PFKA1_YEAST
ID PFKA1_YEAST Reviewed; 987 AA.
AC P16861; D6VV20;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 1.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=ATP-dependent 6-phosphofructokinase subunit alpha {ECO:0000255|HAMAP-Rule:MF_03184};
DE EC=2.7.1.11 {ECO:0000255|HAMAP-Rule:MF_03184};
DE AltName: Full=ATP-dependent 6-phosphofructokinase {ECO:0000255|HAMAP-Rule:MF_03184};
DE Short=ATP-PFK {ECO:0000255|HAMAP-Rule:MF_03184};
DE Short=Phosphofructokinase 1 {ECO:0000255|HAMAP-Rule:MF_03184};
DE AltName: Full=Phosphohexokinase {ECO:0000255|HAMAP-Rule:MF_03184};
GN Name=PFK1; OrderedLocusNames=YGR240C; ORFNames=G8599;
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].
RX PubMed=2528496; DOI=10.1016/0378-1119(89)90233-3;
RA Heinisch J.J., Ritzel R.G., von Borstel R.C., Aguilera A., Rodicio R.,
RA Zimmermann F.K.;
RT "The phosphofructokinase genes of yeast evolved from two duplication
RT events.";
RL Gene 78:309-321(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9090057;
RX DOI=10.1002/(sici)1097-0061(19970315)13:3<275::aid-yea73>3.0.co;2-g;
RA Guerreiro P., Azevedo D., Barreiros T., Rodrigues-Pousada C.;
RT "Sequencing of a 9.9 kb segment on the right arm of yeast chromosome VII
RT reveals four open reading frames, including PFK1, the gene coding for
RT succinyl-CoA synthetase (beta-chain) and two ORFs sharing homology with
RT ORFs of the yeast chromosome VIII.";
RL Yeast 13:275-280(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169869;
RA Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J.,
RA Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M.,
RA Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L.,
RA Coblenz A., Coglievina M., Coissac E., Defoor E., Del Bino S., Delius H.,
RA Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P.,
RA Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M.,
RA Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A.,
RA Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K.,
RA Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P.,
RA Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E.,
RA Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K.,
RA Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A.,
RA Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S.,
RA Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M.,
RA Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C.,
RA Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M.,
RA Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M.,
RA Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y.,
RA Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L.,
RA Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D.,
RA Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F.,
RA Zaccaria P., Zimmermann M., Zollner A., Kleine K.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome VII.";
RL Nature 387:81-84(1997).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 794-987.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8701610;
RX DOI=10.1002/(sici)1097-0061(19960330)12:4<385::aid-yea910>3.0.co;2-g;
RA van der Aart Q.J.M., Kleine K., Steensma H.Y.;
RT "Sequence analysis of the 43 kb CRM1-YLM9-PET54-DIE2-SMI1-PHO81-YHB4-PFK1
RT region from the right arm of Saccharomyces cerevisiae chromosome VII.";
RL Yeast 12:385-390(1996).
RN [6]
RP PROTEIN SEQUENCE OF 1-6; 90-97; 197-205 AND 914-921.
RX PubMed=8223596; DOI=10.1111/j.1432-1033.1993.tb18273.x;
RA Kopperschlaeger G., Baer J., Stellwagen E.;
RT "Limited proteolysis of yeast phosphofructokinase. Sequence locations of
RT cleavage sites created by the actions of different proteinases.";
RL Eur. J. Biochem. 217:527-533(1993).
RN [7]
RP SUBUNIT.
RX PubMed=145942; DOI=10.1111/j.1432-1033.1977.tb11954.x;
RA Kopperschlaeger G., Baer J., Nissler K., Hofmann E.;
RT "Physicochemical parameters and subunit composition of yeast
RT phosphofructokinase.";
RL Eur. J. Biochem. 81:317-325(1977).
RN [8]
RP ACTIVITY REGULATION.
RX PubMed=19473; DOI=10.1016/s0021-9258(17)39970-2;
RA Banuelos M., Gancedo C., Gancedo J.M.;
RT "Activation by phosphate of yeast phosphofructokinase.";
RL J. Biol. Chem. 252:6394-6398(1977).
RN [9]
RP FUNCTION.
RX PubMed=147195; DOI=10.1093/genetics/88.1.1;
RA Clifton D., Weinstock S.B., Fraenkel D.G.;
RT "Glycolysis mutants in Saccharomyces cerevisiae.";
RL Genetics 88:1-11(1978).
RN [10]
RP ACTIVITY REGULATION.
RX PubMed=6458303; DOI=10.1016/0006-291x(81)91635-1;
RA Avigad G.;
RT "Stimulation of yeast phosphofructokinase activity by fructose 2,6-
RT bisphosphate.";
RL Biochem. Biophys. Res. Commun. 102:985-991(1981).
RN [11]
RP FUNCTION.
RX PubMed=6211191; DOI=10.1021/bi00537a037;
RA Clifton D., Fraenkel D.G.;
RT "Mutant studies of yeast phosphofructokinase.";
RL Biochemistry 21:1935-1942(1982).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY
RP REGULATION.
RX PubMed=6219673; DOI=10.1016/s0006-291x(83)80150-8;
RA Nissler K., Otto A., Schellenberger W., Hofmann E.;
RT "Similarity of activation of yeast phosphofructokinase by AMP and fructose-
RT 2,6-bisphosphate.";
RL Biochem. Biophys. Res. Commun. 111:294-300(1983).
RN [13]
RP FUNCTION.
RX PubMed=3000145; DOI=10.1016/0065-2571(85)90055-x;
RA Hofmann E., Eschrich K., Schellenberger W.;
RT "Temporal organization of the phosphofructokinase/fructose-1,6-
RT biphosphatase cycle.";
RL Adv. Enzyme Regul. 23:331-362(1985).
RN [14]
RP SUBUNIT.
RX PubMed=2408613;
RA Nissler K., Hofmann E., Stel'maschchuk V., Orlova E., Kiselev N.;
RT "An electron microscopy study of the quarternary structure of yeast
RT phosphofructokinase.";
RL Biomed. Biochim. Acta 44:251-259(1985).
RN [15]
RP FUNCTION.
RX PubMed=3007939; DOI=10.1007/bf00330520;
RA Heinisch J.;
RT "Isolation and characterization of the two structural genes coding for
RT phosphofructokinase in yeast.";
RL Mol. Gen. Genet. 202:75-82(1986).
RN [16]
RP FUNCTION, AND MUTAGENESIS OF ASP-309; ASP-356; ARG-447 AND HIS-488.
RX PubMed=8132627; DOI=10.1016/s0021-9258(17)37054-0;
RA Arvanitidis A., Heinisch J.J.;
RT "Studies on the function of yeast phosphofructokinase subunits by in vitro
RT mutagenesis.";
RL J. Biol. Chem. 269:8911-8918(1994).
RN [17]
RP FUNCTION, AND MUTAGENESIS OF SER-724 AND HIS-859.
RX PubMed=8663166; DOI=10.1074/jbc.271.27.15928;
RA Heinisch J.J., Boles E., Timpel C.;
RT "A yeast phosphofructokinase insensitive to the Fructose 2,6-bisphosphate;
RT allosteric activator. Glycolysis/metabolic regulation/allosteric control.";
RL J. Biol. Chem. 271:15928-15933(1996).
RN [18]
RP FUNCTION, AND MUTAGENESIS OF PRO-728.
RX PubMed=11221662; DOI=10.1074/jbc.m007131200;
RA Rodicio R., Strauss A., Heinisch J.J.;
RT "Single point mutations in either gene encoding the subunits of the
RT heterooctameric yeast phosphofructokinase abolish allosteric inhibition by
RT ATP.";
RL J. Biol. Chem. 275:40952-40960(2000).
RN [19]
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 [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=YAL6B;
RX PubMed=15665377; DOI=10.1074/mcp.m400219-mcp200;
RA Gruhler A., Olsen J.V., Mohammed S., Mortensen P., Faergeman N.J., Mann M.,
RA Jensen O.N.;
RT "Quantitative phosphoproteomics applied to the yeast pheromone signaling
RT pathway.";
RL Mol. Cell. Proteomics 4:310-327(2005).
RN [21]
RP SUBCELLULAR LOCATION.
RX PubMed=16962558; DOI=10.1016/j.bbabio.2006.07.001;
RA Brandina I., Graham J., Lemaitre-Guillier C., Entelis N.,
RA Krasheninnikov I., Sweetlove L., Tarassov I., Martin R.P.;
RT "Enolase takes part in a macromolecular complex associated to mitochondria
RT in yeast.";
RL Biochim. Biophys. Acta 1757:1217-1228(2006).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-179; SER-185 AND SER-192, AND
RP IDENTIFICATION BY 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 [23]
RP SUBCELLULAR LOCATION.
RX PubMed=18313953; DOI=10.1016/j.fgb.2008.01.003;
RA Barnard E., McFerran N.V., Trudgett A., Nelson J., Timson D.J.;
RT "Detection and localisation of protein-protein interactions in
RT Saccharomyces cerevisiae using a split-GFP method.";
RL Fungal Genet. Biol. 45:597-604(2008).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3; SER-185 AND SER-192, 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 [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166; SER-179; SER-185;
RP SER-189; SER-192; SER-217 AND THR-450, AND IDENTIFICATION BY MASS
RP 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).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [27]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-89 AND LYS-625, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22106047; DOI=10.1002/pmic.201100166;
RA Starita L.M., Lo R.S., Eng J.K., von Haller P.D., Fields S.;
RT "Sites of ubiquitin attachment in Saccharomyces cerevisiae.";
RL Proteomics 12:236-240(2012).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 201-987 IN COMPLEX WITH SUBSTRATE
RP FRUCTOSE 6-PHOSPHATE AND FRUCTOSE 2,6-BISPHOSPHATE; ALLOSTERIC ACTIVATOR.
RX PubMed=21241708; DOI=10.1016/j.jmb.2011.01.019;
RA Banaszak K., Mechin I., Obmolova G., Oldham M., Chang S.H., Ruiz T.,
RA Radermacher M., Kopperschlager G., Rypniewski W.;
RT "The crystal structures of eukaryotic phosphofructokinases from baker's
RT yeast and rabbit skeletal muscle.";
RL J. Mol. Biol. 407:284-297(2011).
CC -!- FUNCTION: Catalyzes the phosphorylation of D-fructose 6-phosphate to
CC fructose 1,6-bisphosphate by ATP, the first committing step of
CC glycolysis. {ECO:0000255|HAMAP-Rule:MF_03184,
CC ECO:0000269|PubMed:11221662, ECO:0000269|PubMed:147195,
CC ECO:0000269|PubMed:3000145, ECO:0000269|PubMed:3007939,
CC ECO:0000269|PubMed:6211191, ECO:0000269|PubMed:6219673,
CC ECO:0000269|PubMed:8132627, ECO:0000269|PubMed:8663166}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + beta-D-fructose 6-phosphate = ADP + beta-D-fructose 1,6-
CC bisphosphate + H(+); Xref=Rhea:RHEA:16109, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:32966, ChEBI:CHEBI:57634,
CC ChEBI:CHEBI:456216; EC=2.7.1.11; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03184, ECO:0000269|PubMed:6219673};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P0A796,
CC ECO:0000255|HAMAP-Rule:MF_03184};
CC -!- ACTIVITY REGULATION: Allosterically activated by ADP, AMP, or fructose
CC 2,6-bisphosphate, and allosterically inhibited by ATP or citrate.
CC {ECO:0000255|HAMAP-Rule:MF_03184, ECO:0000269|PubMed:19473,
CC ECO:0000269|PubMed:6219673, ECO:0000269|PubMed:6458303}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.24 mM for ATP (without effector) {ECO:0000269|PubMed:6219673};
CC KM=0.3 mM for ATP (with 1 mM AMP) {ECO:0000269|PubMed:6219673};
CC KM=0.31 mM for ATP (with 20 uM fructose 2,6-bisphosphate)
CC {ECO:0000269|PubMed:6219673};
CC KM=1.65 mM for fructose 6-phosphate (without effector)
CC {ECO:0000269|PubMed:6219673};
CC KM=0.51 mM for fructose 6-phosphate (with 1 mM AMP)
CC {ECO:0000269|PubMed:6219673};
CC KM=0.11 mM for fructose 6-phosphate (with 20 uM fructose 2,6-
CC bisphosphate) {ECO:0000269|PubMed:6219673};
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC phosphate and glycerone phosphate from D-glucose: step 3/4.
CC {ECO:0000255|HAMAP-Rule:MF_03184}.
CC -!- SUBUNIT: Heterooctamer of 4 alpha and 4 beta chains.
CC {ECO:0000255|HAMAP-Rule:MF_03184, ECO:0000269|PubMed:145942,
CC ECO:0000269|PubMed:21241708, ECO:0000269|PubMed:2408613}.
CC -!- INTERACTION:
CC P16861; P16862: PFK2; NbExp=7; IntAct=EBI-9428, EBI-9435;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03184,
CC ECO:0000269|PubMed:18313953}. Mitochondrion outer membrane; Peripheral
CC membrane protein; Cytoplasmic side {ECO:0000269|PubMed:16962558}.
CC -!- MISCELLANEOUS: Present with 89800 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the phosphofructokinase type A (PFKA) family.
CC ATP-dependent PFK group I subfamily. Eukaryotic two domain clade 'E'
CC sub-subfamily. {ECO:0000255|HAMAP-Rule:MF_03184}.
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DR EMBL; M26943; AAA34859.1; -; Genomic_DNA.
DR EMBL; Z73025; CAA97268.1; -; Genomic_DNA.
DR EMBL; X87941; CAA61193.1; -; Genomic_DNA.
DR EMBL; BK006941; DAA08331.1; -; Genomic_DNA.
DR PIR; JQ0016; JQ0016.
DR RefSeq; NP_011756.1; NM_001181369.1.
DR PDB; 3O8O; X-ray; 2.90 A; A/C/E/G=201-987.
DR PDBsum; 3O8O; -.
DR AlphaFoldDB; P16861; -.
DR SMR; P16861; -.
DR BioGRID; 33492; 295.
DR ComplexPortal; CPX-554; 6-phosphofructokinase complex.
DR DIP; DIP-1505N; -.
DR IntAct; P16861; 72.
DR MINT; P16861; -.
DR STRING; 4932.YGR240C; -.
DR iPTMnet; P16861; -.
DR MaxQB; P16861; -.
DR PaxDb; P16861; -.
DR PRIDE; P16861; -.
DR EnsemblFungi; YGR240C_mRNA; YGR240C; YGR240C.
DR GeneID; 853155; -.
DR KEGG; sce:YGR240C; -.
DR SGD; S000003472; PFK1.
DR VEuPathDB; FungiDB:YGR240C; -.
DR eggNOG; KOG2440; Eukaryota.
DR HOGENOM; CLU_011053_0_0_1; -.
DR InParanoid; P16861; -.
DR OMA; SRYAVKC; -.
DR BioCyc; MetaCyc:YGR240C-MON; -.
DR BioCyc; YEAST:YGR240C-MON; -.
DR Reactome; R-SCE-6798695; Neutrophil degranulation.
DR Reactome; R-SCE-70171; Glycolysis.
DR SABIO-RK; P16861; -.
DR UniPathway; UPA00109; UER00182.
DR PRO; PR:P16861; -.
DR Proteomes; UP000002311; Chromosome VII.
DR RNAct; P16861; protein.
DR GO; GO:0005945; C:6-phosphofructokinase complex; IDA:SGD.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:SGD.
DR GO; GO:0003872; F:6-phosphofructokinase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0016208; F:AMP binding; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IBA:GO_Central.
DR GO; GO:0070095; F:fructose-6-phosphate binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0048029; F:monosaccharide binding; IBA:GO_Central.
DR GO; GO:0061621; P:canonical glycolysis; IBA:GO_Central.
DR GO; GO:0030388; P:fructose 1,6-bisphosphate metabolic process; IBA:GO_Central.
DR GO; GO:0006002; P:fructose 6-phosphate metabolic process; IDA:ComplexPortal.
DR GO; GO:0006096; P:glycolytic process; IDA:SGD.
DR GO; GO:1902600; P:proton transmembrane transport; IGI:UniProtKB.
DR GO; GO:0051453; P:regulation of intracellular pH; IMP:SGD.
DR Gene3D; 3.40.50.460; -; 2.
DR HAMAP; MF_03184; Phosphofructokinase_I_E; 1.
DR InterPro; IPR009161; 6-Pfructokinase_euk.
DR InterPro; IPR022953; ATP_PFK.
DR InterPro; IPR040712; Pfk_N.
DR InterPro; IPR015912; Phosphofructokinase_CS.
DR InterPro; IPR000023; Phosphofructokinase_dom.
DR InterPro; IPR035966; PKF_sf.
DR Pfam; PF00365; PFK; 2.
DR Pfam; PF18468; Pfk_N; 1.
DR PIRSF; PIRSF000533; ATP_PFK_euk; 1.
DR PRINTS; PR00476; PHFRCTKINASE.
DR SUPFAM; SSF53784; SSF53784; 2.
DR TIGRFAMs; TIGR02478; 6PF1K_euk; 1.
DR PROSITE; PS00433; PHOSPHOFRUCTOKINASE; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Allosteric enzyme; ATP-binding; Cytoplasm;
KW Direct protein sequencing; Glycolysis; Isopeptide bond; Kinase; Magnesium;
KW Membrane; Metal-binding; Mitochondrion; Mitochondrion outer membrane;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Transferase;
KW Ubl conjugation.
FT CHAIN 1..987
FT /note="ATP-dependent 6-phosphofructokinase subunit alpha"
FT /id="PRO_0000112045"
FT REGION 1..580
FT /note="N-terminal catalytic PFK domain 1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184,
FT ECO:0000305|PubMed:21241708"
FT REGION 581..594
FT /note="Interdomain linker"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184,
FT ECO:0000305|PubMed:21241708"
FT REGION 595..987
FT /note="C-terminal regulatory PFK domain 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184,
FT ECO:0000305|PubMed:21241708"
FT ACT_SITE 356
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P0A796, ECO:0000255|HAMAP-
FT Rule:MF_03184"
FT BINDING 215
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P0A796, ECO:0000255|HAMAP-
FT Rule:MF_03184"
FT BINDING 278..279
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P0A796, ECO:0000255|HAMAP-
FT Rule:MF_03184"
FT BINDING 308..311
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P0A796, ECO:0000255|HAMAP-
FT Rule:MF_03184"
FT BINDING 309
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P0A796, ECO:0000255|HAMAP-
FT Rule:MF_03184"
FT BINDING 354..356
FT /ligand="beta-D-fructose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:57634"
FT /ligand_label="1"
FT /ligand_note="ligand shared with subunit beta"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184,
FT ECO:0000269|PubMed:21241708"
FT BINDING 391
FT /ligand="beta-D-fructose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:57634"
FT /ligand_label="2"
FT /ligand_note="ligand shared with subunit beta"
FT /evidence="ECO:0000269|PubMed:21241708"
FT BINDING 398..400
FT /ligand="beta-D-fructose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:57634"
FT /ligand_label="1"
FT /ligand_note="ligand shared with subunit beta"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184,
FT ECO:0000269|PubMed:21241708"
FT BINDING 455
FT /ligand="beta-D-fructose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:57634"
FT /ligand_label="1"
FT /ligand_note="ligand shared with subunit beta"
FT /evidence="ECO:0000269|PubMed:21241708"
FT BINDING 482
FT /ligand="beta-D-fructose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:57634"
FT /ligand_label="2"
FT /ligand_note="ligand shared with subunit beta"
FT /evidence="ECO:0000269|PubMed:21241708"
FT BINDING 488..491
FT /ligand="beta-D-fructose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:57634"
FT /ligand_label="1"
FT /ligand_note="ligand shared with subunit beta"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184,
FT ECO:0000269|PubMed:21241708"
FT BINDING 665
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_label="1"
FT /ligand_note="allosteric activator; ligand shared with
FT subunit beta"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184,
FT ECO:0000269|PubMed:21241708"
FT BINDING 722..726
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_label="1"
FT /ligand_note="allosteric activator; ligand shared with
FT subunit beta"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184,
FT ECO:0000269|PubMed:21241708"
FT BINDING 760
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_label="2"
FT /ligand_note="allosteric activator; ligand shared with
FT subunit beta"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184,
FT ECO:0000269|PubMed:21241708"
FT BINDING 767..769
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_label="1"
FT /ligand_note="allosteric activator; ligand shared with
FT subunit beta"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184,
FT ECO:0000269|PubMed:21241708"
FT BINDING 827
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_label="1"
FT /ligand_note="allosteric activator; ligand shared with
FT subunit beta"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184,
FT ECO:0000269|PubMed:21241708"
FT BINDING 853
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_label="2"
FT /ligand_note="allosteric activator; ligand shared with
FT subunit beta"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184,
FT ECO:0000269|PubMed:21241708"
FT BINDING 859..862
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_label="1"
FT /ligand_note="allosteric activator; ligand shared with
FT subunit beta"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184,
FT ECO:0000269|PubMed:21241708"
FT BINDING 952
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_label="1"
FT /ligand_note="allosteric activator; ligand shared with
FT subunit beta"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184,
FT ECO:0000269|PubMed:21241708"
FT MOD_RES 3
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT MOD_RES 166
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 179
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:19779198"
FT MOD_RES 185
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:18407956, ECO:0007744|PubMed:19779198"
FT MOD_RES 189
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 192
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:18407956, ECO:0007744|PubMed:19779198"
FT MOD_RES 217
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 450
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT CROSSLNK 89
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0007744|PubMed:22106047"
FT CROSSLNK 625
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0007744|PubMed:22106047"
FT MUTAGEN 309
FT /note="D->T: Reduces maximal activity of the holoenzyme by
FT 50%. Completely abolishes catalytic activity; when
FT associated with 'S-348' in subunit beta."
FT /evidence="ECO:0000269|PubMed:8132627"
FT MUTAGEN 356
FT /note="D->S: Reduces maximal activity of the holoenzyme by
FT 50%. Completely abolishes catalytic activity; when
FT associated with 'S-348' in subunit beta."
FT /evidence="ECO:0000269|PubMed:8132627"
FT MUTAGEN 447
FT /note="R->S: Reduces maximal activity of the holoenzyme by
FT less than 25%."
FT /evidence="ECO:0000269|PubMed:8132627"
FT MUTAGEN 488
FT /note="H->S: Increases the KM for fructose 6-phosphate 20
FT fold."
FT /evidence="ECO:0000269|PubMed:8132627"
FT MUTAGEN 724
FT /note="S->D: Abolishes sensitivity of the holoenzyme to
FT fructose 2,6-bisphosphate activation; when associated with
FT 'D-718' in subunit beta."
FT /evidence="ECO:0000269|PubMed:8663166"
FT MUTAGEN 728
FT /note="P->L: Drastically reduces sensitivity of the
FT holoenzyme to ATP inhibition."
FT /evidence="ECO:0000269|PubMed:11221662"
FT MUTAGEN 859
FT /note="H->S: Reduces sensitivity of the holoenzyme to
FT fructose 2,6-bisphosphate activation; when associated with
FT 'S-853' in subunit beta."
FT /evidence="ECO:0000269|PubMed:8663166"
FT STRAND 207..215
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 220..233
FT /evidence="ECO:0007829|PDB:3O8O"
FT STRAND 237..241
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 244..250
FT /evidence="ECO:0007829|PDB:3O8O"
FT STRAND 254..257
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 260..263
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 266..268
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 281..283
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 285..297
FT /evidence="ECO:0007829|PDB:3O8O"
FT STRAND 300..307
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 309..319
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 322..330
FT /evidence="ECO:0007829|PDB:3O8O"
FT STRAND 331..334
FT /evidence="ECO:0007829|PDB:3O8O"
FT TURN 337..343
FT /evidence="ECO:0007829|PDB:3O8O"
FT STRAND 347..356
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 368..388
FT /evidence="ECO:0007829|PDB:3O8O"
FT STRAND 392..397
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 404..412
FT /evidence="ECO:0007829|PDB:3O8O"
FT STRAND 416..419
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 421..423
FT /evidence="ECO:0007829|PDB:3O8O"
FT TURN 427..429
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 430..443
FT /evidence="ECO:0007829|PDB:3O8O"
FT STRAND 449..454
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 467..477
FT /evidence="ECO:0007829|PDB:3O8O"
FT STRAND 481..485
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 487..490
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 497..515
FT /evidence="ECO:0007829|PDB:3O8O"
FT STRAND 524..537
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 538..553
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 557..562
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 568..579
FT /evidence="ECO:0007829|PDB:3O8O"
FT STRAND 595..603
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 608..622
FT /evidence="ECO:0007829|PDB:3O8O"
FT STRAND 625..629
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 632..639
FT /evidence="ECO:0007829|PDB:3O8O"
FT STRAND 642..644
FT /evidence="ECO:0007829|PDB:3O8O"
FT TURN 647..652
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 653..655
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 668..670
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 672..681
FT /evidence="ECO:0007829|PDB:3O8O"
FT STRAND 685..692
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 693..705
FT /evidence="ECO:0007829|PDB:3O8O"
FT TURN 706..708
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 710..713
FT /evidence="ECO:0007829|PDB:3O8O"
FT STRAND 716..721
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 736..757
FT /evidence="ECO:0007829|PDB:3O8O"
FT STRAND 758..766
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 773..780
FT /evidence="ECO:0007829|PDB:3O8O"
FT TURN 781..783
FT /evidence="ECO:0007829|PDB:3O8O"
FT STRAND 785..788
FT /evidence="ECO:0007829|PDB:3O8O"
FT STRAND 790..792
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 796..812
FT /evidence="ECO:0007829|PDB:3O8O"
FT STRAND 821..826
FT /evidence="ECO:0007829|PDB:3O8O"
FT STRAND 831..833
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 835..846
FT /evidence="ECO:0007829|PDB:3O8O"
FT STRAND 849..856
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 858..862
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 868..890
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 921..923
FT /evidence="ECO:0007829|PDB:3O8O"
FT STRAND 924..930
FT /evidence="ECO:0007829|PDB:3O8O"
FT STRAND 933..938
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 939..942
FT /evidence="ECO:0007829|PDB:3O8O"
FT TURN 948..951
FT /evidence="ECO:0007829|PDB:3O8O"
FT STRAND 953..955
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 960..969
FT /evidence="ECO:0007829|PDB:3O8O"
FT HELIX 972..978
FT /evidence="ECO:0007829|PDB:3O8O"
SQ SEQUENCE 987 AA; 107970 MW; 995B3DF7C7781B29 CRC64;
MQSQDSCYGV AFRSIITNDE ALFKKTIHFY HTLGFATVKD FNKFKHGENS LLSSGTSQDS
LREVWLESFK LSEVDASGFR IPQQEATNKA QSQGALLKIR LVMSAPIDET FDTNETATIT
YFSTDLNKIV EKFPKQAEKL SDTLVFLKDP MGNNITFSGL ANATDSAPTS KDAFLEATSE
DEIISRASSD ASDLLRQTLG SSQKKKKIAV MTSGGDSPGM NAAVRAVVRT GIHFGCDVFA
VYEGYEGLLR GGKYLKKMAW EDVRGWLSEG GTLIGTARSM EFRKREGRRQ AAGNLISQGI
DALVVCGGDG SLTGADLFRH EWPSLVDELV AEGRFTKEEV APYKNLSIVG LVGSIDNDMS
GTDSTIGAYS ALERICEMVD YIDATAKSHS RAFVVEVMGR HCGWLALMAG IATGADYIFI
PERAVPHGKW QDELKEVCQR HRSKGRRNNT IIVAEGALDD QLNPVTANDV KDALIELGLD
TKVTILGHVQ RGGTAVAHDR WLATLQGVDA VKAVLEFTPE TPSPLIGILE NKIIRMPLVE
SVKLTKSVAT AIENKDFDKA ISLRDTEFIE LYENFLSTTV KDDGSELLPV SDRLNIGIVH
VGAPSAALNA ATRAATLYCL SHGHKPYAIM NGFSGLIQTG EVKELSWIDV ENWHNLGGSE
IGTNRSVASE DLGTIAYYFQ KNKLDGLIIL GGFEGFRSLK QLRDGRTQHP IFNIPMCLIP
ATVSNNVPGT EYSLGVDTCL NALVNYTDDI KQSASATRRR VFVCEVQGGH SGYIASFTGL
ITGAVSVYTP EKKIDLASIR EDITLLKENF RHDKGENRNG KLLVRNEQAS SVYSTQLLAD
IISEASKGKF GVRTAIPGHV QQGGVPSSKD RVTASRFAVK CIKFIEQWNK KNEASPNTDA
KVLRFKFDTH GEKVPTVEHE DDSAAVICVN GSHVSFKPIA NLWENETNVE LRKGFEVHWA
EYNKIGDILS GRLKLRAEVA ALAAENK
