.6; ENSP00000179259.4; ENSG00000078237.7.
DR GeneID; 57103; -.
DR KEGG; hsa:57103; -.
DR MANE-Select; ENST00000179259.6; ENSP00000179259.4; NM_020375.3; NP_065108.1.
DR UCSC; uc001qmp.4; human.
DR CTD; 57103; -.
DR DisGeNET; 57103; -.
DR GeneCards; TIGAR; -.
DR HGNC; HGNC:1185; TIGAR.
DR HPA; ENSG00000078237; Low tissue specificity.
DR MIM; 610775; gene.
DR neXtProt; NX_Q9NQ88; -.
DR OpenTargets; ENSG00000078237; -.
DR PharmGKB; PA25506; -.
DR VEuPathDB; HostDB:ENSG00000078237; -.
DR eggNOG; KOG0235; Eukaryota.
DR GeneTree; ENSGT00390000013224; -.
DR HOGENOM; CLU_033323_16_0_1; -.
DR InParanoid; Q9NQ88; -.
DR OMA; YMRNWIG; -.
DR OrthoDB; 1112626at2759; -.
DR PhylomeDB; Q9NQ88; -.
DR TreeFam; TF329053; -.
DR BioCyc; MetaCyc:HS01277-MON; -.
DR PathwayCommons; Q9NQ88; -.
DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes.
DR SignaLink; Q9NQ88; -.
DR SIGNOR; Q9NQ88; -.
DR BioGRID-ORCS; 57103; 8 hits in 1069 CRISPR screens.
DR ChiTaRS; TIGAR; human.
DR EvolutionaryTrace; Q9NQ88; -.
DR GeneWiki; C12orf5; -.
DR GenomeRNAi; 57103; -.
DR Pharos; Q9NQ88; Tbio.
DR PRO; PR:Q9NQ88; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9NQ88; protein.
DR Bgee; ENSG00000078237; Expressed in monocyte and 103 other tissues.
DR ExpressionAtlas; Q9NQ88; baseline and differential.
DR Genevisible; Q9NQ88; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0004083; F:bisphosphoglycerate 2-phosphatase activity; IDA:UniProtKB.
DR GO; GO:0004331; F:fructose-2,6-bisphosphate 2-phosphatase activity; IDA:UniProtKB.
DR GO; GO:0010659; P:cardiac muscle cell apoptotic process; IEA:Ensembl.
DR GO; GO:0071279; P:cellular response to cobalt ion; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0071456; P:cellular response to hypoxia; IDA:UniProtKB.
DR GO; GO:0030388; P:fructose 1,6-bisphosphate metabolic process; IDA:UniProtKB.
DR GO; GO:0006003; P:fructose 2,6-bisphosphate metabolic process; IDA:UniProtKB.
DR GO; GO:0019661; P:glucose catabolic process to lactate via pyruvate; IEA:Ensembl.
DR GO; GO:0006096; P:glycolytic process; IEA:Ensembl.
DR GO; GO:0060576; P:intestinal epithelial cell development; IEA:Ensembl.
DR GO; GO:0000423; P:mitophagy; IEA:Ensembl.
DR GO; GO:1904024; P:negative regulation of glucose catabolic process to lactate via pyruvate; IEA:Ensembl.
DR GO; GO:0045820; P:negative regulation of glycolytic process; IBA:GO_Central.
DR GO; GO:1901525; P:negative regulation of mitophagy; IEA:Ensembl.
DR GO; GO:1901215; P:negative regulation of neuron death; IEA:Ensembl.
DR GO; GO:0043069; P:negative regulation of programmed cell death; IDA:UniProtKB.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IEA:Ensembl.
DR GO; GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; IEA:Ensembl.
DR GO; GO:0045739; P:positive regulation of DNA repair; IMP:UniProtKB.
DR GO; GO:1903301; P:positive regulation of hexokinase activity; IDA:UniProtKB.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; IEA:Ensembl.
DR GO; GO:0043456; P:regulation of pentose-phosphate shunt; IMP:UniProtKB.
DR GO; GO:1902153; P:regulation of response to DNA damage checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0010332; P:response to gamma radiation; IEA:Ensembl.
DR GO; GO:0002931; P:response to ischemia; ISS:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
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 1: Evidence at protein level;
KW 3D-structure; Acetylation; Apoptosis; Autophagy; Cytoplasm; Hydrolase;
KW Mitochondrion; Nucleus; Reference proteome.
FT CHAIN 1..270
FT /note="Fructose-2,6-bisphosphatase TIGAR"
FT /id="PRO_0000179957"
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:0007744|PubMed:19608861"
FT MUTAGEN 11
FT /note="H->A: Abolishes the ability to lower cellular
FT fructose-2,6-bisphosphate levels, to inhibit the glycolytic
FT activity, to reduce levels of ROS, to increase oxygen
FT consumption and to protect toward hypoxic cell death; when
FT associated with A-11 and A-102. Retains the ability to
FT interact and enhance HK2 activity, to localize to the
FT mitochondria, to limit mitochondrial ROS level increase
FT during hypoxia and to rescued partially crypt growth; when
FT associated with A-102 and A-198. Loss of the ability to
FT protect against cell death during hypoxia; when associated
FT with A-102; A-198 and 258-N--D-261 Del."
FT /evidence="ECO:0000269|PubMed:16839880,
FT ECO:0000269|PubMed:22887998, ECO:0000269|PubMed:23185017,
FT ECO:0000269|PubMed:23726973"
FT MUTAGEN 102
FT /note="E->A: Abolishes the ability to lower cellular
FT fructose-2,6-bisphosphate levels, to inhibit the glycolytic
FT activity, to reduce levels of ROS, to increase oxygen
FT consumption and to protect toward hypoxic cell death; when
FT associated with A-11 and A-198. Retains the ability to
FT interact and enhance HK2 activity, to localize to the
FT mitochondria, to limit mitochondrial ROS level increase
FT during hypoxia and to rescued partially crypt growth; when
FT associated with A-11 and A-198. Loss of the ability to
FT protect against cell death during hypoxia; when associated
FT with A-11; A-198 and 258-N--D-261 Del."
FT /evidence="ECO:0000269|PubMed:16839880,
FT ECO:0000269|PubMed:22887998, ECO:0000269|PubMed:23185017,
FT ECO:0000269|PubMed:23726973"
FT MUTAGEN 198
FT /note="H->A: Abolishes the ability to lower cellular
FT fructose-2,6-bisphosphate levels, to inhibit the glycolytic
FT activity, to reduce levels of ROS, to increase oxygen
FT consumption and to protect toward hypoxic cell death; when
FT associated with A-11 and A-102. Retains the ability to
FT interact and enhance HK2 activity, to localize to the
FT mitochondria, to limit mitochondrial ROS level increase
FT during hypoxia and to rescued partially crypt growth; when
FT associated with A-11 and A-102. Loss of the ability to
FT protect against cell death during hypoxia; when associated
FT with A-11; A-102 and 258-N--D-261 Del."
FT /evidence="ECO:0000269|PubMed:16839880,
FT ECO:0000269|PubMed:22887998, ECO:0000269|PubMed:23185017,
FT ECO:0000269|PubMed:23726973"
FT MUTAGEN 258..261
FT /note="Missing: Inhibits the ability to interact and
FT enhance HK2 activity, to localize to the mitochondria, to
FT protect against the decrease of mitochondrial membrane
FT potential and to limit mitochondrial ROS level increase
FT during hypoxia. Does not abolish the ability to lower
FT cellular fructose-2,6-bisphosphate levels during hypoxia.
FT Loss of the ability to protect against cell death during
FT hypoxia; when associated with A-11; A-102 and A-198."
FT /evidence="ECO:0000269|PubMed:23185017"
FT STRAND 2..10
FT /evidence="ECO:0007829|PDB:3DCY"
FT HELIX 15..19
FT /evidence="ECO:0007829|PDB:3DCY"
FT STRAND 24..27
FT /evidence="ECO:0007829|PDB:3DCY"
FT HELIX 33..45
FT /evidence="ECO:0007829|PDB:3DCY"
FT TURN 46..48
FT /evidence="ECO:0007829|PDB:3DCY"
FT STRAND 52..56
FT /evidence="ECO:0007829|PDB:3DCY"
FT HELIX 60..70
FT /evidence="ECO:0007829|PDB:3DCY"
FT STRAND 81..83
FT /evidence="ECO:0007829|PDB:3DCY"
FT HELIX 85..87
FT /evidence="ECO:0007829|PDB:3DCY"
FT HELIX 93..95
FT /evidence="ECO:0007829|PDB:3DCY"
FT HELIX 100..109
FT /evidence="ECO:0007829|PDB:3DCY"
FT TURN 114..116
FT /evidence="ECO:0007829|PDB:3DCY"
FT HELIX 125..149
FT /evidence="ECO:0007829|PDB:3DCY"
FT HELIX 161..167
FT /evidence="ECO:0007829|PDB:3DCY"
FT STRAND 192..197
FT /evidence="ECO:0007829|PDB:3DCY"
FT HELIX 199..211
FT /evidence="ECO:0007829|PDB:3DCY"
FT HELIX 223..227
FT /evidence="ECO:0007829|PDB:3DCY"
FT STRAND 235..242
FT /evidence="ECO:0007829|PDB:3DCY"
FT STRAND 244..247
FT /evidence="ECO:0007829|PDB:3DCY"
FT STRAND 251..259
FT /evidence="ECO:0007829|PDB:3DCY"
SQ SEQUENCE 270 AA; 30063 MW; B85D59659AD96E39 CRC64;
MARFALTVVR HGETRFNKEK IIQGQGVDEP LSETGFKQAA AAGIFLNNVK FTHAFSSDLM
RTKQTMHGIL ERSKFCKDMT VKYDSRLRER KYGVVEGKAL SELRAMAKAA REECPVFTPP
GGETLDQVKM RGIDFFEFLC QLILKEADQK EQFSQGSPSN CLETSLAEIF PLGKNHSSKV
NSDSGIPGLA ASVLVVSHGA YMRSLFDYFL TDLKCSLPAT LSRSELMSVT PNTGMSLFII
NFEEGREVKP TVQCICMNLQ DHLNGLTETR
