{"gene":"PF3D7_1014100","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":2021,"finding":"MSA180 (PF3D7_1014100) is a protein cofactor required for autocatalytic maturation of the egress cysteine protease SERA6: SUB1 cleaves MSA180, and fragments of MSA180 then interact with SERA6 in multimolecular complexes to enable SERA6 autoproteolytic maturation. Genetic ablation of MSA180 blocks β-spectrin cleavage and RBC rupture, phenocopying SERA6 disruption.","method":"Conditional genetic knockout (CRISPR/Cas9 + DiCre), co-immunoprecipitation of multimolecular complexes, biochemical cleavage assays, egress/β-spectrin cleavage assays","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal complex identification, conditional KO with defined cellular phenotype, multiple orthogonal methods (genetics, biochemistry, egress assays), replicated across P. falciparum and P. knowlesi","pmids":["33932049"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium knowlesi","strain":""}]},{"year":2021,"finding":"Conditional deletion of the pfmsa180 gene using CRISPR/Cas9 and DiCre recombinase technology produces a severe egress defect (preventing schizont rupture) but does not significantly impair erythrocyte invasion, establishing that MSA180 is essential for parasite egress but not invasion.","method":"Conditional gene knockout (CRISPR/Cas9 + DiCre recombinase), growth inhibition assays, invasion assays, light microscopy of schizont rupture","journal":"Scientific reports","confidence":"High","confidence_rationale":"Tier 2 / Moderate — clean conditional KO with specific egress phenotype and negative invasion result, two orthogonal functional assays, single lab","pmids":["34584166"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"The C-terminal region of MSA180 (PF3D7_1014100) contains an erythrocyte-binding domain that specifically interacts with human erythrocyte integrin-associated protein CD47, as demonstrated by surface plasmon resonance; antibodies against this C-terminal region inhibit parasite invasion in growth inhibition assays.","method":"Surface plasmon resonance (binding assay), growth inhibition assay, recombinant protein expression (wheat germ cell-free system), rabbit antibody generation","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding measured by SPR plus functional inhibition assay, single lab, two orthogonal methods","pmids":["30976034"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"The P. vivax ortholog of MSA180 (PvMSA180, PVX_094920) localizes to the merozoite surface at the schizont stage, as determined by immunofluorescence assay using antibodies against PvMSA180 domains D1 and D4.","method":"Immunofluorescence assay (IFA) with domain-specific antibodies on schizont-stage parasites","journal":"Malaria journal","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single localization method (IFA), single lab, no functional consequence directly linked","pmids":["28351409"],"is_preprint":false,"attribution":[{"species":"Plasmodium vivax","strain":""}]},{"year":2026,"finding":"Using a cell-free in vitro reconstitution system, the strict requirement for MSA180 fragments in SUB1-triggered SERA6 autoproteolytic maturation was confirmed: in the absence of MSA180, SERA6 maturation does not occur, validating MSA180 as an essential cofactor in the egress pathway.","method":"Cell-free in vitro reconstitution of SERA6 maturation, synthetic peptide substrate cleavage assay, small molecule inhibitor testing","journal":"Frontiers in parasitology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro reconstitution system directly confirming MSA180 requirement, multiple biochemical methods, corroborates prior genetic findings from a separate lab","pmids":["42662414"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"MSA180 (PF3D7_1014100) is a merozoite surface/parasitophorous vacuole protein that acts as an essential cofactor for egress: SUB1 cleaves MSA180 and the resulting fragments interact with SERA6 in multimolecular complexes to enable SERA6 autocatalytic maturation, which in turn degrades β-spectrin to drive red blood cell rupture; genetic ablation of MSA180 blocks egress without impairing invasion, and its C-terminal region also directly binds the erythrocyte surface protein CD47."},"narrative":{"mechanistic_narrative":"MSA180 (PF3D7_1014100) is a merozoite-associated protein that functions as an essential cofactor for parasite egress from infected erythrocytes [PMID:33932049, PMID:34584166]. During schizont maturation, the subtilisin-like protease SUB1 cleaves MSA180, and the resulting MSA180 fragments assemble into multimolecular complexes with the cysteine protease SERA6, a step strictly required to enable SERA6 autoproteolytic maturation [PMID:33932049]; in vitro reconstitution confirmed that SERA6 maturation does not proceed in the absence of MSA180 fragments [PMID:42662414]. Because mature SERA6 drives β-spectrin cleavage and red blood cell rupture, conditional deletion of MSA180 blocks β-spectrin cleavage and schizont rupture, phenocopying SERA6 disruption, while leaving erythrocyte invasion intact — establishing MSA180 as essential for egress but not invasion [PMID:33932049, PMID:34584166]. Independently, the C-terminal region of MSA180 contains an erythrocyte-binding domain that binds human CD47 by surface plasmon resonance, and antibodies against this region inhibit parasite growth [PMID:30976034]. The findings are consistent across P. falciparum and P. knowlesi for the egress role [PMID:33932049], and the P. vivax ortholog localizes to the merozoite surface at the schizont stage [PMID:28351409].","teleology":[{"year":2017,"claim":"Before functional data existed, it was unknown where the MSA180 protein resides during the blood stage; establishing merozoite-surface localization of the P. vivax ortholog placed the protein at the host-parasite interface.","evidence":"Immunofluorescence with domain-specific antibodies on schizont-stage P. vivax parasites","pmids":["28351409"],"confidence":"Medium","gaps":["Localization shown only for the P. vivax ortholog, not directly for PF3D7_1014100","Single method (IFA) with no functional consequence tested","Does not distinguish merozoite surface from parasitophorous vacuole membrane"],"attribution":[{"species":"Plasmodium vivax","strain":""}]},{"year":2019,"claim":"To probe a possible invasion role, the question was whether MSA180 engages a host erythrocyte receptor; the C-terminal region was shown to bind human CD47 and to be targeted by growth-inhibitory antibodies.","evidence":"Surface plasmon resonance binding assay, recombinant protein from wheat germ cell-free system, and growth inhibition with rabbit antibodies in P. falciparum","pmids":["30976034"],"confidence":"Medium","gaps":["CD47 binding not linked to a defined step in the parasite life cycle by genetic evidence","Functional inhibition by antibody does not distinguish invasion from egress blockade","Single lab, no reciprocal validation of the interaction in situ"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"The central mechanistic question — what MSA180 actually does — was answered by showing it is a SUB1-cleaved cofactor whose fragments enable SERA6 autocatalytic maturation, coupling MSA180 to β-spectrin cleavage and RBC rupture.","evidence":"Conditional CRISPR/Cas9+DiCre knockout, co-immunoprecipitation of multimolecular complexes, and β-spectrin cleavage/egress assays in P. falciparum and P. knowlesi","pmids":["33932049"],"confidence":"High","gaps":["Structural basis of MSA180 fragment–SERA6 complex assembly not resolved","Stoichiometry and identity of other complex members not fully defined","Relationship between the egress cofactor role and the CD47-binding activity unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium knowlesi","strain":""}]},{"year":2021,"claim":"To separate the egress function from a potential invasion function, conditional deletion demonstrated a severe egress/rupture defect with no significant impairment of invasion, defining the specific step at which MSA180 is required.","evidence":"Conditional gene knockout (CRISPR/Cas9+DiCre), growth and invasion assays, and microscopy of schizont rupture in P. falciparum","pmids":["34584166"],"confidence":"High","gaps":["Does not reconcile the retained invasion capacity with the reported CD47-binding/invasion-inhibition activity","Molecular event downstream of egress arrest not detailed in this study"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"claim":"Whether MSA180 acts directly on SERA6 maturation or indirectly was resolved by reconstituting the reaction cell-free, confirming a strict requirement for MSA180 fragments in SUB1-triggered SERA6 autoproteolysis.","evidence":"Cell-free in vitro reconstitution of SERA6 maturation with synthetic peptide substrate cleavage and inhibitor testing in P. falciparum","pmids":["42662414"],"confidence":"High","gaps":["Precise MSA180 fragment(s) responsible and their binding interface not defined","Structure of the reconstituted complex not determined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unresolved how the CD47-binding activity of the MSA180 C-terminus relates mechanistically to its established, genetically-required role as a SERA6 maturation cofactor during egress.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No genetic test linking CD47 binding to a defined phenotype","No structural model of MSA180 or its fragment–SERA6 complex","Whether the same molecule performs both functions sequentially is unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["MSA180 fragment–SERA6 multimolecular complex [#0, #4]"],"partners":["SERA6 (CYSTEINE PROTEASE; INTERACTS WITH SUB1-CLEAVED MSA180 FRAGMENTS) [#0, #4]","SUB1 (SUBTILISIN-LIKE PROTEASE; CLEAVES MSA180) [#0]","CD47 / HUMAN ERYTHROCYTE INTEGRIN-ASSOCIATED PROTEIN (BOUND BY MSA180 C-TERMINAL REGION) [#2]"],"other_free_text":["MSA180 is required for egress but dispensable for invasion; conditional knockout blocks β-spectrin cleavage and RBC rupture, phenocopying SERA6 disruption [#0, #1].","Egress cofactor role demonstrated in P. falciparum and P. knowlesi [#0]; merozoite-surface localization shown for the P. vivax ortholog [#3].","The C-terminal erythrocyte-binding region is a target of growth-inhibitory antibodies [#2]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"33932049","id":"PMC_33932049","title":"Autocatalytic activation of a malarial egress protease is druggable and requires a protein cofactor.","date":"2021","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/33932049","citation_count":18,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSA180"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30976034","id":"PMC_30976034","title":"PfMSA180 is a novel Plasmodium falciparum vaccine antigen that interacts with human erythrocyte integrin associated protein (CD47).","date":"2019","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/30976034","citation_count":18,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfMSA180"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28351409","id":"PMC_28351409","title":"Identification of a novel merozoite surface antigen of Plasmodium vivax, PvMSA180.","date":"2017","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/28351409","citation_count":13,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSA180","PvMSA180"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34584166","id":"PMC_34584166","title":"Genetic disruption of Plasmodium falciparum Merozoite surface antigen 180 (PfMSA180) suggests an essential role during parasite egress from erythrocytes.","date":"2021","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/34584166","citation_count":7,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSA180","PfMSA180"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42662414","id":"PMC_42662414","title":"Ex vivo maturation of the malaria parasite egress protease SERA6 aids pathway dissection and inhibitor development.","date":"2026","source":"Frontiers in parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/42662414","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSA180"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5514,"output_tokens":1508,"usd":0.019581,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6495,"output_tokens":2798,"usd":0.051213,"stage2_stop_reason":"end_turn"},"total_usd":0.070794,"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\": 2021,\n      \"finding\": \"MSA180 (PF3D7_1014100) is a protein cofactor required for autocatalytic maturation of the egress cysteine protease SERA6: SUB1 cleaves MSA180, and fragments of MSA180 then interact with SERA6 in multimolecular complexes to enable SERA6 autoproteolytic maturation. Genetic ablation of MSA180 blocks β-spectrin cleavage and RBC rupture, phenocopying SERA6 disruption.\",\n      \"method\": \"Conditional genetic knockout (CRISPR/Cas9 + DiCre), co-immunoprecipitation of multimolecular complexes, biochemical cleavage assays, egress/β-spectrin cleavage assays\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal complex identification, conditional KO with defined cellular phenotype, multiple orthogonal methods (genetics, biochemistry, egress assays), replicated across P. falciparum and P. knowlesi\",\n      \"pmids\": [\"33932049\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium knowlesi\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Conditional deletion of the pfmsa180 gene using CRISPR/Cas9 and DiCre recombinase technology produces a severe egress defect (preventing schizont rupture) but does not significantly impair erythrocyte invasion, establishing that MSA180 is essential for parasite egress but not invasion.\",\n      \"method\": \"Conditional gene knockout (CRISPR/Cas9 + DiCre recombinase), growth inhibition assays, invasion assays, light microscopy of schizont rupture\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean conditional KO with specific egress phenotype and negative invasion result, two orthogonal functional assays, single lab\",\n      \"pmids\": [\"34584166\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"The C-terminal region of MSA180 (PF3D7_1014100) contains an erythrocyte-binding domain that specifically interacts with human erythrocyte integrin-associated protein CD47, as demonstrated by surface plasmon resonance; antibodies against this C-terminal region inhibit parasite invasion in growth inhibition assays.\",\n      \"method\": \"Surface plasmon resonance (binding assay), growth inhibition assay, recombinant protein expression (wheat germ cell-free system), rabbit antibody generation\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding measured by SPR plus functional inhibition assay, single lab, two orthogonal methods\",\n      \"pmids\": [\"30976034\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"The P. vivax ortholog of MSA180 (PvMSA180, PVX_094920) localizes to the merozoite surface at the schizont stage, as determined by immunofluorescence assay using antibodies against PvMSA180 domains D1 and D4.\",\n      \"method\": \"Immunofluorescence assay (IFA) with domain-specific antibodies on schizont-stage parasites\",\n      \"journal\": \"Malaria journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single localization method (IFA), single lab, no functional consequence directly linked\",\n      \"pmids\": [\"28351409\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium vivax\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"Using a cell-free in vitro reconstitution system, the strict requirement for MSA180 fragments in SUB1-triggered SERA6 autoproteolytic maturation was confirmed: in the absence of MSA180, SERA6 maturation does not occur, validating MSA180 as an essential cofactor in the egress pathway.\",\n      \"method\": \"Cell-free in vitro reconstitution of SERA6 maturation, synthetic peptide substrate cleavage assay, small molecule inhibitor testing\",\n      \"journal\": \"Frontiers in parasitology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstitution system directly confirming MSA180 requirement, multiple biochemical methods, corroborates prior genetic findings from a separate lab\",\n      \"pmids\": [\"42662414\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"MSA180 (PF3D7_1014100) is a merozoite surface/parasitophorous vacuole protein that acts as an essential cofactor for egress: SUB1 cleaves MSA180 and the resulting fragments interact with SERA6 in multimolecular complexes to enable SERA6 autocatalytic maturation, which in turn degrades β-spectrin to drive red blood cell rupture; genetic ablation of MSA180 blocks egress without impairing invasion, and its C-terminal region also directly binds the erythrocyte surface protein CD47.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MSA180 (PF3D7_1014100) is a merozoite-associated protein that functions as an essential cofactor for parasite egress from infected erythrocytes [#0, #1]. During schizont maturation, the subtilisin-like protease SUB1 cleaves MSA180, and the resulting MSA180 fragments assemble into multimolecular complexes with the cysteine protease SERA6, a step strictly required to enable SERA6 autoproteolytic maturation [#0]; in vitro reconstitution confirmed that SERA6 maturation does not proceed in the absence of MSA180 fragments [#4]. Because mature SERA6 drives β-spectrin cleavage and red blood cell rupture, conditional deletion of MSA180 blocks β-spectrin cleavage and schizont rupture, phenocopying SERA6 disruption, while leaving erythrocyte invasion intact — establishing MSA180 as essential for egress but not invasion [#0, #1]. Independently, the C-terminal region of MSA180 contains an erythrocyte-binding domain that binds human CD47 by surface plasmon resonance, and antibodies against this region inhibit parasite growth [#2]. The findings are consistent across P. falciparum and P. knowlesi for the egress role [#0], and the P. vivax ortholog localizes to the merozoite surface at the schizont stage [#3].\"\n,\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Before functional data existed, it was unknown where the MSA180 protein resides during the blood stage; establishing merozoite-surface localization of the P. vivax ortholog placed the protein at the host-parasite interface.\",\n      \"evidence\": \"Immunofluorescence with domain-specific antibodies on schizont-stage P. vivax parasites\",\n      \"pmids\": [\"28351409\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Localization shown only for the P. vivax ortholog, not directly for PF3D7_1014100\", \"Single method (IFA) with no functional consequence tested\", \"Does not distinguish merozoite surface from parasitophorous vacuole membrane\"],\n      \"attribution\": [{\"species\": \"Plasmodium vivax\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"To probe a possible invasion role, the question was whether MSA180 engages a host erythrocyte receptor; the C-terminal region was shown to bind human CD47 and to be targeted by growth-inhibitory antibodies.\",\n      \"evidence\": \"Surface plasmon resonance binding assay, recombinant protein from wheat germ cell-free system, and growth inhibition with rabbit antibodies in P. falciparum\",\n      \"pmids\": [\"30976034\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"CD47 binding not linked to a defined step in the parasite life cycle by genetic evidence\", \"Functional inhibition by antibody does not distinguish invasion from egress blockade\", \"Single lab, no reciprocal validation of the interaction in situ\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"The central mechanistic question — what MSA180 actually does — was answered by showing it is a SUB1-cleaved cofactor whose fragments enable SERA6 autocatalytic maturation, coupling MSA180 to β-spectrin cleavage and RBC rupture.\",\n      \"evidence\": \"Conditional CRISPR/Cas9+DiCre knockout, co-immunoprecipitation of multimolecular complexes, and β-spectrin cleavage/egress assays in P. falciparum and P. knowlesi\",\n      \"pmids\": [\"33932049\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of MSA180 fragment–SERA6 complex assembly not resolved\", \"Stoichiometry and identity of other complex members not fully defined\", \"Relationship between the egress cofactor role and the CD47-binding activity unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}, {\"species\": \"Plasmodium knowlesi\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"To separate the egress function from a potential invasion function, conditional deletion demonstrated a severe egress/rupture defect with no significant impairment of invasion, defining the specific step at which MSA180 is required.\",\n      \"evidence\": \"Conditional gene knockout (CRISPR/Cas9+DiCre), growth and invasion assays, and microscopy of schizont rupture in P. falciparum\",\n      \"pmids\": [\"34584166\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not reconcile the retained invasion capacity with the reported CD47-binding/invasion-inhibition activity\", \"Molecular event downstream of egress arrest not detailed in this study\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Whether MSA180 acts directly on SERA6 maturation or indirectly was resolved by reconstituting the reaction cell-free, confirming a strict requirement for MSA180 fragments in SUB1-triggered SERA6 autoproteolysis.\",\n      \"evidence\": \"Cell-free in vitro reconstitution of SERA6 maturation with synthetic peptide substrate cleavage and inhibitor testing in P. falciparum\",\n      \"pmids\": [\"42662414\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Precise MSA180 fragment(s) responsible and their binding interface not defined\", \"Structure of the reconstituted complex not determined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unresolved how the CD47-binding activity of the MSA180 C-terminus relates mechanistically to its established, genetically-required role as a SERA6 maturation cofactor during egress.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No genetic test linking CD47 binding to a defined phenotype\", \"No structural model of MSA180 or its fragment–SERA6 complex\", \"Whether the same molecule performs both functions sequentially is unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0030674\", \"supporting_discovery_ids\": [0, 4]},\n      {\"term_id\": \"GO:0030246\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0009986\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0035891\", \"supporting_discovery_ids\": [0, 1, 4]}\n    ],\n    \"complexes\": [\n      \"MSA180 fragment–SERA6 multimolecular complex [#0, #4]\"\n    ],\n    \"partners\": [\n      \"SERA6 (cysteine protease; interacts with SUB1-cleaved MSA180 fragments) [#0, #4]\",\n      \"SUB1 (subtilisin-like protease; cleaves MSA180) [#0]\",\n      \"CD47 / human erythrocyte integrin-associated protein (bound by MSA180 C-terminal region) [#2]\"\n    ],\n    \"other_free_text\": [\n      \"MSA180 is required for egress but dispensable for invasion; conditional knockout blocks β-spectrin cleavage and RBC rupture, phenocopying SERA6 disruption [#0, #1].\",\n      \"Egress cofactor role demonstrated in P. falciparum and P. knowlesi [#0]; merozoite-surface localization shown for the P. vivax ortholog [#3].\",\n      \"The C-terminal erythrocyte-binding region is a target of growth-inhibitory antibodies [#2].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1014100","name":null,"product":"merozoite surface protein MSA180","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1212500","name":null,"product":"merozoite surface protein MSA180, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0814000","name":null,"product":"merozoite surface protein MSA180, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"MSA180","evaluation":null}