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Functional annotation of merozoite invasion-related proteins |
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Compilation assited by Tim Gilberger and Andrew Pierce |
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Updated according to: Cowman AF, Berry D, Baum J. The cellular and molecular basis for malaria parasite invasion of the human red blood cell. J Cell Biol. 2012 198(6):961-71 |
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* N = KO attempt unsuccessful; Y = KO generated; ND = KO not attempted; a = EBL and PfRh families show overlap in function and, whilst individually non-essential, overall are essential |
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Name |
PfID |
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KO |
Localization in merozoite before/during invasion |
Potential function |
Feature/Structure |
Transcript |
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Microneme proteins |
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| 6913 |
EBA-140/BAEBL |
PF3D7_1301600 |
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Y |
erythrocyte binding antigen-140 |
Binds to glycophorin C on red cell |
EBL family member with DBL domains |
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| 6876 |
EBA-165 |
PF3D7_0424300 |
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erythrocyte binding antigen-165, pseudogene |
Psuedogene |
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| 6887 |
EBA-175 |
PF3D7_0731500 |
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erythrocyte binding antigen-175 |
Binds to glycophorin A, likely signalling role for invasion; |
EBL family with DBL domains; “handshake” association between region II dimers creates groove for glycophorin A binding, in DRM |
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| 6853 |
EBA-181/JESEBL |
PF3D7_0102500 |
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Y |
erythrocyte binding antigen-181 |
Binds to unknown receptor on red cell |
EBL family member with DBL domains |
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| 6906 |
AMA-1 |
PF3D7_1133400 |
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N |
apical membrane antigen 1 |
Released on merozoite surface; binds RON complex; potential ligand for McLeod antigen, phosphorylation of cytoplasmic tail essential, may be involved in signalling |
PAN (plasminogen, apple, nematode) motifs |
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| 6909 |
PTRAMP/TSP-3 |
PF3D7_1218000 |
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ND |
thrombospondin-related apical membrane protein |
Not known; cleaved by SUB2 on merozoite surface |
highly extended bifunctional protein that binds to an erythrocyte receptor and the merozoite motor. |
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| 6896 |
MTRAP |
PF3D7_1028700 |
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N |
merozoite TRAP-like protein |
Potential motor associated protein; Binds to receptor semiphorin-7A |
Thrombospondin-like domains |
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| 6860 |
SPATR |
PF3D7_0212600 |
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secreted protein with altered thrombospondin repeat domain |
SPATR-like protein, putative; |
altered thrombospondin domain |
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| 6870 |
ASP/RON1 |
PF3D7_0405900 |
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ND |
apical sushi protein |
Not known; has putative GPI anchor |
Sushi domains; Found in DRM |
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| 6907 |
SUB2 |
PF3D7_1136900 |
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N |
subtilisin-like protease 2 |
Protease that processes MSP-1, MSP-6, MSP-7, AMA1, PTRAMP and other proteins to prime merozoite for invasion |
Subtilisin-like serine protease |
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| 6889 |
GAMA |
PF3D7_0828800 |
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ND |
GPI-anchored micronemal antigen |
Binds to red cells; has GPI anchor |
No data |
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| 6866 |
RIPR |
PF3D7_0323400 |
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N |
Rh5 interacting protein |
forms a complex with PfRh5 in merozoites |
10 EGF domains, 87 cysteines |
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| 6865 |
MA |
PF3D7_0316000 |
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N |
microneme associated antigen |
Binds to red cells in a sialic acid independent, chymotrypsin and trypsin resistant manner |
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| 6873 |
CyRPA |
PF3D7_0423800 |
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N |
RH5-Ripr membrane anchoring protein cysteine-rich protective antigen |
Cysteine-rich protective antigen (CyRPA) as an interacting partner of PfRH5-PfRipr that tethers the PfRH5/PfRipr/ CyRPA multiprotein complex on the merozoite surface |
GPI-linked parasite protein, |
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CLAMP |
PF3D7_1030200 |
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N |
claudin-like apicomplexan microneme protein |
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Rhoptry proteins |
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| 6928 |
RAP1 |
PF3D7_1410400 |
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rhoptry-associated protein 1 |
Escorter of RAP2, associated with RAP2 and RAP3, truncation disrupts trafficking of the complex, Not involved in invasion, it appears to be important in setting up the PV |
Found in DRMs |
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| 6878 |
RAP2 |
PF3D7_0501600 |
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rhoptry-associated protein 2 |
Associated with RAP1, unknown function; Not involved in invasion, it appears to be important in setting up the PV |
Found in DRMs |
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| 6877 |
RAP3 |
PF3D7_0501500 |
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rhoptry-associated protein 3 |
Associated with RAP1, unknown function; Not involved in invasion, it appears to be important in setting up the PV |
Found in DRMs |
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| 6864 |
CLAG3.1 |
PF3D7_0302500 |
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cytoadherence linked asexual protein 3.1 |
Associated with RhopH2/H3, proposed to be an anion channed. Not involved in invasion |
Found in DRMs |
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| 6892 |
RhopH2 |
PF3D7_0929400 |
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high molecular weight rhoptry protein 2 |
Associated with RhopH1, unknown function; Not involved in invasion |
Found in DRMs |
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| 6914 |
RhopH2 |
PF3D7_1320000 |
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rhoptry protein 2, putative golgi protein 1 |
Rhoptry protein 2, putative; Not involved in invasion |
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| 6891 |
RhopH3 |
PF3D7_0905400 |
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high molecular weight rhoptry protein 3 |
Associated with RhopH1, unknown function; Not involved in invasion |
Found in DRMs |
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| 6863 |
CLAG3.2 |
PF3D7_0302200 |
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cytoadherence linked asexual protein 3.2 |
High-molecular-weight rhoptry complex; anion channel on the surface of the RBC; Not involved in invasion |
Found in DRMs |
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| 6927 |
Rhop148 |
PF3D7_1366400 |
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rhoptry protein RHOP148 |
Unknown function |
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| 6890 |
CLAG8 |
PF3D7_0831600 |
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cytoadherence linked asexual protein 8 |
cytoadherence linked asexual protein 8; No data on invasion |
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| 6862 |
CLAG2 |
PF3D7_0220800 |
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cytoadherence linked asexual protein 2 |
Cytoadherence linked asexual protein 2, Clag2 No data on invasion |
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| 6894 |
CLAG9 |
PF3D7_0935800 |
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cytoadherence linked asexual protein 9 |
Cytoadherence linked asexual protein 9, Clag9; No data on invasion |
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| 6884 |
RAMA |
PF3D7_0707300 |
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rhoptry-associated membrane antigen |
GPI anchored, processed form binds to the surface of the RBC, associated with RAP1 and RhopH+C11; Involved in trafficking RAP1,2,3 and not invasion |
Found in DRMs |
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| 28055 |
Rhoptry protein |
PF3D7_1466900 |
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conserved plasmodium protein, unknown function |
Rhoptry protein, putative |
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| 6885 |
RALP1 |
PF3D7_0722200 |
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N |
rhoptry-associated leucine zipper-like protein 1 |
Rhoptry-associated leucine zipper-like protein 1; Not involved in invasion |
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| 6915 |
Rab11A |
PF3D7_1320600 |
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ras-related protein Rab-11A |
Has a regulatory role in both parasite growth and invasion |
Glutathionylated and palmitoylated |
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PF3D7_1459900 |
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rhoptry protein, putative |
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| 20595 |
RA |
PF3D7_1012200 |
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rhoptry associated adhesin |
Mediates erythrocyte invasion through the sialic-acid dependent pathway |
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RP |
PF3D7_1459900 |
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rhoptry protein, putative |
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Rhoptry Neck Proteins |
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| 6867 |
Rh1 |
PF3D7_0402300 |
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reticulocyte binding protein homologue 1 normocyte binding protein 1 |
Binds to red cells via receptor Y |
PfRh family |
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| 6925 |
Rh2a |
PF3D7_1335400 |
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Y |
reticulocyte binding protein 2 homologue a |
Binds to red cells via receptor Z |
PfRh family |
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| 6924 |
Rh2b |
PF3D7_1335300 |
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Y |
reticulocyte binding protein 2 homologue b, ALKBH5 |
Binds to red cells via receptor Z |
PfRh family |
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| 6912 |
Rh3 |
PF3D7_1252400 |
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reticulocyte binding protein homologue 3, pseudogene |
Reticulocyte binding protein homologue 3 |
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| 6875 |
Rh4 |
PF3D7_0424200 |
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Y |
reticulocyte binding protein homologue 4 |
Binds to red cells via Complement Receptor 1 |
PfRh family |
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| 6874 |
Rh5 |
PF3D7_0424100 |
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N |
reticulocyte binding protein homologue 5 |
Binds to red cells via Basigin |
Classed as PfRh family but lacks homology and no transmembrane so likely functionally distinct |
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| 6930 |
PfRON2 |
PF3D7_1452000 |
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ND |
rhoptry neck protein 2 |
Inserted in red cell membrane at invasion, forms complex at tight junction with RON proteins and AMA-1 |
Multi-pass transmembrane protein |
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| 6905 |
PfRON4 |
PF3D7_1116000 |
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ND |
rhoptry neck protein 4 |
Injected into red cell, binds to RON2 in membrane at invasion forms complex at tight junction with RON proteins and AMA-1 |
Binds to AMA1 via hydrophobic groove |
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| 6888 |
PfRON5 |
PF3D7_0817700 |
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ND |
rhoptry neck protein 5 |
Forms complex at tight junction with RON proteins and AMA-1 |
No data |
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| 6861 |
PfRON6 |
PF3D7_0214900 |
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Y |
rhoptry neck protein 6 |
rhoptry neck protein PfRON6; No data. |
Cysteine-rich domain |
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| 6895 |
PfRON12 |
PF3D7_1017100 |
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Y |
rhoptry neck protein 12 |
involve steps in the establishment of the PV |
Growth retardation of KO |
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| 6882 |
PfRON14 |
PF3D7_0613300 |
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ND |
rhoptry protein ROP14 |
rhoptry neck protein PfROP14 |
seven predicted transmembrane domains |
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| 23445 |
AARP |
PF3D7_0423400 |
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ND |
apical asparagine-rich protein AARP |
a role in erythrocyte binding and invasion by the merozoite |
N-terminal signal sequence+ a C-terminal attachment motif such as GPI anchor |
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| 6871 |
Pf34 |
PF3D7_0419700 |
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ND |
apical merozoite protein |
formation of the parasitophorous vacuole |
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| 6911 |
PfRON3 |
PF3D7_1252100 |
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ND |
rhoptry neck protein 3 |
Likely also forms complex at tight junction with other RON proteins and AMA-1 |
No data; Found in DRM |
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| 15831 |
ARNP |
PF3D7_0511600 |
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ND |
apical rhoptry neck protein |
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CERLI1 |
PF3D7_0210600 |
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ND |
cytosolically exposed rhoptry leaflet interacting protein, protein CERLI1 |
cytosolically exposed rhoptry leaflet interacting protein, rhoptry apical surface protein RASP2 |
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GPI-Anchored (known or putative) surface proteins |
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| 6893 |
MSP-1 |
PF3D7_0930300 |
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N |
merozoite surface protein 1 |
Putative Band 3 ligand; C-terminal double EGF domain redundant for divergent molecules: processed SUB1 & 2 |
Two C-terminal EGF domains: compact side by side arrangement; Found in DRM |
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| 6854 |
MSP-2 |
PF3D7_0206800 |
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N |
merozoite surface protein 2 |
Highly polymorphic; likely structural role as surface coat |
Unordered repetitive structure; Found in DRM |
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| 6856 |
MSP-4 |
PF3D7_0207000 |
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N |
merozoite surface protein 4 |
Not known |
C-terminal EGF domain; Found in DRM |
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| 6855 |
MSP-5 |
PF3D7_0206900 |
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Y |
merozoite surface protein 5 |
Not known |
C-terminal EGF domain |
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| 6879 |
MSP-8 |
PF3D7_0502400 |
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Y |
ring-stage membrane protein 1 merozoite surface protein 8 |
Unknown function; No data it is involved in invasion |
C-terminal EGF-like domains, a GPI anchor attachment |
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| 6886 |
MSP-8 |
PF3D7_0730800 |
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ND |
Plasmodium exported protein, unknown function |
Ring stage expressed protein |
No data |
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| 6883 |
MSP-10 |
PF3D7_0620400 |
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N |
merozoite surface protein 10 |
Not known |
C-terminal EGF domain |
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| 6869 |
MAg-1 |
PF3D7_0405200 |
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N |
cytosolically exposed rhoptry leaflet interacting protein 2 |
Not known |
No data |
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| 6880 |
Pf38 |
PF3D7_0508000 |
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Y |
6-cysteine protein |
Potential adhesive protein |
6-Cys domains; Found in DRM |
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| 6926 |
Pf92 |
PF3D7_1364100 |
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Y |
6-cysteine protein p92 |
Not known |
6-cysteine protein; Found in DRM |
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| 6881 |
Pf12 |
PF3D7_0612700 |
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Y |
6-cysteine protein p12 |
Potential adhesive protein |
6-Cys domains; Found in DRM |
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| 6868 |
Pf41 |
PF3D7_0404900 |
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Y |
6-cysteine protein |
Potential adhesive protein; binds Pf12 on merozoite |
6-Cys domains; Found in DRM |
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Peripheral surface or parasitophorous vacuole |
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| 6929 |
Pf113 |
PF3D7_1420700 |
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N |
surface protein P113 |
Not known |
No data; Found in DRM |
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| 6899 |
MSP3/MSP3.1 |
PF3D7_1035400 |
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Y |
merozoite surface protein 3 |
Not known; binds to MSP-1 |
Repetitive and Glutamate-rich |
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| 6900 |
MSP6/MSP3.2 |
PF3D7_1035500 |
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Y |
merozoite surface protein 6 |
Not known; binds to MSP-1 |
Leucine zipper-like C-terminal domain |
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| 6901 |
H101/MSP3.3 |
PF3D7_1035600 |
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Y |
merozoite surface protein |
Not known |
MSP-3 family, leucine zipper-like C-terminal domain |
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| 6903 |
MSP-11 |
PF3D7_1036000 |
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ND |
merozoite surface protein 11 |
Not known; No data it is involved in invasion |
MSP-3 family, leucine zipper-like C-terminal domain |
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| 6904 |
DBLMSP2/MSP3.8 |
PF3D7_1036300 |
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Y |
merozoite surface protein |
Binds to unknown receptor on red cell |
Member of EBL family, DBL and leucine zipper-like domains |
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| 6902 |
DBLMSP2/MSP3.4 |
PF3D7_1035700 |
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Y |
duffy binding-like merozoite surface protein |
Binds to unknown receptor on red cell |
Member of EBL family, DBL and leucine zipper-like domains |
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| 6923 |
MSP-7 |
PF3D7_1335100 |
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Y |
merozoite surface protein 7 |
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No data; Found in DRM |
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| 6922 |
MSRP1 |
PF3D7_1335000 |
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ND |
MSP7-like protein |
Putative MSP1 binding protein, associated with detergent-resistant membrane protein; Not detectable |
MSP-7 like; Found in DRM |
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| 6917 |
MSRP4 |
PF3D7_1334400 |
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ND |
MSP7-like protein |
Putative MSP1 binding protein |
MSP-7 like |
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| 6920 |
MSP-7 like |
PF3D7_1334800 |
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Y |
MSP7-like protein |
Not known; may associate with MSP-1 |
MSP-7 family |
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| 6918 |
MSP-7 like |
PF3D7_1334600 |
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ND |
MSP7-like protein |
Putative MSP1 binding protein; Not detectable |
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| 6916 |
MSP-7 like |
PF3D7_1334300 |
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ND |
MSP7-like protein |
MSP7-like protein; Not detectable |
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| 15832 |
msp7-like protein MSRP6 |
PF3D7_1334500 |
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ND |
MSP7-like protein |
Not known |
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| 6919 |
msp7-like protein |
PF3D7_1334700 |
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ND |
MSP7-like protein |
Not known |
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| 6921 |
MSP-7 like fragment |
PF3D7_1334900 |
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ND |
MSP7-like protein, fragment, pseudogene |
Putative MSP1 binding protein |
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| 6910 |
MSP-9 |
PF3D7_1228600 |
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Y |
merozoite surface protein 9 |
Putative protease |
No data |
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| 6897 |
S-Antigen |
PF3D7_1035200 |
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N |
S-antigen |
Not known; potential immunomodulatory role |
Highly repetitive and diverse protein |
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| 6898 |
GLURP |
PF3D7_1035300 |
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Y |
glutamate-rich protein GLURP |
Not known |
Repetitive Glutamate-rich |
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| 6859 |
SERA3 |
PF3D7_0207800 |
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Y |
serine repeat antigen 3 |
Cysteine protease domain with active site serine |
Cysteine protease domain |
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| 6858 |
SERA4 |
PF3D7_0207700 |
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N |
serine repeat antigen 4 |
Cysteine protease domain with active site serine |
Cysteine protease domain |
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| 6857 |
SERA5 |
PF3D7_0207600 |
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N |
serine repeat antigen 5 |
Cysteine protease domain with active site serine |
Cysteine protease domain |
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| 15833 |
SERA6 |
PF3D7_0207500 |
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N |
serine repeat antigen 6 |
Cysteine protease domain with active site cysteine |
Cysteine protease domain |
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| 25950 |
MSA180 |
PF3D7_1014100 |
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N |
merozoite surface protein msa180 |
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| 30542 |
RSA |
PF3D7_1431400 |
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N |
surface-related antigen SRA |
Has signal peptide and a predicted GPI attachment signal |
Coiled-coil structures |
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| 33896 |
Trx-mero |
PF3D7_1104400 |
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N |
thioredoxin-like mero protein |
specific antibodies blocked invasion |
a mutated sequence character at the Trx domain |
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CERLI1 |
PF3D7_0210600 |
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cytosolically exposed rhoptry leaflet interacting protein, protein CERLI1 |
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