Functional annotation of merozoite invasion-related proteins
Compilation assited by Tim Gilberger and Andrew Pierce
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
* 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
Name PfID KO Localization in merozoite before/during invasion Potential function Feature/Structure Transcript
Microneme proteins
6913 EBA-140/BAEBL PF3D7_1301600
Y erythrocyte binding antigen-140 Binds to glycophorin C on red cell EBL family member with DBL domains
6876 EBA-165 PF3D7_0424300 erythrocyte binding antigen-165, pseudogene Psuedogene
6887 EBA-175 PF3D7_0731500
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
6853 EBA-181/JESEBL PF3D7_0102500
Y erythrocyte binding antigen-181 Binds to unknown receptor on red cell EBL family member with DBL domains
6906 AMA-1 PF3D7_1133400
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
6909 PTRAMP/TSP-3 PF3D7_1218000
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.
6896 MTRAP PF3D7_1028700
N merozoite TRAP-like protein Potential motor associated protein; Binds to receptor semiphorin-7A Thrombospondin-like domains
6860 SPATR PF3D7_0212600
secreted protein with altered thrombospondin repeat domain SPATR-like protein, putative; altered thrombospondin domain
6870 ASP/RON1  PF3D7_0405900
ND apical sushi protein Not known; has putative GPI anchor Sushi domains; Found in DRM
6907 SUB2 PF3D7_1136900
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
6889 GAMA PF3D7_0828800
ND GPI-anchored micronemal antigen Binds to red cells; has GPI anchor No data
6866 RIPR PF3D7_0323400
N Rh5 interacting protein forms a complex with PfRh5 in merozoites 10 EGF domains, 87 cysteines
6865 MA PF3D7_0316000
N microneme associated antigen Binds to red cells in a sialic acid independent, chymotrypsin and trypsin resistant manner
6873 CyRPA PF3D7_0423800
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,
CLAMP PF3D7_1030200 N claudin-like apicomplexan microneme protein
Rhoptry proteins
6928 RAP1 PF3D7_1410400
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
6878 RAP2 PF3D7_0501600
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
6877 RAP3 PF3D7_0501500
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
6864 CLAG3.1 PF3D7_0302500
cytoadherence linked asexual protein 3.1 Associated with RhopH2/H3, proposed to be an anion channed. Not involved in invasion Found in DRMs
6892 RhopH2 PF3D7_0929400
high molecular weight rhoptry protein 2 Associated with RhopH1, unknown function; Not involved in invasion Found in DRMs
6914 RhopH2 PF3D7_1320000
rhoptry protein 2, putative golgi protein 1 Rhoptry protein 2, putative; Not involved in invasion
6891 RhopH3 PF3D7_0905400
high molecular weight rhoptry protein 3 Associated with RhopH1, unknown function; Not involved in invasion Found in DRMs
6863 CLAG3.2 PF3D7_0302200
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
6927 Rhop148 PF3D7_1366400
rhoptry protein RHOP148 Unknown function
6890 CLAG8 PF3D7_0831600
cytoadherence linked asexual protein 8 cytoadherence linked asexual protein 8; No data on invasion
6862 CLAG2 PF3D7_0220800
cytoadherence linked asexual protein 2 Cytoadherence linked asexual protein 2, Clag2  No data on invasion
6894 CLAG9 PF3D7_0935800
cytoadherence linked asexual protein 9 Cytoadherence linked asexual protein 9, Clag9; No data on invasion
6884 RAMA  PF3D7_0707300
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
28055 Rhoptry protein PF3D7_1466900 conserved plasmodium protein, unknown function Rhoptry protein, putative
6885 RALP1 PF3D7_0722200
N rhoptry-associated leucine zipper-like protein 1 Rhoptry-associated leucine zipper-like protein 1; Not involved in invasion
6915 Rab11A PF3D7_1320600
ras-related protein Rab-11A Has a regulatory role in both parasite growth and invasion Glutathionylated and palmitoylated
20595 RA PF3D7_1012200
rhoptry associated adhesin Mediates erythrocyte invasion through the sialic-acid dependent pathway
Rhoptry Neck Proteins
6867 Rh1 PF3D7_0402300
reticulocyte binding protein homologue 1 normocyte binding protein 1 Binds to red cells via receptor Y PfRh family
6925 Rh2a PF3D7_1335400
Y reticulocyte binding protein 2 homologue a Binds to red cells via receptor Z PfRh family
6924 Rh2b PF3D7_1335300
Y reticulocyte binding protein 2 homologue b, ALKBH5 Binds to red cells via receptor Z PfRh family
6912 Rh3 PF3D7_1252400
reticulocyte binding protein homologue 3, pseudogene Reticulocyte binding protein homologue 3
6875 Rh4 PF3D7_0424200
Y reticulocyte binding protein homologue 4 Binds to red cells via Complement Receptor 1 PfRh family
6874 Rh5 PF3D7_0424100
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
6930 PfRON2 PF3D7_1452000
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
6905 PfRON4 PF3D7_1116000
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
6888 PfRON5 PF3D7_0817700
ND rhoptry neck protein 5 Forms complex at tight junction with RON proteins and AMA-1 No data
6861 PfRON6 PF3D7_0214900
Y rhoptry neck protein 6 rhoptry neck protein PfRON6; No data. Cysteine-rich domain
6895 PfRON12 PF3D7_1017100
Y rhoptry neck protein 12 involve steps in the establishment of the PV Growth retardation of KO
6882 PfRON14 PF3D7_0613300
ND rhoptry protein ROP14 rhoptry neck protein PfROP14 seven predicted transmembrane domains
23445 AARP PF3D7_0423400
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
6871 Pf34 PF3D7_0419700
ND apical merozoite protein formation of the parasitophorous vacuole
6911 PfRON3 PF3D7_1252100
ND rhoptry neck protein 3 Likely also forms complex at tight junction with other RON proteins and AMA-1 No data; Found in DRM
15831 ARNP PF3D7_0511600
ND apical rhoptry neck protein
GPI-Anchored (known or putative) surface proteins
6893 MSP-1 PF3D7_0930300
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
6854 MSP-2 PF3D7_0206800
N merozoite surface protein 2 Highly polymorphic; likely structural role as surface coat Unordered repetitive structure; Found in DRM
6856 MSP-4 PF3D7_0207000
N merozoite surface protein 4 Not known C-terminal EGF domain; Found in DRM
6855 MSP-5 PF3D7_0206900
Y merozoite surface protein 5 Not known C-terminal EGF domain
6879 MSP-8 PF3D7_0502400
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
6886 MSP-8 PF3D7_0730800 ND Plasmodium exported protein, unknown function Ring stage expressed protein No data
6883 MSP-10 PF3D7_0620400
N merozoite surface protein 10 Not known C-terminal EGF domain
6869 MAg-1 PF3D7_0405200
N ag-1 blood stage membrane protein homologue Not known No data
6880 Pf38 PF3D7_0508000
Y 6-cysteine protein Potential adhesive protein 6-Cys domains; Found in DRM
6926 Pf92 PF3D7_1364100
Y 6-cysteine protein Not known 6-cysteine protein; Found in DRM
6881 Pf12 PF3D7_0612700
Y 6-cysteine protein p12 Potential adhesive protein 6-Cys domains; Found in DRM
6868 Pf41  PF3D7_0404900
Y 6-cysteine protein Potential adhesive protein; binds Pf12 on merozoite 6-Cys domains; Found in DRM
Peripheral surface or parasitophorous vacuole
6929 Pf113  PF3D7_1420700
N surface protein P113 Not known No data; Found in DRM
6899 MSP3/MSP3.1 PF3D7_1035400
Y merozoite surface protein 3 Not known; binds to MSP-1 Repetitive and Glutamate-rich
6900 MSP6/MSP3.2 PF3D7_1035500
Y merozoite surface protein 6 Not known; binds to MSP-1 Leucine zipper-like C-terminal domain
6901 H101/MSP3.3 PF3D7_1035600
Y merozoite surface protein Not known MSP-3 family, leucine zipper-like C-terminal domain
6903 MSP-11 PF3D7_1036000
ND merozoite surface protein 11 Not known; No data it is involved in invasion MSP-3 family, leucine zipper-like C-terminal domain
6904 DBLMSP2/MSP3.8 PF3D7_1036300
Y merozoite surface protein Binds to unknown receptor on red cell Member of EBL family, DBL and leucine zipper-like domains
6902 DBLMSP2/MSP3.4 PF3D7_1035700
Y duffy binding-like merozoite surface protein Binds to unknown receptor on red cell Member of EBL family, DBL and leucine zipper-like domains
6923 MSP-7 PF3D7_1335100
Y merozoite surface protein 7 No data; Found in DRM
6922 MSRP1 PF3D7_1335000
ND MSP7-like protein Putative MSP1 binding protein, associated with detergent-resistant membrane protein; Not detectable MSP-7 like; Found in DRM
6917 MSRP4 PF3D7_1334400 ND MSP7-like protein Putative MSP1 binding protein MSP-7 like
6920 MSP-7 like PF3D7_1334800
Y MSP7-like protein Not known; may associate with MSP-1 MSP-7 family
6918 MSP-7 like PF3D7_1334600 ND MSP7-like protein Putative MSP1 binding protein; Not detectable
6916 MSP-7 like PF3D7_1334300
ND MSP7-like protein MSP7-like protein; Not detectable
15832 msp7-like protein MSRP6 PF3D7_1334500
ND MSP7-like protein Not known
6919 msp7-like protein PF3D7_1334700
ND MSP7-like protein Not known
6921 MSP-7 like fragment PF3D7_1334900 ND MSP7-like protein, fragment, pseudogene Putative MSP1 binding protein
6910 MSP-9 PF3D7_1228600
Y merozoite surface protein 9 Putative protease No data
6897 S-Antigen PF3D7_1035200
N S-antigen Not known; potential immunomodulatory role Highly repetitive and diverse protein
6898 GLURP PF3D7_1035300
Y glutamate-rich protein GLURP Not known Repetitive Glutamate-rich
6859 SERA3 PF3D7_0207800
Y serine repeat antigen 3 Cysteine protease domain with active site serine Cysteine protease domain
6858 SERA4 PF3D7_0207700
N serine repeat antigen 4 Cysteine protease domain with active site serine Cysteine protease domain
6857 SERA5 PF3D7_0207600
N serine repeat antigen 5 Cysteine protease domain with active site serine Cysteine protease domain
15833 SERA6 PF3D7_0207500
N serine repeat antigen 6 Cysteine protease domain with active site cysteine Cysteine protease domain
25950 MSA180 PF3D7_1014100 N merozoite surface protein msa180
30542 RSA PF3D7_1431400
N surface-related antigen SRA Has signal peptide and a predicted GPI attachment signal Coiled-coil structures
33896 Trx-mero PF3D7_1104400
N thioredoxin-like mero protein specific antibodies blocked invasion a mutated sequence character at the Trx domain
Online articles related to Functional annotation of merozoite invasion-related proteins retrieved from PubMed