ID PFKA_DICDI Reviewed; 834 AA.
AC P90521; Q555B1; Q86HR6; Q95023;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 04-DEC-2007, sequence version 2.
DT 27-MAR-2024, entry version 143.
DE RecName: Full=ATP-dependent 6-phosphofructokinase {ECO:0000255|HAMAP-Rule:MF_03184};
DE Short=ATP-PFK {ECO:0000255|HAMAP-Rule:MF_03184};
DE Short=Phosphofructokinase {ECO:0000255|HAMAP-Rule:MF_03184};
DE EC=2.7.1.11 {ECO:0000255|HAMAP-Rule:MF_03184};
DE AltName: Full=Phosphohexokinase {ECO:0000255|HAMAP-Rule:MF_03184};
GN Name=pfkA; Synonyms=pfk; ORFNames=DDB_G0274111;
OS Dictyostelium discoideum (Social amoeba).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=AX3;
RX PubMed=9030771; DOI=10.1111/j.1432-1033.1997.0442a.x;
RA Estevez A.M., Martinez-Costa O.H., Sanchez V., Aragon J.J.;
RT "Cloning, sequencing and developmental expression of phosphofructokinase
RT from Dictyostelium discoideum.";
RL Eur. J. Biochem. 243:442-451(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=12097910; DOI=10.1038/nature00847;
RA Gloeckner G., Eichinger L., Szafranski K., Pachebat J.A., Bankier A.T.,
RA Dear P.H., Lehmann R., Baumgart C., Parra G., Abril J.F., Guigo R.,
RA Kumpf K., Tunggal B., Cox E.C., Quail M.A., Platzer M., Rosenthal A.,
RA Noegel A.A.;
RT "Sequence and analysis of chromosome 2 of Dictyostelium discoideum.";
RL Nature 418:79-85(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND
RP COFACTOR.
RX PubMed=7813455; DOI=10.1111/j.1432-1033.1994.01007.x;
RA Martinez-Costa O.H., Estevez A.M., Sanchez V., Aragon J.J.;
RT "Purification and properties of phosphofructokinase from Dictyostelium
RT discoideum.";
RL Eur. J. Biochem. 226:1007-1017(1994).
RN [5]
RP FUNCTION.
RX PubMed=22530721; DOI=10.1042/bj20120173;
RA Martinez-Costa O.H., Sanchez V., Lazaro A., Hernandez E.D., Tornheim K.,
RA Aragon J.J.;
RT "Distinct functional roles of the two terminal halves of eukaryotic
RT phosphofructokinase.";
RL Biochem. J. 445:213-218(2012).
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:22530721, ECO:0000269|PubMed:7813455}.
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:7813455};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03184,
CC ECO:0000269|PubMed:7813455};
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=16 uM for ATP {ECO:0000269|PubMed:7813455};
CC KM=22 uM for fructose 6-phosphate {ECO:0000269|PubMed:7813455};
CC Vmax=89 umol/min/mg enzyme {ECO:0000269|PubMed:7813455};
CC pH dependence:
CC Optimum pH is 7.6. {ECO:0000269|PubMed:7813455};
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: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_03184,
CC ECO:0000269|PubMed:7813455}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03184}.
CC -!- PTM: The N-terminus is blocked.
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; X89039; CAA61438.2; -; mRNA.
DR EMBL; X94340; CAA64065.1; -; mRNA.
DR EMBL; AAFI02000012; EAL69948.1; -; Genomic_DNA.
DR RefSeq; XP_644162.1; XM_639070.1.
DR AlphaFoldDB; P90521; -.
DR SMR; P90521; -.
DR STRING; 44689.P90521; -.
DR PaxDb; 44689-DDB0191364; -.
DR EnsemblProtists; EAL69948; EAL69948; DDB_G0274111.
DR GeneID; 8619591; -.
DR KEGG; ddi:DDB_G0274111; -.
DR dictyBase; DDB_G0274111; pfkA.
DR eggNOG; KOG2440; Eukaryota.
DR HOGENOM; CLU_011053_0_0_1; -.
DR InParanoid; P90521; -.
DR OMA; EWQDQMC; -.
DR PhylomeDB; P90521; -.
DR BRENDA; 2.7.1.11; 1939.
DR SABIO-RK; P90521; -.
DR UniPathway; UPA00109; UER00182.
DR PRO; PR:P90521; -.
DR Proteomes; UP000002195; Chromosome 2.
DR GO; GO:0005945; C:6-phosphofructokinase complex; IDA:dictyBase.
DR GO; GO:0005829; C:cytosol; IDA:dictyBase.
DR GO; GO:0003872; F:6-phosphofructokinase activity; IDA:dictyBase.
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:0015631; F:tubulin binding; IPI:dictyBase.
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:dictyBase.
DR GO; GO:0006007; P:glucose catabolic process; IGI:dictyBase.
DR GO; GO:0031115; P:negative regulation of microtubule polymerization; IDA:dictyBase.
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; IPR015912; Phosphofructokinase_CS.
DR InterPro; IPR000023; Phosphofructokinase_dom.
DR InterPro; IPR035966; PKF_sf.
DR NCBIfam; TIGR02478; 6PF1K_euk; 1.
DR PANTHER; PTHR13697:SF4; ATP-DEPENDENT 6-PHOSPHOFRUCTOKINASE; 1.
DR PANTHER; PTHR13697; PHOSPHOFRUCTOKINASE; 1.
DR Pfam; PF00365; PFK; 2.
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..834
FT /note="ATP-dependent 6-phosphofructokinase"
FT /id="PRO_0000112030"
FT REGION 1..426
FT /note="N-terminal catalytic PFK domain 1"
FT REGION 427..437
FT /note="Interdomain linker"
FT REGION 438..834
FT /note="C-terminal regulatory PFK domain 2"
FT REGION 799..834
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 811..834
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 201
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 62
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 123..124
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 153..156
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 154
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 199..201
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 236
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 243..245
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 299
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 326
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 332..335
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 507
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 566..570
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 603
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 610..612
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 666
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 692
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 698..701
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 764
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT CONFLICT 110..112
FT /note="GII -> WLY (in Ref. 1; CAA61438/CAA64065)"
FT /evidence="ECO:0000305"
FT CONFLICT 302..303
FT /note="ID -> MH (in Ref. 1; CAA64065)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 834 AA; 92235 MW; F9E4F2DF798FE78B CRC64;
MTTTSKIIND GEGEDVKGNK NINKKSLIDE NRLDEKKDLL SDKVESKTHC SVKRMAVLTS
GGDSSGMNPA IRAFARQVML KGAKVFAVRE GYNGLVNDSI VPLNWGSVAG IISRGGTIIG
TARSAEFRTR EGRKRAVFNL VKNRIDNLLV IGGDGSLTGA NLLRTEWCSL LEELVKDGKL
TLDVMEHFPI LSIAGIVGSI DNDMCGTDLT VGADTATKRI LEAIDSILST AVSHQRSFVI
EVMGRNCGWL ALASGVATGA DYILIPESPP DDGWEQTMAD NLERGRLSGR RCSLVIVSEG
AIDRQGKPIT SAYVRQFLED KGHDARITIL GHVQRGGTPT FLDRYIATRM GIEAANYFYD
STIEQLKQPV LIGMSGMDTI RSPLMECVQK TQSIASLIKE RRFNEVVDVR GGMFKEFYEI
FIACSNLHRR KVESKGMGVL ILHSGGPSPG MNPCVRAFTR LGIDHGYTMY GCFNGFGGLA
LGEIEQLHWM TVNGWSVMGG AELGTNRSIP NDSNIEAIIA TLERFKINAI LMFGGFNGYL
GIAKLYEYRE KYQQLKRISI IGAPGTIANN VPGTNISIGS DTSLNNTLDA LDKIKQSAVA
SRRLFVVEVM GAHCGYLAAM SSLTSGAERS YIMERGITLN TLTKDLEMFV ERFKREHRIG
LIIKSELASN TYSTHFIYSL FKEEGKHLFD VRESILGHLQ QGGTPSAIDR IFSTRLMNHY
YQFLENDLKE HGHLQMNGCI GFIDGGIHYT PMQEMIEEMS DKFRRPRSQW WMDLVETSQN
ISVFPLDDPS STNFEGCNSN LSEQDRPIKK SDISSPTSYS QKTFDPNVNP QFTL
//
