PLM1_PLAFX
ID PLM1_PLAFX Reviewed; 452 AA.
AC P39898; A0A0L7K6M8;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 2.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Plasmepsin I {ECO:0000303|PubMed:8844673};
DE EC=3.4.23.38 {ECO:0000269|PubMed:2007860, ECO:0000269|PubMed:8313875, ECO:0000269|PubMed:8844673};
DE AltName: Full=Aspartic hemoglobinase I {ECO:0000303|PubMed:8313875};
DE AltName: Full=Plasmepsin 1 {ECO:0000305};
DE Flags: Precursor;
GN Name=PMI {ECO:0000303|PubMed:8844673};
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 [MRNA], FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR
RP LOCATION, AND DEVELOPMENTAL STAGE.
RC STRAIN=FAF-2;
RX PubMed=8313875; DOI=10.1002/j.1460-2075.1994.tb06263.x;
RA Francis S.E., Gluzman I.Y., Oksman A., Knickerbocker A., Mueller R.,
RA Bryant M.L., Sherman D.R., Russell D.G., Goldberg D.E.;
RT "Molecular characterization and inhibition of a Plasmodium falciparum
RT aspartic hemoglobinase.";
RL EMBO J. 13:306-317(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 PROTEIN SEQUENCE OF 125-146, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=2007860; DOI=10.1084/jem.173.4.961;
RA Goldberg D.E., Slater A.F.G., Beavis R., Chait B., Cerami A.,
RA Henderson G.B.;
RT "Hemoglobin degradation in the human malaria pathogen Plasmodium
RT falciparum: a catabolic pathway initiated by a specific aspartic
RT protease.";
RL J. Exp. Med. 173:961-969(1991).
RN [4]
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 [5]
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, PROTEOLYTIC CLEAVAGE, TOPOLOGY,
RP AND LACK 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 [6]
RP SUBCELLULAR LOCATION, AND DEVELOPMENTAL 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 [7]
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 [8] {ECO:0007744|PDB:3QRV, ECO:0007744|PDB:3QS1}
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 117-452 IN COMPLEX WITH
RP INHIBITOR, AND DISULFIDE BONDS.
RX PubMed=21521654; DOI=10.1016/j.jsb.2011.04.009;
RA Bhaumik P., Horimoto Y., Xiao H., Miura T., Hidaka K., Kiso Y.,
RA Wlodawer A., Yada R.Y., Gustchina A.;
RT "Crystal structures of the free and inhibited forms of plasmepsin I (PMI)
RT from Plasmodium falciparum.";
RL J. Struct. Biol. 175:73-84(2011).
CC -!- FUNCTION: During the asexual blood stage, catalyzes the initial
CC cleavage of native host hemoglobin (Hb) resulting in Hb denaturation;
CC specifically cleaves between Phe-33 and Leu-34 of Hb alpha-chain
CC (PubMed:8313875, PubMed:2007860, PubMed:8844673). Digestion of host Hb
CC is an essential step which provides the parasite with amino acids for
CC protein synthesis, and regulates osmolarity (Probable).
CC {ECO:0000269|PubMed:2007860, ECO:0000269|PubMed:8313875,
CC ECO:0000269|PubMed:8844673, ECO:0000305}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of the 33-Phe-|-Leu-34 bond in the alpha-chain of
CC hemoglobin, leading to denaturation of molecule.; EC=3.4.23.38;
CC Evidence={ECO:0000269|PubMed:2007860, ECO:0000269|PubMed:8313875,
CC ECO:0000269|PubMed:8844673};
CC -!- ACTIVITY REGULATION: Inhibited by pepstatin A.
CC {ECO:0000269|PubMed:8844673}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 4.5-5. {ECO:0000269|PubMed:2007860};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:9169469}; Single-
CC pass type II membrane protein {ECO:0000269|PubMed:9169469}. Vacuole
CC lumen {ECO:0000269|PubMed:11782538, ECO:0000269|PubMed:2007860,
CC ECO:0000269|PubMed:8313875, ECO:0000269|PubMed:9169469}. Vacuole
CC membrane {ECO:0000305|PubMed:9169469}. Note=At the beginning of the
CC asexual blood stage, the transmembrane zymogen is transported to the
CC cytostome, an endocytic structure spanning the parasite cell membrane
CC and the parasitophorous vacuole membrane where host proteins such as
CC hemoglobin are endocytosed (PubMed:9169469). Following endocytosis,
CC localizes to the cytostome vacuole membrane to be then delivered to the
CC digestive (or food) vacuole where it is cleaved into the soluble and
CC active enzyme (PubMed:9169469). In trophozoites, localizes to the
CC digestive vacuole, an acidic vacuole where host hemoglobin is digested
CC (PubMed:8313875, PubMed:9169469). {ECO:0000269|PubMed:8313875,
CC 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:2007860, ECO:0000269|PubMed:8313875,
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, PubMed:12850260). Proteolysis
CC requires an acidic environment (PubMed:9169469, PubMed:12850260).
CC {ECO:0000269|PubMed:12850260, ECO:0000269|PubMed:9169469}.
CC -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000305}.
CC -!- CAUTION: The position of the proteolytic cleavage is unclear
CC (PubMed:2007860, PubMed:12850260). One study shows a cleavage between
CC Asn-124 and Ala-125 (PubMed:2007860). Another study shows a cleavage
CC between Gly-123 and Asn-124 (PubMed:12850260).
CC {ECO:0000269|PubMed:12850260, ECO:0000269|PubMed:2007860}.
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DR EMBL; X75787; CAA53432.1; -; mRNA.
DR EMBL; CH671923; KOB58716.1; -; Genomic_DNA.
DR PIR; S41717; S41717.
DR PDB; 3QRV; X-ray; 2.40 A; A/B=117-452.
DR PDB; 3QS1; X-ray; 3.10 A; A/B/C/D=117-452.
DR PDBsum; 3QRV; -.
DR PDBsum; 3QS1; -.
DR AlphaFoldDB; P39898; -.
DR SMR; P39898; -.
DR BindingDB; P39898; -.
DR ChEMBL; CHEMBL4687; -.
DR MEROPS; A01.022; -.
DR EnsemblProtists; CZT99786; CZT99786; PF3D7_1407900.
DR EnsemblProtists; KOB58716; KOB58716; PFHG_00464.
DR VEuPathDB; PlasmoDB:PF3D7_1407900; -.
DR VEuPathDB; PlasmoDB:Pf7G8-2_000483100; -.
DR VEuPathDB; PlasmoDB:Pf7G8_140013300; -.
DR VEuPathDB; PlasmoDB:PfCD01_140013600; -.
DR VEuPathDB; PlasmoDB:PfDd2_140012500; -.
DR VEuPathDB; PlasmoDB:PfGA01_140013600; -.
DR VEuPathDB; PlasmoDB:PfGB4_140014100; -.
DR VEuPathDB; PlasmoDB:PfGN01_140013200; -.
DR VEuPathDB; PlasmoDB:PfHB3_140013800; -.
DR VEuPathDB; PlasmoDB:PfIT_140014500; -.
DR VEuPathDB; PlasmoDB:PfKE01_140013200; -.
DR VEuPathDB; PlasmoDB:PfKH01_140013500; -.
DR VEuPathDB; PlasmoDB:PfKH02_140013800; -.
DR VEuPathDB; PlasmoDB:PfML01_140013400; -.
DR VEuPathDB; PlasmoDB:PfNF135_140013400; -.
DR VEuPathDB; PlasmoDB:PfNF166_140012100; -.
DR VEuPathDB; PlasmoDB:PfNF54_140012900; -.
DR VEuPathDB; PlasmoDB:PfSD01_140011400; -.
DR VEuPathDB; PlasmoDB:PfSN01_140015300; -.
DR VEuPathDB; PlasmoDB:PfTG01_140013300; -.
DR OMA; GVECANL; -.
DR BioCyc; MetaCyc:MON-15375; -.
DR BRENDA; 3.4.23.38; 4889.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; -; 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; PTHR47966; 1.
DR Pfam; PF00026; Asp; 1.
DR PRINTS; PR00792; PEPSIN.
DR SUPFAM; SSF50630; SSF50630; 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..123
FT /evidence="ECO:0000269|PubMed:12850260"
FT /id="PRO_0000025928"
FT CHAIN 124..452
FT /note="Plasmepsin I"
FT /id="PRO_0000025929"
FT TOPO_DOM 1..37
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:9169469"
FT TRANSMEM 38..58
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 59..452
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:9169469"
FT DOMAIN 139..446
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 157
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT ACT_SITE 337
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT DISULFID 170..175
FT /evidence="ECO:0000269|PubMed:21521654,
FT ECO:0007744|PDB:3QRV, ECO:0007744|PDB:3QS1"
FT DISULFID 372..408
FT /evidence="ECO:0000269|PubMed:21521654,
FT ECO:0007744|PDB:3QRV, ECO:0007744|PDB:3QS1"
FT STRAND 127..134
FT /evidence="ECO:0007829|PDB:3QRV"
FT TURN 135..137
FT /evidence="ECO:0007829|PDB:3QRV"
FT STRAND 138..145
FT /evidence="ECO:0007829|PDB:3QRV"
FT TURN 146..149
FT /evidence="ECO:0007829|PDB:3QRV"
FT STRAND 150..157
FT /evidence="ECO:0007829|PDB:3QRV"
FT STRAND 162..167
FT /evidence="ECO:0007829|PDB:3QRV"
FT HELIX 175..177
FT /evidence="ECO:0007829|PDB:3QRV"
FT HELIX 183..185
FT /evidence="ECO:0007829|PDB:3QRV"
FT STRAND 190..196
FT /evidence="ECO:0007829|PDB:3QRV"
FT STRAND 205..216
FT /evidence="ECO:0007829|PDB:3QRV"
FT STRAND 219..234
FT /evidence="ECO:0007829|PDB:3QRV"
FT TURN 238..240
FT /evidence="ECO:0007829|PDB:3QRV"
FT STRAND 244..248
FT /evidence="ECO:0007829|PDB:3QRV"
FT HELIX 252..254
FT /evidence="ECO:0007829|PDB:3QRV"
FT HELIX 262..268
FT /evidence="ECO:0007829|PDB:3QRV"
FT STRAND 271..280
FT /evidence="ECO:0007829|PDB:3QRV"
FT STRAND 283..287
FT /evidence="ECO:0007829|PDB:3QS1"
FT STRAND 289..295
FT /evidence="ECO:0007829|PDB:3QRV"
FT HELIX 298..300
FT /evidence="ECO:0007829|PDB:3QRV"
FT STRAND 301..309
FT /evidence="ECO:0007829|PDB:3QRV"
FT TURN 313..316
FT /evidence="ECO:0007829|PDB:3QRV"
FT STRAND 317..324
FT /evidence="ECO:0007829|PDB:3QRV"
FT STRAND 327..336
FT /evidence="ECO:0007829|PDB:3QRV"
FT STRAND 341..345
FT /evidence="ECO:0007829|PDB:3QRV"
FT HELIX 347..354
FT /evidence="ECO:0007829|PDB:3QRV"
FT TURN 355..358
FT /evidence="ECO:0007829|PDB:3QRV"
FT STRAND 368..371
FT /evidence="ECO:0007829|PDB:3QRV"
FT STRAND 380..383
FT /evidence="ECO:0007829|PDB:3QRV"
FT STRAND 388..391
FT /evidence="ECO:0007829|PDB:3QRV"
FT HELIX 393..396
FT /evidence="ECO:0007829|PDB:3QRV"
FT STRAND 397..401
FT /evidence="ECO:0007829|PDB:3QRV"
FT STRAND 403..405
FT /evidence="ECO:0007829|PDB:3QRV"
FT STRAND 407..414
FT /evidence="ECO:0007829|PDB:3QRV"
FT STRAND 421..424
FT /evidence="ECO:0007829|PDB:3QRV"
FT HELIX 426..431
FT /evidence="ECO:0007829|PDB:3QRV"
FT STRAND 432..437
FT /evidence="ECO:0007829|PDB:3QRV"
FT TURN 438..441
FT /evidence="ECO:0007829|PDB:3QRV"
FT STRAND 442..448
FT /evidence="ECO:0007829|PDB:3QRV"
SQ SEQUENCE 452 AA; 51461 MW; 8F8F8478F2F7D931 CRC64;
MALSIKEDFS SAFAKNESAV NSSTFNNNMK TWKIQKRFQI LYVFFFLLIT GALFYYLIDN
VLFPKNKKIN EIMNTSKHVI IGFSIENSHD RIMKTVKQHR LKNYIKESLK FFKTGLTQKP
HLGNAGDSVT LNDVANVMYY GEAQIGDNKQ KFAFIFDTGS ANLWVPSAQC NTIGCKTKNL
YDSNKSKTYE KDGTKVEMNY VSGTVSGFFS KDIVTIANLS FPYKFIEVTD TNGFEPAYTL
GQFDGIVGLG WKDLSIGSVD PVVVELKNQN KIEQAVFTFY LPFDDKHKGY LTIGGIEDRF
YEGQLTYEKL NHDLYWQVDL DLHFGNLTVE KATAIVDSGT SSITAPTEFL NKFFEGLDVV
KIPFLPLYIT TCNNPKLPTL EFRSATNVYT LEPEYYLQQI FDFGISLCMV SIIPVDLNKN
TFILGDPFMR KYFTVFDYDN HTVGFALAKK KL
