ID   PFKA1_KLULA             Reviewed;         992 AA.
AC   Q03215;
DT   01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1993, sequence version 1.
DT   02-SEP-2026, entry version 158.
DE   RecName: Full=ATP-dependent 6-phosphofructokinase subunit alpha {ECO:0000255|HAMAP-Rule:MF_03184};
DE            Short=ATP-PFK 1 {ECO:0000255|HAMAP-Rule:MF_03184};
DE            Short=Phosphofructokinase 1 {ECO:0000255|HAMAP-Rule:MF_03184};
DE            EC=2.7.1.11 {ECO:0000255|HAMAP-Rule:MF_03184};
DE   AltName: Full=Phosphohexokinase 1 {ECO:0000255|HAMAP-Rule:MF_03184};
GN   Name=PFK1; OrderedLocusNames=KLLA0A05544g;
OS   Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 /
OS   NRRL Y-1140 / WM37) (Yeast) (Candida sphaerica).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Kluyveromyces.
OX   NCBI_TaxID=284590;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND CHARACTERIZATION.
RX   PubMed=8326866; DOI=10.1111/j.1365-2958.1993.tb01600.x;
RA   Heinisch J.J., Kirchrath L., Liesen T., Vogelsang K., Hollenberg C.P.;
RT   "Molecular genetics of phosphofructokinase in the yeast Kluyveromyces
RT   lactis.";
RL   Mol. Microbiol. 8:559-570(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 /
RC   WM37;
RX   PubMed=15229592; DOI=10.1038/nature02579;
RA   Dujon B., Sherman D., Fischer G., Durrens P., Casaregola S., Lafontaine I.,
RA   de Montigny J., Marck C., Neuveglise C., Talla E., Goffard N., Frangeul L.,
RA   Aigle M., Anthouard V., Babour A., Barbe V., Barnay S., Blanchin S.,
RA   Beckerich J.-M., Beyne E., Bleykasten C., Boisrame A., Boyer J.,
RA   Cattolico L., Confanioleri F., de Daruvar A., Despons L., Fabre E.,
RA   Fairhead C., Ferry-Dumazet H., Groppi A., Hantraye F., Hennequin C.,
RA   Jauniaux N., Joyet P., Kachouri R., Kerrest A., Koszul R., Lemaire M.,
RA   Lesur I., Ma L., Muller H., Nicaud J.-M., Nikolski M., Oztas S.,
RA   Ozier-Kalogeropoulos O., Pellenz S., Potier S., Richard G.-F.,
RA   Straub M.-L., Suleau A., Swennen D., Tekaia F., Wesolowski-Louvel M.,
RA   Westhof E., Wirth B., Zeniou-Meyer M., Zivanovic Y., Bolotin-Fukuhara M.,
RA   Thierry A., Bouchier C., Caudron B., Scarpelli C., Gaillardin C.,
RA   Weissenbach J., Wincker P., Souciet J.-L.;
RT   "Genome evolution in yeasts.";
RL   Nature 430:35-44(2004).
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   -!- CATALYTIC ACTIVITY:
CC       Reaction=beta-D-fructose 6-phosphate + ATP = beta-D-fructose 1,6-
CC         bisphosphate + ADP + 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};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000255|HAMAP-
CC         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}.
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   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03184}.
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; Z17315; CAA78963.1; -; Genomic_DNA.
DR   EMBL; CR382121; CAH02833.1; -; Genomic_DNA.
DR   PIR; S32902; S32902.
DR   RefSeq; XP_451245.1; XM_451245.1.
DR   AlphaFoldDB; Q03215; -.
DR   SMR; Q03215; -.
DR   FunCoup; Q03215; 980.
DR   STRING; 284590.Q03215; -.
DR   PaxDb; 284590-Q03215; -.
DR   GeneID; 2896656; -.
DR   KEGG; kla:KLLA0_A05544g; -.
DR   eggNOG; KOG2440; Eukaryota.
DR   HOGENOM; CLU_011053_0_0_1; -.
DR   InParanoid; Q03215; -.
DR   OMA; WHNLGGS; -.
DR   SABIO-RK; Q03215; -.
DR   UniPathway; UPA00109; UER00182.
DR   Proteomes; UP000000598; Chromosome A.
DR   GO; GO:0005945; C:6-phosphofructokinase complex; IEA:TreeGrafter.
DR   GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-ARBA.
DR   GO; GO:0003872; F:6-phosphofructokinase activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0016208; F:AMP binding; IEA:TreeGrafter.
DR   GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR   GO; GO:0070095; F:fructose-6-phosphate binding; IEA:TreeGrafter.
DR   GO; GO:0042802; F:identical protein binding; IEA:TreeGrafter.
DR   GO; GO:0048029; F:monosaccharide binding; IEA:TreeGrafter.
DR   GO; GO:0061621; P:canonical glycolysis; IEA:TreeGrafter.
DR   GO; GO:0030388; P:fructose 1,6-bisphosphate metabolic process; IEA:TreeGrafter.
DR   GO; GO:0006002; P:fructose 6-phosphate metabolic process; IEA:InterPro.
DR   GO; GO:1902600; P:proton transmembrane transport; IEA:UniProtKB-ARBA.
DR   GO; GO:0051453; P:regulation of intracellular pH; IEA:UniProtKB-ARBA.
DR   CDD; cd00764; Eukaryotic_PFK; 1.
DR   FunFam; 3.40.50.450:FF:000010; ATP-dependent 6-phosphofructokinase; 1.
DR   FunFam; 3.40.50.460:FF:000007; ATP-dependent 6-phosphofructokinase; 1.
DR   FunFam; 3.40.50.460:FF:000008; ATP-dependent 6-phosphofructokinase; 1.
DR   Gene3D; 3.10.180.90; -; 1.
DR   Gene3D; 3.40.50.450; -; 2.
DR   Gene3D; 3.40.50.460; Phosphofructokinase domain; 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; IPR041914; PFK_vert-type.
DR   InterPro; IPR015912; Phosphofructokinase_CS.
DR   InterPro; IPR000023; Phosphofructokinase_dom.
DR   InterPro; IPR035966; PKF_sf.
DR   NCBIfam; TIGR02478; 6PF1K_euk; 1.
DR   PANTHER; PTHR13697:SF57; ATP-DEPENDENT 6-PHOSPHOFRUCTOKINASE SUBUNIT ALPHA; 1.
DR   PANTHER; PTHR13697; PHOSPHOFRUCTOKINASE; 1.
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; Phosphofructokinase; 2.
DR   PROSITE; PS00433; PHOSPHOFRUCTOKINASE; 2.
PE   1: Evidence at protein level;
KW   Allosteric enzyme; ATP-binding; Cytoplasm; Glycolysis; Kinase; Magnesium;
KW   Metal-binding; Nucleotide-binding; Reference proteome; Transferase.
FT   CHAIN           1..992
FT                   /note="ATP-dependent 6-phosphofructokinase subunit alpha"
FT                   /id="PRO_0000112040"
FT   REGION          1..558
FT                   /note="N-terminal catalytic PFK domain 1"
FT   REGION          559..572
FT                   /note="Interdomain linker"
FT   REGION          573..992
FT                   /note="C-terminal regulatory PFK domain 2"
FT   ACT_SITE        334
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT   BINDING         193
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT   BINDING         256..257
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT   BINDING         286..289
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT   BINDING         287
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT   BINDING         332..334
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   BINDING         369
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:0000255|HAMAP-Rule:MF_03184"
FT   BINDING         376..378
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   BINDING         433
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   BINDING         460
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:0000255|HAMAP-Rule:MF_03184"
FT   BINDING         466..469
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   BINDING         643
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   BINDING         700..704
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   BINDING         738
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   BINDING         745..747
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   BINDING         805
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   BINDING         831
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   BINDING         837..840
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   BINDING         929
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"
SQ   SEQUENCE   992 AA;  109336 MW;  724687F850F27F79 CRC64;
     MNNSVYGVAF RSLSTGDEKL YKEATRFYHS LGFQTVKLYD NFKNHDDSNL IVGTSKNSVK
     ECWLESFKLS ELDSQGFRVP QQEASNQLQT DGVMIKLRLV DTEPLNQTAD TVVYYTVSLD
     EVSKIGERVD DHNVKLVDPL GNVVLVTDSH DGKELNASEF IAPKDSSVEQ KITVELVDKD
     SKKKKIAVMT SGGDSQGMNA AVRAVVRSSI YYGCDVYAVY EGYEGLVKGG DYLRKMEWKD
     VRGWLSEGGT LIGTARSKEF RERWGRKQAC SNLIDQGIDA LVVIGGDGSL TGADLFRSEW
     PSLVEELVKD GKFTEDEVAL YQNLTIVGMV GSIDNDMSGT DSTIGAYSAL ERICEMVDYI
     DATAKSHSRA FVVEVMGRHC GWLGLMSGIA TAADYIFIPE RAAPHGKWQD ELKRVCQRHR
     EKGRRNNTVI VAEGALDDQL NPITAEQVKD VLVELGLDTK ITTLGHVQRG GTAVAHDRWL
     ATLQGVDAVK AILNMTPETP SPLIGILENK VIRMPLVESV KLTKQVAAAI EAKDFDKAIS
     LRDTEFIELY SNFMSTTVND DGSQLLPEAD RLNIAIVHVG APSAALNAAT RAATLYCLAH
     GHRPYAITNG FSGLIQTGQV KELSWIDVED WHNLGGSEIG TNRSVAAEDM GTIAYHFQKN
     KFDGVIILGG FEGFKSLKQL RDGRDQYPIF NIPMCLIPAT VSNNVPGTEY SLGSDTCLNA
     LVKYTDAIKQ SASSTRRRVF VVEVQGGHSG YVASFTGLVT GAVSVYTPEN AINLKTIQED
     LALLKESFKH EQGETRNGKL VIRNEMASDV YTTELLADII TEQSNDRFGV RTAIPGHVQQ
     GGVPSSKDRV IASRFAVKCV KFIEQWNKKN TAADNEDFKI LRFNYVNGVK QYTVLDEDLS
     AAVICVNGSK ISFKPIAHIW ENETNIELRK GQEIHWEEYN EIGDILSGRS MLRRKIQKEQ
     QEESSLPSVA DTPLSSVTVS TSAAKEDSAL YV
//