{"gene":"PF3D7_0620400","run_date":"2026-09-08T12:51:26","timeline":{"discoveries":[{"year":2003,"finding":"MSP10 (PF3D7_0620400) contains a signal peptide and GPI-attachment site, is expressed in trophozoites, schizonts, and free merozoites, partitions in the detergent-enriched phase after Triton X-114 fractionation (consistent with GPI anchoring), and localizes to the surfaces of these stages in an apical distribution. Antisera to C-terminal fragments detect two bands (80 kDa and 36 kDa) in parasite lysates, suggesting processing similar to MSP1 and MSP8 but with fewer cleavage events.","method":"RT-PCR, immunoblot of stage-specific samples, Triton X-114 phase fractionation, immunofluorescence with stage-specific antisera","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (fractionation, immunofluorescence, immunoblot) in a single focused study establishing GPI anchoring, surface localization, and processing","pmids":["12615336"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"finding":"Proteomic analysis using radioactive glucosamine labeling confirmed GPI anchoring on MSP10 (PF3D7_0620400) in the schizont/merozoite stage. MSP10 was identified as one of 11 GPI-anchored proteins comprising ~94% of the GPI-anchored schizont/merozoite proteome.","method":"Proteomics with radioactive glucosamine labeling of GPI-anchored proteins","journal":"Molecular & cellular proteomics : MCP","confidence":"High","confidence_rationale":"Tier 1 / Strong — direct biochemical labeling of GPI modification confirmed experimentally, replicated the earlier Triton X-114 fractionation result with an orthogonal method","pmids":["16603573"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2005,"finding":"Synthetic peptides spanning the MSP10 (PF3D7_0620400) sequence identified three High Activity Binding Peptides (HABPs) that bind human erythrocyte membrane receptors in a saturable manner sensitive to neuraminidase, trypsin, and chymotrypsin treatment. Some HABPs specifically recognized a 50 kDa erythrocyte membrane protein. HABPs inhibited P. falciparum merozoite invasion of erythrocytes in vitro by up to ~70%.","method":"Synthetic peptide-erythrocyte binding assays, enzyme sensitivity assays, in vitro invasion inhibition assays","journal":"Biochimie","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct erythrocyte binding assays with enzyme sensitivity controls and functional inhibition readout, single lab but multiple orthogonal approaches","pmids":["15820753"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"PfGAMA co-immunoprecipitates with MSP10 (PF3D7_0620400), and this interaction was validated as direct by surface plasmon resonance. The N-terminal region of MSP10 (designated R1) is critical for the PfGAMA/MSP10 interaction. Antibodies against the MSP10 R1 region inhibit P. falciparum parasite growth in culture.","method":"Co-immunoprecipitation, surface plasmon resonance, growth inhibition assays","journal":"Frontiers in immunology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — direct protein-protein interaction confirmed by two orthogonal methods (co-IP and SPR) with functional consequence (growth inhibition), single lab","pmids":["31824483"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"Human monoclonal antibodies targeting the EGF-like domains (domain 1 or domain 2) of MSP10 (PF3D7_0620400) inhibit P. falciparum 3D7A growth in vitro, with EC50 values in the mg/ml range, demonstrating that the EGF-like folds are accessible targets on the parasite surface.","method":"Growth inhibition assays (GIA) with recombinant human monoclonal antibodies; affinity measured by surface plasmon resonance and ELISA","journal":"Malaria journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional GIA with characterized antibodies targeting defined domains, single lab, multiple antibody clones tested","pmids":["26174014"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"3D7A"}]},{"year":2021,"finding":"The recombinant C-terminal region of P. vivax MSP10 (rPvMSP10-C, containing the EGF-like domains) binds to adult human reticulocytes but not to normocytes. Two 20-residue peptides derived from the EGF-like domains (residues 388-407 and 415-434) inhibit rPvMSP10-C binding to reticulocytes and inhibit rosette formation with enriched target cells.","method":"Protein-cell binding assays (two independent methods), peptide competition/inhibition assays, rosette formation assay with enriched reticulocytes","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct protein-cell binding confirmed by two orthogonal assays with peptide competition controls, single lab, P. vivax ortholog","pmids":["33562650"],"is_preprint":false,"attribution":[{"species":"Plasmodium vivax","strain":""}]}],"current_model":"MSP10 (PF3D7_0620400) is a GPI-anchored merozoite surface protein with two C-terminal EGF-like domains that localizes apically on the merozoite surface (confirmed by Triton X-114 fractionation and proteomics), undergoes proteolytic processing from ~80 kDa to a ~36 kDa C-terminal fragment, directly interacts with PfGAMA via its N-terminal R1 region (confirmed by co-IP and surface plasmon resonance), and participates in erythrocyte invasion—as evidenced by peptide-based binding to a 50 kDa erythrocyte receptor and growth inhibition by antibodies targeting its EGF-like domains."},"narrative":{"mechanistic_narrative":"MSP10 (PF3D7_0620400) is a GPI-anchored merozoite surface protein of Plasmodium falciparum that participates in erythrocyte invasion during the blood stage [PMID:12615336, PMID:15820753]. It carries a signal peptide and a C-terminal GPI-attachment site, partitions into the detergent phase upon Triton X-114 fractionation, and is displayed in an apical distribution on the surface of trophozoites, schizonts, and free merozoites [PMID:12615336]; GPI modification was independently confirmed by glucosamine metabolic labeling, placing MSP10 among the GPI-anchored schizont/merozoite proteome [PMID:16603573]. The protein undergoes limited proteolytic processing, detected as ~80 kDa and ~36 kDa species [PMID:12615336]. Functionally, MSP10 engages the erythrocyte surface: synthetic peptides spanning the sequence bind human erythrocytes in a saturable, enzyme-sensitive manner, recognize a 50 kDa erythrocyte membrane protein, and inhibit merozoite invasion [PMID:15820753]. Its two C-terminal EGF-like domains are surface-accessible targets whose antibodies inhibit parasite growth in vitro [PMID:26174014], and MSP10 directly binds the invasion ligand PfGAMA through its N-terminal R1 region, with anti-R1 antibodies inhibiting growth [PMID:31824483]. In the ortholog P. vivax, the C-terminal EGF-containing region binds reticulocytes but not normocytes, a binding blocked by EGF-domain-derived peptides [PMID:33562650].","teleology":[{"year":2003,"claim":"Establishing MSP10 as a bona fide surface protein was the first step, defining where and when it acts during the blood stage and whether it is membrane-attached.","evidence":"RT-PCR, stage-specific immunoblot, Triton X-114 phase fractionation, and immunofluorescence in P. falciparum","pmids":["12615336"],"confidence":"Medium","gaps":["Functional consequence of the 80 kDa to 36 kDa processing not defined","Protease responsible for cleavage not identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2005,"claim":"To ask whether MSP10 contributes to invasion mechanistically, peptides were tested for erythrocyte binding, showing the protein engages a specific host receptor and that this engagement is functionally required.","evidence":"Synthetic peptide-erythrocyte binding assays with neuraminidase/trypsin/chymotrypsin sensitivity and in vitro invasion inhibition in P. falciparum","pmids":["15820753"],"confidence":"Medium","gaps":["The 50 kDa erythrocyte receptor was not molecularly identified","Peptide binding may not reflect binding by the full-length folded protein"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"claim":"Whether the earlier Triton X-114 result truly reflected GPI anchoring was resolved by direct biochemical labeling, confirming MSP10 as a GPI-anchored member of the merozoite surface proteome.","evidence":"Radioactive glucosamine labeling and proteomics in P. falciparum schizonts/merozoites","pmids":["16603573"],"confidence":"High","gaps":["Does not address MSP10's functional role or partners"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"To test whether MSP10's structural domains are exposed and vaccine-relevant, monoclonal antibodies against each EGF-like domain were tested, showing the folds are accessible on the parasite surface and functionally targetable.","evidence":"Growth inhibition assays with recombinant human monoclonal antibodies against EGF domains 1 and 2 in P. falciparum 3D7A, with SPR/ELISA affinity measurement","pmids":["26174014"],"confidence":"Medium","gaps":["EC50 values in the mg/ml range indicate weak inhibitory potency","Mechanism by which anti-EGF antibodies block invasion not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":"3D7A"}]},{"year":2019,"claim":"Placing MSP10 in a molecular invasion complex, this work identified a direct binding partner and the region mediating the interaction, linking MSP10 to the PfGAMA invasion ligand.","evidence":"Co-immunoprecipitation, surface plasmon resonance, and growth inhibition assays in P. falciparum","pmids":["31824483"],"confidence":"High","gaps":["Functional role of the MSP10-PfGAMA complex during invasion not defined","Whether the R1-PfGAMA interaction is required for erythrocyte receptor engagement unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Extending the host-binding role to a second species, the P. vivax ortholog's C-terminal EGF region was shown to selectively bind reticulocytes, indicating a conserved receptor-engagement function localized to the EGF domains.","evidence":"Protein-cell binding assays, peptide competition, and rosette formation assays with enriched reticulocytes for P. vivax MSP10","pmids":["33562650"],"confidence":"Medium","gaps":["The reticulocyte receptor for PvMSP10 not identified","Species-divergent cell tropism (reticulocyte-selective in P. vivax) not directly compared to the P. falciparum protein"],"attribution":[{"species":"Plasmodium vivax","strain":""}]},{"year":null,"claim":"The identity of the erythrocyte receptor(s) bound by MSP10 and the functional requirement of MSP10 (and its PfGAMA complex) for invasion in vivo remain open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["The 50 kDa P. falciparum erythrocyte receptor and the P. vivax reticulocyte receptor are unidentified","No genetic knockout/knockdown phenotype for MSP10 in the corpus","How MSP10, PfGAMA, and erythrocyte receptor binding are coordinated during invasion is unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["MSP10-PfGAMA interaction (direct, via MSP10 N-terminal R1 region) [#3]"],"partners":["PFGAMA (DIRECT BINDING PARTNER, VIA MSP10 R1 REGION) [#3]","50 KDA HUMAN ERYTHROCYTE MEMBRANE PROTEIN (BOUND BY MSP10-DERIVED HABPS; UNIDENTIFIED) [#2]"],"other_free_text":["GPI-anchored, apically distributed on trophozoite, schizont, and free merozoite surfaces [#0, #1]","Processed from ~80 kDa to a ~36 kDa C-terminal fragment [#0]","Contains two C-terminal EGF-like domains that are surface-accessible; anti-EGF antibodies inhibit P. falciparum growth [#4]","In P. vivax, the C-terminal EGF-containing region binds reticulocytes but not normocytes [#5]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"16603573","id":"PMC_16603573","title":"Identification and stoichiometry of glycosylphosphatidylinositol-anchored membrane proteins of the human malaria parasite Plasmodium falciparum.","date":"2006","source":"Molecular & cellular proteomics : MCP","url":"https://pubmed.ncbi.nlm.nih.gov/16603573","citation_count":216,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"12615336","id":"PMC_12615336","title":"Apical location of a novel EGF-like domain-containing protein of Plasmodium falciparum.","date":"2003","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/12615336","citation_count":53,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSP10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22414917","id":"PMC_22414917","title":"Evidence of purifying selection on merozoite surface protein 8 (MSP8) and 10 (MSP10) in Plasmodium spp.","date":"2012","source":"Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases","url":"https://pubmed.ncbi.nlm.nih.gov/22414917","citation_count":51,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSP10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"29037202","id":"PMC_29037202","title":"High prevalence of very-low Plasmodium falciparum and Plasmodium vivax parasitaemia carriers in the Peruvian Amazon: insights into local and occupational mobility-related transmission.","date":"2017","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/29037202","citation_count":42,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSP10","PfMSP10","PvMSP10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"15972477","id":"PMC_15972477","title":"Plasmodium falciparum merozoite surface protein 8 is a ring-stage membrane protein that localizes to the parasitophorous vacuole of infected erythrocytes.","date":"2005","source":"Infection and immunity","url":"https://pubmed.ncbi.nlm.nih.gov/15972477","citation_count":33,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSP10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"15883000","id":"PMC_15883000","title":"Identifying and characterising the Plasmodium falciparum merozoite surface protein 10 Plasmodium vivax homologue.","date":"2005","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/15883000","citation_count":27,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["merozoite surface protein 10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21182986","id":"PMC_21182986","title":"Low genetic polymorphism of merozoite surface proteins 7 and 10 in Colombian Plasmodium vivax isolates.","date":"2010","source":"Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases","url":"https://pubmed.ncbi.nlm.nih.gov/21182986","citation_count":21,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSP10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26174014","id":"PMC_26174014","title":"Isolation, production and characterization of fully human monoclonal antibodies directed to Plasmodium falciparum MSP10.","date":"2015","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/26174014","citation_count":19,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSP10","merozoite surface protein 10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"15820753","id":"PMC_15820753","title":"Identifying Plasmodium falciparum merozoite surface protein-10 human erythrocyte specific binding regions.","date":"2005","source":"Biochimie","url":"https://pubmed.ncbi.nlm.nih.gov/15820753","citation_count":19,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSP10","merozoite surface protein 10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24764159","id":"PMC_24764159","title":"Immunogenicity and antigenicity of Plasmodium vivax merozoite surface protein 10.","date":"2014","source":"Parasitology research","url":"https://pubmed.ncbi.nlm.nih.gov/24764159","citation_count":16,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSP10","merozoite surface protein 10","PvMSP10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19782110","id":"PMC_19782110","title":"Vaccination with recombinant Plasmodium vivax MSP-10 formulated in different adjuvants induces strong immunogenicity but no protection.","date":"2009","source":"Vaccine","url":"https://pubmed.ncbi.nlm.nih.gov/19782110","citation_count":16,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSP10","merozoite surface protein 10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31770108","id":"PMC_31770108","title":"Anti-MSP-10 IgG indicates recent exposure to Plasmodium vivax infection in the Peruvian Amazon.","date":"2020","source":"JCI insight","url":"https://pubmed.ncbi.nlm.nih.gov/31770108","citation_count":13,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSP10","merozoite surface protein 10","PfMSP10","PvMSP10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31952523","id":"PMC_31952523","title":"A panel of recombinant proteins from human-infective Plasmodium species for serological surveillance.","date":"2020","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/31952523","citation_count":12,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSP10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27706158","id":"PMC_27706158","title":"Colorimetric Detection of Plasmodium vivax in Urine Using MSP10 Oligonucleotides and Gold Nanoparticles.","date":"2016","source":"PLoS neglected tropical diseases","url":"https://pubmed.ncbi.nlm.nih.gov/27706158","citation_count":11,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSP10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30995911","id":"PMC_30995911","title":"Hospital-derived antibody profiles of malaria patients in Southwest India.","date":"2019","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/30995911","citation_count":11,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSP10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31824483","id":"PMC_31824483","title":"The N-Terminal Region of Plasmodium falciparum MSP10 Is a Target of Protective Antibodies in Malaria and Is Important for PfGAMA/PfMSP10 Interaction.","date":"2019","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/31824483","citation_count":10,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSP10","PfMSP10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31547821","id":"PMC_31547821","title":"Evaluation of Plasmodium falciparum MSP10 and its development as a serological tool for the Peruvian Amazon region.","date":"2019","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/31547821","citation_count":4,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSP10","merozoite surface protein 10","PfMSP10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33562650","id":"PMC_33562650","title":"Two 20-Residue-Long Peptides Derived from Plasmodium vivax Merozoite Surface Protein 10 EGF-Like Domains Are Involved in Binding to Human Reticulocytes.","date":"2021","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/33562650","citation_count":3,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["merozoite surface protein 10","PvMSP10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41128014","id":"PMC_41128014","title":"Extreme Genetic Diversity and Signatures of Balancing Selection in Plasmodium vivax Blood-Stage Antigens.","date":"2026","source":"The Journal of infectious diseases","url":"https://pubmed.ncbi.nlm.nih.gov/41128014","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSP10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27828953","id":"PMC_27828953","title":"Correction: Colorimetric Detection of Plasmodium vivax in Urine Using MSP10 Oligonucleotides and Gold Nanoparticles.","date":"2016","source":"PLoS neglected tropical diseases","url":"https://pubmed.ncbi.nlm.nih.gov/27828953","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSP10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":13639,"output_tokens":1883,"usd":0.034581,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7030,"output_tokens":2972,"usd":0.054725,"stage2_stop_reason":"end_turn"},"total_usd":0.089306,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2003,\n      \"finding\": \"MSP10 (PF3D7_0620400) contains a signal peptide and GPI-attachment site, is expressed in trophozoites, schizonts, and free merozoites, partitions in the detergent-enriched phase after Triton X-114 fractionation (consistent with GPI anchoring), and localizes to the surfaces of these stages in an apical distribution. Antisera to C-terminal fragments detect two bands (80 kDa and 36 kDa) in parasite lysates, suggesting processing similar to MSP1 and MSP8 but with fewer cleavage events.\",\n      \"method\": \"RT-PCR, immunoblot of stage-specific samples, Triton X-114 phase fractionation, immunofluorescence with stage-specific antisera\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (fractionation, immunofluorescence, immunoblot) in a single focused study establishing GPI anchoring, surface localization, and processing\",\n      \"pmids\": [\"12615336\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Proteomic analysis using radioactive glucosamine labeling confirmed GPI anchoring on MSP10 (PF3D7_0620400) in the schizont/merozoite stage. MSP10 was identified as one of 11 GPI-anchored proteins comprising ~94% of the GPI-anchored schizont/merozoite proteome.\",\n      \"method\": \"Proteomics with radioactive glucosamine labeling of GPI-anchored proteins\",\n      \"journal\": \"Molecular & cellular proteomics : MCP\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — direct biochemical labeling of GPI modification confirmed experimentally, replicated the earlier Triton X-114 fractionation result with an orthogonal method\",\n      \"pmids\": [\"16603573\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Synthetic peptides spanning the MSP10 (PF3D7_0620400) sequence identified three High Activity Binding Peptides (HABPs) that bind human erythrocyte membrane receptors in a saturable manner sensitive to neuraminidase, trypsin, and chymotrypsin treatment. Some HABPs specifically recognized a 50 kDa erythrocyte membrane protein. HABPs inhibited P. falciparum merozoite invasion of erythrocytes in vitro by up to ~70%.\",\n      \"method\": \"Synthetic peptide-erythrocyte binding assays, enzyme sensitivity assays, in vitro invasion inhibition assays\",\n      \"journal\": \"Biochimie\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct erythrocyte binding assays with enzyme sensitivity controls and functional inhibition readout, single lab but multiple orthogonal approaches\",\n      \"pmids\": [\"15820753\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"PfGAMA co-immunoprecipitates with MSP10 (PF3D7_0620400), and this interaction was validated as direct by surface plasmon resonance. The N-terminal region of MSP10 (designated R1) is critical for the PfGAMA/MSP10 interaction. Antibodies against the MSP10 R1 region inhibit P. falciparum parasite growth in culture.\",\n      \"method\": \"Co-immunoprecipitation, surface plasmon resonance, growth inhibition assays\",\n      \"journal\": \"Frontiers in immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — direct protein-protein interaction confirmed by two orthogonal methods (co-IP and SPR) with functional consequence (growth inhibition), single lab\",\n      \"pmids\": [\"31824483\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Human monoclonal antibodies targeting the EGF-like domains (domain 1 or domain 2) of MSP10 (PF3D7_0620400) inhibit P. falciparum 3D7A growth in vitro, with EC50 values in the mg/ml range, demonstrating that the EGF-like folds are accessible targets on the parasite surface.\",\n      \"method\": \"Growth inhibition assays (GIA) with recombinant human monoclonal antibodies; affinity measured by surface plasmon resonance and ELISA\",\n      \"journal\": \"Malaria journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional GIA with characterized antibodies targeting defined domains, single lab, multiple antibody clones tested\",\n      \"pmids\": [\"26174014\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7A\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"The recombinant C-terminal region of P. vivax MSP10 (rPvMSP10-C, containing the EGF-like domains) binds to adult human reticulocytes but not to normocytes. Two 20-residue peptides derived from the EGF-like domains (residues 388-407 and 415-434) inhibit rPvMSP10-C binding to reticulocytes and inhibit rosette formation with enriched target cells.\",\n      \"method\": \"Protein-cell binding assays (two independent methods), peptide competition/inhibition assays, rosette formation assay with enriched reticulocytes\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct protein-cell binding confirmed by two orthogonal assays with peptide competition controls, single lab, P. vivax ortholog\",\n      \"pmids\": [\"33562650\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium vivax\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"MSP10 (PF3D7_0620400) is a GPI-anchored merozoite surface protein with two C-terminal EGF-like domains that localizes apically on the merozoite surface (confirmed by Triton X-114 fractionation and proteomics), undergoes proteolytic processing from ~80 kDa to a ~36 kDa C-terminal fragment, directly interacts with PfGAMA via its N-terminal R1 region (confirmed by co-IP and surface plasmon resonance), and participates in erythrocyte invasion—as evidenced by peptide-based binding to a 50 kDa erythrocyte receptor and growth inhibition by antibodies targeting its EGF-like domains.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MSP10 (PF3D7_0620400) is a GPI-anchored merozoite surface protein of Plasmodium falciparum that participates in erythrocyte invasion during the blood stage [#0, #2]. It carries a signal peptide and a C-terminal GPI-attachment site, partitions into the detergent phase upon Triton X-114 fractionation, and is displayed in an apical distribution on the surface of trophozoites, schizonts, and free merozoites [#0]; GPI modification was independently confirmed by glucosamine metabolic labeling, placing MSP10 among the GPI-anchored schizont/merozoite proteome [#1]. The protein undergoes limited proteolytic processing, detected as ~80 kDa and ~36 kDa species [#0]. Functionally, MSP10 engages the erythrocyte surface: synthetic peptides spanning the sequence bind human erythrocytes in a saturable, enzyme-sensitive manner, recognize a 50 kDa erythrocyte membrane protein, and inhibit merozoite invasion [#2]. Its two C-terminal EGF-like domains are surface-accessible targets whose antibodies inhibit parasite growth in vitro [#4], and MSP10 directly binds the invasion ligand PfGAMA through its N-terminal R1 region, with anti-R1 antibodies inhibiting growth [#3]. In the ortholog P. vivax, the C-terminal EGF-containing region binds reticulocytes but not normocytes, a binding blocked by EGF-domain-derived peptides [#5].\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Establishing MSP10 as a bona fide surface protein was the first step, defining where and when it acts during the blood stage and whether it is membrane-attached.\",\n      \"evidence\": \"RT-PCR, stage-specific immunoblot, Triton X-114 phase fractionation, and immunofluorescence in P. falciparum\",\n      \"pmids\": [\"12615336\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of the 80 kDa to 36 kDa processing not defined\", \"Protease responsible for cleavage not identified\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"To ask whether MSP10 contributes to invasion mechanistically, peptides were tested for erythrocyte binding, showing the protein engages a specific host receptor and that this engagement is functionally required.\",\n      \"evidence\": \"Synthetic peptide-erythrocyte binding assays with neuraminidase/trypsin/chymotrypsin sensitivity and in vitro invasion inhibition in P. falciparum\",\n      \"pmids\": [\"15820753\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"The 50 kDa erythrocyte receptor was not molecularly identified\", \"Peptide binding may not reflect binding by the full-length folded protein\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Whether the earlier Triton X-114 result truly reflected GPI anchoring was resolved by direct biochemical labeling, confirming MSP10 as a GPI-anchored member of the merozoite surface proteome.\",\n      \"evidence\": \"Radioactive glucosamine labeling and proteomics in P. falciparum schizonts/merozoites\",\n      \"pmids\": [\"16603573\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not address MSP10's functional role or partners\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"To test whether MSP10's structural domains are exposed and vaccine-relevant, monoclonal antibodies against each EGF-like domain were tested, showing the folds are accessible on the parasite surface and functionally targetable.\",\n      \"evidence\": \"Growth inhibition assays with recombinant human monoclonal antibodies against EGF domains 1 and 2 in P. falciparum 3D7A, with SPR/ELISA affinity measurement\",\n      \"pmids\": [\"26174014\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"EC50 values in the mg/ml range indicate weak inhibitory potency\", \"Mechanism by which anti-EGF antibodies block invasion not defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7A\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Placing MSP10 in a molecular invasion complex, this work identified a direct binding partner and the region mediating the interaction, linking MSP10 to the PfGAMA invasion ligand.\",\n      \"evidence\": \"Co-immunoprecipitation, surface plasmon resonance, and growth inhibition assays in P. falciparum\",\n      \"pmids\": [\"31824483\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional role of the MSP10-PfGAMA complex during invasion not defined\", \"Whether the R1-PfGAMA interaction is required for erythrocyte receptor engagement unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Extending the host-binding role to a second species, the P. vivax ortholog's C-terminal EGF region was shown to selectively bind reticulocytes, indicating a conserved receptor-engagement function localized to the EGF domains.\",\n      \"evidence\": \"Protein-cell binding assays, peptide competition, and rosette formation assays with enriched reticulocytes for P. vivax MSP10\",\n      \"pmids\": [\"33562650\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"The reticulocyte receptor for PvMSP10 not identified\", \"Species-divergent cell tropism (reticulocyte-selective in P. vivax) not directly compared to the P. falciparum protein\"],\n      \"attribution\": [{\"species\": \"Plasmodium vivax\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The identity of the erythrocyte receptor(s) bound by MSP10 and the functional requirement of MSP10 (and its PfGAMA complex) for invasion in vivo remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"The 50 kDa P. falciparum erythrocyte receptor and the P. vivax reticulocyte receptor are unidentified\", \"No genetic knockout/knockdown phenotype for MSP10 in the corpus\", \"How MSP10, PfGAMA, and erythrocyte receptor binding are coordinated during invasion is unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0030246\", \"supporting_discovery_ids\": [2, 5]},\n      {\"term_id\": \"GO:0005515\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0009986\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0046658\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [2, 3, 5]}\n    ],\n    \"complexes\": [\n      \"MSP10-PfGAMA interaction (direct, via MSP10 N-terminal R1 region) [#3]\"\n    ],\n    \"partners\": [\n      \"PfGAMA (direct binding partner, via MSP10 R1 region) [#3]\",\n      \"50 kDa human erythrocyte membrane protein (bound by MSP10-derived HABPs; unidentified) [#2]\"\n    ],\n    \"other_free_text\": [\n      \"GPI-anchored, apically distributed on trophozoite, schizont, and free merozoite surfaces [#0, #1]\",\n      \"Processed from ~80 kDa to a ~36 kDa C-terminal fragment [#0]\",\n      \"Contains two C-terminal EGF-like domains that are surface-accessible; anti-EGF antibodies inhibit P. falciparum growth [#4]\",\n      \"In P. vivax, the C-terminal EGF-containing region binds reticulocytes but not normocytes [#5]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0620400","name":null,"product":"merozoite surface protein 10","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1119600","name":null,"product":"merozoite surface protein 10, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1129800","name":null,"product":"merozoite surface protein 10, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"MSP10","evaluation":null}