ENO_PLAFO
ID ENO_PLAFO Reviewed; 446 AA.
AC W7JLR6;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 42.
DE RecName: Full=Enolase {ECO:0000303|PubMed:15606772};
DE Short=PfEN {ECO:0000303|PubMed:15606772};
DE EC=4.2.1.11 {ECO:0000269|PubMed:15606772};
GN Name=ENO {ECO:0000250|UniProtKB:Q8IJN7};
GN ORFNames=CK202_4802 {ECO:0000312|EMBL:PKC43580.1},
GN PFNF54_05495 {ECO:0000312|EMBL:EWC85828.1};
OS Plasmodium falciparum (isolate NF54).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=5843 {ECO:0000312|Proteomes:UP000030673};
RN [1] {ECO:0000312|Proteomes:UP000030673}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NF54 {ECO:0000312|Proteomes:UP000030673};
RG The Broad Institute Genome Sequencing Platform;
RG The Broad Institute Genome Sequencing Center for Infectious Disease;
RA Neafsey D., Cheeseman I., Volkman S., Adams J., Walker B., Young S.K.,
RA Zeng Q., Gargeya S., Fitzgerald M., Haas B., Abouelleil A., Alvarado L.,
RA Arachchi H.M., Berlin A.M., Chapman S.B., Dewar J., Goldberg J., Griggs A.,
RA Gujja S., Hansen M., Howarth C., Imamovic A., Larimer J., McCowan C.,
RA Murphy C., Neiman D., Pearson M., Priest M., Roberts A., Saif S., Shea T.,
RA Sisk P., Sykes S., Wortman J., Nusbaum C., Birren B.;
RT "The Genome Sequence of Plasmodium falciparum NF54.";
RL Submitted (FEB-2013) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000312|EMBL:PKC43580.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NF54 {ECO:0000312|EMBL:PKC43580.1};
RA Bryant J.M., Baumgarten S., Scheidig-Benatar C., Scherf A.;
RT "Plasmodium falciparum NF54 genome assembly.";
RL Submitted (NOV-2017) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, AND SUBUNIT.
RX PubMed=15606772; DOI=10.1111/j.1432-1033.2004.04450.x;
RA Pal-Bhowmick I., Sadagopan K., Vora H.K., Sehgal A., Sharma S.,
RA Jarori G.K.;
RT "Cloning, over-expression, purification and characterization of Plasmodium
RT falciparum enolase.";
RL Eur. J. Biochem. 271:4845-4854(2004).
RN [4] {ECO:0000305}
RP SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=19642995; DOI=10.1186/1475-2875-8-179;
RA Bhowmick I.P., Kumar N., Sharma S., Coppens I., Jarori G.K.;
RT "Plasmodium falciparum enolase: stage-specific expression and sub-cellular
RT localization.";
RL Malar. J. 8:179-179(2009).
RN [5] {ECO:0000305}
RP FUNCTION, INTERACTION WITH HOST PLG, SUBCELLULAR LOCATION, MOTIF,
RP BIOTECHNOLOGY, AND DEVELOPMENTAL STAGE.
RX PubMed=21949403; DOI=10.1073/pnas.1103657108;
RA Ghosh A.K., Coppens I., Gaardsvoll H., Ploug M., Jacobs-Lorena M.;
RT "Plasmodium ookinetes coopt mammalian plasminogen to invade the mosquito
RT midgut.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:17153-17158(2011).
RN [6] {ECO:0000305}
RP INTERACTION WITH A.GAMBIAE EBP, AND BIOTECHNOLOGY.
RX PubMed=24474798; DOI=10.1073/pnas.1315517111;
RA Vega-Rodriguez J., Ghosh A.K., Kanzok S.M., Dinglasan R.R., Wang S.,
RA Bongio N.J., Kalume D.E., Miura K., Long C.A., Pandey A., Jacobs-Lorena M.;
RT "Multiple pathways for Plasmodium ookinete invasion of the mosquito
RT midgut.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:E492-E500(2014).
CC -!- FUNCTION: Glycolytic enzyme that catalyzes the conversion of 2-
CC phosphoglycerate to phosphoenolpyruvate (PubMed:15606772). In addition
CC to glycolysis, involved in various processes such as parasite
CC development and invasion (PubMed:21949403). Plays an essential role
CC during ookinete invasion of the mosquito vector midgut by mediating the
CC interaction of the ookinete with the midgut epithelium and, further, by
CC binding to mammalian host plasminogen in the blood meal, whose
CC conversion to active plasmin promotes the invasion process
CC (PubMed:21949403). {ECO:0000269|PubMed:15606772,
CC ECO:0000269|PubMed:21949403}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R)-2-phosphoglycerate = H2O + phosphoenolpyruvate;
CC Xref=Rhea:RHEA:10164, ChEBI:CHEBI:15377, ChEBI:CHEBI:58289,
CC ChEBI:CHEBI:58702; EC=4.2.1.11;
CC Evidence={ECO:0000269|PubMed:15606772};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10165;
CC Evidence={ECO:0000269|PubMed:15606772};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:10166;
CC Evidence={ECO:0000269|PubMed:15606772};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:15606772};
CC Note=Binds 2 Mg(2+) ions per subunit (By similarity). Mg(2+) is
CC required for catalysis and for stabilizing the dimer (By similarity).
CC Unlike for mammalian and yeast enolases, Mg(2+) is dispensable to form
CC an active closed conformation (By similarity). Inhibited by high levels
CC of Mg(2+) (PubMed:15606772). {ECO:0000250|UniProtKB:Q8IJN7,
CC ECO:0000269|PubMed:15606772};
CC -!- ACTIVITY REGULATION: Inhibited by Na(2+).
CC {ECO:0000269|PubMed:15606772}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.041 mM for 2-phosphoglyceric acid (at 20 degrees Celsius and pH
CC 7.4) {ECO:0000269|PubMed:15606772};
CC KM=0.25 mM for phosphoenolpyruvate (at 20 degrees Celsius and pH 7.4)
CC {ECO:0000269|PubMed:15606772};
CC pH dependence:
CC Optimum pH is 7.4-7.6. {ECO:0000269|PubMed:15606772};
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D-
CC glyceraldehyde 3-phosphate: step 4/5. {ECO:0000305|PubMed:15606772}.
CC -!- SUBUNIT: Homodimer (PubMed:15606772). Forms a complex at least composed
CC of DegP, ENO and HSP70 (By similarity). Interacts with G-actin (By
CC similarity). Interacts (via the DKSLVK motif) with mammalian host
CC PLG/plasminogen (present in the mosquito blood meal); the interaction
CC occurs at the ookinete cell surface and is required for ookinete
CC invasion of the mosquito midgut (PubMed:21949403). Interacts with
CC A.gambiae EBP; depending on the Plasmodium species, the interaction is
CC either involved in ookinete invasion of the mosquito midgut (P.berghei)
CC or is dispensable (P.falciparum) (PubMed:24474798).
CC {ECO:0000250|UniProtKB:Q8IJN7, ECO:0000269|PubMed:15606772,
CC ECO:0000269|PubMed:21949403, ECO:0000269|PubMed:24474798}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19642995}. Nucleus
CC {ECO:0000250|UniProtKB:Q8IJN7}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:19642995}. Cell surface
CC {ECO:0000269|PubMed:21949403}. Cell membrane
CC {ECO:0000250|UniProtKB:Q7RA60}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000250|UniProtKB:Q7RA60}. Vacuole
CC {ECO:0000250|UniProtKB:Q8IJN7}. Note=Partially localizes to the nucleus
CC in rings and trophozoites. Localization to the nucleus and food vacuole
CC is higher in early and mid-stage trophozoites compared to the late-
CC stage trophozoites and schizonts (By similarity). In the nucleus,
CC localizes to heterochromatin region (By similarity). In rings, nuclear
CC localization is dependent on the actin cytoskeleton (By similarity).
CC Localizes to the cell surface of merozoites (By similarity). In
CC gametocytes, predominantly localizes to the actin cytoskeleton
CC (PubMed:19642995). In the trophozoite food vacuole, colocalizes with
CC hemozoin, a product of heme detoxification (By similarity). In
CC sporozoites, localizes to punctate structures beneath the cell membrane
CC (By similarity). Localizes to the cell surface of ookinetes, especially
CC on the apical pellicle complex that is involved in invasion
CC (PubMed:21949403). When phosphorylated at Thr-339, localizes to the
CC cytoskeleton (By similarity). When phosphorylated at Ser-42, localizes
CC to the cytoplasm (By similarity). When ubiquitinated at Lys-138,
CC acetylated at Lys-133 and Lys-375 and phosphorylated at Tyr-139,
CC localizes to the food vacuole (By similarity). When triubiquitinated at
CC Lys-138, appears to colocalize with hemozoin in the food vacuole (By
CC similarity). {ECO:0000250|UniProtKB:Q7RA60,
CC ECO:0000250|UniProtKB:Q8IJN7, ECO:0000269|PubMed:19642995,
CC ECO:0000269|PubMed:21949403}.
CC -!- DEVELOPMENTAL STAGE: Expressed in gametocytes and gametes (at protein
CC level); expression in stage II gametocytes is lower compared to stages
CC IV/V gametocytes (PubMed:19642995). Expressed in ookinetes (at protein
CC level) (PubMed:21949403). {ECO:0000269|PubMed:19642995,
CC ECO:0000269|PubMed:21949403}.
CC -!- DOMAIN: The pentapeptide insert motif is required for the stabilization
CC of the apo-enzyme in an active closed conformation, independently of
CC Mg(2+) binding. The motif is also required for homodimerization. This
CC motif is only present in Apicomplexa and plant enolases.
CC {ECO:0000250|UniProtKB:Q8IJN7}.
CC -!- DOMAIN: The DKSLVK motif binds to the lysine-binding Kringle domains of
CC plasminogen from various mammalian species (PubMed:21949403). This
CC motif is present only in enolases of plant and several microbial
CC pathogens including Plasmodium species (PubMed:21949403).
CC {ECO:0000269|PubMed:21949403}.
CC -!- BIOTECHNOLOGY: The salivary gland and midgut peptide SM1 (PCQRAIFQSICK)
CC is an artificial dodecapeptide that mimics enolase DKSLVK motif. By
CC binding the EBP receptor on the luminal surface of the female mosquito
CC midgut epithelium, SM1 inhibits ookinete invasion of P.berghei and
CC thus, could potentially be used to prevent parasite transmission by the
CC mosquito vector (PubMed:21949403, PubMed:24474798). Similarly, another
CC artificial peptide, MP2 (ACYIKTLHPPCS), also inhibits ookinete invasion
CC of P.berghei and P.falciparum and could potentially be used to prevent
CC parasite transmission by the mosquito vector (PubMed:24474798).
CC {ECO:0000269|PubMed:21949403, ECO:0000269|PubMed:24474798}.
CC -!- SIMILARITY: Belongs to the enolase 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; KE123882; EWC85828.1; -; Genomic_DNA.
DR EMBL; NYMT01000016; PKC43580.1; -; Genomic_DNA.
DR SMR; W7JLR6; -.
DR PRIDE; W7JLR6; -.
DR EnsemblProtists; EWC85828; EWC85828; PFNF54_05495.
DR VEuPathDB; PlasmoDB:PfNF54_100021100; -.
DR OMA; EFMIIPV; -.
DR UniPathway; UPA00109; UER00187.
DR Proteomes; UP000030673; Unassembled WGS sequence.
DR Proteomes; UP000232684; Unassembled WGS sequence.
DR GO; GO:0000015; C:phosphopyruvate hydratase complex; IEA:InterPro.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0004634; F:phosphopyruvate hydratase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0006096; P:glycolytic process; IEA:UniProtKB-UniPathway.
DR CDD; cd03313; enolase; 1.
DR Gene3D; 3.20.20.120; -; 1.
DR Gene3D; 3.30.390.10; -; 1.
DR HAMAP; MF_00318; Enolase; 1.
DR InterPro; IPR000941; Enolase.
DR InterPro; IPR036849; Enolase-like_C_sf.
DR InterPro; IPR029017; Enolase-like_N.
DR InterPro; IPR020810; Enolase_C.
DR InterPro; IPR020809; Enolase_CS.
DR InterPro; IPR020811; Enolase_N.
DR PANTHER; PTHR11902; PTHR11902; 1.
DR Pfam; PF00113; Enolase_C; 1.
DR Pfam; PF03952; Enolase_N; 1.
DR PIRSF; PIRSF001400; Enolase; 1.
DR PRINTS; PR00148; ENOLASE.
DR SFLD; SFLDF00002; enolase; 1.
DR SMART; SM01192; Enolase_C; 1.
DR SMART; SM01193; Enolase_N; 1.
DR SUPFAM; SSF51604; SSF51604; 1.
DR SUPFAM; SSF54826; SSF54826; 1.
DR TIGRFAMs; TIGR01060; eno; 1.
DR PROSITE; PS00164; ENOLASE; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cell membrane; Cytoplasm; Cytoskeleton; Glycolysis;
KW Isopeptide bond; Lyase; Magnesium; Membrane; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Ubl conjugation; Vacuole.
FT CHAIN 1..446
FT /note="Enolase"
FT /id="PRO_0000456086"
FT MOTIF 104..108
FT /note="Pentapeptide insert"
FT /evidence="ECO:0000250|UniProtKB:Q8IJN7"
FT MOTIF 277..282
FT /note="DKSLVK motif"
FT /evidence="ECO:0000269|PubMed:21949403"
FT ACT_SITE 218
FT /note="Proton donor"
FT /evidence="ECO:0000255|PIRSR:PIRSR001400-1"
FT ACT_SITE 356
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PIRSR:PIRSR001400-1"
FT BINDING 42
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P06733"
FT BINDING 166
FT /ligand="substrate"
FT /evidence="ECO:0000255|PIRSR:PIRSR001400-2"
FT BINDING 175
FT /ligand="substrate"
FT /evidence="ECO:0000255|PIRSR:PIRSR001400-2"
FT BINDING 253
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P06733"
FT BINDING 304
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P06733"
FT BINDING 304
FT /ligand="substrate"
FT /evidence="ECO:0000255|PIRSR:PIRSR001400-2"
FT BINDING 331
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P06733"
FT BINDING 331
FT /ligand="substrate"
FT /evidence="ECO:0000255|PIRSR:PIRSR001400-2"
FT BINDING 383..386
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P06733"
FT BINDING 407
FT /ligand="substrate"
FT /evidence="ECO:0000255|PIRSR:PIRSR001400-2"
FT MOD_RES 42
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8IJN7"
FT MOD_RES 133
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q7RA60"
FT MOD_RES 139
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q7RA60"
FT MOD_RES 339
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q7RA60"
FT MOD_RES 375
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q7RA60"
FT CROSSLNK 138
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q7RA60"
SQ SEQUENCE 446 AA; 48678 MW; 21ED9FF01BA50DB2 CRC64;
MAHVITRINA REILDSRGNP TVEVDLETNL GIFRAAVPSG ASTGIYEALE LRDNDKSRYL
GKGVQKAIKN INEIIAPKLI GMNCTEQKKI DNLMVEELDG SKNEWGWSKS KLGANAILAI
SMAVCRAGAA ANKVSLYKYL AQLAGKKSDQ MVLPVPCLNV INGGSHAGNK LSFQEFMIVP
VGAPSFKEAL RYGAEVYHTL KSEIKKKYGI DATNVGDEGG FAPNILNANE ALDLLVTAIK
SAGYEGKVKI AMDVAASEFY NSENKTYDLD FKTPNNDKSL VKTGAQLVDL YIDLVKKYPI
VSIEDPFDQD DWENYAKLTA AIGKDVQIVG DDLLVTNPTR ITKALEKNAC NALLLKVNQI
GSITEAIEAC LLSQKNNWGV MVSHRSGETE DVFIADLVVA LRTGQIKTGA PCRSERNAKY
NQLLRIEESL GNNAVFAGEK FRLQLN
