ALF_PLAFA
ID ALF_PLAFA Reviewed; 369 AA.
AC P14223;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Fructose-bisphosphate aldolase {ECO:0000305};
DE Short=PfAldo {ECO:0000303|PubMed:9521758};
DE EC=4.1.2.13 {ECO:0000305|PubMed:2190085};
DE AltName: Full=41 kDa antigen {ECO:0000303|PubMed:2693962};
GN Name=FBPA {ECO:0000305};
OS Plasmodium falciparum.
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=5833;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND DEVELOPMENTAL STAGE.
RC STRAIN=FCBR {ECO:0000269|PubMed:2693962};
RX PubMed=2693962; DOI=10.1016/0166-6851(89)90101-1;
RA Knapp B., Hundt E., Kuepper H.A.;
RT "A new blood stage antigen of Plasmodium falciparum transported to the
RT erythrocyte surface.";
RL Mol. Biochem. Parasitol. 37:47-56(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR
RP LOCATION, FUNCTION, AND DEVELOPMENTAL STAGE.
RC STRAIN=FCBR {ECO:0000269|PubMed:2190085};
RX PubMed=2190085; DOI=10.1016/0166-6851(90)90074-v;
RA Knapp B., Hundt E., Kuepper H.A.;
RT "Plasmodium falciparum aldolase: gene structure and localization.";
RL Mol. Biochem. Parasitol. 40:1-12(1990).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS), AND SUBUNIT.
RX PubMed=9521758; DOI=10.1021/bi972233h;
RA Kim H., Certa U., Dobeli H., Jakob P., Hol W.G.J.;
RT "Crystal structure of fructose-1,6-bisphosphate aldolase from the human
RT malaria parasite Plasmodium falciparum.";
RL Biochemistry 37:4388-4396(1998).
RN [4] {ECO:0007744|PDB:2EPH, ECO:0007744|PDB:2PC4}
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) IN COMPLEX WITH P.BERGHEI TRAP
RP PEPTIDE (601-606), ACTIVITY REGULATION, AND MUTAGENESIS OF ASP-40; GLU-41;
RP ARG-49; LYS-152; ARG-154; ARG-310; GLN-313; ALA-314 AND LEU-317.
RX PubMed=17426153; DOI=10.1073/pnas.0605301104;
RA Bosch J., Buscaglia C.A., Krumm B., Ingason B.P., Lucas R., Roach C.,
RA Cardozo T., Nussenzweig V., Hol W.G.;
RT "Aldolase provides an unusual binding site for thrombospondin-related
RT anonymous protein in the invasion machinery of the malaria parasite.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:7015-7020(2007).
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:2190085). 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 (By similarity). Stimulates actin
CC polymerisation (By similarity). {ECO:0000250|UniProtKB:Q7KQL9,
CC ECO:0000269|PubMed:2190085}.
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:0000305|PubMed:2190085};
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:0000305|PubMed:17426153}.
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC phosphate and glycerone phosphate from D-glucose: step 4/4.
CC {ECO:0000305|PubMed:2190085}.
CC -!- SUBUNIT: Homotetramer (PubMed:9521758). Interacts with TRAP (via
CC cytoplasmic domain); the interaction prevents substrate binding and
CC thereby inhibits aldolase activity (PubMed:17426153). Interacts with
CC MTRAP (via cytoplasmic domain); MTRAP phosphorylation may increase the
CC binding to FBPA (By similarity). Interact with RH1 (via cytoplasmic
CC domain) (By similarity). Interacts with RH2b (via cytoplasmic domain)
CC (By similarity). Interacts with RH4 (via cytoplasmic domain) (By
CC similarity). Interacts with AMA1 (via cytoplasmic domain); the
CC interaction is weak, however it may be increased upon AMA1
CC phosphorylation (By similarity). Interacts with EBA140 (via cytoplasmic
CC domain); the interaction is weak (By similarity). Interacts with EBA175
CC (via cytoplasmic domain); the interaction is weak (By similarity).
CC Interacts with EBA181 (via cytoplasmic domain); the interaction is weak
CC (By similarity). Interacts with G-actin and F-actin (By similarity).
CC May interact with ACT2/actin II; the interaction inhibits FBPA
CC catalytic activity (By similarity). Interacts with human SLC4A1/band 3
CC (via N-terminus); the interaction inhibits FBPA catalytic activity (By
CC similarity). {ECO:0000250|UniProtKB:Q27744,
CC ECO:0000250|UniProtKB:Q7KQL9, ECO:0000269|PubMed:17426153,
CC ECO:0000269|PubMed:9521758}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:2190085}. Membrane
CC {ECO:0000269|PubMed:2190085}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Host cell membrane
CC {ECO:0000250|UniProtKB:Q27744}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}.
CC -!- DEVELOPMENTAL STAGE: Expressed during parasite asexual blood stages,
CC including in schizonts and free merozoites (at protein level).
CC {ECO:0000269|PubMed:2190085, ECO:0000269|PubMed:2693962}.
CC -!- SIMILARITY: Belongs to the class I fructose-bisphosphate aldolase
CC family. {ECO:0000305}.
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DR EMBL; M28881; AAA29473.1; -; Genomic_DNA.
DR EMBL; A13461; CAA01107.1; -; Unassigned_DNA.
DR EMBL; A13481; CAA01117.1; -; Unassigned_DNA.
DR PIR; A44942; A44942.
DR PDB; 1A5C; X-ray; 3.00 A; A/B=2-369.
DR PDB; 2EPH; X-ray; 2.70 A; A/B/C/D=1-369.
DR PDB; 2PC4; X-ray; 2.40 A; A/B/C/D=1-369.
DR PDBsum; 1A5C; -.
DR PDBsum; 2EPH; -.
DR PDBsum; 2PC4; -.
DR AlphaFoldDB; P14223; -.
DR SMR; P14223; -.
DR DIP; DIP-60915N; -.
DR IntAct; P14223; 1.
DR DrugBank; DB11638; Artenimol.
DR ABCD; P14223; 1 sequenced antibody.
DR EnsemblProtists; CZU00144; CZU00144; PF3D7_1444800.
DR VEuPathDB; PlasmoDB:PF3D7_1444800; -.
DR VEuPathDB; PlasmoDB:Pf7G8-2_000518600; -.
DR VEuPathDB; PlasmoDB:Pf7G8_140050000; -.
DR VEuPathDB; PlasmoDB:PfCD01_140050200; -.
DR VEuPathDB; PlasmoDB:PfDd2_140049200; -.
DR VEuPathDB; PlasmoDB:PfGA01_140050300; -.
DR VEuPathDB; PlasmoDB:PfGB4_140050900; -.
DR VEuPathDB; PlasmoDB:PfGN01_140050100; -.
DR VEuPathDB; PlasmoDB:PfHB3_140050500; -.
DR VEuPathDB; PlasmoDB:PfIT_140051200; -.
DR VEuPathDB; PlasmoDB:PfKE01_140049700; -.
DR VEuPathDB; PlasmoDB:PfKH01_140050300; -.
DR VEuPathDB; PlasmoDB:PfKH02_140050500; -.
DR VEuPathDB; PlasmoDB:PfML01_140050400; -.
DR VEuPathDB; PlasmoDB:PfNF135_140048900; -.
DR VEuPathDB; PlasmoDB:PfNF166_140047700; -.
DR VEuPathDB; PlasmoDB:PfNF54_140048500; -.
DR VEuPathDB; PlasmoDB:PfSD01_140048100; -.
DR VEuPathDB; PlasmoDB:PfSN01_140052000; -.
DR VEuPathDB; PlasmoDB:PfTG01_140050100; -.
DR OMA; DYREMLF; -.
DR SABIO-RK; P14223; -.
DR UniPathway; UPA00109; UER00183.
DR EvolutionaryTrace; P14223; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
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; IEA:UniProtKB-KW.
DR GO; GO:0004332; F:fructose-bisphosphate aldolase activity; IEA:UniProtKB-EC.
DR GO; GO:0006096; P:glycolytic process; IEA:UniProtKB-UniPathway.
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; Schiff base.
FT CHAIN 1..369
FT /note="Fructose-bisphosphate aldolase"
FT /id="PRO_0000216930"
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 MUTAGEN 40
FT /note="D->G: Reduces binding to TRAP."
FT /evidence="ECO:0000269|PubMed:17426153"
FT MUTAGEN 41
FT /note="E->G: Abolishes binding to TRAP."
FT /evidence="ECO:0000269|PubMed:17426153"
FT MUTAGEN 49
FT /note="R->D,G: Abolishes binding to TRAP."
FT /evidence="ECO:0000269|PubMed:17426153"
FT MUTAGEN 152
FT /note="K->D: Severe reduction in the binding to TRAP."
FT /evidence="ECO:0000269|PubMed:17426153"
FT MUTAGEN 154
FT /note="R->G: Abolishes binding to TRAP."
FT /evidence="ECO:0000269|PubMed:17426153"
FT MUTAGEN 310
FT /note="R->S: Severe reduction in the binding to TRAP."
FT /evidence="ECO:0000269|PubMed:17426153"
FT MUTAGEN 313
FT /note="Q->S: Severe reduction in the binding to TRAP."
FT /evidence="ECO:0000269|PubMed:17426153"
FT MUTAGEN 314
FT /note="A->G: Reduces binding to TRAP."
FT /evidence="ECO:0000269|PubMed:17426153"
FT MUTAGEN 317
FT /note="L->D: Abolishes binding to TRAP."
FT /evidence="ECO:0000269|PubMed:17426153"
FT HELIX 16..29
FT /evidence="ECO:0007829|PDB:2PC4"
FT STRAND 35..39
FT /evidence="ECO:0007829|PDB:2PC4"
FT HELIX 43..52
FT /evidence="ECO:0007829|PDB:2PC4"
FT HELIX 59..70
FT /evidence="ECO:0007829|PDB:2PC4"
FT TURN 76..78
FT /evidence="ECO:0007829|PDB:2PC4"
FT STRAND 79..84
FT /evidence="ECO:0007829|PDB:2PC4"
FT HELIX 86..89
FT /evidence="ECO:0007829|PDB:2PC4"
FT HELIX 99..106
FT /evidence="ECO:0007829|PDB:2PC4"
FT STRAND 109..113
FT /evidence="ECO:0007829|PDB:2PC4"
FT STRAND 118..120
FT /evidence="ECO:0007829|PDB:2PC4"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:2PC4"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:2PC4"
FT TURN 133..135
FT /evidence="ECO:0007829|PDB:1A5C"
FT HELIX 136..146
FT /evidence="ECO:0007829|PDB:2PC4"
FT STRAND 150..157
FT /evidence="ECO:0007829|PDB:2PC4"
FT HELIX 161..163
FT /evidence="ECO:0007829|PDB:2PC4"
FT HELIX 168..187
FT /evidence="ECO:0007829|PDB:2PC4"
FT STRAND 191..198
FT /evidence="ECO:0007829|PDB:2PC4"
FT HELIX 206..226
FT /evidence="ECO:0007829|PDB:2PC4"
FT HELIX 231..233
FT /evidence="ECO:0007829|PDB:2PC4"
FT HELIX 253..267
FT /evidence="ECO:0007829|PDB:2PC4"
FT STRAND 274..277
FT /evidence="ECO:0007829|PDB:2PC4"
FT HELIX 284..296
FT /evidence="ECO:0007829|PDB:2PC4"
FT STRAND 301..309
FT /evidence="ECO:0007829|PDB:2PC4"
FT HELIX 310..318
FT /evidence="ECO:0007829|PDB:2PC4"
FT TURN 319..322
FT /evidence="ECO:0007829|PDB:2PC4"
FT TURN 324..326
FT /evidence="ECO:0007829|PDB:2PC4"
FT HELIX 327..346
FT /evidence="ECO:0007829|PDB:2PC4"
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
