PLM10_PLAF7
ID PLM10_PLAF7 Reviewed; 573 AA.
AC Q8IAS0;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Plasmepsin X {ECO:0000303|Ref.5};
DE Short=PfPMX {ECO:0000303|PubMed:29074775};
DE EC=3.4.23.- {ECO:0000269|PubMed:29074775, ECO:0000269|PubMed:32109369};
DE AltName: Full=Plasmepsin 10 {ECO:0000305};
DE Flags: Precursor;
GN Name=PMX {ECO:0000303|Ref.5};
GN ORFNames=PF3D7_0808200 {ECO:0000312|EMBL:CAD51290.1};
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:0000312|Proteomes:UP000001450}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7 {ECO:0000312|Proteomes:UP000001450};
RX PubMed=12368867; DOI=10.1038/nature01095;
RA Hall N., Pain A., Berriman M., Churcher C.M., Harris B., Harris D.,
RA Mungall K.L., Bowman S., Atkin R., Baker S., Barron A., Brooks K.,
RA Buckee C.O., Burrows C., Cherevach I., Chillingworth C., Chillingworth T.,
RA Christodoulou Z., Clark L., Clark R., Corton C., Cronin A., Davies R.M.,
RA Davis P., Dear P., Dearden F., Doggett J., Feltwell T., Goble A.,
RA Goodhead I., Gwilliam R., Hamlin N., Hance Z., Harper D., Hauser H.,
RA Hornsby T., Holroyd S., Horrocks P., Humphray S., Jagels K., James K.D.,
RA Johnson D., Kerhornou A., Knights A., Konfortov B., Kyes S., Larke N.,
RA Lawson D., Lennard N., Line A., Maddison M., Mclean J., Mooney P.,
RA Moule S., Murphy L., Oliver K., Ormond D., Price C., Quail M.A.,
RA Rabbinowitsch E., Rajandream M.A., Rutter S., Rutherford K.M., Sanders M.,
RA Simmonds M., Seeger K., Sharp S., Smith R., Squares R., Squares S.,
RA Stevens K., Taylor K., Tivey A., Unwin L., Whitehead S., Woodward J.R.,
RA Sulston J.E., Craig A., Newbold C., Barrell B.G.;
RT "Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.";
RL Nature 419:527-531(2002).
RN [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND MUTAGENESIS OF
RP ASP-266.
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 [4] {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).
RN [5] {ECO:0007744|PDB:7RY7}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 28-573, DISULFIDE BONDS, AND
RP GLYCOSYLATION AT ASN-334.
RA Abendroth J., Fox D., Lorimer D.D., Horanyi P.S., Edwards T.E.;
RT "Structure of Plasmepsin X (PM10, PMX) from Plasmodium falciparum 3D7.";
RL Submitted (APR-2019) to the PDB data bank.
CC -!- FUNCTION: During the asexual blood stage, processes key proteins
CC essential for merozoite egress and invasion of host erythrocytes
CC (PubMed:29074775, PubMed:32109369). Cleaves and activates proteases
CC SUB1 and SUB2 (PubMed:29074775, PubMed:32109369). May process members
CC of the EBL and Rh protein families (PubMed:32109369). Also cleaves
CC apical membrane protein AMA1 (PubMed:29074775). During the mosquito
CC vector stage and probably in ookinetes, cleaves CelTOS
CC (PubMed:29074775). {ECO:0000269|PubMed:29074775,
CC ECO:0000269|PubMed:32109369}.
CC -!- ACTIVITY REGULATION: Inhibited by small molecule 49c (PubMed:29074775).
CC Inhibited by small molecules WM382, WM4, and WM5 (PubMed:32109369).
CC {ECO:0000269|PubMed:29074775, ECO:0000269|PubMed:32109369}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle
CC {ECO:0000250|UniProtKB:W7JWW5}. Note=In schizonts, localizes to
CC exonemes which are secretory vesicles that discharge their content
CC during egress into the parasitophorous vacuole.
CC {ECO:0000250|UniProtKB:W7JWW5}.
CC -!- PTM: Autocleaved into a p16 prodomain form and two mature forms p44 and
CC p51. {ECO:0000269|PubMed:32109369}.
CC -!- SIMILARITY: Belongs to the peptidase A1 family.
CC {ECO:0000255|RuleBase:RU000454}.
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DR EMBL; AL844507; CAD51290.1; -; Genomic_DNA.
DR RefSeq; XP_001349441.1; XM_001349405.1.
DR PDB; 7RY7; X-ray; 2.10 A; A=28-573.
DR PDBsum; 7RY7; -.
DR AlphaFoldDB; Q8IAS0; -.
DR SMR; Q8IAS0; -.
DR IntAct; Q8IAS0; 2.
DR STRING; 5833.PF08_0108; -.
DR ChEMBL; CHEMBL4523390; -.
DR GuidetoPHARMACOLOGY; 3071; -.
DR MEROPS; A01.A93; -.
DR PRIDE; Q8IAS0; -.
DR EnsemblProtists; CAD51290; CAD51290; PF3D7_0808200.
DR GeneID; 2655308; -.
DR KEGG; pfa:PF3D7_0808200; -.
DR VEuPathDB; PlasmoDB:PF3D7_0808200; -.
DR HOGENOM; CLU_500120_0_0_1; -.
DR InParanoid; Q8IAS0; -.
DR OMA; PQEIHPI; -.
DR PhylomeDB; Q8IAS0; -.
DR Proteomes; UP000001450; Chromosome 8.
DR GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0085017; P:entry into host cell by a symbiont-containing vacuole; IGI:UniProtKB.
DR GO; GO:0016540; P:protein autoprocessing; IDA:UniProtKB.
DR GO; GO:0016485; P:protein processing; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; ISS:GeneDB.
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 3D-structure; Aspartyl protease; Cytoplasmic vesicle; Disulfide bond;
KW Glycoprotein; Hydrolase; Protease; Reference proteome; Signal; Zymogen.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT PROPEP 27..?
FT /evidence="ECO:0000305"
FT /id="PRO_0000453739"
FT CHAIN ?..573
FT /note="Plasmepsin X"
FT /evidence="ECO:0000255"
FT /id="PRO_0000453740"
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:0000269|Ref.5, ECO:0007744|PDB:7RY7"
FT DISULFID 39..51
FT /evidence="ECO:0000269|Ref.5, ECO:0007744|PDB:7RY7"
FT DISULFID 42..48
FT /evidence="ECO:0000269|Ref.5, ECO:0007744|PDB:7RY7"
FT DISULFID 279..284
FT /evidence="ECO:0000269|Ref.5, ECO:0007744|PDB:7RY7"
FT DISULFID 447..448
FT /evidence="ECO:0000269|Ref.5, ECO:0007744|PDB:7RY7"
FT DISULFID 482..521
FT /evidence="ECO:0000269|Ref.5, ECO:0007744|PDB:7RY7"
FT MUTAGEN 266
FT /note="D->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:29074775"
FT STRAND 29..31
FT /evidence="ECO:0007829|PDB:7RY7"
FT HELIX 39..41
FT /evidence="ECO:0007829|PDB:7RY7"
FT TURN 45..47
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 60..66
FT /evidence="ECO:0007829|PDB:7RY7"
FT HELIX 75..82
FT /evidence="ECO:0007829|PDB:7RY7"
FT TURN 83..86
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 89..92
FT /evidence="ECO:0007829|PDB:7RY7"
FT HELIX 99..101
FT /evidence="ECO:0007829|PDB:7RY7"
FT HELIX 111..113
FT /evidence="ECO:0007829|PDB:7RY7"
FT HELIX 114..128
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 236..239
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 247..250
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:7RY7"
FT TURN 255..258
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 259..261
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 264..266
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 271..275
FT /evidence="ECO:0007829|PDB:7RY7"
FT HELIX 292..294
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 317..327
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 330..341
FT /evidence="ECO:0007829|PDB:7RY7"
FT HELIX 354..356
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 361..365
FT /evidence="ECO:0007829|PDB:7RY7"
FT TURN 371..375
FT /evidence="ECO:0007829|PDB:7RY7"
FT HELIX 379..386
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 392..397
FT /evidence="ECO:0007829|PDB:7RY7"
FT TURN 400..402
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 406..412
FT /evidence="ECO:0007829|PDB:7RY7"
FT HELIX 414..416
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 417..425
FT /evidence="ECO:0007829|PDB:7RY7"
FT TURN 429..432
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 433..436
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 438..441
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 444..447
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 452..456
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 461..465
FT /evidence="ECO:0007829|PDB:7RY7"
FT HELIX 467..476
FT /evidence="ECO:0007829|PDB:7RY7"
FT TURN 483..485
FT /evidence="ECO:0007829|PDB:7RY7"
FT HELIX 487..490
FT /evidence="ECO:0007829|PDB:7RY7"
FT HELIX 491..493
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 497..501
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 504..508
FT /evidence="ECO:0007829|PDB:7RY7"
FT HELIX 510..513
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 514..517
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 520..523
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 525..527
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 533..540
FT /evidence="ECO:0007829|PDB:7RY7"
FT TURN 542..544
FT /evidence="ECO:0007829|PDB:7RY7"
FT HELIX 545..548
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 549..554
FT /evidence="ECO:0007829|PDB:7RY7"
FT STRAND 563..569
FT /evidence="ECO:0007829|PDB:7RY7"
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
