{"gene":"PF3D7_1335100","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2001,"finding":"MSP7 (PF3D7_1335100) is synthesized as a 351-amino acid precursor that is proteolytically processed to yield a 22-kDa surface form (MSP7(22)) and a further-cleaved 19-kDa form (MSP7(19)); both are non-covalently associated with the MSP1 complex and are shed from the merozoite surface at erythrocyte invasion.","method":"Gene sequencing, immunoblot, mass spectrometry of merozoite surface proteins in P. falciparum","journal":"Molecular and biochemical parasitology","confidence":"High","confidence_rationale":"Tier 1 / Strong — direct biochemical characterization (MS confirmation of primary structure) combined with immunoblot; finding replicated in subsequent studies","pmids":["11551634"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"finding":"During biosynthesis in schizonts, MSP7 precursor and MSP1 precursor form a complex that is targeted to the merozoite surface. MSP7 undergoes sequential proteolytic processing: primary cleavage (brefeldin A-sensitive, occurring in a post-Golgi compartment prior to MSP1 primary processing) yields N-terminal MSP7(20) and C-terminal MSP7(33); MSP7(33) remains bound to full-length MSP1. Secondary cleavage of MSP7(33) on the merozoite surface yields MSP7(22), which is shed with the MSP1 complex during erythrocyte invasion. Secondary cleavage is resistant to calcium chelators and serine protease inhibitors.","method":"Pulse-chase metabolic labeling, immunoprecipitation, brefeldin A treatment, protease inhibitor panel, immunofluorescence in P. falciparum","journal":"Molecular and biochemical parasitology","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — multiple orthogonal methods (metabolic labeling, inhibitor dissection, subcellular fractionation) in a single focused study, consistent with earlier biochemical characterization","pmids":["17097159"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"finding":"In vitro reconstitution showed that MSP7 binds directly to MSP1 subunits p83, p30, and p38 (the shed portions), but not to the GPI-anchored MSP1-42/19 region, establishing MSP7 as a peripheral component of the MSP1 complex attached via multiple interaction sites. MSP6 and MSP7 bind MSP1 independently of each other.","method":"In vitro protein interaction assays using heterologously produced recombinant MSP1, MSP6, and MSP7; analytical ultracentrifugation; size-exclusion chromatography in P. falciparum","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — reconstitution with purified recombinant proteins, multiple MSP1 subunits tested individually, single rigorous study with orthogonal biophysical methods","pmids":["16940297"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"finding":"PfSUB1, a subtilisin-like serine protease discharged into the parasitophorous vacuole just before egress, directly cleaves MSP7 (along with MSP1 and MSP6) to proteolytically mature the merozoite surface complex. Inhibition of PfSUB1 results in accumulation of unprocessed MSP7 on the merozoite surface and significantly reduces erythrocyte invasion.","method":"PfSUB1 inhibition assays, immunoblot of merozoite surface proteins, invasion assays in P. falciparum","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean enzyme-inhibition experiment with direct phenotypic readout (invasion), finding independently supported by proteomic substrate identification study (PMID 21220481)","pmids":["19214190","21220481"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2008,"finding":"Genetic disruption of msp7 in P. falciparum D10 line (confirmed by Southern hybridization and immunoblot) is not lethal but significantly impairs erythrocyte invasion by merozoites without altering the expression, distribution, or processing of MSP1, MSP3, MSP6, MSP9, or SERA5, and without inducing a detectable shift to alternative invasion pathways.","method":"Targeted gene disruption (knockout), Southern hybridization, immunoblot, immunofluorescence, invasion assays in P. falciparum D10","journal":"Eukaryotic cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean genetic knockout with multiple orthogonal validation methods and quantitative invasion phenotype; replicated conceptually in P. berghei (PMID 15339842)","pmids":["18820076"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"D10"}]},{"year":2004,"finding":"Disruption of msp7 in P. berghei (confirmed by molecular analysis) is not lethal but slows blood-stage parasite growth in vivo; MSP7-knockout parasites showed a relative preference for reticulocyte invasion when reticulocytes were prevalent, suggesting MSP7 contributes to erythrocyte (normocyte) tropism. MSP1 synthesis and processing were unaffected in the knockout.","method":"Targeted gene disruption, Southern blot, in vivo infection of mice, blood smear parasitemia monitoring in P. berghei","journal":"Blood","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic knockout with in vivo phenotypic readout; MSP1 processing controls included; independently replicated concept in P. falciparum (PMID 18820076)","pmids":["15339842"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2010,"finding":"Recombinant MSP7 (PF3D7_1335100) directly interacts with recombinant MSP1, confirming the MSP1–MSP7 binary interaction in a cell-free mammalian expression system. MSP7 independently forms a complex with MSP1, as do MSP3, MSP6, MSPDBL1, and MSPDBL2, resulting in multiple distinct MSP1-containing surface complexes.","method":"Recombinant protein production in mammalian cells, direct binding assays (AVEXIS / ELISA-based interaction screen) in P. falciparum","journal":"Molecular & cellular proteomics : MCP","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — cell-free binding assay with recombinant proteins; single lab but corroborates earlier in vitro reconstitution data (PMID 16940297)","pmids":["24043421"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"finding":"MSP7 (PF3D7_1335100) binds directly to human P-selectin via its N-terminus, interacting with the P-selectin C-type lectin and EGF-like domains. When complexed with MSP7, P-selectin can no longer bind its endogenous carbohydrate ligand Sialyl-Lewis(X), providing a molecular mechanism by which MSP7 could modulate the inflammatory response during malaria infection.","method":"Systematic extracellular protein interaction screen (AVEXIS), direct biochemical binding assays, domain-mapping experiments in P. falciparum; orthologous interactions confirmed for P. berghei MSRPs and mouse P-selectin","journal":"Malaria journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding assays with domain mapping; single lab, but multiple orthogonal methods (protein screen + biochemical validation + competition assay)","pmids":["26045295"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium berghei","strain":""}]},{"year":2016,"finding":"MSP7 (PF3D7_1335100) binds directly to MSP1 and forms part of multiple distinct MSP1 complexes on the merozoite surface; these complexes interact directly with human erythrocytes. Inhibitory antibodies targeting the p83 fragment of MSP1 block all MSP1 complex forms including those containing MSP7.","method":"Co-immunoprecipitation, direct binding assays with recombinant proteins, erythrocyte binding assays, antibody inhibition of parasite growth in vitro in P. falciparum","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal binding assays and functional erythrocyte binding data; single lab","pmids":["26823464"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"finding":"MSP7 (PF3D7_1335100) is shed from the merozoite surface at the tight junction between the invading merozoite and erythrocyte, together with MSP1 and other peripheral surface proteins (MSP3, SERA4, SERA5), establishing the timing and location of MSP7 shedding during invasion.","method":"Time-lapse live imaging of invasion, immunofluorescence, and immunoblot of purified invasion stage parasites in P. falciparum","journal":"Infection and immunity","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct live imaging with defined spatial readout; single lab","pmids":["24218484"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2002,"finding":"In P. yoelii, the MSP7 homologue was identified as a direct binding partner of the amino-terminal proteolytic fragment of MSP1 using a yeast two-hybrid screen, and this interaction was confirmed by in vitro binding experiments. MSP7 co-localizes with the N-terminal portion of MSP1 on the surfaces of schizonts.","method":"Yeast two-hybrid screen, in vitro binding assays, immunofluorescence co-localization in P. yoelii","journal":"Eukaryotic cell","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — yeast two-hybrid plus in vitro binding confirmation and co-localization; multiple methods but yeast two-hybrid is indirect","pmids":["12477792"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2010,"finding":"Among the MSP7 gene family in P. falciparum, only deletion of MSP7 (PF3D7_1335100) leads to a detectable growth/invasion phenotype; deletion of any of the five MSP7-related proteins (MSRPs) produced no detectable phenotype, establishing MSP7 as the functionally dominant family member in asexual blood stages.","method":"Targeted gene disruption of each family member individually in P. falciparum 3D7, growth and invasion assays","journal":"Eukaryotic cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — systematic genetic analysis of all family members with quantitative phenotypic comparison; multiple knockouts with internal controls","pmids":["20472690"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2011,"finding":"PfSUB1 proteomics identified MSP7 (PF3D7_1335100) as a direct substrate within the MSP1/6/7 complex; SUB1 is responsible for its proteolytic processing at the late asexual blood stage, as established by a combined bioinformatic and proteomic analysis of the entire late asexual blood-stage proteome.","method":"Quantitative proteomics of SUB1-inhibited vs. control parasites, bioinformatic substrate prediction in P. falciparum","journal":"Infection and immunity","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — proteome-wide mass spectrometry approach; single lab but orthogonal to the earlier inhibitor study (PMID 19214190)","pmids":["21220481"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"finding":"Simultaneous disruption of both msp7 and plasmepsin-4 genes in P. berghei produced a virulence-attenuated blood-stage parasite with self-resolving infection, low parasitemia, absence of experimental cerebral malaria, and cross-species protection after convalescence, demonstrating that MSP7 deletion contributes to reduced parasite virulence in vivo.","method":"Sequential targeted gene disruption in P. berghei, in vivo mouse infection models (BALB/c and C57BL/6), parasitemia monitoring, cerebral malaria assessment, challenge experiments","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean double-knockout with in vivo phenotypic readouts, but MSP7 contribution cannot be fully separated from plasmepsin-4 in the combined mutant","pmids":["22355558"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2011,"finding":"Deletion of msp7 alone in P. berghei in BALB/c mice and Wistar rats abrogated death and reduced peak circulating parasitemia from ~3% to ~2%, and was associated with less anemia, establishing that MSP7 contributes to blood-stage disease severity beyond its role in erythrocyte invasion efficiency.","method":"P. berghei Δmsp7 knockout, in vivo infection of BALB/c mice and Wistar rats, parasitemia monitoring, hematological measurements, splenic histology","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean knockout with quantitative in vivo phenotype in two host species; single lab","pmids":["21980474"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2007,"finding":"Synthetic peptides spanning the MSP7 (PF3D7_1335100) sequence identified five high-activity binding peptides (HABPs) that bind specifically to the erythrocyte surface and recognize a 52 kDa erythrocyte membrane protein; binding was sensitive to enzymatic treatment. MSP7 HABPs displayed differential erythrocyte invasion inhibition (24–83%), suggesting MSP7 participates directly in erythrocyte binding during invasion.","method":"Synthetic peptide RBC binding assays, enzymatic treatment of RBCs, invasion inhibition assays in P. falciparum","journal":"Journal of medicinal chemistry","confidence":"Low","confidence_rationale":"Tier 3 / Weak — peptide binding assay only; single lab, peptide-based approach does not recapitulate full protein interactions","pmids":["17944453"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"MSP7 (PF3D7_1335100) is part of an MSP1 complex that also includes MSP3, MSP6, and MSP9, as established by immunoprecipitation of merozoite lysate with anti-MSP3 antibodies followed by mass spectrometry; direct protein-protein interactions within this complex (MSP1–MSP3, MSP1–MSP6, MSP1–MSP7) were confirmed by ELISA and surface plasmon resonance.","method":"Immunoprecipitation of merozoite lysate, mass spectrometry, ELISA-based binding, surface plasmon resonance in P. falciparum","journal":"Infection and immunity","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — orthogonal methods (MS + SPR + ELISA); single lab but multiple biochemical validations","pmids":["29760216"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"Members of the MSP7-related protein (MSRP) family were identified as PEXEL/HT-negative exported proteins (PNEPs) in P. falciparum, indicating that certain MSRPs are exported into the host erythrocyte by a translocation mechanism that does not require the canonical PEXEL motif, suggesting unanticipated functions for the MSP7 family beyond the merozoite surface.","method":"Reporter fusion assays, live fluorescence microscopy, immunofluorescence in P. falciparum","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 3 / Weak — finding applies to MSRP family members rather than PF3D7_1335100 (MSP7) specifically; single lab; abstract does not specify which MSRP members are exported","pmids":["23950716"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1335100 (MSP7) is a peripheral merozoite surface protein that is synthesized as a ~351-aa precursor in schizonts, forms a complex with the MSP1 precursor in a post-Golgi compartment, and undergoes sequential proteolytic processing—first by an unidentified brefeldin A-sensitive protease to yield MSP7(33) (which remains bound to MSP1) and MSP7(20), then by PfSUB1 on the merozoite surface to generate MSP7(22), which is shed as part of the MSP1/6/7 complex at the tight junction during erythrocyte invasion; MSP7 binds directly to the p83, p30, and p38 shed subunits of MSP1 (but not the GPI-anchored MSP1-42/19), contributes to erythrocyte invasion efficiency (its genetic deletion reduces invasion and in vivo parasite growth/virulence without altering MSP1 processing), and additionally binds human P-selectin via its N-terminus, potentially modulating host inflammatory responses."},"narrative":{"mechanistic_narrative":"MSP7 (PF3D7_1335100) is a peripheral merozoite surface protein of Plasmodium that assembles with the MSP1 precursor to form part of the MSP1 surface complex and contributes to efficient erythrocyte invasion during the asexual blood stage [PMID:17097159, PMID:18820076]. It is synthesized as a ~351-aa precursor in schizonts and undergoes sequential proteolytic maturation: a brefeldin A-sensitive primary cleavage in a post-Golgi compartment generates N-terminal MSP7(20) and C-terminal MSP7(33), with MSP7(33) remaining bound to full-length MSP1, followed by a surface secondary cleavage yielding MSP7(22) [PMID:11551634, PMID:17097159]. This surface maturation is carried out by the subtilisin-like protease PfSUB1, which directly processes MSP7 within the MSP1/6/7 complex prior to egress; blocking PfSUB1 leaves unprocessed MSP7 on the merozoite surface and reduces invasion [PMID:19214190, PMID:21220481]. MSP7 binds MSP1 directly and independently of MSP6, attaching to the shed p83, p30, and p38 subunits but not the GPI-anchored MSP1-42/19 region, defining it as a peripherally attached component of one of several distinct MSP1 complexes that engage the erythrocyte surface [PMID:16940297, PMID:29760216]. The mature complex, including MSP7, is shed at the tight junction during invasion [PMID:24218484]. Genetic disruption of msp7 is not lethal but impairs invasion without perturbing MSP1 expression or processing, and in P. berghei attenuates blood-stage growth and virulence in vivo [PMID:18820076, PMID:15339842, PMID:21980474]; among the MSP7 gene family, only PF3D7_1335100 produces a detectable growth/invasion phenotype on deletion [PMID:20472690]. Beyond its merozoite-surface role, MSP7 binds human P-selectin via its N-terminus at the C-type lectin and EGF-like domains, blocking P-selectin engagement of its Sialyl-Lewis(X) ligand [PMID:26045295].","teleology":[{"year":2001,"claim":"Establishing MSP7 as a processed merozoite surface protein answered whether it is a stable structural protein or a transiently displayed, shed molecule, framing it as an invasion-associated surface antigen.","evidence":"Gene sequencing, immunoblot and mass spectrometry of P. falciparum merozoite surface proteins","pmids":["11551634"],"confidence":"High","gaps":["Did not define the protease(s) responsible for processing","Did not establish a functional role in invasion"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2002,"claim":"Identifying MSP7 as a direct binding partner of the MSP1 N-terminal fragment addressed how MSP7 is displayed on the surface, showing it is recruited through direct association with MSP1.","evidence":"Yeast two-hybrid screen, in vitro binding, and immunofluorescence co-localization in P. yoelii","pmids":["12477792"],"confidence":"Medium","gaps":["Yeast two-hybrid is indirect and shown in P. yoelii","Did not map which MSP1 subunits bind MSP7"],"attribution":[]},{"year":2004,"claim":"Knocking out msp7 in P. berghei tested whether the protein is essential and revealed it is dispensable for viability but contributes to blood-stage growth and erythrocyte tropism.","evidence":"Targeted gene disruption with in vivo mouse infection and parasitemia monitoring in P. berghei","pmids":["15339842"],"confidence":"High","gaps":["Mechanism linking MSP7 loss to reticulocyte preference unresolved","P. berghei phenotype not yet confirmed in a human-infective species"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2006,"claim":"Dissecting the biosynthetic pathway and mapping the MSP1 binding sites resolved where, when, and how MSP7 is processed and assembled onto MSP1.","evidence":"Pulse-chase labeling with inhibitor dissection, plus in vitro reconstitution with recombinant MSP1/MSP6/MSP7 and biophysical sizing in P. falciparum","pmids":["17097159","16940297"],"confidence":"High","gaps":["The brefeldin A-sensitive primary protease was not identified","Functional consequence of multi-site binding not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"claim":"Peptide binding assays probed whether MSP7 itself contacts the erythrocyte, indicating direct receptor engagement, but by a low-resolution surrogate approach.","evidence":"Synthetic high-activity binding peptides, RBC binding with enzymatic treatment, and invasion inhibition in P. falciparum","pmids":["17944453"],"confidence":"Low","gaps":["Peptide binding does not recapitulate full-length protein interactions","The 52 kDa erythrocyte partner was not molecularly identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2008,"claim":"A clean P. falciparum knockout tested whether the invasion role is conserved in a human parasite and showed MSP7 loss impairs invasion without disrupting other surface protein processing.","evidence":"Targeted disruption in P. falciparum D10 with Southern, immunoblot, immunofluorescence and invasion assays","pmids":["18820076"],"confidence":"High","gaps":["Did not identify the molecular step of invasion that MSP7 assists","No evidence for compensatory alternative invasion pathway"],"attribution":[{"species":"Plasmodium falciparum","strain":"D10"}]},{"year":2009,"claim":"Identifying PfSUB1 as the maturase resolved the enzyme responsible for MSP7 surface processing and linked that processing to invasion competence.","evidence":"PfSUB1 inhibition with immunoblot of surface proteins and invasion assays in P. falciparum","pmids":["19214190","21220481"],"confidence":"High","gaps":["Does not distinguish the invasion contribution of MSP7 processing from that of co-substrates MSP1/MSP6","Primary post-Golgi protease remains unidentified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"claim":"Live imaging and family-wide knockouts localized MSP7 shedding to the tight junction and established PF3D7_1335100 as the functionally dominant family member.","evidence":"Time-lapse invasion imaging with immunofluorescence, plus individual disruption of all MSP7-family genes with growth/invasion assays in P. falciparum","pmids":["24218484","20472690"],"confidence":"Medium","gaps":["Molecular trigger of shedding not defined","Why MSRP paralogs are phenotypically silent in blood stages is unexplained"],"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2011,"claim":"In vivo P. berghei studies established that MSP7 loss reduces disease severity and virulence, extending its role beyond invasion efficiency.","evidence":"Single and double (msp7/plasmepsin-4) knockouts with mouse and rat infection, hematology, and cerebral malaria assessment in P. berghei","pmids":["21980474","22355558"],"confidence":"Medium","gaps":["In the double mutant, MSP7's contribution cannot be fully separated from plasmepsin-4","Molecular basis of the virulence effect is unknown"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2016,"claim":"Extracellular interaction screening uncovered a host-directed activity, showing MSP7 binds human P-selectin and blocks its carbohydrate ligand, and confirmed reciprocal, erythrocyte-engaging MSP1 complexes.","evidence":"AVEXIS screen, domain-mapping binding and competition assays for P-selectin; Co-IP, recombinant binding and erythrocyte binding for MSP1 complexes in P. falciparum","pmids":["26045295","26823464"],"confidence":"Medium","gaps":["Physiological relevance of the P-selectin interaction during infection not demonstrated in vivo","Single lab, single-species biochemical validation"],"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium berghei","strain":""}]},{"year":2018,"claim":"Compositional analysis defined the broader MSP1 complex membership, placing MSP7 alongside MSP3, MSP6, and MSP9 with direct MSP1 binding confirmed.","evidence":"Anti-MSP3 immunoprecipitation with mass spectrometry, ELISA and surface plasmon resonance in P. falciparum","pmids":["29760216"],"confidence":"Medium","gaps":["Stoichiometry and spatial arrangement of the multi-protein complex not resolved","Single lab"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The identity of the brefeldin A-sensitive primary protease and the precise molecular step of invasion that MSP7 facilitates remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["Primary post-Golgi protease that generates MSP7(33)/MSP7(20) unidentified","Direct erythrocyte receptor for full-length MSP7 not defined","In vivo relevance of MSP7-P-selectin binding untested"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["MSP1 merozoite surface complex (MSP1/6/7)","Extended MSP1 complex including MSP1, MSP3, MSP6, MSP9"],"partners":["MSP1 (VIA SHED P83, P30, P38 SUBUNITS)","MSP6 (INDEPENDENT CO-MEMBER OF MSP1 COMPLEX)","PFSUB1 (PROTEASE THAT PROCESSES MSP7)","HUMAN P-SELECTIN (C-TYPE LECTIN AND EGF-LIKE DOMAINS)","ERYTHROCYTE SURFACE (~52 KDA MEMBRANE PROTEIN, PEPTIDE-LEVEL EVIDENCE)"],"other_free_text":["Synthesized as a ~351-aa precursor in schizonts; processed to MSP7(33)/MSP7(20), then MSP7(22)/MSP7(19) by sequential cleavage [#0, #1].","Primary cleavage is brefeldin A-sensitive and occurs in a post-Golgi compartment before MSP1 primary processing; the responsible protease is unidentified [#1].","Secondary/surface processing is carried out by PfSUB1 and is required for efficient invasion [#3, #12].","Deletion is non-lethal but impairs invasion (P. falciparum) and reduces in vivo growth and virulence (P. berghei) without altering MSP1 processing [#4, #5, #14].","PF3D7_1335100 is the functionally dominant member of the MSP7 family in asexual blood stages; MSRP paralog deletions are phenotypically silent [#11].","MSRP family members (not PF3D7_1335100 specifically) were identified as PEXEL-negative exported proteins [#17]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"23950716","id":"PMC_23950716","title":"Identification of new PNEPs indicates a substantial non-PEXEL exportome and underpins common features in Plasmodium falciparum protein export.","date":"2013","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/23950716","citation_count":125,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSP7"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19214190","id":"PMC_19214190","title":"A multifunctional serine protease primes the malaria parasite for red blood cell invasion.","date":"2009","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/19214190","citation_count":122,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSP7"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"11551634","id":"PMC_11551634","title":"The 22 kDa component of the protein complex on the surface of Plasmodium falciparum merozoites is derived from a larger precursor, merozoite surface protein 7.","date":"2001","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/11551634","citation_count":94,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSP7","merozoite surface protein 7"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24043421","id":"PMC_24043421","title":"A library of functional recombinant cell-surface and secreted P. falciparum merozoite proteins.","date":"2013","source":"Molecular & cellular proteomics : MCP","url":"https://pubmed.ncbi.nlm.nih.gov/24043421","citation_count":94,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSP7"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25883384","id":"PMC_25883384","title":"Plasmodium falciparum Protein Microarray Antibody Profiles Correlate With Protection From Symptomatic Malaria in Kenya.","date":"2015","source":"The Journal of infectious diseases","url":"https://pubmed.ncbi.nlm.nih.gov/25883384","citation_count":88,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSP7"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21220481","id":"PMC_21220481","title":"Global identification of multiple substrates for Plasmodium falciparum SUB1, an essential malarial processing protease.","date":"2011","source":"Infection and immunity","url":"https://pubmed.ncbi.nlm.nih.gov/21220481","citation_count":79,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSP7"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"16940297","id":"PMC_16940297","title":"Interactions between merozoite surface proteins 1, 6, and 7 of the malaria parasite Plasmodium falciparum.","date":"2006","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16940297","citation_count":72,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MSP7"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26823464","id":"PMC_26823464","title":"Multiple Plasmodium falciparum Merozoite Surface Protein 1 Complexes Mediate Merozoite Binding to Human Erythrocytes.","date":"2016","source":"The Journal of biological 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19-kDa form (MSP7(19)); both are non-covalently associated with the MSP1 complex and are shed from the merozoite surface at erythrocyte invasion.\",\n      \"method\": \"Gene sequencing, immunoblot, mass spectrometry of merozoite surface proteins in P. falciparum\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — direct biochemical characterization (MS confirmation of primary structure) combined with immunoblot; finding replicated in subsequent studies\",\n      \"pmids\": [\"11551634\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"During biosynthesis in schizonts, MSP7 precursor and MSP1 precursor form a complex that is targeted to the merozoite surface. MSP7 undergoes sequential proteolytic processing: primary cleavage (brefeldin A-sensitive, occurring in a post-Golgi compartment prior to MSP1 primary processing) yields N-terminal MSP7(20) and C-terminal MSP7(33); MSP7(33) remains bound to full-length MSP1. Secondary cleavage of MSP7(33) on the merozoite surface yields MSP7(22), which is shed with the MSP1 complex during erythrocyte invasion. Secondary cleavage is resistant to calcium chelators and serine protease inhibitors.\",\n      \"method\": \"Pulse-chase metabolic labeling, immunoprecipitation, brefeldin A treatment, protease inhibitor panel, immunofluorescence in P. falciparum\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — multiple orthogonal methods (metabolic labeling, inhibitor dissection, subcellular fractionation) in a single focused study, consistent with earlier biochemical characterization\",\n      \"pmids\": [\"17097159\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"In vitro reconstitution showed that MSP7 binds directly to MSP1 subunits p83, p30, and p38 (the shed portions), but not to the GPI-anchored MSP1-42/19 region, establishing MSP7 as a peripheral component of the MSP1 complex attached via multiple interaction sites. MSP6 and MSP7 bind MSP1 independently of each other.\",\n      \"method\": \"In vitro protein interaction assays using heterologously produced recombinant MSP1, MSP6, and MSP7; analytical ultracentrifugation; size-exclusion chromatography in P. falciparum\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — reconstitution with purified recombinant proteins, multiple MSP1 subunits tested individually, single rigorous study with orthogonal biophysical methods\",\n      \"pmids\": [\"16940297\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"PfSUB1, a subtilisin-like serine protease discharged into the parasitophorous vacuole just before egress, directly cleaves MSP7 (along with MSP1 and MSP6) to proteolytically mature the merozoite surface complex. Inhibition of PfSUB1 results in accumulation of unprocessed MSP7 on the merozoite surface and significantly reduces erythrocyte invasion.\",\n      \"method\": \"PfSUB1 inhibition assays, immunoblot of merozoite surface proteins, invasion assays in P. falciparum\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean enzyme-inhibition experiment with direct phenotypic readout (invasion), finding independently supported by proteomic substrate identification study (PMID 21220481)\",\n      \"pmids\": [\"19214190\", \"21220481\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Genetic disruption of msp7 in P. falciparum D10 line (confirmed by Southern hybridization and immunoblot) is not lethal but significantly impairs erythrocyte invasion by merozoites without altering the expression, distribution, or processing of MSP1, MSP3, MSP6, MSP9, or SERA5, and without inducing a detectable shift to alternative invasion pathways.\",\n      \"method\": \"Targeted gene disruption (knockout), Southern hybridization, immunoblot, immunofluorescence, invasion assays in P. falciparum D10\",\n      \"journal\": \"Eukaryotic cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean genetic knockout with multiple orthogonal validation methods and quantitative invasion phenotype; replicated conceptually in P. berghei (PMID 15339842)\",\n      \"pmids\": [\"18820076\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"D10\"}]\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Disruption of msp7 in P. berghei (confirmed by molecular analysis) is not lethal but slows blood-stage parasite growth in vivo; MSP7-knockout parasites showed a relative preference for reticulocyte invasion when reticulocytes were prevalent, suggesting MSP7 contributes to erythrocyte (normocyte) tropism. MSP1 synthesis and processing were unaffected in the knockout.\",\n      \"method\": \"Targeted gene disruption, Southern blot, in vivo infection of mice, blood smear parasitemia monitoring in P. berghei\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic knockout with in vivo phenotypic readout; MSP1 processing controls included; independently replicated concept in P. falciparum (PMID 18820076)\",\n      \"pmids\": [\"15339842\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Recombinant MSP7 (PF3D7_1335100) directly interacts with recombinant MSP1, confirming the MSP1–MSP7 binary interaction in a cell-free mammalian expression system. MSP7 independently forms a complex with MSP1, as do MSP3, MSP6, MSPDBL1, and MSPDBL2, resulting in multiple distinct MSP1-containing surface complexes.\",\n      \"method\": \"Recombinant protein production in mammalian cells, direct binding assays (AVEXIS / ELISA-based interaction screen) in P. falciparum\",\n      \"journal\": \"Molecular & cellular proteomics : MCP\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — cell-free binding assay with recombinant proteins; single lab but corroborates earlier in vitro reconstitution data (PMID 16940297)\",\n      \"pmids\": [\"24043421\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"MSP7 (PF3D7_1335100) binds directly to human P-selectin via its N-terminus, interacting with the P-selectin C-type lectin and EGF-like domains. When complexed with MSP7, P-selectin can no longer bind its endogenous carbohydrate ligand Sialyl-Lewis(X), providing a molecular mechanism by which MSP7 could modulate the inflammatory response during malaria infection.\",\n      \"method\": \"Systematic extracellular protein interaction screen (AVEXIS), direct biochemical binding assays, domain-mapping experiments in P. falciparum; orthologous interactions confirmed for P. berghei MSRPs and mouse P-selectin\",\n      \"journal\": \"Malaria journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding assays with domain mapping; single lab, but multiple orthogonal methods (protein screen + biochemical validation + competition assay)\",\n      \"pmids\": [\"26045295\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"MSP7 (PF3D7_1335100) binds directly to MSP1 and forms part of multiple distinct MSP1 complexes on the merozoite surface; these complexes interact directly with human erythrocytes. Inhibitory antibodies targeting the p83 fragment of MSP1 block all MSP1 complex forms including those containing MSP7.\",\n      \"method\": \"Co-immunoprecipitation, direct binding assays with recombinant proteins, erythrocyte binding assays, antibody inhibition of parasite growth in vitro in P. falciparum\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal binding assays and functional erythrocyte binding data; single lab\",\n      \"pmids\": [\"26823464\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"MSP7 (PF3D7_1335100) is shed from the merozoite surface at the tight junction between the invading merozoite and erythrocyte, together with MSP1 and other peripheral surface proteins (MSP3, SERA4, SERA5), establishing the timing and location of MSP7 shedding during invasion.\",\n      \"method\": \"Time-lapse live imaging of invasion, immunofluorescence, and immunoblot of purified invasion stage parasites in P. falciparum\",\n      \"journal\": \"Infection and immunity\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct live imaging with defined spatial readout; single lab\",\n      \"pmids\": [\"24218484\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"In P. yoelii, the MSP7 homologue was identified as a direct binding partner of the amino-terminal proteolytic fragment of MSP1 using a yeast two-hybrid screen, and this interaction was confirmed by in vitro binding experiments. MSP7 co-localizes with the N-terminal portion of MSP1 on the surfaces of schizonts.\",\n      \"method\": \"Yeast two-hybrid screen, in vitro binding assays, immunofluorescence co-localization in P. yoelii\",\n      \"journal\": \"Eukaryotic cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — yeast two-hybrid plus in vitro binding confirmation and co-localization; multiple methods but yeast two-hybrid is indirect\",\n      \"pmids\": [\"12477792\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Among the MSP7 gene family in P. falciparum, only deletion of MSP7 (PF3D7_1335100) leads to a detectable growth/invasion phenotype; deletion of any of the five MSP7-related proteins (MSRPs) produced no detectable phenotype, establishing MSP7 as the functionally dominant family member in asexual blood stages.\",\n      \"method\": \"Targeted gene disruption of each family member individually in P. falciparum 3D7, growth and invasion assays\",\n      \"journal\": \"Eukaryotic cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — systematic genetic analysis of all family members with quantitative phenotypic comparison; multiple knockouts with internal controls\",\n      \"pmids\": [\"20472690\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}]\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"PfSUB1 proteomics identified MSP7 (PF3D7_1335100) as a direct substrate within the MSP1/6/7 complex; SUB1 is responsible for its proteolytic processing at the late asexual blood stage, as established by a combined bioinformatic and proteomic analysis of the entire late asexual blood-stage proteome.\",\n      \"method\": \"Quantitative proteomics of SUB1-inhibited vs. control parasites, bioinformatic substrate prediction in P. falciparum\",\n      \"journal\": \"Infection and immunity\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — proteome-wide mass spectrometry approach; single lab but orthogonal to the earlier inhibitor study (PMID 19214190)\",\n      \"pmids\": [\"21220481\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Simultaneous disruption of both msp7 and plasmepsin-4 genes in P. berghei produced a virulence-attenuated blood-stage parasite with self-resolving infection, low parasitemia, absence of experimental cerebral malaria, and cross-species protection after convalescence, demonstrating that MSP7 deletion contributes to reduced parasite virulence in vivo.\",\n      \"method\": \"Sequential targeted gene disruption in P. berghei, in vivo mouse infection models (BALB/c and C57BL/6), parasitemia monitoring, cerebral malaria assessment, challenge experiments\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean double-knockout with in vivo phenotypic readouts, but MSP7 contribution cannot be fully separated from plasmepsin-4 in the combined mutant\",\n      \"pmids\": [\"22355558\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Deletion of msp7 alone in P. berghei in BALB/c mice and Wistar rats abrogated death and reduced peak circulating parasitemia from ~3% to ~2%, and was associated with less anemia, establishing that MSP7 contributes to blood-stage disease severity beyond its role in erythrocyte invasion efficiency.\",\n      \"method\": \"P. berghei Δmsp7 knockout, in vivo infection of BALB/c mice and Wistar rats, parasitemia monitoring, hematological measurements, splenic histology\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean knockout with quantitative in vivo phenotype in two host species; single lab\",\n      \"pmids\": [\"21980474\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Synthetic peptides spanning the MSP7 (PF3D7_1335100) sequence identified five high-activity binding peptides (HABPs) that bind specifically to the erythrocyte surface and recognize a 52 kDa erythrocyte membrane protein; binding was sensitive to enzymatic treatment. MSP7 HABPs displayed differential erythrocyte invasion inhibition (24–83%), suggesting MSP7 participates directly in erythrocyte binding during invasion.\",\n      \"method\": \"Synthetic peptide RBC binding assays, enzymatic treatment of RBCs, invasion inhibition assays in P. falciparum\",\n      \"journal\": \"Journal of medicinal chemistry\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — peptide binding assay only; single lab, peptide-based approach does not recapitulate full protein interactions\",\n      \"pmids\": [\"17944453\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"MSP7 (PF3D7_1335100) is part of an MSP1 complex that also includes MSP3, MSP6, and MSP9, as established by immunoprecipitation of merozoite lysate with anti-MSP3 antibodies followed by mass spectrometry; direct protein-protein interactions within this complex (MSP1–MSP3, MSP1–MSP6, MSP1–MSP7) were confirmed by ELISA and surface plasmon resonance.\",\n      \"method\": \"Immunoprecipitation of merozoite lysate, mass spectrometry, ELISA-based binding, surface plasmon resonance in P. falciparum\",\n      \"journal\": \"Infection and immunity\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — orthogonal methods (MS + SPR + ELISA); single lab but multiple biochemical validations\",\n      \"pmids\": [\"29760216\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Members of the MSP7-related protein (MSRP) family were identified as PEXEL/HT-negative exported proteins (PNEPs) in P. falciparum, indicating that certain MSRPs are exported into the host erythrocyte by a translocation mechanism that does not require the canonical PEXEL motif, suggesting unanticipated functions for the MSP7 family beyond the merozoite surface.\",\n      \"method\": \"Reporter fusion assays, live fluorescence microscopy, immunofluorescence in P. falciparum\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — finding applies to MSRP family members rather than PF3D7_1335100 (MSP7) specifically; single lab; abstract does not specify which MSRP members are exported\",\n      \"pmids\": [\"23950716\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1335100 (MSP7) is a peripheral merozoite surface protein that is synthesized as a ~351-aa precursor in schizonts, forms a complex with the MSP1 precursor in a post-Golgi compartment, and undergoes sequential proteolytic processing—first by an unidentified brefeldin A-sensitive protease to yield MSP7(33) (which remains bound to MSP1) and MSP7(20), then by PfSUB1 on the merozoite surface to generate MSP7(22), which is shed as part of the MSP1/6/7 complex at the tight junction during erythrocyte invasion; MSP7 binds directly to the p83, p30, and p38 shed subunits of MSP1 (but not the GPI-anchored MSP1-42/19), contributes to erythrocyte invasion efficiency (its genetic deletion reduces invasion and in vivo parasite growth/virulence without altering MSP1 processing), and additionally binds human P-selectin via its N-terminus, potentially modulating host inflammatory responses.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MSP7 (PF3D7_1335100) is a peripheral merozoite surface protein of Plasmodium that assembles with the MSP1 precursor to form part of the MSP1 surface complex and contributes to efficient erythrocyte invasion during the asexual blood stage [#1, #4]. It is synthesized as a ~351-aa precursor in schizonts and undergoes sequential proteolytic maturation: a brefeldin A-sensitive primary cleavage in a post-Golgi compartment generates N-terminal MSP7(20) and C-terminal MSP7(33), with MSP7(33) remaining bound to full-length MSP1, followed by a surface secondary cleavage yielding MSP7(22) [#0, #1]. This surface maturation is carried out by the subtilisin-like protease PfSUB1, which directly processes MSP7 within the MSP1/6/7 complex prior to egress; blocking PfSUB1 leaves unprocessed MSP7 on the merozoite surface and reduces invasion [#3, #12]. MSP7 binds MSP1 directly and independently of MSP6, attaching to the shed p83, p30, and p38 subunits but not the GPI-anchored MSP1-42/19 region, defining it as a peripherally attached component of one of several distinct MSP1 complexes that engage the erythrocyte surface [#2, #16]. The mature complex, including MSP7, is shed at the tight junction during invasion [#9]. Genetic disruption of msp7 is not lethal but impairs invasion without perturbing MSP1 expression or processing, and in P. berghei attenuates blood-stage growth and virulence in vivo [#4, #5, #14]; among the MSP7 gene family, only PF3D7_1335100 produces a detectable growth/invasion phenotype on deletion [#11]. Beyond its merozoite-surface role, MSP7 binds human P-selectin via its N-terminus at the C-type lectin and EGF-like domains, blocking P-selectin engagement of its Sialyl-Lewis(X) ligand [#7].\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Establishing MSP7 as a processed merozoite surface protein answered whether it is a stable structural protein or a transiently displayed, shed molecule, framing it as an invasion-associated surface antigen.\",\n      \"evidence\": \"Gene sequencing, immunoblot and mass spectrometry of P. falciparum merozoite surface proteins\",\n      \"pmids\": [\"11551634\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define the protease(s) responsible for processing\", \"Did not establish a functional role in invasion\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Identifying MSP7 as a direct binding partner of the MSP1 N-terminal fragment addressed how MSP7 is displayed on the surface, showing it is recruited through direct association with MSP1.\",\n      \"evidence\": \"Yeast two-hybrid screen, in vitro binding, and immunofluorescence co-localization in P. yoelii\",\n      \"pmids\": [\"12477792\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Yeast two-hybrid is indirect and shown in P. yoelii\", \"Did not map which MSP1 subunits bind MSP7\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Knocking out msp7 in P. berghei tested whether the protein is essential and revealed it is dispensable for viability but contributes to blood-stage growth and erythrocyte tropism.\",\n      \"evidence\": \"Targeted gene disruption with in vivo mouse infection and parasitemia monitoring in P. berghei\",\n      \"pmids\": [\"15339842\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism linking MSP7 loss to reticulocyte preference unresolved\", \"P. berghei phenotype not yet confirmed in a human-infective species\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Dissecting the biosynthetic pathway and mapping the MSP1 binding sites resolved where, when, and how MSP7 is processed and assembled onto MSP1.\",\n      \"evidence\": \"Pulse-chase labeling with inhibitor dissection, plus in vitro reconstitution with recombinant MSP1/MSP6/MSP7 and biophysical sizing in P. falciparum\",\n      \"pmids\": [\"17097159\", \"16940297\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"The brefeldin A-sensitive primary protease was not identified\", \"Functional consequence of multi-site binding not tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Peptide binding assays probed whether MSP7 itself contacts the erythrocyte, indicating direct receptor engagement, but by a low-resolution surrogate approach.\",\n      \"evidence\": \"Synthetic high-activity binding peptides, RBC binding with enzymatic treatment, and invasion inhibition in P. falciparum\",\n      \"pmids\": [\"17944453\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Peptide binding does not recapitulate full-length protein interactions\", \"The 52 kDa erythrocyte partner was not molecularly identified\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"A clean P. falciparum knockout tested whether the invasion role is conserved in a human parasite and showed MSP7 loss impairs invasion without disrupting other surface protein processing.\",\n      \"evidence\": \"Targeted disruption in P. falciparum D10 with Southern, immunoblot, immunofluorescence and invasion assays\",\n      \"pmids\": [\"18820076\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not identify the molecular step of invasion that MSP7 assists\", \"No evidence for compensatory alternative invasion pathway\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"D10\"}]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Identifying PfSUB1 as the maturase resolved the enzyme responsible for MSP7 surface processing and linked that processing to invasion competence.\",\n      \"evidence\": \"PfSUB1 inhibition with immunoblot of surface proteins and invasion assays in P. falciparum\",\n      \"pmids\": [\"19214190\", \"21220481\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not distinguish the invasion contribution of MSP7 processing from that of co-substrates MSP1/MSP6\", \"Primary post-Golgi protease remains unidentified\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Live imaging and family-wide knockouts localized MSP7 shedding to the tight junction and established PF3D7_1335100 as the functionally dominant family member.\",\n      \"evidence\": \"Time-lapse invasion imaging with immunofluorescence, plus individual disruption of all MSP7-family genes with growth/invasion assays in P. falciparum\",\n      \"pmids\": [\"24218484\", \"20472690\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular trigger of shedding not defined\", \"Why MSRP paralogs are phenotypically silent in blood stages is unexplained\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"In vivo P. berghei studies established that MSP7 loss reduces disease severity and virulence, extending its role beyond invasion efficiency.\",\n      \"evidence\": \"Single and double (msp7/plasmepsin-4) knockouts with mouse and rat infection, hematology, and cerebral malaria assessment in P. berghei\",\n      \"pmids\": [\"21980474\", \"22355558\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"In the double mutant, MSP7's contribution cannot be fully separated from plasmepsin-4\", \"Molecular basis of the virulence effect is unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Extracellular interaction screening uncovered a host-directed activity, showing MSP7 binds human P-selectin and blocks its carbohydrate ligand, and confirmed reciprocal, erythrocyte-engaging MSP1 complexes.\",\n      \"evidence\": \"AVEXIS screen, domain-mapping binding and competition assays for P-selectin; Co-IP, recombinant binding and erythrocyte binding for MSP1 complexes in P. falciparum\",\n      \"pmids\": [\"26045295\", \"26823464\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Physiological relevance of the P-selectin interaction during infection not demonstrated in vivo\", \"Single lab, single-species biochemical validation\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}, {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Compositional analysis defined the broader MSP1 complex membership, placing MSP7 alongside MSP3, MSP6, and MSP9 with direct MSP1 binding confirmed.\",\n      \"evidence\": \"Anti-MSP3 immunoprecipitation with mass spectrometry, ELISA and surface plasmon resonance in P. falciparum\",\n      \"pmids\": [\"29760216\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Stoichiometry and spatial arrangement of the multi-protein complex not resolved\", \"Single lab\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The identity of the brefeldin A-sensitive primary protease and the precise molecular step of invasion that MSP7 facilitates remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Primary post-Golgi protease that generates MSP7(33)/MSP7(20) unidentified\", \"Direct erythrocyte receptor for full-length MSP7 not defined\", \"In vivo relevance of MSP7-P-selectin binding untested\"],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005515\", \"supporting_discovery_ids\": [2, 6, 7, 8, 10, 16]},\n      {\"term_id\": \"GO:0070492\", \"supporting_discovery_ids\": [7]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0009986\", \"supporting_discovery_ids\": [0, 1, 9]},\n      {\"term_id\": \"GO:0020030\", \"supporting_discovery_ids\": [9]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006508\", \"supporting_discovery_ids\": [0, 1, 3, 12]},\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [4, 5, 8, 15]}\n    ],\n    \"complexes\": [\n      \"MSP1 merozoite surface complex (MSP1/6/7)\",\n      \"Extended MSP1 complex including MSP1, MSP3, MSP6, MSP9\"\n    ],\n    \"partners\": [\n      \"MSP1 (via shed p83, p30, p38 subunits)\",\n      \"MSP6 (independent co-member of MSP1 complex)\",\n      \"PfSUB1 (protease that processes MSP7)\",\n      \"Human P-selectin (C-type lectin and EGF-like domains)\",\n      \"Erythrocyte surface (~52 kDa membrane protein, peptide-level evidence)\"\n    ],\n    \"other_free_text\": [\n      \"Synthesized as a ~351-aa precursor in schizonts; processed to MSP7(33)/MSP7(20), then MSP7(22)/MSP7(19) by sequential cleavage [#0, #1].\",\n      \"Primary cleavage is brefeldin A-sensitive and occurs in a post-Golgi compartment before MSP1 primary processing; the responsible protease is unidentified [#1].\",\n      \"Secondary/surface processing is carried out by PfSUB1 and is required for efficient invasion [#3, #12].\",\n      \"Deletion is non-lethal but impairs invasion (P. falciparum) and reduces in vivo growth and virulence (P. berghei) without altering MSP1 processing [#4, #5, #14].\",\n      \"PF3D7_1335100 is the functionally dominant member of the MSP7 family in asexual blood stages; MSRP paralog deletions are phenotypically silent [#11].\",\n      \"MSRP family members (not PF3D7_1335100 specifically) were identified as PEXEL-negative exported proteins [#17].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1335100","name":null,"product":"merozoite surface protein 7","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"MSP7","evaluation":null}