ID PLM2_PLAFX Reviewed; 453 AA. AC P46925; A0A0L7K5Z5; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 1. DT 27-MAR-2024, entry version 126. DE RecName: Full=Plasmepsin II {ECO:0000303|PubMed:9169469}; DE Short=PLM II {ECO:0000303|PubMed:8816746}; DE EC=3.4.23.39 {ECO:0000269|PubMed:11782538, ECO:0000269|PubMed:15574427, ECO:0000269|PubMed:19271776, ECO:0000269|PubMed:24900843, ECO:0000269|PubMed:26670264, ECO:0000269|PubMed:8816746, ECO:0000269|PubMed:8844673}; DE AltName: Full=Aspartic hemoglobinase II {ECO:0000303|PubMed:7935597}; DE AltName: Full=PfAPD {ECO:0000303|PubMed:7935597}; DE AltName: Full=PfPM1 {ECO:0000303|PubMed:19271776}; DE AltName: Full=Plasmepsin 2 {ECO:0000305}; DE Flags: Precursor; GN Name=PMII {ECO:0000303|PubMed:9169469}; OS Plasmodium falciparum (isolate HB3). OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida; OC Plasmodiidae; Plasmodium; Plasmodium (Laverania). OX NCBI_TaxID=137071 {ECO:0000312|Proteomes:UP000054289}; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PARTIAL PROTEIN SEQUENCE, AND RP 3D-STRUCTURE MODELING. RC STRAIN=HB3; RX PubMed=7935597; DOI=10.1016/0166-6851(94)90024-8; RA Dame J.B., Reddy G.R., Yowell C.A., Dunn B.M., Kay J., Berry C.; RT "Sequence, expression and modeled structure of an aspartic proteinase from RT the human malaria parasite Plasmodium falciparum."; RL Mol. Biochem. Parasitol. 64:177-190(1994). RN [2] {ECO:0000312|Proteomes:UP000054289} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=HB3 {ECO:0000312|Proteomes:UP000054289}; RG The Broad Institute Genome Sequencing Platform; RA Volkman S.K., Neafsey D.E., Dash A.P., Chitnis C.E., Hartl D.L., RA Young S.K., Zeng Q., Koehrsen M., Alvarado L., Berlin A., Borenstein D., RA Chapman S.B., Chen Z., Engels R., Freedman E., Gellesch M., Goldberg J., RA Griggs A., Gujja S., Heilman E.R., Heiman D.I., Howarth C., Jen D., RA Larson L., Mehta T., Neiman D., Park D., Pearson M., Roberts A., Saif S., RA Shea T., Shenoy N., Sisk P., Stolte C., Sykes S., Walk T., White J., RA Yandava C., Haas B., Henn M.R., Nusbaum C., Birren B.; RT "Annotation of Plasmodium falciparum HB3."; RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases. RN [3] RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=8844673; DOI=10.1016/0166-6851(96)02651-5; RA Luker K.E., Francis S.E., Gluzman I.Y., Goldberg D.E.; RT "Kinetic analysis of plasmepsins I and II aspartic proteases of the RT Plasmodium falciparum digestive vacuole."; RL Mol. Biochem. Parasitol. 79:71-78(1996). RN [4] RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, PROTEOLYTIC CLEAVAGE, AND LACK RP OF GLYCOSYLATION. RX PubMed=9169469; DOI=10.1074/jbc.272.23.14961; RA Francis S.E., Banerjee R., Goldberg D.E.; RT "Biosynthesis and maturation of the malaria aspartic hemoglobinases RT plasmepsins I and II."; RL J. Biol. Chem. 272:14961-14968(1997). RN [5] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND DEVELOPMENTAL RP STAGE. RX PubMed=11782538; DOI=10.1073/pnas.022630099; RA Banerjee R., Liu J., Beatty W., Pelosof L., Klemba M., Goldberg D.E.; RT "Four plasmepsins are active in the Plasmodium falciparum food vacuole, RT including a protease with an active-site histidine."; RL Proc. Natl. Acad. Sci. U.S.A. 99:990-995(2002). RN [6] RP DEVELOPMENTAL STAGE, AND PROTEOLYTIC CLEAVAGE. RX PubMed=12850260; DOI=10.1016/s0166-6851(03)00119-1; RA Banerjee R., Francis S.E., Goldberg D.E.; RT "Food vacuole plasmepsins are processed at a conserved site by an acidic RT convertase activity in Plasmodium falciparum."; RL Mol. Biochem. Parasitol. 129:157-165(2003). RN [7] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ALA-241 AND PHE-244. RX PubMed=15574427; DOI=10.1074/jbc.m412086200; RA Istvan E.S., Goldberg D.E.; RT "Distal substrate interactions enhance plasmepsin activity."; RL J. Biol. Chem. 280:6890-6896(2005). RN [8] {ECO:0007744|PDB:1SME} RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 125-453, CATALYTIC ACTIVITY, AND RP DISULFIDE BONDS. RX PubMed=8816746; DOI=10.1073/pnas.93.19.10034; RA Silva A.M., Lee A.Y., Gulnik S.V., Maier P., Collins J., Bhat T.N., RA Collins P.J., Cachau R.E., Luker K.E., Gluzman I.Y., Francis S.E., RA Oksman A., Goldberg D.E., Erickson J.W.; RT "Structure and inhibition of plasmepsin II, a hemoglobin-degrading enzyme RT from Plasmodium falciparum."; RL Proc. Natl. Acad. Sci. U.S.A. 93:10034-10039(1996). RN [9] {ECO:0007744|PDB:1PFZ} RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 75-453, AND DISULFIDE BONDS. RX PubMed=9886289; DOI=10.1038/4905; RA Bernstein N.K., Cherney M.M., Loetscher H., Ridley R.G., James M.N.; RT "Crystal structure of the novel aspartic proteinase zymogen proplasmepsin RT II from Plasmodium falciparum."; RL Nat. Struct. Biol. 6:32-37(1999). RN [10] {ECO:0007744|PDB:1LEE, ECO:0007744|PDB:1LF2} RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 123-453 OF MUTANT SER-330 IN RP COMPLEX WITH INHIBITOR, AND DISULFIDE BONDS. RX PubMed=12454457; DOI=10.1107/s0907444902014695; RA Asojo O.A., Afonina E., Gulnik S.V., Yu B., Erickson J.W., Randad R., RA Medjahed D., Silva A.M.; RT "Structures of Ser205 mutant plasmepsin II from Plasmodium falciparum at RT 1.8 A in complex with the inhibitors rs367 and rs370."; RL Acta Crystallogr. D 58:2001-2008(2002). RN [11] {ECO:0007744|PDB:1M43} RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 123-453 IN COMPLEX WITH RP INHIBITOR, AND DISULFIDE BONDS. RA Asojo O.A., Silva A.M., Gulnik S.; RT "Novel uncomplexed and complex structures of PM II, an aspartic protease RT from P. falciparum."; RL Submitted (JUL-2002) to the PDB data bank. RN [12] {ECO:0007744|PDB:1ME6} RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 125-453 IN COMPLEX WITH RP INHIBITOR, AND DISULFIDE BONDS. RA Freire E., Nezami A.G., Amzel L.M.; RT "CRYSTAL STRUCTURE OF PLASMEPSIN II, AN ASPARTYL PROTEASE FROM PLASMODIUM RT FALCIPARUM, IN COMPLEX WITH A STATINE-BASED INHIBITOR."; RL Submitted (AUG-2002) to the PDB data bank. RN [13] {ECO:0007744|PDB:1LF3, ECO:0007744|PDB:1LF4} RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 123-453 IN COMPLEX WITH RP INHIBITOR, AND DISULFIDE BONDS. RX PubMed=12614616; DOI=10.1016/s0022-2836(03)00036-6; RA Asojo O.A., Gulnik S.V., Afonina E., Yu B., Ellman J.A., Haque T.S., RA Silva A.M.; RT "Novel uncomplexed and complexed structures of plasmepsin II, an aspartic RT protease from Plasmodium falciparum."; RL J. Mol. Biol. 327:173-181(2003). RN [14] {ECO:0007744|PDB:1W6H, ECO:0007744|PDB:1W6I} RP X-RAY CRYSTALLOGRAPHY (2.24 ANGSTROMS) OF 123-453 IN COMPLEX WITH RP INHIBITOR, AND DISULFIDE BONDS. RA Lindberg J., Johansson P.-O., Rosenquist A., Kvarnstroem I., Vrang L., RA Samuelsson B., Unge T.; RT "Structural Study of a Novel Inhibitor with Bulky P1 Side Chain in Complex RT with Plasmepsin II -Implications for Drug Design."; RL Submitted (AUG-2004) to the PDB data bank. RN [15] {ECO:0007744|PDB:1XDH} RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 123-453 IN COMPLEX WITH RP INHIBITOR, AND DISULFIDE BONDS. RA Prade L.; RT "Structure of plasmepsin II in complex with pepstatin A."; RL Submitted (SEP-2004) to the PDB data bank. RN [16] {ECO:0007744|PDB:1XE5, ECO:0007744|PDB:1XE6} RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 125-453 IN COMPLEX WITH RP INHIBITOR, AND DISULFIDE BONDS. RA Prade L.; RT "Structure of plasmepsin II in complex of an pepstatin analogue."; RL Submitted (SEP-2004) to the PDB data bank. RN [17] {ECO:0007744|PDB:2BJU} RP X-RAY CRYSTALLOGRAPHY (1.56 ANGSTROMS) IN COMPLEX WITH INHIBITOR, AND RP DISULFIDE BONDS. RX PubMed=15840589; DOI=10.1074/jbc.m501519200; RA Prade L., Jones A.F., Boss C., Richard-Bildstein S., Meyer S., Binkert C., RA Bur D.; RT "X-ray structure of plasmepsin II complexed with a potent achiral RT inhibitor."; RL J. Biol. Chem. 280:23837-23843(2005). RN [18] {ECO:0007744|PDB:2IGX, ECO:0007744|PDB:2IGY} RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 125-453 IN COMPLEX WITH RP INHIBITOR, AND DISULFIDE BONDS. RX PubMed=17091526; DOI=10.1002/cmdc.200600223; RA Boss C., Corminboeuf O., Grisostomi C., Meyer S., Jones A.F., Prade L., RA Binkert C., Fischli W., Weller T., Bur D.; RT "Achiral, cheap, and potent inhibitors of Plasmepsins I, II, and IV."; RL ChemMedChem 1:1341-1345(2006). RN [19] {ECO:0007744|PDB:3F9Q} RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 125-453, AND DISULFIDE BONDS. RX PubMed=19237752; DOI=10.1107/s0907444908041632; RA Robbins A.H., Dunn B.M., Agbandje-McKenna M., McKenna R.; RT "Crystallographic evidence for noncoplanar catalytic aspartic acids in RT plasmepsin II resides in the Protein Data Bank."; RL Acta Crystallogr. D 65:294-296(2009). RN [20] {ECO:0007744|PDB:2R9B} RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 125-453 IN COMPLEX WITH RP INHIBITOR, CATALYTIC ACTIVITY, AND DISULFIDE BONDS. RX PubMed=19271776; DOI=10.1021/bi802059r; RA Liu P., Marzahn M.R., Robbins A.H., Gutierrez-de-Teran H., Rodriguez D., RA McClung S.H., Stevens S.M. Jr., Yowell C.A., Dame J.B., McKenna R., RA Dunn B.M.; RT "Recombinant plasmepsin 1 from the human malaria parasite plasmodium RT falciparum: enzymatic characterization, active site inhibitor design, and RT structural analysis."; RL Biochemistry 48:4086-4099(2009). RN [21] {ECO:0007744|PDB:4CKU} RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 125-453 IN COMPLEX WITH RP INHIBITOR, CATALYTIC ACTIVITY, AND DISULFIDE BONDS. RX PubMed=24900843; DOI=10.1021/ml4004952; RA Jaudzems K., Tars K., Maurops G., Ivdra N., Otikovs M., Leitans J., RA Kanepe-Lapsa I., Domraceva I., Mutule I., Trapencieris P., Blackman M.J., RA Jirgensons A.; RT "Plasmepsin inhibitory activity and structure-guided optimization of a RT potent hydroxyethylamine-based antimalarial hit."; RL ACS Med. Chem. Lett. 5:373-377(2014). RN [22] {ECO:0007744|PDB:4Y6M, ECO:0007744|PDB:4YA8} RP X-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS) OF 125-453 OF WILD TYPE AND OF RP MUTANT SER-330 IN COMPLEX WITH INHIBITOR, AND DISULFIDE BONDS. RX PubMed=26625296; DOI=10.1107/s2053230x15022049; RA Recacha R., Leitans J., Akopjana I., Aprupe L., Trapencieris P., RA Jaudzems K., Jirgensons A., Tars K.; RT "Structures of plasmepsin II from Plasmodium falciparum in complex with two RT hydroxyethylamine-based inhibitors."; RL Acta Crystallogr. F 71:1531-1539(2015). RN [23] {ECO:0007744|PDB:5BWY} RP X-RAY CRYSTALLOGRAPHY (2.64 ANGSTROMS) OF 78-453, AND DISULFIDE BONDS. RX PubMed=27599854; DOI=10.1107/s2053230x16011663; RA Recacha R., Jaudzems K., Akopjana I., Jirgensons A., Tars K.; RT "Crystal structure of Plasmodium falciparum proplasmepsin IV: the RT plasticity of proplasmepsins."; RL Acta Crystallogr. F 72:659-666(2016). RN [24] {ECO:0007744|PDB:4Z22} RP X-RAY CRYSTALLOGRAPHY (2.62 ANGSTROMS) OF 125-453 IN COMPLEX WITH RP INHIBITOR, CATALYTIC ACTIVITY, AND DISULFIDE BONDS. RX PubMed=26670264; DOI=10.1021/acs.jmedchem.5b01558; RA Rasina D., Otikovs M., Leitans J., Recacha R., Borysov O.V., RA Kanepe-Lapsa I., Domraceva I., Pantelejevs T., Tars K., Blackman M.J., RA Jaudzems K., Jirgensons A.; RT "Fragment-Based Discovery of 2-Aminoquinazolin-4(3H)-ones As Novel Class RT Nonpeptidomimetic Inhibitors of the Plasmepsins I, II, and IV."; RL J. Med. Chem. 59:374-387(2016). CC -!- FUNCTION: During the asexual blood stage, participates in initial CC cleavage of native host hemoglobin (Hb) resulting in Hb denaturation CC (PubMed:8844673, PubMed:11782538, PubMed:15574427). May cleave CC preferentially denatured hemoglobin that has been cleaved by PMI CC (PubMed:8844673). Digestion of host Hb is an essential step which CC provides the parasite with amino acids for protein synthesis, and CC regulates osmolarity (Probable). {ECO:0000269|PubMed:11782538, CC ECO:0000269|PubMed:15574427, ECO:0000269|PubMed:8844673, ECO:0000305}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Hydrolysis of the bonds linking certain hydrophobic residues CC in hemoglobin or globin. Also cleaves small molecules substrates such CC as Ala-Leu-Glu-Arg-Thr-Phe-|-Phe(NO2)-Ser-Phe-Pro-Thr.; EC=3.4.23.39; CC Evidence={ECO:0000269|PubMed:11782538, ECO:0000269|PubMed:15574427, CC ECO:0000269|PubMed:19271776, ECO:0000269|PubMed:24900843, CC ECO:0000269|PubMed:26670264, ECO:0000269|PubMed:8816746, CC ECO:0000269|PubMed:8844673}; CC -!- ACTIVITY REGULATION: Inhibited by pepstatin A. CC {ECO:0000269|PubMed:8844673}. CC -!- SUBUNIT: Component of the hemozoin formation complex (HFC) composed of CC falcipains FP2A and/or FP2B, plasmepsins PMII, PMIII/HAP and PMIV, heme CC detoxifying protein HDP and falcilysin FLN. The HFC complex is involved CC in hemoglobin degradation and detoxification of heme in the food CC vacuole during the asexual blood stage. {ECO:0000250|UniProtKB:Q8I6V3}. CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:9169469}; Single- CC pass type II membrane protein {ECO:0000250|UniProtKB:P39898}. Vacuole CC lumen {ECO:0000269|PubMed:11782538, ECO:0000269|PubMed:9169469}. CC Vacuole membrane {ECO:0000269|PubMed:9169469}. Note=At the beginning of CC the asexual blood stage, the transmembrane zymogen is transported to CC the cytostome, an endocytic structure spanning the parasite cell CC membrane and the parasitophorous vacuole membrane where host proteins CC such as hemoglobin are endocytosed (PubMed:9169469). Following CC endocytosis, localizes to the cytostome vacuole membrane to be then CC delivered to the digestive (or food) vacuole where it is cleaved into CC the soluble and active enzyme (PubMed:9169469). In trophozoites, CC localizes to the digestive vacuole, an acidic vacuole where host CC hemoglobin is digested (PubMed:9169469, PubMed:11782538). CC {ECO:0000269|PubMed:11782538, ECO:0000269|PubMed:9169469}. CC -!- DEVELOPMENTAL STAGE: Expressed during the asexual blood stage; CC expression begins in late rings, increases in trophozoites and CC continues in schizonts (at protein level). CC {ECO:0000269|PubMed:11782538, ECO:0000269|PubMed:12850260, CC ECO:0000269|PubMed:9169469}. CC -!- PTM: Not N-glycosylated. {ECO:0000269|PubMed:9169469}. CC -!- PTM: Proteolytically cleaved into the soluble active mature form in the CC digestive vacuole by cysteine protease falcipains; the process begins CC at the early ring stage (PubMed:9169469). Proteolysis requires an CC acidic environment (By similarity). In absence of falcipains, CC autoprocessing may serve as an alternate activation system (By CC similarity). {ECO:0000250|UniProtKB:Q8I6V3, CC ECO:0000269|PubMed:9169469}. CC -!- SIMILARITY: Belongs to the peptidase A1 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; L10740; AAA68217.1; -; Genomic_DNA. DR EMBL; CH671923; KOB58717.1; -; Genomic_DNA. DR PDB; 1LEE; X-ray; 1.90 A; A=123-453. DR PDB; 1LF2; X-ray; 1.80 A; A=123-453. DR PDB; 1LF3; X-ray; 2.70 A; A=123-453. DR PDB; 1LF4; X-ray; 1.90 A; A=123-453. DR PDB; 1M43; X-ray; 2.40 A; A/B=123-453. DR PDB; 1ME6; X-ray; 2.70 A; A/B=125-453. DR PDB; 1PFZ; X-ray; 1.85 A; A/B/C/D=77-453. DR PDB; 1SME; X-ray; 2.70 A; A/B=125-453. DR PDB; 1W6H; X-ray; 2.24 A; A/B=123-453. DR PDB; 1W6I; X-ray; 2.70 A; A/C=123-453. DR PDB; 1XDH; X-ray; 1.70 A; A/B=123-453. DR PDB; 1XE5; X-ray; 2.40 A; A/B=125-453. DR PDB; 1XE6; X-ray; 2.80 A; A/B=125-453. DR PDB; 2BJU; X-ray; 1.56 A; A=1-453. DR PDB; 2IGX; X-ray; 1.70 A; A=125-453. DR PDB; 2IGY; X-ray; 2.60 A; A/B=125-453. DR PDB; 2R9B; X-ray; 2.80 A; A/B=125-453. DR PDB; 3F9Q; X-ray; 1.90 A; A=125-453. DR PDB; 4CKU; X-ray; 1.85 A; A/B/C/D/E/F=125-453. DR PDB; 4Y6M; X-ray; 2.27 A; A/B/C=125-453. DR PDB; 4YA8; X-ray; 3.30 A; A/B/C/D=125-453. DR PDB; 4Z22; X-ray; 2.62 A; A/B=125-453. DR PDB; 5BWY; X-ray; 2.64 A; A=78-453. DR PDBsum; 1LEE; -. DR PDBsum; 1LF2; -. DR PDBsum; 1LF3; -. DR PDBsum; 1LF4; -. DR PDBsum; 1M43; -. DR PDBsum; 1ME6; -. DR PDBsum; 1PFZ; -. DR PDBsum; 1SME; -. DR PDBsum; 1W6H; -. DR PDBsum; 1W6I; -. DR PDBsum; 1XDH; -. DR PDBsum; 1XE5; -. DR PDBsum; 1XE6; -. DR PDBsum; 2BJU; -. DR PDBsum; 2IGX; -. DR PDBsum; 2IGY; -. DR PDBsum; 2R9B; -. DR PDBsum; 3F9Q; -. DR PDBsum; 4CKU; -. DR PDBsum; 4Y6M; -. DR PDBsum; 4YA8; -. DR PDBsum; 4Z22; -. DR PDBsum; 5BWY; -. DR AlphaFoldDB; P46925; -. DR SMR; P46925; -. DR BindingDB; P46925; -. DR ChEMBL; CHEMBL4414; -. DR DrugBank; DB04378; 3-Amino-N-{4-[2-(2,6-Dimethyl-Phenoxy)-Acetylamino]-3-Hydroxy-1-Isobutyl-5-Phenyl-Pentyl}-Benzamide. DR DrugBank; DB04373; 4-Amino-N-{4-[2-(2,6-Dimethyl-Phenoxy)-Acetylamino]-3-Hydroxy-1-Isobutyl-5-Phenyl-Pentyl}-Benzamide. DR DrugBank; DB11638; Artenimol. DR DrugBank; DB01218; Halofantrine. DR DrugBank; DB02505; N-(R-Carboxy-Ethyl)-Alpha-(S)-(2-Phenylethyl). DR DrugBank; DB03063; N-[(2S,3S)-4-[2-[(5S)-3a,4,5,6,7,7a-Hexahydro-1,3-benzodioxol-5-yl]ethyl-[3-(1,3-dioxoisoindol-2-yl)propanoyl]amino]-3-hydroxy-1-phenylbutan-2-yl]-3,5-dimethoxy-4-phenylmethoxybenzamide. DR MEROPS; A01.023; -. DR EnsemblProtists; KOB58717; KOB58717; PFHG_00465. DR VEuPathDB; PlasmoDB:PF3D7_1408000; -. DR VEuPathDB; PlasmoDB:Pf7G8-2_000483200; -. DR VEuPathDB; PlasmoDB:Pf7G8_140013400; -. DR VEuPathDB; PlasmoDB:PfCD01_140013700; -. DR VEuPathDB; PlasmoDB:PfDd2_140012600; -. DR VEuPathDB; PlasmoDB:PfGA01_140013700; -. DR VEuPathDB; PlasmoDB:PfGB4_140014200; -. DR VEuPathDB; PlasmoDB:PfGN01_140013300; -. DR VEuPathDB; PlasmoDB:PfHB3_140013900; -. DR VEuPathDB; PlasmoDB:PfIT_140014600; -. DR VEuPathDB; PlasmoDB:PfKE01_140013300; -. DR VEuPathDB; PlasmoDB:PfKH01_140013600; -. DR VEuPathDB; PlasmoDB:PfKH02_140013900; -. DR VEuPathDB; PlasmoDB:PfML01_140013500; -. DR VEuPathDB; PlasmoDB:PfNF135_140013500; -. DR VEuPathDB; PlasmoDB:PfNF166_140012200; -. DR VEuPathDB; PlasmoDB:PfNF54_140013000; -. DR VEuPathDB; PlasmoDB:PfSD01_140011500; -. DR VEuPathDB; PlasmoDB:PfSN01_140015400; -. DR VEuPathDB; PlasmoDB:PfTG01_140013400; -. DR OMA; KYDHDAS; -. DR BioCyc; MetaCyc:MONOMER-15374; -. DR BRENDA; 3.4.23.39; 4889. DR EvolutionaryTrace; P46925; -. DR Proteomes; UP000054289; Unassembled WGS sequence. DR GO; GO:0031910; C:cytostome; IDA:UniProtKB. DR GO; GO:0020020; C:food vacuole; IDA:UniProtKB. DR GO; GO:0005775; C:vacuolar lumen; IEA:UniProtKB-SubCell. DR GO; GO:0005774; C:vacuolar membrane; IEA:UniProtKB-SubCell. DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IDA:UniProtKB. DR GO; GO:0044002; P:acquisition of nutrients from host; IDA:UniProtKB. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR CDD; cd05471; pepsin_like; 1. DR Gene3D; 2.40.70.10; Acid Proteases; 2. DR InterPro; IPR001461; Aspartic_peptidase_A1. DR InterPro; IPR001969; Aspartic_peptidase_AS. DR InterPro; IPR034164; Pepsin-like_dom. DR InterPro; IPR033121; PEPTIDASE_A1. DR InterPro; IPR021109; Peptidase_aspartic_dom_sf. DR PANTHER; PTHR47966; BETA-SITE APP-CLEAVING ENZYME, ISOFORM A-RELATED; 1. DR PANTHER; PTHR47966:SF51; BETA-SITE APP-CLEAVING ENZYME, ISOFORM A-RELATED; 1. DR Pfam; PF00026; Asp; 1. DR PRINTS; PR00792; PEPSIN. DR SUPFAM; SSF50630; Acid proteases; 1. DR PROSITE; PS00141; ASP_PROTEASE; 2. DR PROSITE; PS51767; PEPTIDASE_A1; 1. PE 1: Evidence at protein level; KW 3D-structure; Aspartyl protease; Direct protein sequencing; Disulfide bond; KW Hydrolase; Membrane; Protease; Reference proteome; Signal-anchor; KW Transmembrane; Transmembrane helix; Vacuole; Zymogen. FT PROPEP 1..124 FT /evidence="ECO:0000269|PubMed:12850260" FT /id="PRO_0000025930" FT CHAIN 125..453 FT /note="Plasmepsin II" FT /id="PRO_0000025931" FT TOPO_DOM 1..37 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 38..58 FT /note="Helical; Signal-anchor for type II membrane protein" FT /evidence="ECO:0000255" FT TOPO_DOM 59..453 FT /note="Lumenal" FT /evidence="ECO:0000305" FT DOMAIN 140..447 FT /note="Peptidase A1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103" FT ACT_SITE 158 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094" FT ACT_SITE 338 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094" FT DISULFID 171..176 FT /evidence="ECO:0000269|PubMed:12454457, FT ECO:0000269|PubMed:12614616, ECO:0000269|PubMed:15840589, FT ECO:0000269|PubMed:17091526, ECO:0000269|PubMed:19237752, FT ECO:0000269|PubMed:19271776, ECO:0000269|PubMed:24900843, FT ECO:0000269|PubMed:26625296, ECO:0000269|PubMed:26670264, FT ECO:0000269|PubMed:27599854, ECO:0000269|PubMed:8816746, FT ECO:0000269|PubMed:9886289, ECO:0000269|Ref.11, FT ECO:0000269|Ref.12, ECO:0000269|Ref.14, ECO:0000269|Ref.15, FT ECO:0000269|Ref.16, ECO:0007744|PDB:1LEE, FT ECO:0007744|PDB:1LF2, ECO:0007744|PDB:1LF3, FT ECO:0007744|PDB:1LF4, ECO:0007744|PDB:1M43, FT ECO:0007744|PDB:1ME6, ECO:0007744|PDB:1PFZ, FT ECO:0007744|PDB:1SME, ECO:0007744|PDB:1W6H, FT ECO:0007744|PDB:1W6I, ECO:0007744|PDB:1XDH, FT ECO:0007744|PDB:1XE5, ECO:0007744|PDB:1XE6, FT ECO:0007744|PDB:2BJU, ECO:0007744|PDB:2IGX, FT ECO:0007744|PDB:2IGY, ECO:0007744|PDB:3F9Q, FT ECO:0007744|PDB:4CKU, ECO:0007744|PDB:4Y6M, FT ECO:0007744|PDB:4YA8, ECO:0007744|PDB:4Z22, FT ECO:0007744|PDB:5BWY" FT DISULFID 373..409 FT /evidence="ECO:0000269|PubMed:12454457, FT ECO:0000269|PubMed:12614616, ECO:0000269|PubMed:15840589, FT ECO:0000269|PubMed:17091526, ECO:0000269|PubMed:19237752, FT ECO:0000269|PubMed:19271776, ECO:0000269|PubMed:24900843, FT ECO:0000269|PubMed:26625296, ECO:0000269|PubMed:26670264, FT ECO:0000269|PubMed:27599854, ECO:0000269|PubMed:8816746, FT ECO:0000269|PubMed:9886289, ECO:0000269|Ref.11, FT ECO:0000269|Ref.12, ECO:0000269|Ref.14, ECO:0000269|Ref.15, FT ECO:0000269|Ref.16, ECO:0007744|PDB:1LEE, FT ECO:0007744|PDB:1LF2, ECO:0007744|PDB:1LF3, FT ECO:0007744|PDB:1LF4, ECO:0007744|PDB:1M43, FT ECO:0007744|PDB:1ME6, ECO:0007744|PDB:1PFZ, FT ECO:0007744|PDB:1SME, ECO:0007744|PDB:1W6H, FT ECO:0007744|PDB:1W6I, ECO:0007744|PDB:1XDH, FT ECO:0007744|PDB:1XE5, ECO:0007744|PDB:1XE6, FT ECO:0007744|PDB:2BJU, ECO:0007744|PDB:2IGX, FT ECO:0007744|PDB:2IGY, ECO:0007744|PDB:3F9Q, FT ECO:0007744|PDB:4CKU, ECO:0007744|PDB:4Y6M, FT ECO:0007744|PDB:4YA8, ECO:0007744|PDB:4Z22, FT ECO:0007744|PDB:5BWY" FT MUTAGEN 241 FT /note="Missing: Reduces catalytic activity towards host FT hemoglobin." FT /evidence="ECO:0000269|PubMed:15574427" FT MUTAGEN 244 FT /note="F->A,K: No effect on catalytic activity." FT /evidence="ECO:0000269|PubMed:15574427" FT MUTAGEN 244 FT /note="F->E: Reduces catalytic activity towards host FT hemoglobin." FT /evidence="ECO:0000269|PubMed:15574427" FT STRAND 80..87 FT /evidence="ECO:0007829|PDB:1PFZ" FT HELIX 89..99 FT /evidence="ECO:0007829|PDB:1PFZ" FT HELIX 103..113 FT /evidence="ECO:0007829|PDB:1PFZ" FT TURN 114..116 FT /evidence="ECO:0007829|PDB:1PFZ" FT STRAND 118..120 FT /evidence="ECO:0007829|PDB:1PFZ" FT STRAND 127..135 FT /evidence="ECO:0007829|PDB:2BJU" FT TURN 136..138 FT /evidence="ECO:0007829|PDB:2BJU" FT STRAND 139..146 FT /evidence="ECO:0007829|PDB:2BJU" FT TURN 147..150 FT /evidence="ECO:0007829|PDB:2BJU" FT STRAND 151..158 FT /evidence="ECO:0007829|PDB:2BJU" FT STRAND 164..168 FT /evidence="ECO:0007829|PDB:2BJU" FT HELIX 176..178 FT /evidence="ECO:0007829|PDB:2BJU" FT HELIX 184..186 FT /evidence="ECO:0007829|PDB:2BJU" FT STRAND 191..200 FT /evidence="ECO:0007829|PDB:2BJU" FT STRAND 202..217 FT /evidence="ECO:0007829|PDB:2BJU" FT STRAND 220..231 FT /evidence="ECO:0007829|PDB:2BJU" FT HELIX 233..235 FT /evidence="ECO:0007829|PDB:2BJU" FT HELIX 238..241 FT /evidence="ECO:0007829|PDB:2BJU" FT STRAND 246..249 FT /evidence="ECO:0007829|PDB:2BJU" FT HELIX 253..255 FT /evidence="ECO:0007829|PDB:2BJU" FT STRAND 256..258 FT /evidence="ECO:0007829|PDB:1XDH" FT HELIX 263..269 FT /evidence="ECO:0007829|PDB:2BJU" FT STRAND 272..275 FT /evidence="ECO:0007829|PDB:2BJU" FT STRAND 277..281 FT /evidence="ECO:0007829|PDB:2BJU" FT TURN 285..287 FT /evidence="ECO:0007829|PDB:2BJU" FT STRAND 290..296 FT /evidence="ECO:0007829|PDB:2BJU" FT HELIX 299..301 FT /evidence="ECO:0007829|PDB:2BJU" FT STRAND 302..313 FT /evidence="ECO:0007829|PDB:2BJU" FT TURN 314..317 FT /evidence="ECO:0007829|PDB:2BJU" FT STRAND 318..325 FT /evidence="ECO:0007829|PDB:2BJU" FT STRAND 328..337 FT /evidence="ECO:0007829|PDB:2BJU" FT STRAND 343..346 FT /evidence="ECO:0007829|PDB:2BJU" FT HELIX 348..354 FT /evidence="ECO:0007829|PDB:2BJU" FT TURN 355..357 FT /evidence="ECO:0007829|PDB:2BJU" FT STRAND 358..362 FT /evidence="ECO:0007829|PDB:1LF2" FT STRAND 364..366 FT /evidence="ECO:0007829|PDB:1LF2" FT STRAND 369..372 FT /evidence="ECO:0007829|PDB:2BJU" FT STRAND 381..384 FT /evidence="ECO:0007829|PDB:2BJU" FT STRAND 389..392 FT /evidence="ECO:0007829|PDB:2BJU" FT HELIX 394..397 FT /evidence="ECO:0007829|PDB:2BJU" FT STRAND 398..400 FT /evidence="ECO:0007829|PDB:2BJU" FT TURN 402..404 FT /evidence="ECO:0007829|PDB:2BJU" FT STRAND 408..411 FT /evidence="ECO:0007829|PDB:2BJU" FT STRAND 413..415 FT /evidence="ECO:0007829|PDB:2BJU" FT STRAND 422..425 FT /evidence="ECO:0007829|PDB:2BJU" FT HELIX 427..432 FT /evidence="ECO:0007829|PDB:2BJU" FT STRAND 433..438 FT /evidence="ECO:0007829|PDB:2BJU" FT TURN 439..442 FT /evidence="ECO:0007829|PDB:2BJU" FT STRAND 443..449 FT /evidence="ECO:0007829|PDB:2BJU" SQ SEQUENCE 453 AA; 51490 MW; 0D78A8A65D0C80B5 CRC64; MDITVREHDF KHGFIKSNST FDGLNIDNSK NKKKIQKGFQ ILYVLLFCSV MCGLFYYVYE NVWLQRDNEM NEILKNSEHL TIGFKVENAH DRILKTIKTH KLKNYIKESV NFLNSGLTKT NYLGSSNDNI ELVDFQNIMF YGDAEVGDNQ QPFTFILDTG SANLWVPSVK CTTAGCLTKH LYDSSKSRTY EKDGTKVEMN YVSGTVSGFF SKDLVTVGNL SLPYKFIEVI DTNGFEPTYT ASTFDGILGL GWKDLSIGSV DPIVVELKNQ NKIENALFTF YLPVHDKHTG FLTIGGIEER FYEGPLTYEK LNHDLYWQIT LDAHVGNIML EKANCIVDSG TSAITVPTDF LNKMLQNLDV IKVPFLPFYV TLCNNSKLPT FEFTSENGKY TLEPEYYLQH IEDVGPGLCM LNIIGLDFPV PTFILGDPFM RKYFTVFDYD NHSVGIALAK KNL //