ALF_PLAF7
ID ALF_PLAF7 Reviewed; 369 AA.
AC Q7KQL9; A0A144A3T1;
DT 02-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Fructose-bisphosphate aldolase {ECO:0000305};
DE EC=4.1.2.13 {ECO:0000269|PubMed:26289816};
GN Name=FBPA {ECO:0000305}; ORFNames=PF14_0425, PF3D7_1444800;
OS Plasmodium falciparum (isolate 3D7).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=36329;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7;
RX PubMed=12368864; DOI=10.1038/nature01097;
RA Gardner M.J., Hall N., Fung E., White O., Berriman M., Hyman R.W.,
RA Carlton J.M., Pain A., Nelson K.E., Bowman S., Paulsen I.T., James K.D.,
RA Eisen J.A., Rutherford K.M., Salzberg S.L., Craig A., Kyes S., Chan M.-S.,
RA Nene V., Shallom S.J., Suh B., Peterson J., Angiuoli S., Pertea M.,
RA Allen J., Selengut J., Haft D., Mather M.W., Vaidya A.B., Martin D.M.A.,
RA Fairlamb A.H., Fraunholz M.J., Roos D.S., Ralph S.A., McFadden G.I.,
RA Cummings L.M., Subramanian G.M., Mungall C., Venter J.C., Carucci D.J.,
RA Hoffman S.L., Newbold C., Davis R.W., Fraser C.M., Barrell B.G.;
RT "Genome sequence of the human malaria parasite Plasmodium falciparum.";
RL Nature 419:498-511(2002).
RN [2]
RP FUNCTION, INTERACTION WITH TRAP AND MTRAP, AND DEVELOPMENTAL STAGE.
RX PubMed=16321976; DOI=10.1074/jbc.m509807200;
RA Baum J., Richard D., Healer J., Rug M., Krnajski Z., Gilberger T.W.,
RA Green J.L., Holder A.A., Cowman A.F.;
RT "A conserved molecular motor drives cell invasion and gliding motility
RT across malaria life cycle stages and other apicomplexan parasites.";
RL J. Biol. Chem. 281:5197-5208(2006).
RN [3]
RP FUNCTION, AND INTERACTION WITH TRAP; RH1; RH2B AND RH4.
RX PubMed=22991428; DOI=10.1128/mbio.00292-12;
RA Pal-Bhowmick I., Andersen J., Srinivasan P., Narum D.L., Bosch J.,
RA Miller L.H.;
RT "Binding of aldolase and glyceraldehyde-3-phosphate dehydrogenase to the
RT cytoplasmic tails of Plasmodium falciparum merozoite duffy binding-like and
RT reticulocyte homology ligands.";
RL MBio 3:0-0(2012).
RN [4]
RP FUNCTION, AND INTERACTION WITH G ACTIN AND F ACTIN.
RX PubMed=25261592; DOI=10.1016/j.molbiopara.2014.09.006;
RA Diaz S.A., Martin S.R., Grainger M., Howell S.A., Green J.L., Holder A.A.;
RT "Plasmodium falciparum aldolase and the C-terminal cytoplasmic domain of
RT certain apical organellar proteins promote actin polymerization.";
RL Mol. Biochem. Parasitol. 197:9-14(2014).
RN [5]
RP FUNCTION, AND INTERACTION WITH TRAP; MTRAP; RH1; RH2B; RH4; AMA1; EBA140;
RP EBA175 AND EBA181.
RX PubMed=27607074; DOI=10.1371/journal.pone.0161850;
RA Diaz S.A., Martin S.R., Howell S.A., Grainger M., Moon R.W., Green J.L.,
RA Holder A.A.;
RT "The Binding of Plasmodium falciparum Adhesins and Erythrocyte Invasion
RT Proteins to Aldolase Is Enhanced by Phosphorylation.";
RL PLoS ONE 11:e0161850-e0161850(2016).
RN [6] {ECO:0007744|PDB:4TR9}
RP X-RAY CRYSTALLOGRAPHY (2.11 ANGSTROMS) IN COMPLEX WITH P.BERGHEI TRAP
RP PEPTIDE (604-606) AND INHIBITOR, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP PATHWAY, AND SUBUNIT.
RX PubMed=26289816; DOI=10.1186/s12936-015-0834-9;
RA Nemetski S.M., Cardozo T.J., Bosch G., Weltzer R., O'Malley K., Ejigiri I.,
RA Kumar K.A., Buscaglia C.A., Nussenzweig V., Sinnis P., Levitskaya J.,
RA Bosch J.;
RT "Inhibition by stabilization: targeting the Plasmodium falciparum aldolase-
RT TRAP complex.";
RL Malar. J. 14:324-324(2015).
CC -!- FUNCTION: Plays a key role in glycolysis by catalyzing the cleavage of
CC fructose 1,6-bisphosphate into dihydroxyacetone phosphate and
CC glyceraldehyde 3-phosphate (PubMed:26289816). Independently of its
CC catalytic activity, connects the actin filaments, and thus the
CC actomyosin motor, to cell surface adhesins of the thrombospondin-
CC related anonymous protein (TRAP), the erythrocyte binding ligand (EBL)
CC and reticulocyte binding homolog (RH) protein families; this
CC interaction is probably involved in transducing the motor force across
CC the parasite surface required for sporozoite and ookinete gliding
CC motility and merozoite invasion (PubMed:22991428, PubMed:25261592)
CC (Probable). Stimulates actin polymerisation (PubMed:25261592).
CC {ECO:0000269|PubMed:22991428, ECO:0000269|PubMed:25261592,
CC ECO:0000269|PubMed:26289816, ECO:0000305|PubMed:16321976,
CC ECO:0000305|PubMed:22991428, ECO:0000305|PubMed:27607074}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-fructose 1,6-bisphosphate = D-glyceraldehyde 3-
CC phosphate + dihydroxyacetone phosphate; Xref=Rhea:RHEA:14729,
CC ChEBI:CHEBI:32966, ChEBI:CHEBI:57642, ChEBI:CHEBI:59776; EC=4.1.2.13;
CC Evidence={ECO:0000269|PubMed:26289816};
CC -!- ACTIVITY REGULATION: The cytoplasmic tail of TRAP and probably other
CC adhesins acts as a competitive inhibitor as the binding sites of the
CC glycolytic substrate fructose 1,6-bisphosphate and TRAP partially
CC overlap. {ECO:0000269|PubMed:26289816}.
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC phosphate and glycerone phosphate from D-glucose: step 4/4.
CC {ECO:0000269|PubMed:26289816}.
CC -!- SUBUNIT: Homotetramer (PubMed:26289816). Interacts with TRAP (via
CC cytoplasmic domain); the interaction prevents substrate binding and
CC thereby inhibits aldolase activity (PubMed:26289816, PubMed:16321976)
CC (Probable). Interacts with MTRAP (via cytoplasmic domain); MTRAP
CC phosphorylation may increase the binding to FBPA (PubMed:16321976).
CC Interact with RH1 (via cytoplasmic domain) (PubMed:22991428,
CC PubMed:27607074). Interacts with RH2b (via cytoplasmic domain)
CC (PubMed:22991428, PubMed:27607074). Interacts with RH4 (via cytoplasmic
CC domain) (PubMed:22991428, PubMed:27607074). Interacts with AMA1 (via
CC cytoplasmic domain); the interaction is weak, however it may be
CC increased upon AMA1 phosphorylation (PubMed:27607074). Interacts with
CC EBA140 (via cytoplasmic domain); the interaction is weak
CC (PubMed:27607074). Interacts with EBA175 (via cytoplasmic domain); the
CC interaction is weak (PubMed:27607074). Interacts with EBA181 (via
CC cytoplasmic domain); the interaction is weak (PubMed:27607074).
CC Interacts with G-actin and F-actin (PubMed:25261592). May interact with
CC ACT2/actin II; the interaction inhibits FBPA catalytic activity (By
CC similarity). Interacts with human SLC4A1/band 3 (via N-terminus); the
CC interaction inhibits FBPA catalytic activity (By similarity).
CC {ECO:0000250|UniProtKB:Q27744, ECO:0000269|PubMed:16321976,
CC ECO:0000269|PubMed:22991428, ECO:0000269|PubMed:25261592,
CC ECO:0000269|PubMed:26289816, ECO:0000269|PubMed:27607074,
CC ECO:0000305|PubMed:22991428}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P14223}.
CC Membrane {ECO:0000250|UniProtKB:P14223}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P14223}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P14223}. Host cell membrane
CC {ECO:0000250|UniProtKB:Q27744}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P14223}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P14223}.
CC -!- DEVELOPMENTAL STAGE: Expressed during parasite asexual blood stages,
CC including in schizonts (at protein level).
CC {ECO:0000269|PubMed:16321976}.
CC -!- SIMILARITY: Belongs to the class I fructose-bisphosphate aldolase
CC family. {ECO:0000305}.
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DR EMBL; LN999946; CZU00144.1; -; Genomic_DNA.
DR RefSeq; XP_001348599.1; XM_001348563.2.
DR PDB; 4TR9; X-ray; 2.11 A; A/B/C/D=1-369, E=360-366, G=358-366.
DR PDBsum; 4TR9; -.
DR AlphaFoldDB; Q7KQL9; -.
DR SMR; Q7KQL9; -.
DR BioGRID; 1207364; 4.
DR IntAct; Q7KQL9; 4.
DR STRING; 5833.PF14_0425; -.
DR SwissPalm; Q7KQL9; -.
DR PRIDE; Q7KQL9; -.
DR EnsemblProtists; CZU00144; CZU00144; PF3D7_1444800.
DR GeneID; 812007; -.
DR KEGG; pfa:PF3D7_1444800; -.
DR VEuPathDB; PlasmoDB:PF3D7_1444800; -.
DR HOGENOM; CLU_031243_0_0_1; -.
DR InParanoid; Q7KQL9; -.
DR OMA; DYREMLF; -.
DR PhylomeDB; Q7KQL9; -.
DR Reactome; R-PFA-114608; Platelet degranulation.
DR Reactome; R-PFA-6798695; Neutrophil degranulation.
DR Reactome; R-PFA-70171; Glycolysis.
DR Reactome; R-PFA-70263; Gluconeogenesis.
DR Reactome; R-PFA-70350; Fructose catabolism.
DR UniPathway; UPA00109; UER00183.
DR Proteomes; UP000001450; Chromosome 14.
DR GO; GO:0005737; C:cytoplasm; IDA:GeneDB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003779; F:actin binding; IDA:GeneDB.
DR GO; GO:0004332; F:fructose-bisphosphate aldolase activity; IDA:UniProtKB.
DR GO; GO:0008154; P:actin polymerization or depolymerization; IDA:GeneDB.
DR GO; GO:0030388; P:fructose 1,6-bisphosphate metabolic process; IBA:GO_Central.
DR GO; GO:0006096; P:glycolytic process; IDA:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR029768; Aldolase_I_AS.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR000741; FBA_I.
DR PANTHER; PTHR11627; PTHR11627; 1.
DR Pfam; PF00274; Glycolytic; 1.
DR PROSITE; PS00158; ALDOLASE_CLASS_I; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Cytoplasm; Glycolysis; Host cell membrane;
KW Host membrane; Lyase; Membrane; Reference proteome; Schiff base.
FT CHAIN 1..369
FT /note="Fructose-bisphosphate aldolase"
FT /id="PRO_0000233386"
FT ACT_SITE 195
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P00883"
FT ACT_SITE 237
FT /note="Schiff-base intermediate with dihydroxyacetone-P"
FT /evidence="ECO:0000250|UniProtKB:P00883"
FT BINDING 62
FT /ligand="beta-D-fructose 1,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:32966"
FT /evidence="ECO:0000250|UniProtKB:P00883"
FT BINDING 152
FT /ligand="beta-D-fructose 1,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:32966"
FT /evidence="ECO:0000250|UniProtKB:P00883"
FT SITE 369
FT /note="Necessary for preference for fructose 1,6-
FT bisphosphate over fructose 1-phosphate"
FT /evidence="ECO:0000250|UniProtKB:P00883"
FT HELIX 16..29
FT /evidence="ECO:0007829|PDB:4TR9"
FT STRAND 35..39
FT /evidence="ECO:0007829|PDB:4TR9"
FT HELIX 43..52
FT /evidence="ECO:0007829|PDB:4TR9"
FT HELIX 59..70
FT /evidence="ECO:0007829|PDB:4TR9"
FT HELIX 75..77
FT /evidence="ECO:0007829|PDB:4TR9"
FT STRAND 79..84
FT /evidence="ECO:0007829|PDB:4TR9"
FT HELIX 86..89
FT /evidence="ECO:0007829|PDB:4TR9"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:4TR9"
FT HELIX 99..105
FT /evidence="ECO:0007829|PDB:4TR9"
FT STRAND 109..113
FT /evidence="ECO:0007829|PDB:4TR9"
FT STRAND 118..120
FT /evidence="ECO:0007829|PDB:4TR9"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:4TR9"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:4TR9"
FT HELIX 136..146
FT /evidence="ECO:0007829|PDB:4TR9"
FT STRAND 150..157
FT /evidence="ECO:0007829|PDB:4TR9"
FT HELIX 161..163
FT /evidence="ECO:0007829|PDB:4TR9"
FT HELIX 168..187
FT /evidence="ECO:0007829|PDB:4TR9"
FT STRAND 191..198
FT /evidence="ECO:0007829|PDB:4TR9"
FT HELIX 206..226
FT /evidence="ECO:0007829|PDB:4TR9"
FT HELIX 231..233
FT /evidence="ECO:0007829|PDB:4TR9"
FT HELIX 253..267
FT /evidence="ECO:0007829|PDB:4TR9"
FT STRAND 274..278
FT /evidence="ECO:0007829|PDB:4TR9"
FT HELIX 284..295
FT /evidence="ECO:0007829|PDB:4TR9"
FT STRAND 301..309
FT /evidence="ECO:0007829|PDB:4TR9"
FT HELIX 310..320
FT /evidence="ECO:0007829|PDB:4TR9"
FT HELIX 324..326
FT /evidence="ECO:0007829|PDB:4TR9"
FT HELIX 327..346
FT /evidence="ECO:0007829|PDB:4TR9"
FT HELIX 362..366
FT /evidence="ECO:0007829|PDB:4TR9"
SQ SEQUENCE 369 AA; 40105 MW; 2AE9CDED4F5C96A4 CRC64;
MAHCTEYMNA PKKLPADVAE ELATTAQKLV QAGKGILAAD ESTQTIKKRF DNIKLENTIE
NRASYRDLLF GTKGLGKFIS GAILFEETLF QKNEAGVPMV NLLHNENIIP GIKVDKGLVN
IPCTDEEKST QGLDGLAERC KEYYKAGARF AKWRTVLVID TAKGKPTDLS IHETAWGLAR
YASICQQNRL VPIVEPEILA DGPHSIEVCA VVTQKVLSCV FKALQENGVL LEGALLKPNM
VTAGYECTAK TTTQDVGFLT VRTLRRTVPP ALPGVVFLSG GQSEEEASVN LNSINALGPH
PWALTFSYGR ALQASVLNTW QGKKENVAKA REVLLQRAEA NSLATYGKYK GGAGGENAGA
SLYEKKYVY
