PLM10_PLAFO
ID PLM10_PLAFO Reviewed; 573 AA.
AC W7JWW5;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 50.
DE RecName: Full=Plasmepsin X {ECO:0000303|PubMed:29074774};
DE EC=3.4.23.- {ECO:0000269|PubMed:29074774};
DE AltName: Full=Plasmepsin 10 {ECO:0000305};
DE Flags: Precursor;
GN Name=PMX {ECO:0000303|PubMed:29074774};
GN ORFNames=CK202_2307 {ECO:0000312|EMBL:PKC47425.1},
GN PFNF54_02086 {ECO:0000312|EMBL:EWC89121.1};
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|Proteomes:UP000232684}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NF54 {ECO:0000312|Proteomes:UP000232684};
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, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP DEVELOPMENTAL STAGE, PROTEOLYTIC CLEAVAGE, DISRUPTION PHENOTYPE, AND
RP MUTAGENESIS OF ASP-266.
RX PubMed=29074774; DOI=10.1126/science.aan1478;
RA Nasamu A.S., Glushakova S., Russo I., Vaupel B., Oksman A., Kim A.S.,
RA Fremont D.H., Tolia N., Beck J.R., Meyers M.J., Niles J.C., Zimmerberg J.,
RA Goldberg D.E.;
RT "Plasmepsins IX and X are essential and druggable mediators of malaria
RT parasite egress and invasion.";
RL Science 358:518-522(2017).
CC -!- FUNCTION: During the asexual blood stage, processes key proteins
CC essential for merozoite egress and invasion of host erythrocytes
CC (PubMed:29074774). Cleaves and activates proteases SUB1 and SUB2
CC (PubMed:29074774). May process members of the EBL and Rh protein
CC families (By similarity). Also cleaves apical membrane protein AMA1 (By
CC similarity). During the mosquito vector stage and probably in
CC ookinetes, cleaves CelTOS (By similarity).
CC {ECO:0000250|UniProtKB:Q8IAS0, ECO:0000269|PubMed:29074774}.
CC -!- ACTIVITY REGULATION: Inhibited by aminohydantoin compounds such as
CC CWHM-117. {ECO:0000269|PubMed:29074774}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle
CC {ECO:0000269|PubMed:29074774}. Note=In schizonts, localizes to exonemes
CC which are secretory vesicles that discharge their content during egress
CC into the parasitophorous vacuole. {ECO:0000269|PubMed:29074774}.
CC -!- DEVELOPMENTAL STAGE: Expressed during the asexual blood stage, in
CC schizonts (at protein level). {ECO:0000269|PubMed:29074774}.
CC -!- PTM: Autocleaved into a p16 prodomain form and two mature forms p44 and
CC p51. {ECO:0000250|UniProtKB:Q8IAS0}.
CC -!- DISRUPTION PHENOTYPE: Normal asexual development in host erythrocytes;
CC however merozoite egress from erythrocyte is impaired
CC (PubMed:29074774). Erythrocyte invasion by the few newly released
CC merozoites is severly impaired (PubMed:29074774). Impaired SUB1
CC proteolytic processing (PubMed:29074774).
CC {ECO:0000269|PubMed:29074774}.
CC -!- SIMILARITY: Belongs to the peptidase A1 family.
CC {ECO:0000255|RuleBase:RU000454}.
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DR EMBL; KE123790; EWC89121.1; -; Genomic_DNA.
DR EMBL; NYMT01000006; PKC47425.1; -; Genomic_DNA.
DR SMR; W7JWW5; -.
DR PRIDE; W7JWW5; -.
DR EnsemblProtists; EWC89121; EWC89121; PFNF54_02086.
DR VEuPathDB; PlasmoDB:PfNF54_080012200; -.
DR OMA; PQEIHPI; -.
DR Proteomes; UP000030673; Unassembled WGS sequence.
DR Proteomes; UP000232684; Unassembled WGS sequence.
DR GO; GO:0044311; C:exoneme; IDA:UniProtKB.
DR GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IMP:UniProtKB.
DR GO; GO:0085017; P:entry into host cell by a symbiont-containing vacuole; IMP:UniProtKB.
DR GO; GO:0035891; P:exit from host cell; IMP:UniProtKB.
DR GO; GO:0016485; P:protein processing; IMP:UniProtKB.
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; 1.
DR PROSITE; PS51767; PEPTIDASE_A1; 1.
PE 1: Evidence at protein level;
KW Aspartyl protease; Cytoplasmic vesicle; Disulfide bond; Glycoprotein;
KW Hydrolase; Protease; Reference proteome; Signal; Zymogen.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT PROPEP 27..?
FT /evidence="ECO:0000305"
FT /id="PRO_0000454297"
FT CHAIN ?..573
FT /note="Plasmepsin X"
FT /evidence="ECO:0000255"
FT /id="PRO_0000454298"
FT DOMAIN 248..567
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT REGION 167..211
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 266
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 457
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT CARBOHYD 334
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q8IAS0"
FT DISULFID 39..51
FT /evidence="ECO:0000250|UniProtKB:Q8IAS0"
FT DISULFID 42..48
FT /evidence="ECO:0000250|UniProtKB:Q8IAS0"
FT DISULFID 279..284
FT /evidence="ECO:0000250|UniProtKB:Q8IAS0"
FT DISULFID 447..448
FT /evidence="ECO:0000250|UniProtKB:Q8IAS0"
FT DISULFID 482..521
FT /evidence="ECO:0000250|UniProtKB:Q8IAS0"
FT MUTAGEN 266
FT /note="D->G: Reduces asexual blood stage growth. Loss of
FT protease SUB1 proteolytic processing. Does not affect PMX
FT processing into its mature form."
FT /evidence="ECO:0000269|PubMed:29074774"
SQ SEQUENCE 573 AA; 65114 MW; 1381CB0D4519A54F CRC64;
MKRISPLNTL FYLSLFFSYT FKGLKCTRIY KIGTKALPCS ECHDVFDCTG CLFEEKESSH
VIPLKLNKKN PNDHKKLQKH HESLKLGDVK YYVNRGEGIS GSLGTSSGNT LDDMDLINEE
INKKRTNAQL DEKNFLDFTT YNKNKAQDIS DHLSDIQKHV YEQDAQKGNK NFTNNENNSD
NENNSDNENN SDNENNLDNE NNLDNENNSD NSSIEKNFIA LENKNATVEQ TKENIFLVPL
KHLRDSQFVG ELLVGTPPQT VYPIFDTGST NVWVVTTACE EESCKKVRRY DPNKSKTFRR
SFIEKNLHIV FGSGSISGSV GTDTFMLGKH LVRNQTFGLV ESESNNNKNG GDNIFDYISF
EGIVGLGFPG MLSAGNIPFF DNLLKQNPNV DPQFSFYISP YDGKSTLIIG GISKSFYEGD
IYMLPVLKES YWEVKLDELY IGKERICCDE ESYVIFDTGT SYNTMPSSQM KTFLNLIHST
ACTEQNYKDI LKSYPIIKYV FGELIIELHP EEYMILNDDV CMPAYMQIDV PSERNHAYLL
GSLSFMRNFF TVFVRGTESR PSMVGVARAK SKN
