PLM9_PLAF7
ID PLM9_PLAF7 Reviewed; 627 AA.
AC Q8ILG2;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Plasmepsin IX {ECO:0000303|PubMed:29074775};
DE Short=PfPMIX {ECO:0000303|PubMed:29074775};
DE EC=3.4.23.- {ECO:0000269|PubMed:29074775, ECO:0000269|PubMed:32109369};
DE AltName: Full=Plasmepsin 9 {ECO:0000305};
DE Flags: Precursor;
GN Name=PMIX {ECO:0000303|PubMed:29074775};
GN ORFNames=PF3D7_1430200 {ECO:0000312|EMBL:CZT99999.1};
OS Plasmodium falciparum (isolate 3D7).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=36329 {ECO:0000312|Proteomes:UP000001450};
RN [1] {ECO:0000312|Proteomes:UP000001450}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7 {ECO:0000312|Proteomes:UP000001450};
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] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ASP-246.
RX PubMed=29074775; DOI=10.1126/science.aaf8675;
RA Pino P., Caldelari R., Mukherjee B., Vahokoski J., Klages N., Maco B.,
RA Collins C.R., Blackman M.J., Kursula I., Heussler V., Brochet M.,
RA Soldati-Favre D.;
RT "A multistage antimalarial targets the plasmepsins IX and X essential for
RT invasion and egress.";
RL Science 358:522-528(2017).
RN [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND PROTEOLYTIC
RP CLEAVAGE.
RX PubMed=32109369; DOI=10.1016/j.chom.2020.02.005;
RA Favuzza P., de Lera Ruiz M., Thompson J.K., Triglia T., Ngo A.,
RA Steel R.W.J., Vavrek M., Christensen J., Healer J., Boyce C., Guo Z.,
RA Hu M., Khan T., Murgolo N., Zhao L., Penington J.S., Reaksudsan K.,
RA Jarman K., Dietrich M.H., Richardson L., Guo K.Y., Lopaticki S., Tham W.H.,
RA Rottmann M., Papenfuss T., Robbins J.A., Boddey J.A., Sleebs B.E.,
RA Sabroux H.J., McCauley J.A., Olsen D.B., Cowman A.F.;
RT "Dual Plasmepsin-Targeting Antimalarial Agents Disrupt Multiple Stages of
RT the Malaria Parasite Life Cycle.";
RL Cell Host Microbe 27:642-658.e12(2020).
CC -!- FUNCTION: During the asexual blood stage, initiates the proteolytic
CC maturation of several rhoptry proteins and thus, is required for
CC merozoite invasion of host erythrocytes and probably the subsequent
CC development of the ring-stage (PubMed:29074775, PubMed:32109369).
CC Cleaves rhoptry associated protein 1 RAP1 and apical sushi protein ASP
CC during schizont maturation (PubMed:29074775, PubMed:32109369). Also
CC cleaves rhoptry protein RON3 (PubMed:32109369).
CC {ECO:0000269|PubMed:29074775, ECO:0000269|PubMed:32109369}.
CC -!- ACTIVITY REGULATION: Inhibited by small molecule 49c (PubMed:29074775).
CC Inhibited by small molecule WM382 (PubMed:32109369).
CC {ECO:0000269|PubMed:29074775, ECO:0000269|PubMed:32109369}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass type II
CC membrane protein {ECO:0000305}. Cytoplasmic vesicle, secretory vesicle,
CC rhoptry {ECO:0000269|PubMed:29074775}. Note=In schizonts, localizes to
CC the bulb of rhoptries. {ECO:0000269|PubMed:29074775}.
CC -!- DEVELOPMENTAL STAGE: Expressed during the asexual blood stage, in
CC schizonts and free merozoites (at protein level).
CC {ECO:0000269|PubMed:29074775}.
CC -!- PTM: Autocleaved into a p55 mature form. {ECO:0000269|PubMed:32109369}.
CC -!- DISRUPTION PHENOTYPE: Normal asexual development in host erythrocytes
CC (PubMed:29074775). Egress from erythrocytes is normal; however,
CC subsequent erythrocyte invasion by newly released merozoites is
CC severely impaired (PubMed:29074775). Accumulation of RAP1 p86 precursor
CC resulting from impaired processing (PubMed:29074775). Impaired ASP
CC processing (PubMed:29074775). Impaired secretion of CyRPA during
CC merozoite egress from erythrocytes (PubMed:29074775).
CC {ECO:0000269|PubMed:29074775}.
CC -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000305}.
CC -!- CAUTION: It is unclear if PMIX is glycosylated as other members of the
CC same enzyme family, i.e. PMI and PMII, are not. {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; LN999946; CZT99999.1; -; Genomic_DNA.
DR RefSeq; XP_001348455.1; XM_001348419.1.
DR AlphaFoldDB; Q8ILG2; -.
DR SMR; Q8ILG2; -.
DR STRING; 5833.PF14_0281; -.
DR MEROPS; A01.A95; -.
DR PRIDE; Q8ILG2; -.
DR EnsemblProtists; CZT99999; CZT99999; PF3D7_1430200.
DR GeneID; 811863; -.
DR KEGG; pfa:PF3D7_1430200; -.
DR VEuPathDB; PlasmoDB:PF3D7_1430200; -.
DR HOGENOM; CLU_395639_0_0_1; -.
DR InParanoid; Q8ILG2; -.
DR OMA; KCDANNI; -.
DR PhylomeDB; Q8ILG2; -.
DR Proteomes; UP000001450; Chromosome 14.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020008; C:rhoptry; IDA:UniProtKB.
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:0016540; P:protein autoprocessing; IMP:UniProtKB.
DR GO; GO:0016485; P:protein processing; IMP:UniProtKB.
DR GO; GO:0006508; P:proteolysis; ISS:GeneDB.
DR CDD; cd05471; pepsin_like; 1.
DR Gene3D; 2.40.70.10; -; 3.
DR InterPro; IPR001461; Aspartic_peptidase_A1.
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; 2.
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; Hydrolase; Membrane; Protease;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix;
KW Zymogen.
FT PROPEP 1..?
FT /evidence="ECO:0000305"
FT /id="PRO_0000453735"
FT CHAIN ?..627
FT /note="Plasmepsin IX"
FT /id="PRO_0000453736"
FT TOPO_DOM 1..13
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 14..34
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 35..627
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT DOMAIN 228..605
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 246
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 495
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT MUTAGEN 246
FT /note="D->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:29074775"
SQ SEQUENCE 627 AA; 74183 MW; 3F838C4676AD4280 CRC64;
MFFINFKKIK KKQFPIYLTQ HRIITVFLIF IYFINLKDCF HINNSRILSD VDKHRGLYYN
IPKCNVCHKC SICTHENGEA QNVIPMVAIP SKRKHIQDIN KEREENKYPL HIFEEKDIYN
NKDNVVKKED IYKLRKKKKQ KKNCLNFLEK DTMFLSPSHD KETFHINHMN KIKDEKYKQE
YEEEKEIYDN TNTSQEKNET NNEQNLNINL INNDKVTLPL QQLEDSQYVG YIQIGTPPQT
IRPIFDTGST NIWIVSTKCK DETCLKVHRY NHKLSSSFKY YEPHTNLDIM FGTGIIQGVI
GVETFKIGPF EIKNQSFGLV KREKASDNKS NVFERINFEG IVGLAFPEML STGKSTLYEN
LMSSYKLQHN EFSIYIGKDS KYSALIFGGV DKNFFEGDIY MFPVVKEYYW EIHFDGLYID
HQKFCCGVNS IVYDLKKKDQ ENNKLFFTRK YFRKNKFKTH LRKYLLKKIK HQKKQKHSNH
KKKKLNKKKN YLIFDSGTSF NSVPKDEIEY FFRVVPSKKC DDSNIDQVVS SYPNLTYVIN
KMPFTLTPSQ YLVRKNDMCK PAFMEIEVSS EYGHAYILGN ATFMRYYYTV YRRGNNNNSS
YVGIAKAVHT EENEKYLSSL HNKINNL
