{"gene":"PF3D7_1475500","run_date":"2026-09-08T15:24:04","timeline":{"discoveries":[{"year":2004,"finding":"CCp1 (PfCCp1) is a secreted, multi-domain adhesion protein with sexual stage-specific expression; it localizes to the parasitophorous vacuole membrane of mature gametocytes and is released during gametogenesis to surround newly emerged microgametes and macrogametes, with expression markedly decreasing after zygote formation.","method":"Transcript and protein expression analysis, cellular localization studies (immunofluorescence), genome annotation","journal":"The Journal of experimental medicine","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — localization established by direct immunofluorescence in a single lab study; functional consequence (transmission) established for paralogues PfCCp2/3 by gene disruption, not for CCp1 itself","pmids":["15184503"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"finding":"CCp1 (PfCCp1) protein expression is co-dependent with PfCCp2 and PfCCp3: disruption of PfCCp3 leads to loss of PfCCp1 and PfCCp2 protein but not their transcripts, indicating post-transcriptional co-dependent regulation consistent with protein complex formation.","method":"Gene disruption (PfCCp3 knockout), Western blot, RT-PCR","journal":"Experimental parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean gene disruptant with paired protein/mRNA analysis, single lab, two orthogonal methods","pmids":["16388802"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"finding":"CCp1 (PfCCp1) is expressed in gametocyte stages II–V and during early gamete formation, is associated with the surface of both male and female gametocytes and macrogametes but absent from exflagellating microgametes; antibodies directed against distinct domains of PfCCp1 support complement-mediated decrease in gametocyte emergence (exflagellation inhibition).","method":"Immunofluorescence, exflagellation assay with domain-specific antibodies and complement","journal":"International journal for parasitology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization by immunofluorescence and functional antibody inhibition assay, single lab","pmids":["17950739"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"finding":"CCp1 (PfCCp1) participates in multi-protein complexes with other PfCCp family members during gametocyte development: co-immunoprecipitation assays on gametocyte lysates demonstrated complex formation involving PfCCp1 alongside other PfCCp proteins, and affinity chromatography co-elution with recombinant PfCCp domains indicated direct binding between distinct adhesion domains. Loss of any single PfCCp protein leads to loss of other family members.","method":"Co-immunoprecipitation, affinity chromatography co-elution with recombinant domains, five gene-disruptant parasite lines, latex bead binding assay","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP on native lysates, recombinant domain binding, gene disruptants, and bead-binding assay all in one study; multiple orthogonal methods replicated the complex formation conclusion","pmids":["19304662"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"CCp1 (PfCCp1) associates with the WD40-repeat protein PfWLP1 in gametocytes, as identified by co-immunoprecipitation followed by mass spectrometry; PfCCp1 co-localises with PfWLP1 underneath the gametocyte plasma membrane.","method":"Co-immunoprecipitation, mass spectrometry, immunolocalization","journal":"Malaria journal","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — Co-IP/MS identification of interaction, supported by co-localization, single lab","pmids":["26537493"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"CCp1 (PfCCp1) binds complement factors C3b and C4b, inhibits activation of the classical complement pathway in a biochemical assay, binds dendritic cells, and down-regulates TLR2-mediated signalling and pro-inflammatory cytokine expression, indicating an immunomodulatory function.","method":"Biochemical complement activation assay, protein-binding assay with recombinant PfCCp1, dendritic cell stimulation assay, TLR signalling measurement","journal":"The Biochemical journal","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — in vitro biochemical and cell-based assays with recombinant protein, single lab, no mutagenesis confirming active site","pmids":["30049893"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"CCp1 (PfCCp1) protein levels are reduced upon knockdown of PfWLP1, demonstrating that PfWLP1 is required for stability of the PfCCp1-containing adhesion complex in gametocytes; this complex stability is linked to gametocyte maturation and exflagellation.","method":"Reverse genetics (PfWLP1 knockdown), Western blot for PfCCp1 protein levels, exflagellation assay","journal":"Frontiers in cellular and infection microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function knockdown with specific protein-level readout for CCp1, single lab, two orthogonal functional endpoints","pmids":["35923798"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"CCp1 (PF3D7_1475500) is a secreted, multi-domain adhesion protein expressed on the surface of gametocytes and macrogametes in P. falciparum; it forms multi-protein complexes with other PfCCp family members (whose stability is mutually co-dependent at the protein level) and with the WD40-repeat protein PfWLP1, and it can bind human complement factors C3b/C4b to inhibit complement activation and down-regulate dendritic cell TLR2 signalling, implicating it in immune evasion during the extracellular sexual stages."},"narrative":{"mechanistic_narrative":"CCp1 (PF3D7_1475500) is a secreted, multi-domain adhesion protein of Plasmodium falciparum whose expression is restricted to the sexual stages, functioning at the interface of gametocyte maturation and host immune evasion [PMID:15184503, PMID:30049893]. It is expressed in gametocyte stages II–V, localizes to the parasitophorous vacuole membrane of mature gametocytes, and is released during gametogenesis to surround emerging macro- and microgametes, with expression falling sharply after zygote formation [PMID:15184503, PMID:17950739]. CCp1 does not act alone: it assembles into multi-protein complexes with other PfCCp family members and with the WD40-repeat protein PfWLP1, and the stability of these partners is mutually co-dependent at the protein level—disruption of PfCCp3 or knockdown of PfWLP1 depletes CCp1 protein without loss of its transcript [PMID:16388802, PMID:19304662, PMID:35923798]. Beyond its structural role in this adhesion complex, recombinant CCp1 binds the human complement factors C3b and C4b, inhibits classical-pathway complement activation, and engages dendritic cells to down-regulate TLR2 signalling and pro-inflammatory cytokine output, implicating it in immune evasion during the extracellular sexual stages [PMID:30049893]. No structural model of CCp1 or mutational mapping of its complement-binding or adhesion activities has been characterized in the available corpus.","teleology":[{"year":2004,"claim":"Establishing when and where CCp1 acts required defining its expression and localization; this showed it is a sexual-stage-specific secreted adhesion protein positioned to act on emerging gametes.","evidence":"Transcript/protein expression and immunofluorescence localization in P. falciparum gametocytes","pmids":["15184503"],"confidence":"Medium","gaps":["Functional consequence for transmission not tested for CCp1 itself","Single-lab localization"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"claim":"Whether CCp1 abundance depends on other family members was unknown; disruption of PfCCp3 abolished CCp1 protein but not transcript, revealing post-transcriptional co-dependence indicative of complex assembly.","evidence":"PfCCp3 gene disruption with paired Western blot and RT-PCR","pmids":["16388802"],"confidence":"Medium","gaps":["Direct physical interaction not shown in this study","Mechanism of post-transcriptional stabilization unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"claim":"To test functional relevance during gamete formation, domain-specific antibodies plus complement were used, showing CCp1 is surface-associated on gametocytes/macrogametes and its targeting reduces gametocyte emergence.","evidence":"Immunofluorescence and complement-dependent exflagellation-inhibition assay with domain-specific antibodies","pmids":["17950739"],"confidence":"Medium","gaps":["Absent from exflagellating microgametes—stage-specific role unclear","Antibody inhibition is indirect evidence of function"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"claim":"Direct evidence for complex membership was needed; reciprocal Co-IP, recombinant domain binding, and gene disruptants together demonstrated CCp1 forms multi-protein complexes with other PfCCp proteins via defined adhesion domains.","evidence":"Co-IP on native lysates, affinity co-elution with recombinant domains, five gene-disruptant lines, latex bead binding assay","pmids":["19304662"],"confidence":"High","gaps":["Stoichiometry and architecture of the complex not resolved","Which specific domain pairings mediate CCp1 contacts not fully mapped"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"To extend the interaction network beyond the PfCCp family, Co-IP/MS identified PfWLP1 as a CCp1 partner co-localizing beneath the gametocyte plasma membrane.","evidence":"Co-immunoprecipitation with mass spectrometry and immunolocalization","pmids":["26537493"],"confidence":"Medium","gaps":["Direct versus indirect binding not distinguished","Functional role of the CCp1–PfWLP1 association not tested here"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Whether CCp1 has activity toward the host was unknown; recombinant CCp1 was shown to bind C3b/C4b, inhibit classical complement activation, and dampen dendritic-cell TLR2 signalling, defining an immunomodulatory function.","evidence":"Biochemical complement-activation and protein-binding assays with recombinant CCp1, dendritic cell stimulation, TLR signalling readouts","pmids":["30049893"],"confidence":"Medium","gaps":["No mutagenesis mapping the complement/TLR-active regions","Activity shown in vitro with recombinant protein, not validated in intact parasites"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"To establish the direction of the CCp1–PfWLP1 dependency, PfWLP1 knockdown was shown to reduce CCp1 protein, defining PfWLP1 as required for stability of the CCp1-containing complex and linking it to maturation and exflagellation.","evidence":"PfWLP1 knockdown with Western blot for CCp1 and exflagellation assay","pmids":["35923798"],"confidence":"Medium","gaps":["Whether stabilization is direct or via the broader complex unclear","Effect on the complement/immunomodulatory function not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The structural basis of CCp1's adhesion and complement-binding activities, and whether its immunomodulatory function operates during natural transmission in vivo, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of CCp1 or its complexes","No mutational mapping of complement/TLR-binding determinants","In vivo relevance of immune evasion not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfCCp multi-protein adhesion complex (with other PfCCp family members)","CCp1–PfWLP1 subplasmalemmal complex"],"partners":["PFCCP2","PFCCP3","PFWLP1 (WD40-REPEAT PROTEIN)","HUMAN COMPLEMENT FACTOR C3B","HUMAN COMPLEMENT FACTOR C4B"],"other_free_text":["Expressed in gametocyte stages II–V and early gamete formation; released during gametogenesis to surround emerging gametes, with expression decreasing after zygote formation [#0, #2].","Protein-level abundance is co-dependent on other complex members: PfCCp3 disruption or PfWLP1 knockdown depletes CCp1 protein without loss of transcript [#1, #6].","Complex stability is linked to gametocyte maturation and exflagellation [#6]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"15184503","id":"PMC_15184503","title":"A multidomain adhesion protein family expressed in Plasmodium falciparum is essential for transmission to the mosquito.","date":"2004","source":"The Journal of experimental 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surround newly emerged microgametes and macrogametes, with expression markedly decreasing after zygote formation.\",\n      \"method\": \"Transcript and protein expression analysis, cellular localization studies (immunofluorescence), genome annotation\",\n      \"journal\": \"The Journal of experimental medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — localization established by direct immunofluorescence in a single lab study; functional consequence (transmission) established for paralogues PfCCp2/3 by gene disruption, not for CCp1 itself\",\n      \"pmids\": [\"15184503\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"CCp1 (PfCCp1) protein expression is co-dependent with PfCCp2 and PfCCp3: disruption of PfCCp3 leads to loss of PfCCp1 and PfCCp2 protein but not their transcripts, indicating post-transcriptional co-dependent regulation consistent with protein complex formation.\",\n      \"method\": \"Gene disruption (PfCCp3 knockout), Western blot, RT-PCR\",\n      \"journal\": \"Experimental parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean gene disruptant with paired protein/mRNA analysis, single lab, two orthogonal methods\",\n      \"pmids\": [\"16388802\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"CCp1 (PfCCp1) is expressed in gametocyte stages II–V and during early gamete formation, is associated with the surface of both male and female gametocytes and macrogametes but absent from exflagellating microgametes; antibodies directed against distinct domains of PfCCp1 support complement-mediated decrease in gametocyte emergence (exflagellation inhibition).\",\n      \"method\": \"Immunofluorescence, exflagellation assay with domain-specific antibodies and complement\",\n      \"journal\": \"International journal for parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization by immunofluorescence and functional antibody inhibition assay, single lab\",\n      \"pmids\": [\"17950739\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"CCp1 (PfCCp1) participates in multi-protein complexes with other PfCCp family members during gametocyte development: co-immunoprecipitation assays on gametocyte lysates demonstrated complex formation involving PfCCp1 alongside other PfCCp proteins, and affinity chromatography co-elution with recombinant PfCCp domains indicated direct binding between distinct adhesion domains. Loss of any single PfCCp protein leads to loss of other family members.\",\n      \"method\": \"Co-immunoprecipitation, affinity chromatography co-elution with recombinant domains, five gene-disruptant parasite lines, latex bead binding assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP on native lysates, recombinant domain binding, gene disruptants, and bead-binding assay all in one study; multiple orthogonal methods replicated the complex formation conclusion\",\n      \"pmids\": [\"19304662\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"CCp1 (PfCCp1) associates with the WD40-repeat protein PfWLP1 in gametocytes, as identified by co-immunoprecipitation followed by mass spectrometry; PfCCp1 co-localises with PfWLP1 underneath the gametocyte plasma membrane.\",\n      \"method\": \"Co-immunoprecipitation, mass spectrometry, immunolocalization\",\n      \"journal\": \"Malaria journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — Co-IP/MS identification of interaction, supported by co-localization, single lab\",\n      \"pmids\": [\"26537493\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"CCp1 (PfCCp1) binds complement factors C3b and C4b, inhibits activation of the classical complement pathway in a biochemical assay, binds dendritic cells, and down-regulates TLR2-mediated signalling and pro-inflammatory cytokine expression, indicating an immunomodulatory function.\",\n      \"method\": \"Biochemical complement activation assay, protein-binding assay with recombinant PfCCp1, dendritic cell stimulation assay, TLR signalling measurement\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — in vitro biochemical and cell-based assays with recombinant protein, single lab, no mutagenesis confirming active site\",\n      \"pmids\": [\"30049893\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CCp1 (PfCCp1) protein levels are reduced upon knockdown of PfWLP1, demonstrating that PfWLP1 is required for stability of the PfCCp1-containing adhesion complex in gametocytes; this complex stability is linked to gametocyte maturation and exflagellation.\",\n      \"method\": \"Reverse genetics (PfWLP1 knockdown), Western blot for PfCCp1 protein levels, exflagellation assay\",\n      \"journal\": \"Frontiers in cellular and infection microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function knockdown with specific protein-level readout for CCp1, single lab, two orthogonal functional endpoints\",\n      \"pmids\": [\"35923798\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"CCp1 (PF3D7_1475500) is a secreted, multi-domain adhesion protein expressed on the surface of gametocytes and macrogametes in P. falciparum; it forms multi-protein complexes with other PfCCp family members (whose stability is mutually co-dependent at the protein level) and with the WD40-repeat protein PfWLP1, and it can bind human complement factors C3b/C4b to inhibit complement activation and down-regulate dendritic cell TLR2 signalling, implicating it in immune evasion during the extracellular sexual stages.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CCp1 (PF3D7_1475500) is a secreted, multi-domain adhesion protein of Plasmodium falciparum whose expression is restricted to the sexual stages, functioning at the interface of gametocyte maturation and host immune evasion [#0, #5]. It is expressed in gametocyte stages II\\u2013V, localizes to the parasitophorous vacuole membrane of mature gametocytes, and is released during gametogenesis to surround emerging macro- and microgametes, with expression falling sharply after zygote formation [#0, #2]. CCp1 does not act alone: it assembles into multi-protein complexes with other PfCCp family members and with the WD40-repeat protein PfWLP1, and the stability of these partners is mutually co-dependent at the protein level\\u2014disruption of PfCCp3 or knockdown of PfWLP1 depletes CCp1 protein without loss of its transcript [#1, #3, #6]. Beyond its structural role in this adhesion complex, recombinant CCp1 binds the human complement factors C3b and C4b, inhibits classical-pathway complement activation, and engages dendritic cells to down-regulate TLR2 signalling and pro-inflammatory cytokine output, implicating it in immune evasion during the extracellular sexual stages [#5]. No structural model of CCp1 or mutational mapping of its complement-binding or adhesion activities has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"Establishing when and where CCp1 acts required defining its expression and localization; this showed it is a sexual-stage-specific secreted adhesion protein positioned to act on emerging gametes.\",\n      \"evidence\": \"Transcript/protein expression and immunofluorescence localization in P. falciparum gametocytes\",\n      \"pmids\": [\"15184503\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence for transmission not tested for CCp1 itself\", \"Single-lab localization\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Whether CCp1 abundance depends on other family members was unknown; disruption of PfCCp3 abolished CCp1 protein but not transcript, revealing post-transcriptional co-dependence indicative of complex assembly.\",\n      \"evidence\": \"PfCCp3 gene disruption with paired Western blot and RT-PCR\",\n      \"pmids\": [\"16388802\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct physical interaction not shown in this study\", \"Mechanism of post-transcriptional stabilization unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"To test functional relevance during gamete formation, domain-specific antibodies plus complement were used, showing CCp1 is surface-associated on gametocytes/macrogametes and its targeting reduces gametocyte emergence.\",\n      \"evidence\": \"Immunofluorescence and complement-dependent exflagellation-inhibition assay with domain-specific antibodies\",\n      \"pmids\": [\"17950739\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Absent from exflagellating microgametes\\u2014stage-specific role unclear\", \"Antibody inhibition is indirect evidence of function\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Direct evidence for complex membership was needed; reciprocal Co-IP, recombinant domain binding, and gene disruptants together demonstrated CCp1 forms multi-protein complexes with other PfCCp proteins via defined adhesion domains.\",\n      \"evidence\": \"Co-IP on native lysates, affinity co-elution with recombinant domains, five gene-disruptant lines, latex bead binding assay\",\n      \"pmids\": [\"19304662\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Stoichiometry and architecture of the complex not resolved\", \"Which specific domain pairings mediate CCp1 contacts not fully mapped\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"To extend the interaction network beyond the PfCCp family, Co-IP/MS identified PfWLP1 as a CCp1 partner co-localizing beneath the gametocyte plasma membrane.\",\n      \"evidence\": \"Co-immunoprecipitation with mass spectrometry and immunolocalization\",\n      \"pmids\": [\"26537493\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct versus indirect binding not distinguished\", \"Functional role of the CCp1\\u2013PfWLP1 association not tested here\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether CCp1 has activity toward the host was unknown; recombinant CCp1 was shown to bind C3b/C4b, inhibit classical complement activation, and dampen dendritic-cell TLR2 signalling, defining an immunomodulatory function.\",\n      \"evidence\": \"Biochemical complement-activation and protein-binding assays with recombinant CCp1, dendritic cell stimulation, TLR signalling readouts\",\n      \"pmids\": [\"30049893\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No mutagenesis mapping the complement/TLR-active regions\", \"Activity shown in vitro with recombinant protein, not validated in intact parasites\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"To establish the direction of the CCp1\\u2013PfWLP1 dependency, PfWLP1 knockdown was shown to reduce CCp1 protein, defining PfWLP1 as required for stability of the CCp1-containing complex and linking it to maturation and exflagellation.\",\n      \"evidence\": \"PfWLP1 knockdown with Western blot for CCp1 and exflagellation assay\",\n      \"pmids\": [\"35923798\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether stabilization is direct or via the broader complex unclear\", \"Effect on the complement/immunomodulatory function not tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The structural basis of CCp1's adhesion and complement-binding activities, and whether its immunomodulatory function operates during natural transmission in vivo, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of CCp1 or its complexes\", \"No mutational mapping of complement/TLR-binding determinants\", \"In vivo relevance of immune evasion not established\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005102\", \"supporting_discovery_ids\": [3, 5]},\n      {\"term_id\": \"GO:0001848\", \"supporting_discovery_ids\": [5]},\n      {\"term_id\": \"GO:0030449\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [2, 4]},\n      {\"term_id\": \"GO:0020005\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005576\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0009986\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0019953\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0042832\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"complexes\": [\n      \"PfCCp multi-protein adhesion complex (with other PfCCp family members)\",\n      \"CCp1\\u2013PfWLP1 subplasmalemmal complex\"\n    ],\n    \"partners\": [\n      \"PfCCp2\",\n      \"PfCCp3\",\n      \"PfWLP1 (WD40-repeat protein)\",\n      \"human complement factor C3b\",\n      \"human complement factor C4b\"\n    ],\n    \"other_free_text\": [\n      \"Expressed in gametocyte stages II\\u2013V and early gamete formation; released during gametogenesis to surround emerging gametes, with expression decreasing after zygote formation [#0, #2].\",\n      \"Protein-level abundance is co-dependent on other complex members: PfCCp3 disruption or PfWLP1 knockdown depletes CCp1 protein without loss of transcript [#1, #6].\",\n      \"Complex stability is linked to gametocyte maturation and exflagellation [#6].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1475500","name":null,"product":"LCCL domain-containing protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1300700","name":null,"product":"LCCL domain-containing protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1245800","name":null,"product":"LCCL domain-containing protein","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"CCp1","evaluation":null}