Table 1.

The invasion-related proteins of the P. falciparum merozoite

Name PlasmoDB accession number Genetic knockout Localization in merozoite before/during invasion Potential function Feature/structure 
GPI-anchored MSPs      
MSP-1 PF3D7_0930300 Surface/complex shed during invasion with MSP1/19 EGF C-terminal domain retained in PV of ring stage Putative Band 3 ligand; C-terminal double EGF domain redundant for divergent molecules: processed SUB1 and -2 Two C-terminal EGF domains: compact side by side arrangement 
MSP-2 PF3D7_0206800 Surface Highly polymorphic; likely structural role as surface coat Unordered repetitive structure 
MSP-5 PF3D7_0207000 Surface Not known C-terminal EGF domain 
MSP-4 PF3D7_0206900.1 Surface Not known C-terminal EGF domain 
MSP-10 PF3D7_0620400 Surface Not known C-terminal EGF domain 
Pf12 PF3D7_0612700 Surface/shed Potential adhesive protein 6-Cys domains 
Pf38 PF3D7_0508000 Surface/shed Potential adhesive protein 6-Cys domains 
Pf92 PF3D7_1364100 Surface/shed Not known Cys-rich protein 
Peripheral surface proteins      
Pf113 PF3D7_1420700 Surface/shed Not known No data 
MSP-9 (ABRA) PF3D7_1228600 Surface/shed Putative protease No data 
S-antigen PF3D7_1035200 Secreted into PV of schizont and released on egress Not known; potential immunomodulatory role Highly repetitive and diverse protein 
GLURP PF3D7_1035300 Secreted into PV of schizont and released on egress Not known Repetitive Glutamate-rich 
MSP-3 PF3D7_1035400 Surface/shed Not known; binds to MSP-1 Repetitive and Glutamate-rich 
MSP-6 PF3D7_1035500 Surface/shed Not known; binds to MSP-1 Leucine zipper-like C-terminal domain 
H101 (MSP-11) PF3D7_1035600 Surface/shed Not known MSP-3 family, leucine zipper-like C-terminal domain 
H103 PF3D7_1035900 Surface/shed Not known MSP-3 family, leucine zipper-like C-terminal domain 
MSP-7 PF3D7_1335100 Surface/shed Associates with MSP-1, gene knockout in P. berghei shows important in invasion of mature erythrocytes No data 
MSP-7-like (MSRP2) PF3D7_1334800 Surface/shed Not known; may associate with MSP-1 MSP-7 family 
MSPDBL-1 PF3D7_1036300 Surface/shed Binds to unknown receptor on red cell Member of EBL family, DBL and leucine zipper-like domains 
MSPDBL-2 PF3D7_1035700 Surface/shed Binds to unknown receptor on red cell Member of EBL family, DBL and leucine zipper-like domains 
SERA3 PF3D7_0207800 Secreted into PV of schizont and released on egress Cysteine protease domain with active site serine Cysteine protease domain 
SERA4 PF3D7_0207700 Most secreted into PV of schizont and released on egress Cysteine protease domain with active site serine Cysteine protease domain 
SERA5 PF3D7_0207600 Secreted into PV of schizont and released on egress Cysteine protease domain with active site serine Cysteine protease domain 
SERA6 PF3D7_0207500 Most secreted into PV of schizont and released on egress Cysteine protease domain with active site cysteine Cysteine protease domain 
Pf41 PF3D7_0404900 Surface/shed Potential adhesive protein; binds Pf12 on merozoite 6-Cys domains 
Plasma membrane proteins      
ROM1 PF3D7_1114100 Mononeme (proposed new apical organelle) or microneme/surface Rhomboid protease; cleaves AMA1, MAEBL, EBLs, PfRh proteins; likely role after invasion in PV formation Multipass transmembrane protein 
ROM4 PF3D7_0506900 ND Surface/shed Rhomboid protease; cleaves AMA1, MTRAP, EBL, and PfRh proteins in transmembrane to allow shedding during invasion Multipass transmembrane protein 
Microneme proteins      
AMA 1 PF3D7_1133400 Micronemes/surface and binds to RON2 that has been inserted into red cell membrane and tracks with tight junction Released on merozoite surface; binds RON complex; potential ligand for McLeod antigen, phosphorylation of cytoplasmic tail essential, may be involved in signaling PAN (plasminogen, apple, nematode) motifs 
EBA-175 PF3D7_0731500 Ya Micronemes/surface and binds to glycophorin A Binds to glycophorin A, likely signaling role for invasion EBL family with DBL domains; “handshake” association between region II dimers creates groove for glycophorin A binding 
EBA-181/JESEBL PF3D7_0102500 Micronemes/surface and binds to unknown receptor Binds to unknown receptor on red cell EBL family member with DBL domains 
EBA-140/BAEBL PF3D7_1301600 Micronemes/surface and binds to glycophorin C Binds to glycophorin C on red cell EBL family member with DBL domains 
EBL-1 PF3D7_1371600 No data Binds to glycophorin B, nonfunctional because of mutations causing truncated protein EBL family member with DBL domains 
PTRAMP PF3D7_1218000 ND  Not known; cleaved by SUB2 on merozoite surface Long extended structure 
PfRipr PF3D7_0323400 Micronemes/surface and binds to PfRh5 Binds to PfRh5 10 EGF domains, 87 cysteines 
MTRAP PF3D7_1028700 Micronemes/PV Potential motor-associated protein Thrombospondin-like domains 
PTRAMP PF3D7_1218000 Micronemes/surface Potential motor-associated protein Thrombospondin-like domains 
SPATR PF3D7_0405900 ND Micronemes/surface Not known for blood stages Thrombospondin-like domains 
GAMA PF3D7_0828800 ND Micronemes/surface Binds to red cells; has GPI anchor No data 
SUB2 PF3D7_1136900 Micronemes/PV Protease that processes MSP-1, MSP-6, MSP-7, AMA1, PTRAMP and other proteins to prime merozoite for invasion Subtilisin-like serine protease 
Exoneme proteins      
SUB1 PF3D7_0507500 Exonemes/PV Protease that processes MSP-1, MSP-6, MSP-7, AMA1, RAP1, MSRP2 and SERAs to prime merozoite for invasion Subtilisin-like serine protease 
Rhoptry neck proteins      
PfRh1 PF3D7_0402300 Ya Rhoptry neck/surface Binds to red cells via receptor Y PfRh family 
PfRh2a PF3D7_1335400 Rhoptry neck/surface Binds to red cells via receptor Z PfRh family 
PfRh2b PF3D7_1335300 Rhoptry neck/surface Binds to red cells via receptor Z PfRh family 
PfRh4 PF3D7_0424200 Rhoptry neck/surface Binds to red cells via complement receptor 1 PfRh family 
PfRh5 PF3D7_0424100 Rhoptry neck/surface forms complex with Ripr Binds to red cells via Basigin Classed as PfRh family but lacks homology and no transmembrane so likely functionally distinct 
RON2 PF3D7_1452000 ND Rhoptry neck/into red cell membrane Inserted in red cell membrane at invasion, forms complex at tight junction with RON proteins and AMA-1 Multipass transmembrane protein 
RON3 PF3D7_1252100 ND Rhoptry neck/into red cell Likely also forms complex at tight junction with other RON proteins and AMA-1 No data 
RON4 PF3D7_1116000 ND Rhoptry neck/into red cell Injected into red cell, binds to RON2 and forms a complex at tight junction with RON proteins and AMA-1 Binds to AMA1 via hydrophobic groove 
RON5 PF3D7_0817700 ND Rhoptry neck/into red cell Forms complex at tight junction with RON proteins and AMA-1 No data 
ASP PF3D7_0405900 ND Rhoptry neck/surface Not known; has putative GPI anchor Sushi domains 
Name PlasmoDB accession number Genetic knockout Localization in merozoite before/during invasion Potential function Feature/structure 
GPI-anchored MSPs      
MSP-1 PF3D7_0930300 Surface/complex shed during invasion with MSP1/19 EGF C-terminal domain retained in PV of ring stage Putative Band 3 ligand; C-terminal double EGF domain redundant for divergent molecules: processed SUB1 and -2 Two C-terminal EGF domains: compact side by side arrangement 
MSP-2 PF3D7_0206800 Surface Highly polymorphic; likely structural role as surface coat Unordered repetitive structure 
MSP-5 PF3D7_0207000 Surface Not known C-terminal EGF domain 
MSP-4 PF3D7_0206900.1 Surface Not known C-terminal EGF domain 
MSP-10 PF3D7_0620400 Surface Not known C-terminal EGF domain 
Pf12 PF3D7_0612700 Surface/shed Potential adhesive protein 6-Cys domains 
Pf38 PF3D7_0508000 Surface/shed Potential adhesive protein 6-Cys domains 
Pf92 PF3D7_1364100 Surface/shed Not known Cys-rich protein 
Peripheral surface proteins      
Pf113 PF3D7_1420700 Surface/shed Not known No data 
MSP-9 (ABRA) PF3D7_1228600 Surface/shed Putative protease No data 
S-antigen PF3D7_1035200 Secreted into PV of schizont and released on egress Not known; potential immunomodulatory role Highly repetitive and diverse protein 
GLURP PF3D7_1035300 Secreted into PV of schizont and released on egress Not known Repetitive Glutamate-rich 
MSP-3 PF3D7_1035400 Surface/shed Not known; binds to MSP-1 Repetitive and Glutamate-rich 
MSP-6 PF3D7_1035500 Surface/shed Not known; binds to MSP-1 Leucine zipper-like C-terminal domain 
H101 (MSP-11) PF3D7_1035600 Surface/shed Not known MSP-3 family, leucine zipper-like C-terminal domain 
H103 PF3D7_1035900 Surface/shed Not known MSP-3 family, leucine zipper-like C-terminal domain 
MSP-7 PF3D7_1335100 Surface/shed Associates with MSP-1, gene knockout in P. berghei shows important in invasion of mature erythrocytes No data 
MSP-7-like (MSRP2) PF3D7_1334800 Surface/shed Not known; may associate with MSP-1 MSP-7 family 
MSPDBL-1 PF3D7_1036300 Surface/shed Binds to unknown receptor on red cell Member of EBL family, DBL and leucine zipper-like domains 
MSPDBL-2 PF3D7_1035700 Surface/shed Binds to unknown receptor on red cell Member of EBL family, DBL and leucine zipper-like domains 
SERA3 PF3D7_0207800 Secreted into PV of schizont and released on egress Cysteine protease domain with active site serine Cysteine protease domain 
SERA4 PF3D7_0207700 Most secreted into PV of schizont and released on egress Cysteine protease domain with active site serine Cysteine protease domain 
SERA5 PF3D7_0207600 Secreted into PV of schizont and released on egress Cysteine protease domain with active site serine Cysteine protease domain 
SERA6 PF3D7_0207500 Most secreted into PV of schizont and released on egress Cysteine protease domain with active site cysteine Cysteine protease domain 
Pf41 PF3D7_0404900 Surface/shed Potential adhesive protein; binds Pf12 on merozoite 6-Cys domains 
Plasma membrane proteins      
ROM1 PF3D7_1114100 Mononeme (proposed new apical organelle) or microneme/surface Rhomboid protease; cleaves AMA1, MAEBL, EBLs, PfRh proteins; likely role after invasion in PV formation Multipass transmembrane protein 
ROM4 PF3D7_0506900 ND Surface/shed Rhomboid protease; cleaves AMA1, MTRAP, EBL, and PfRh proteins in transmembrane to allow shedding during invasion Multipass transmembrane protein 
Microneme proteins      
AMA 1 PF3D7_1133400 Micronemes/surface and binds to RON2 that has been inserted into red cell membrane and tracks with tight junction Released on merozoite surface; binds RON complex; potential ligand for McLeod antigen, phosphorylation of cytoplasmic tail essential, may be involved in signaling PAN (plasminogen, apple, nematode) motifs 
EBA-175 PF3D7_0731500 Ya Micronemes/surface and binds to glycophorin A Binds to glycophorin A, likely signaling role for invasion EBL family with DBL domains; “handshake” association between region II dimers creates groove for glycophorin A binding 
EBA-181/JESEBL PF3D7_0102500 Micronemes/surface and binds to unknown receptor Binds to unknown receptor on red cell EBL family member with DBL domains 
EBA-140/BAEBL PF3D7_1301600 Micronemes/surface and binds to glycophorin C Binds to glycophorin C on red cell EBL family member with DBL domains 
EBL-1 PF3D7_1371600 No data Binds to glycophorin B, nonfunctional because of mutations causing truncated protein EBL family member with DBL domains 
PTRAMP PF3D7_1218000 ND  Not known; cleaved by SUB2 on merozoite surface Long extended structure 
PfRipr PF3D7_0323400 Micronemes/surface and binds to PfRh5 Binds to PfRh5 10 EGF domains, 87 cysteines 
MTRAP PF3D7_1028700 Micronemes/PV Potential motor-associated protein Thrombospondin-like domains 
PTRAMP PF3D7_1218000 Micronemes/surface Potential motor-associated protein Thrombospondin-like domains 
SPATR PF3D7_0405900 ND Micronemes/surface Not known for blood stages Thrombospondin-like domains 
GAMA PF3D7_0828800 ND Micronemes/surface Binds to red cells; has GPI anchor No data 
SUB2 PF3D7_1136900 Micronemes/PV Protease that processes MSP-1, MSP-6, MSP-7, AMA1, PTRAMP and other proteins to prime merozoite for invasion Subtilisin-like serine protease 
Exoneme proteins      
SUB1 PF3D7_0507500 Exonemes/PV Protease that processes MSP-1, MSP-6, MSP-7, AMA1, RAP1, MSRP2 and SERAs to prime merozoite for invasion Subtilisin-like serine protease 
Rhoptry neck proteins      
PfRh1 PF3D7_0402300 Ya Rhoptry neck/surface Binds to red cells via receptor Y PfRh family 
PfRh2a PF3D7_1335400 Rhoptry neck/surface Binds to red cells via receptor Z PfRh family 
PfRh2b PF3D7_1335300 Rhoptry neck/surface Binds to red cells via receptor Z PfRh family 
PfRh4 PF3D7_0424200 Rhoptry neck/surface Binds to red cells via complement receptor 1 PfRh family 
PfRh5 PF3D7_0424100 Rhoptry neck/surface forms complex with Ripr Binds to red cells via Basigin Classed as PfRh family but lacks homology and no transmembrane so likely functionally distinct 
RON2 PF3D7_1452000 ND Rhoptry neck/into red cell membrane Inserted in red cell membrane at invasion, forms complex at tight junction with RON proteins and AMA-1 Multipass transmembrane protein 
RON3 PF3D7_1252100 ND Rhoptry neck/into red cell Likely also forms complex at tight junction with other RON proteins and AMA-1 No data 
RON4 PF3D7_1116000 ND Rhoptry neck/into red cell Injected into red cell, binds to RON2 and forms a complex at tight junction with RON proteins and AMA-1 Binds to AMA1 via hydrophobic groove 
RON5 PF3D7_0817700 ND Rhoptry neck/into red cell Forms complex at tight junction with RON proteins and AMA-1 No data 
ASP PF3D7_0405900 ND Rhoptry neck/surface Not known; has putative GPI anchor Sushi domains 

N, knockout attempt unsuccessful; Y, knockout generated; ND, knockout not attempted; PV, parasitophorous vacuole; MSP, merozoite surface protein

a

EBL and PfRh families show overlap in function and, while individually nonessential, overall are essential.

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