ENO_PLAF7
ID ENO_PLAF7 Reviewed; 446 AA.
AC Q8IJN7; A0A143ZZ61;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Enolase {ECO:0000303|PubMed:19268421};
DE Short=Pfen {ECO:0000303|PubMed:19268421};
DE Short=Pfeno {ECO:0000303|PubMed:24009698};
DE EC=4.2.1.11 {ECO:0000269|PubMed:19268421, ECO:0000269|PubMed:25787157};
DE AltName: Full=2-phospho-D-glycerate hydro-lyase {ECO:0000305};
DE AltName: Full=2-phosphoglycerate dehydratase {ECO:0000305};
GN Name=ENO {ECO:0000303|PubMed:24009698}; ORFNames=PF10_0155, PF3D7_1015900;
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, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES,
RP PATHWAY, SUBUNIT, MOTIF, AND MUTAGENESIS OF 104-GLU--SER-108.
RX PubMed=19268421; DOI=10.1016/j.abb.2009.02.012;
RA Vora H.K., Shaik F.R., Pal-Bhowmick I., Mout R., Jarori G.K.;
RT "Effect of deletion of a plant like pentapeptide insert on kinetic,
RT structural and immunological properties of enolase from Plasmodium
RT falciparum.";
RL Arch. Biochem. Biophys. 485:128-138(2009).
RN [3]
RP INTERACTION WITH G-ACTIN AND HOST PLG, SUBCELLULAR LOCATION, AND
RP 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 [4]
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND PHOSPHORYLATION AT SER-42.
RX PubMed=24009698; DOI=10.1371/journal.pone.0072687;
RA Shevade S., Jindal N., Dutta S., Jarori G.K.;
RT "Food vacuole associated enolase in plasmodium undergoes multiple post-
RT translational modifications: evidence for atypical ubiquitination.";
RL PLoS ONE 8:e72687-e72687(2013).
RN [5]
RP IDENTIFICATION IN A COMPLEX WITH HSP70 AND DEGP, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=24494818; DOI=10.1111/febs.12732;
RA Sharma S., Jadli M., Singh A., Arora K., Malhotra P.;
RT "A secretory multifunctional serine protease, DegP of Plasmodium
RT falciparum, plays an important role in thermo-oxidative stress, parasite
RT growth and development.";
RL FEBS J. 281:1679-1699(2014).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBUNIT, MOTIF, AND MUTAGENESIS OF
RP SER-108.
RX PubMed=25787157; DOI=10.1111/febs.13272;
RA Dutta S., Mukherjee D., Jarori G.K.;
RT "Replacement of Ser108 in Plasmodium falciparum enolase results in weak
RT Mg(II) binding: role of a parasite-specific pentapeptide insert in
RT stabilizing the active conformation of the enzyme.";
RL FEBS J. 282:2296-2308(2015).
CC -!- FUNCTION: Glycolytic enzyme that catalyzes the conversion of 2-
CC phosphoglycerate to phosphoenolpyruvate (PubMed:19268421,
CC PubMed:25787157). In addition to glycolysis, involved in various
CC processes such as parasite development and invasion (By similarity).
CC Plays an essential role during ookinete invasion of the mosquito vector
CC midgut by mediating the interaction of the ookinete with the midgut
CC epithelium and, further, by binding to mammalian host plasminogen in
CC the blood meal, whose conversion to active plasmin promotes the
CC invasion process (By similarity). {ECO:0000250|UniProtKB:W7JLR6,
CC ECO:0000269|PubMed:19268421, ECO:0000269|PubMed:25787157}.
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:19268421, ECO:0000269|PubMed:25787157};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10165;
CC Evidence={ECO:0000269|PubMed:19268421, ECO:0000269|PubMed:25787157};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:10166;
CC Evidence={ECO:0000250|UniProtKB:W7JLR6};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:19268421, ECO:0000269|PubMed:25787157};
CC Note=Binds 2 Mg(2+) ions per subunit (PubMed:25787157). Mg(2+) is
CC required for catalysis and for stabilizing the dimer (PubMed:25787157).
CC Unlike for mammalian and yeast enolases, Mg(2+) is dispensable to form
CC an active closed conformation (PubMed:25787157). Inhibited by high
CC levels of Mg(2+) (By similarity). {ECO:0000250|UniProtKB:W7JLR6,
CC ECO:0000269|PubMed:25787157};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=40 uM for 2-phosphoglyceric acid (at 21 degrees Celsius and pH
CC 7.5) {ECO:0000269|PubMed:19268421};
CC KM=61 uM for 2-phosphoglyceric acid (at 25 degrees Celsius and pH
CC 7.5) {ECO:0000269|PubMed:25787157};
CC Note=kcat is 20.6 sec(-1) with 2-phosphoglyceric acid as substrate
CC (at 21 degrees Celsius and pH 7.5). {ECO:0000269|PubMed:19268421};
CC Temperature dependence:
CC Optimum temperature is between 20-50 degrees Celsius.
CC {ECO:0000269|PubMed:19268421};
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D-
CC glyceraldehyde 3-phosphate: step 4/5. {ECO:0000305|PubMed:19268421}.
CC -!- SUBUNIT: Homodimer (PubMed:19268421, PubMed:25787157). Forms a complex
CC at least composed of DegP, ENO and HSP70 (PubMed:24494818). Interacts
CC with G-actin (PubMed:19642995). Interacts (via the DKSLVK motif) with
CC mammalian host PLG/plasminogen (present in the mosquito blood meal);
CC the interaction occurs at the ookinete cell surface and is required for
CC ookinete invasion of the mosquito midgut (PubMed:19642995). Interacts
CC with A.gambiae EBP; depending on the Plasmodium species, the
CC interaction is either involved in ookinete invasion of the mosquito
CC midgut (P.berghei) or is dispensable (P.falciparum) (By similarity).
CC {ECO:0000250|UniProtKB:W7JLR6, ECO:0000269|PubMed:19268421,
CC ECO:0000269|PubMed:19642995, ECO:0000269|PubMed:24494818,
CC ECO:0000269|PubMed:25787157}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19642995,
CC ECO:0000269|PubMed:24009698}. Nucleus {ECO:0000269|PubMed:19642995}.
CC Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:W7JLR6}. Cell surface
CC {ECO:0000269|PubMed:19642995, ECO:0000269|PubMed:24009698}. Cell
CC membrane {ECO:0000250|UniProtKB:Q7RA60}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000250|UniProtKB:Q7RA60}. Vacuole
CC {ECO:0000269|PubMed:19642995}. Note=Partially localizes to the nucleus
CC in rings and trophozoites (PubMed:19642995). Localization to the
CC nucleus and food vacuole is higher in early and mid-stage trophozoites
CC compared to the late-stage trophozoites and schizonts
CC (PubMed:19642995). In the nucleus, localizes to heterochromatin region
CC (PubMed:19642995). In rings, nuclear localization is dependent on the
CC actin cytoskeleton (PubMed:19642995). In the trophozoite food vacuole,
CC colocalizes with hemozoin, a product of heme detoxification
CC (PubMed:19642995). Localizes to the cell surface of merozoites
CC (PubMed:19642995). In gametocytes, predominantly localizes to the actin
CC cytoskeleton (By similarity). In sporozoites, localizes to punctate
CC structures beneath the cell membrane (By similarity). Localizes to the
CC cell surface of ookinetes, especially on the apical pellicle complex
CC that is involved in invasion (By similarity). When phosphorylated at
CC Thr-339, localizes to the cytoskeleton (By similarity). When
CC phosphorylated at Ser-42, localizes to the cytoplasm (PubMed:24009698).
CC When ubiquitinated at Lys-138, acetylated at Lys-133 and Lys-375 and
CC phosphorylated at Tyr-139, localizes to the food vacuole (By
CC similarity). When triubiquitinated at Lys-138, appears to colocalize
CC with hemozoin in the food vacuole (By similarity).
CC {ECO:0000250|UniProtKB:Q7RA60, ECO:0000250|UniProtKB:W7JLR6,
CC ECO:0000269|PubMed:19642995, ECO:0000269|PubMed:24009698}.
CC -!- DEVELOPMENTAL STAGE: During the asexual blood stage, expressed in
CC rings, trophozoites, schizonts and merozoites (at protein level).
CC {ECO:0000269|PubMed:19642995, ECO:0000269|PubMed:24009698}.
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 (PubMed:19268421, PubMed:25787157). The motif is also
CC required for homodimerization (PubMed:19268421, PubMed:25787157). This
CC motif is only present in Apicomplexa and plant enolases (Probable).
CC {ECO:0000269|PubMed:19268421, ECO:0000269|PubMed:25787157,
CC ECO:0000305|PubMed:19268421, ECO:0000305|PubMed:25787157}.
CC -!- DOMAIN: The DKSLVK motif binds to the lysine-binding Kringle domains of
CC plasminogen from various mammalian species (By similarity). This motif
CC is present only in enolases of plant and several microbial pathogens
CC including Plasmodium species (By similarity).
CC {ECO:0000250|UniProtKB:W7JLR6}.
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; LN999944; CZT98412.1; -; Genomic_DNA.
DR RefSeq; XP_001347440.1; XM_001347404.2.
DR AlphaFoldDB; Q8IJN7; -.
DR SMR; Q8IJN7; -.
DR BioGRID; 1205736; 9.
DR IntAct; Q8IJN7; 9.
DR MINT; Q8IJN7; -.
DR STRING; 5833.PF10_0155; -.
DR DrugBank; DB11638; Artenimol.
DR SwissPalm; Q8IJN7; -.
DR PRIDE; Q8IJN7; -.
DR EnsemblProtists; CZT98412; CZT98412; PF3D7_1015900.
DR GeneID; 810313; -.
DR KEGG; pfa:PF3D7_1015900; -.
DR VEuPathDB; PlasmoDB:PF3D7_1015900; -.
DR HOGENOM; CLU_031223_0_0_1; -.
DR InParanoid; Q8IJN7; -.
DR OMA; EFMIIPV; -.
DR PhylomeDB; Q8IJN7; -.
DR BRENDA; 4.2.1.11; 4889.
DR Reactome; R-PFA-70171; Glycolysis.
DR Reactome; R-PFA-70263; Gluconeogenesis.
DR SABIO-RK; Q8IJN7; -.
DR UniPathway; UPA00109; UER00187.
DR Proteomes; UP000001450; Chromosome 10.
DR GO; GO:0009986; C:cell surface; IDA:GeneDB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IDA:GeneDB.
DR GO; GO:0020020; C:food vacuole; IDA:GeneDB.
DR GO; GO:0005634; C:nucleus; IDA:GeneDB.
DR GO; GO:0000015; C:phosphopyruvate hydratase complex; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:GeneDB.
DR GO; GO:0003779; F:actin binding; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0004634; F:phosphopyruvate hydratase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0002253; P:activation of immune response; IDA:GeneDB.
DR GO; GO:0000045; P:autophagosome assembly; TAS:GeneDB.
DR GO; GO:0006096; P:glycolytic process; IBA:GO_Central.
DR GO; GO:0006351; P:transcription, DNA-templated; TAS:GeneDB.
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_0000134089"
FT MOTIF 104..108
FT /note="Pentapeptide insert"
FT /evidence="ECO:0000269|PubMed:19268421,
FT ECO:0000269|PubMed:25787157"
FT MOTIF 277..282
FT /note="DKSLVK motif"
FT /evidence="ECO:0000250|UniProtKB:W7JLR6"
FT ACT_SITE 218
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P06733"
FT ACT_SITE 356
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P06733"
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:0000250|UniProtKB:P06733"
FT BINDING 175
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P06733"
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:0000250|UniProtKB:P06733"
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:0000250|UniProtKB:P06733"
FT BINDING 383..386
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P06733"
FT BINDING 407
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P06733"
FT MOD_RES 42
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:24009698"
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"
FT MUTAGEN 104..108
FT /note="Missing: Impairs homodimerization. 30-fold decrease
FT in catalytic activity without affecting affinity for
FT substrate 2-phosphoglyceric acid. Decreases affinity for
FT Mg(2+)."
FT /evidence="ECO:0000269|PubMed:19268421"
FT MUTAGEN 108
FT /note="S->A: Reduces homodimerization efficiency. Decreases
FT catalytic activity without affecting affinity for substrate
FT 2-phosphoglyceric acid. Loss of Mg(2+) binding."
FT /evidence="ECO:0000269|PubMed:25787157"
FT MUTAGEN 108
FT /note="S->G: No effect on homodimerization. Decreases
FT catalytic activity without affecting affinity for substrate
FT 2-phosphoglyceric acid. Loss of Mg(2+) binding."
FT /evidence="ECO:0000269|PubMed:25787157"
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
