ID   F26_YEAST               Reviewed;         452 AA.
AC   P32604; D6VW32;
DT   01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 2.
DT   02-SEP-2026, entry version 209.
DE   RecName: Full=Fructose-2,6-bisphosphatase {ECO:0000305};
DE            Short=FBPase 2 {ECO:0000303|PubMed:2831055};
DE            EC=3.1.3.46 {ECO:0000305|PubMed:1322693, ECO:0000305|PubMed:2825652, ECO:0000305|PubMed:2831055};
GN   Name=FBP26 {ECO:0000303|PubMed:1322693}; OrderedLocusNames=YJL155C;
GN   ORFNames=J0575;
OS   Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=559292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=1322693; DOI=10.1021/bi00146a014;
RA   Paravicini G., Kretschmer M.;
RT   "The yeast FBP26 gene codes for a fructose-2,6-bisphosphatase.";
RL   Biochemistry 31:7126-7133(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=8641269; DOI=10.1002/j.1460-2075.1996.tb00557.x;
RA   Galibert F., Alexandraki D., Baur A., Boles E., Chalwatzis N., Chuat J.-C.,
RA   Coster F., Cziepluch C., de Haan M., Domdey H., Durand P., Entian K.-D.,
RA   Gatius M., Goffeau A., Grivell L.A., Hennemann A., Herbert C.J.,
RA   Heumann K., Hilger F., Hollenberg C.P., Huang M.-E., Jacq C.,
RA   Jauniaux J.-C., Katsoulou C., Kirchrath L., Kleine K., Kordes E.,
RA   Koetter P., Liebl S., Louis E.J., Manus V., Mewes H.-W., Miosga T.,
RA   Obermaier B., Perea J., Pohl T.M., Portetelle D., Pujol A., Purnelle B.,
RA   Ramezani Rad M., Rasmussen S.W., Rose M., Rossau R.,
RA   Schaaff-Gerstenschlaeger I., Smits P.H.M., Scarcez T., Soriano N.,
RA   To Van D., Tzermia M., Van Broekhoven A., Vandenbol M., Wedler H.,
RA   von Wettstein D., Wambutt R., Zagulski M., Zollner A., Karpfinger-Hartl L.;
RT   "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X.";
RL   EMBO J. 15:2031-2049(1996).
RN   [3]
RP   GENOME REANNOTATION.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=24374639; DOI=10.1534/g3.113.008995;
RA   Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA   Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA   Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT   "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL   G3 (Bethesda) 4:389-398(2014).
RN   [4]
RP   FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX   PubMed=2825652; DOI=10.1042/bj2460755;
RA   Kretschmer M., Schellenberger W., Otto A., Kessler R., Hofmann E.;
RT   "Fructose-2,6-bisphosphatase and 6-phosphofructo-2-kinase are separable in
RT   yeast.";
RL   Biochem. J. 246:755-759(1987).
RN   [5]
RP   FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX   PubMed=2831055; DOI=10.1111/j.1432-1033.1988.tb13830.x;
RA   Francois J., Van Schaftigen E., Hers H.G.;
RT   "Characterization of phosphofructokinase 2 and of enzymes involved in the
RT   degradation of fructose 2,6-bisphosphate in yeast.";
RL   Eur. J. Biochem. 171:599-608(1988).
RN   [6]
RP   LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX   PubMed=14562106; DOI=10.1038/nature02046;
RA   Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA   O'Shea E.K., Weissman J.S.;
RT   "Global analysis of protein expression in yeast.";
RL   Nature 425:737-741(2003).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-446, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   STRAIN=ADR376;
RX   PubMed=17330950; DOI=10.1021/pr060559j;
RA   Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA   Elias J.E., Gygi S.P.;
RT   "Large-scale phosphorylation analysis of alpha-factor-arrested
RT   Saccharomyces cerevisiae.";
RL   J. Proteome Res. 6:1190-1197(2007).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-435 AND SER-446, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA   Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT   "A multidimensional chromatography technology for in-depth phosphoproteome
RT   analysis.";
RL   Mol. Cell. Proteomics 7:1389-1396(2008).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-446, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19779198; DOI=10.1126/science.1172867;
RA   Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT   "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT   into evolution.";
RL   Science 325:1682-1686(2009).
CC   -!- FUNCTION: Monofunctional, high-specificity fructose-2,6-bisphosphatase,
CC       which releases phosphate from the 2-position of fructose 2,6-
CC       bisphosphate. Has no detectable 6-phosphofructo-2-kinase activity.
CC       {ECO:0000269|PubMed:1322693, ECO:0000305|PubMed:2825652,
CC       ECO:0000305|PubMed:2831055}.
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:0000305|PubMed:1322693, ECO:0000305|PubMed:2825652,
CC         ECO:0000305|PubMed:2831055};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17290;
CC         Evidence={ECO:0000305|PubMed:1322693, ECO:0000305|PubMed:2825652,
CC         ECO:0000305|PubMed:2831055};
CC   -!- ACTIVITY REGULATION: Inhibited by fructose 6-P, activated by glycerol
CC       3-P. {ECO:0000305|PubMed:2825652, ECO:0000305|PubMed:2831055}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.3 uM for fructose 2,6-bisphosphate {ECO:0000305|PubMed:2825652};
CC         KM=0.1 uM for fructose 2,6-bisphosphate {ECO:0000305|PubMed:2831055};
CC   -!- INTERACTION:
CC       P32604; Q06137: YLR345W; NbExp=4; IntAct=EBI-6749, EBI-33827;
CC   -!- MISCELLANEOUS: Present with 1680 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the phosphoglycerate
CC       mutase family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; S42124; AAB22823.1; -; Genomic_DNA.
DR   EMBL; Z49430; CAA89450.1; -; Genomic_DNA.
DR   EMBL; BK006943; DAA08648.1; -; Genomic_DNA.
DR   PIR; S56938; S56938.
DR   RefSeq; NP_012380.1; NM_001181588.1.
DR   AlphaFoldDB; P32604; -.
DR   SMR; P32604; -.
DR   BioGRID; 33605; 86.
DR   DIP; DIP-2593N; -.
DR   FunCoup; P32604; 623.
DR   IntAct; P32604; 6.
DR   MINT; P32604; -.
DR   STRING; 4932.YJL155C; -.
DR   iPTMnet; P32604; -.
DR   PaxDb; 4932-YJL155C; -.
DR   PeptideAtlas; P32604; -.
DR   EnsemblFungi; YJL155C_mRNA; YJL155C; YJL155C.
DR   GeneID; 853286; -.
DR   KEGG; sce:YJL155C; -.
DR   AGR; SGD:S000003691; -.
DR   SGD; S000003691; FBP26.
DR   VEuPathDB; FungiDB:YJL155C; -.
DR   eggNOG; KOG0234; Eukaryota.
DR   HOGENOM; CLU_006383_1_0_1; -.
DR   InParanoid; P32604; -.
DR   OMA; RWIQERC; -.
DR   OrthoDB; 267323at2759; -.
DR   BioCyc; YEAST:YJL155C-MONOMER; -.
DR   Reactome; R-SCE-9634600; Regulation of glycolysis by fructose 2,6-bisphosphate metabolism.
DR   BioGRID-ORCS; 853286; 0 hits in 10 CRISPR screens.
DR   PRO; PR:P32604; -.
DR   Proteomes; UP000002311; Chromosome X.
DR   RNAct; P32604; protein.
DR   GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0003873; F:6-phosphofructo-2-kinase activity; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR   GO; GO:0004331; F:fructose-2,6-bisphosphate 2-phosphatase activity; IMP:SGD.
DR   GO; GO:0006003; P:fructose 2,6-bisphosphate metabolic process; IEA:InterPro.
DR   GO; GO:0006000; P:fructose metabolic process; IEA:InterPro.
DR   GO; GO:0006006; P:glucose metabolic process; IMP:SGD.
DR   CDD; cd07067; HP_PGM_like; 1.
DR   FunFam; 3.40.50.1240:FF:000005; GpmB, Fructose-2,6-bisphosphatase; 1.
DR   FunFam; 3.40.50.300:FF:000644; GpmB, Fructose-2,6-bisphosphatase; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR   Gene3D; 3.40.50.1240; Phosphoglycerate mutase-like; 1.
DR   InterPro; IPR003094; 6Pfruct_kin.
DR   InterPro; IPR013079; 6Phosfructo_kin.
DR   InterPro; IPR013078; His_Pase_superF_clade-1.
DR   InterPro; IPR029033; His_PPase_superfam.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR001345; PG/BPGM_mutase_AS.
DR   PANTHER; PTHR10606:SF44; 6-PHOSPHOFRUCTO 2-KINASE_FRUCTOSE 2,6-BISPHOSPHATASE LONG FORM; 1.
DR   PANTHER; PTHR10606; 6-PHOSPHOFRUCTO-2-KINASE/FRUCTOSE-2,6-BISPHOSPHATASE; 1.
DR   Pfam; PF01591; 6PF2K; 1.
DR   Pfam; PF00300; His_Phos_1; 1.
DR   PIRSF; PIRSF000709; 6PFK_2-Ptase; 1.
DR   PRINTS; PR00991; 6PFRUCTKNASE.
DR   SMART; SM00855; PGAM; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR   SUPFAM; SSF53254; Phosphoglycerate mutase-like; 1.
DR   PROSITE; PS00175; PG_MUTASE; 1.
PE   1: Evidence at protein level;
KW   ATP-binding; Hydrolase; Nucleotide-binding; Phosphoprotein;
KW   Reference proteome.
FT   CHAIN           1..452
FT                   /note="Fructose-2,6-bisphosphatase"
FT                   /id="PRO_0000179975"
FT   REGION          1..223
FT                   /note="6-phosphofructo-2-kinase"
FT                   /evidence="ECO:0000250"
FT   REGION          224..452
FT                   /note="Fructose-2,6-bisphosphatase"
FT   ACT_SITE        104
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        232
FT                   /note="Tele-phosphohistidine intermediate"
FT                   /evidence="ECO:0000250|UniProtKB:Q16875"
FT   ACT_SITE        302
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:Q16875"
FT   BINDING         20..28
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q16875"
FT   BINDING         53
FT                   /ligand="beta-D-fructose 6-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:57634"
FT                   /evidence="ECO:0000250|UniProtKB:Q16875"
FT   BINDING         78
FT                   /ligand="beta-D-fructose 6-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:57634"
FT                   /evidence="ECO:0000250|UniProtKB:Q16875"
FT   BINDING         106
FT                   /ligand="beta-D-fructose 6-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:57634"
FT                   /evidence="ECO:0000250|UniProtKB:Q16875"
FT   BINDING         112
FT                   /ligand="beta-D-fructose 6-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:57634"
FT                   /evidence="ECO:0000250|UniProtKB:Q16875"
FT   BINDING         143..148
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q16875"
FT   BINDING         169
FT                   /ligand="beta-D-fructose 6-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:57634"
FT                   /evidence="ECO:0000250|UniProtKB:Q16875"
FT   BINDING         173
FT                   /ligand="beta-D-fructose 6-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:57634"
FT                   /evidence="ECO:0000250|UniProtKB:Q16875"
FT   BINDING         231
FT                   /ligand="beta-D-fructose 2,6-bisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58579"
FT                   /evidence="ECO:0000250|UniProtKB:Q16875"
FT   BINDING         238
FT                   /ligand="beta-D-fructose 2,6-bisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58579"
FT                   /evidence="ECO:0000250|UniProtKB:Q16875"
FT   BINDING         244
FT                   /ligand="beta-D-fructose 2,6-bisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58579"
FT                   /evidence="ECO:0000250|UniProtKB:Q16875"
FT   BINDING         313
FT                   /ligand="beta-D-fructose 2,6-bisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58579"
FT                   /evidence="ECO:0000250|UniProtKB:Q16875"
FT   BINDING         324..327
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P07953"
FT   BINDING         327
FT                   /ligand="beta-D-fructose 2,6-bisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58579"
FT                   /evidence="ECO:0000250|UniProtKB:Q16875"
FT   BINDING         331
FT                   /ligand="beta-D-fructose 2,6-bisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58579"
FT                   /evidence="ECO:0000250|UniProtKB:Q16875"
FT   BINDING         342
FT                   /ligand="beta-D-fructose 2,6-bisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58579"
FT                   /evidence="ECO:0000250|UniProtKB:Q16875"
FT   BINDING         368..372
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P07953"
FT   BINDING         368
FT                   /ligand="beta-D-fructose 2,6-bisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58579"
FT                   /evidence="ECO:0000250|UniProtKB:Q16875"
FT   BINDING         372
FT                   /ligand="beta-D-fructose 2,6-bisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58579"
FT                   /evidence="ECO:0000250|UniProtKB:P07953"
FT   BINDING         404
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q16875"
FT   SITE            231
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000250|UniProtKB:Q16875"
FT   SITE            238
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000250|UniProtKB:Q16875"
FT   SITE            367
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000250|UniProtKB:Q16875"
FT   MOD_RES         435
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18407956"
FT   MOD_RES         446
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17330950,
FT                   ECO:0007744|PubMed:18407956, ECO:0007744|PubMed:19779198"
FT   CONFLICT        199
FT                   /note="E -> Q (in Ref. 1; AAB22823)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        362
FT                   /note="V -> E (in Ref. 1; AAB22823)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        448..449
FT                   /note="LE -> FQ (in Ref. 1; AAB22823)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   452 AA;  52595 MW;  228766A302F32F82 CRC64;
     MGYSTISNDN DIKVCVIMVG LPARGKSFIS QKIIRYLSWL SIKAKCFNVG NYRRDVSGNV
     PMDAEFFNFE NTDNFKLREL AAQNAIKDIV NFFTKEDGSV AVFDATNSTR KRRKWLKDIC
     EKNNIQPMFL ESWSNDHELI INNAKDIGST SPDYENSEPH VAEADFLERI RQYERFYEPL
     DPQKDKDMTF IKLVNIIEEV VINKIRTYLE SRIVFYVMNI RPKPKYIWLS RHGESIYNVE
     KKIGGDSSLS ERGFQYAKKL EQLVKESAGE INLTVWTSTL KRTQQTANYL PYKKLQWKAL
     DELDAGVCDG MTYEEIEKEY PEDFKARDND KYEYRYRGGE SYRDVVIRLE PVIMELERQE
     NVLIITHQAV LRCIYAYFMN VPQEESPWMS IPLHTLIKLE PRAYGTKVTK IKANIPAVST
     YKEKGTSQVG ELSQSSTKLH QLLNDSPLED KF
//