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 02-SEP-2026, entry version 118. 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; 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 (Probable) (PubMed:22991428, CC PubMed:25261592). Stimulates actin polymerization (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 (Probable) (PubMed:16321976, CC PubMed:26289816). 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}. 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; LN999946; CZU00144.1; -; Genomic_DNA. DR RefSeq; XP_001348599.1; XM_001348563.3. DR PDB; 4TR9; X-ray; 2.11 A; A/B/C/D=1-369, E=360-366, G=358-366. DR AlphaFoldDB; Q7KQL9; -. DR SMR; Q7KQL9; -. DR BioGRID; 1207364; 5. DR FunCoup; Q7KQL9; 64. DR IntAct; Q7KQL9; 4. DR STRING; 36329.Q7KQL9; -. DR SwissPalm; Q7KQL9; -. DR PaxDb; 36329-Q7KQL9; -. DR EnsemblProtists; PF3D7_1444800.1; PF3D7_1444800.1-p1; 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; WRAVITI; -. DR OrthoDB; 36455at2759; -. 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 EvolutionaryTrace; Q7KQL9; -. DR Proteomes; UP000001450; Chromosome 14. DR GO; GO:0005737; C:cytoplasm; IDA:GeneDB. DR GO; GO:0020002; C:host cell plasma membrane; ISS:UniProtKB. DR GO; GO:0016020; C:membrane; ISS:UniProtKB. 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 CDD; cd00948; FBP_aldolase_I_a; 1. DR FunFam; 3.20.20.70:FF:000187; Fructose-bisphosphate aldolase; 1. DR Gene3D; 3.20.20.70; Aldolase class I; 1. DR InterPro; IPR029768; Aldolase_I_AS. DR InterPro; IPR013785; Aldolase_TIM. DR InterPro; IPR000741; FBA_I. DR NCBIfam; NF033379; FrucBisAld_I; 1. DR PANTHER; PTHR11627; FRUCTOSE-BISPHOSPHATE ALDOLASE; 1. DR Pfam; PF00274; Glycolytic; 1. DR SUPFAM; SSF51569; Aldolase; 1. DR PROSITE; PS00158; ALDOLASE_CLASS_I; 1. DR PDBsum; 4TR9; -. 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:Q8I8I2" FT ACT_SITE 237 FT /note="Schiff-base intermediate with dihydroxyacetone FT phosphate" FT /evidence="ECO:0000250|UniProtKB:Q8I8I2" FT BINDING 40 FT /ligand="dihydroxyacetone phosphate" FT /ligand_id="ChEBI:CHEBI:57642" FT /evidence="ECO:0000250|UniProtKB:Q8I8I2" FT BINDING 42 FT /ligand="D-glyceraldehyde 3-phosphate" FT /ligand_id="ChEBI:CHEBI:59776" FT /evidence="ECO:0000250|UniProtKB:Q8I8I2" FT BINDING 45 FT /ligand="D-glyceraldehyde 3-phosphate" FT /ligand_id="ChEBI:CHEBI:59776" FT /evidence="ECO:0000250|UniProtKB:Q8I8I2" FT BINDING 49 FT /ligand="beta-D-fructose 1,6-bisphosphate" FT /ligand_id="ChEBI:CHEBI:32966" FT /evidence="ECO:0000250|UniProtKB:P00883" FT BINDING 113 FT /ligand="D-glyceraldehyde 3-phosphate" FT /ligand_id="ChEBI:CHEBI:59776" FT /evidence="ECO:0000250|UniProtKB:Q8I8I2" FT BINDING 152 FT /ligand="dihydroxyacetone phosphate" FT /ligand_id="ChEBI:CHEBI:57642" FT /evidence="ECO:0000250|UniProtKB:Q8I8I2" FT BINDING 195 FT /ligand="D-glyceraldehyde 3-phosphate" FT /ligand_id="ChEBI:CHEBI:59776" FT /evidence="ECO:0000250|UniProtKB:Q8I8I2" FT BINDING 237 FT /ligand="dihydroxyacetone phosphate" FT /ligand_id="ChEBI:CHEBI:57642" FT /evidence="ECO:0000250|UniProtKB:Q8I8I2" FT BINDING 279..281 FT /ligand="beta-D-fructose 1,6-bisphosphate" FT /ligand_id="ChEBI:CHEBI:32966" FT /evidence="ECO:0000250|UniProtKB:P00883" FT BINDING 279 FT /ligand="dihydroxyacetone phosphate" FT /ligand_id="ChEBI:CHEBI:57642" FT /evidence="ECO:0000250|UniProtKB:Q8I8I2" FT BINDING 280 FT /ligand="dihydroxyacetone phosphate" FT /ligand_id="ChEBI:CHEBI:57642" FT /evidence="ECO:0000250|UniProtKB:Q8I8I2" FT BINDING 307 FT /ligand="beta-D-fructose 1,6-bisphosphate" FT /ligand_id="ChEBI:CHEBI:32966" FT /evidence="ECO:0000250|UniProtKB:P00883" FT BINDING 309 FT /ligand="dihydroxyacetone phosphate" FT /ligand_id="ChEBI:CHEBI:57642" FT /evidence="ECO:0000250|UniProtKB:Q8I8I2" FT BINDING 310 FT /ligand="beta-D-fructose 1,6-bisphosphate" FT /ligand_id="ChEBI:CHEBI:32966" FT /evidence="ECO:0000250|UniProtKB:P00883" FT BINDING 310 FT /ligand="dihydroxyacetone phosphate" FT /ligand_id="ChEBI:CHEBI:57642" FT /evidence="ECO:0000250|UniProtKB:Q8I8I2" 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 11..15 FT /evidence="ECO:0007829|PDB:4TR9" 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 //