{"gene":"PF3D7_1455800","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2004,"finding":"Disruption of the CCp2 (PfCCp2) gene locus by homologous recombination produced parasites capable of forming oocyst sporozoites but blocked in the salivary gland transition, establishing an essential role for CCp2 in mosquito-stage parasite development beyond oocyst sporozoite formation.","method":"Targeted gene disruption by homologous recombination; phenotypic analysis of transgenic parasites","journal":"The Journal of experimental medicine","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean knockout with defined developmental phenotype, replicated in sibling study (PMID:17950739)","pmids":["15184503"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2004,"finding":"CCp2 (PfCCp2) protein is expressed in a sexual stage-specific manner, localizes to the plasma membrane of mature gametocytes within the parasitophorous vacuole, is released during gametogenesis to surround complexes of newly emerged microgametes and macrogametes, and its expression markedly decreases after zygote formation.","method":"Transcript and protein expression analysis; cellular localization studies (immunofluorescence)","journal":"The Journal of experimental medicine","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — immunofluorescence localization replicated across multiple papers (PMIDs 15184503, 17950739, 16388802)","pmids":["15184503","17950739","16388802"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"finding":"Abrogation of PfCCp3 in gene-disruptant parasites leads to loss of CCp2 (PfCCp2) protein but not its transcript, indicating co-dependent protein expression among PfCCp1, PfCCp2, and PfCCp3 consistent with protein complex formation during gametocytogenesis.","method":"Gene disruption; Western blot and RT-PCR comparison of protein vs. mRNA levels in disruptant lines","journal":"Experimental parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic loss-of-function with orthogonal protein and transcript readouts, single lab","pmids":["16388802"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"finding":"CCp2 (PfCCp2) is expressed in stages II–V of gametocytogenesis and during early gamete formation, is present on the surface of both male and female gametocytes and macrogametes but absent from exflagellating microgametes; targeted gene disruption of CCp2 inhibits parasite development in the mosquito vector.","method":"Immunofluorescence; targeted gene disruption; mosquito infection assays","journal":"International journal for parasitology","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct localization experiments combined with genetic knockout and functional mosquito-stage phenotype, replicated across labs","pmids":["17950739"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"finding":"Antibodies directed against distinct domains of CCp2 (PfCCp2) support a complement-mediated decrease in gametocyte exflagellation, implicating CCp2 surface exposure in complement-mediated inhibition.","method":"Exflagellation assay with domain-specific antibodies in the presence of complement","journal":"International journal for parasitology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — functional antibody inhibition assay, single lab, mechanism inferred from inhibition rather than direct binding","pmids":["17950739"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"finding":"Co-immunoprecipitation of gametocyte lysates and affinity chromatography co-elution binding assays with recombinant PfCCp domains demonstrated that CCp2 (PfCCp2) participates in multi-protein complexes involving all six PfCCp proteins, with direct binding between distinct adhesion domains; loss of any single PfCCp protein leads to loss of others at the protein level, consistent with complex-dependent stabilization.","method":"Co-immunoprecipitation from gametocyte lysates; affinity chromatography co-elution with recombinant domains; five gene-disruptant parasite lines","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP plus recombinant domain binding assay plus multiple genetic knockouts, single lab but orthogonal methods","pmids":["19304662"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"Knockdown of the WD40-repeat protein PfWLP1 led to reduced protein levels of CCp2 (PfCCp2) in P. falciparum gametocytes, indicating that PfWLP1 interaction with the PfCCp-based adhesion complex is required for the stability of CCp2 within that complex.","method":"Reverse genetics (knockdown); Western blot quantification of CCp2 protein levels","journal":"Frontiers in cellular and infection microbiology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — genetic knockdown with protein-level readout for CCp2, single lab","pmids":["35923798"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"In Plasmodium yoelii, the ccp2 locus was used as a genomic insertion site to drive mCherry expression specifically in female gametocytes, confirming that ccp2 expression is female gametocyte-specific in this rodent malaria species.","method":"CRISPR/Cas9-mediated knockin of mCherry downstream of the ccp2 coding region; fluorescence imaging","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct genetic tagging experiment confirming female-specific expression, single lab","pmids":["30040976"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii","strain":""}]}],"current_model":"CCp2 (PF3D7_1455800) is a secreted, multi-adhesion-domain protein expressed exclusively in sexual-stage P. falciparum (stages II–V gametocytes and early gametes) that localizes to the parasitophorous vacuole membrane of gametocytes, is released extracellularly during gametogenesis to surround gamete complexes, participates as a member of a multi-protein complex with the other five PfCCp family proteins (stabilized in part by PfWLP1), and is essential for parasite development in the mosquito vector at a step after oocyst sporozoite formation but before salivary gland invasion; its surface exposure on gametocytes also renders it susceptible to complement-mediated inhibition of exflagellation by domain-specific antibodies."},"narrative":{"mechanistic_narrative":"CCp2 (PF3D7_1455800) is a sexual-stage-specific adhesion-domain protein of Plasmodium falciparum that is essential for parasite transmission through the mosquito vector [PMID:15184503, PMID:17950739]. It is expressed across gametocyte stages II–V and during early gamete formation, localizing to the plasma membrane of mature gametocytes within the parasitophorous vacuole and being released during gametogenesis to surround complexes of newly emerged micro- and macrogametes, with expression falling sharply after zygote formation [PMID:15184503, PMID:17950739, PMID:16388802]. CCp2 does not act in isolation: it assembles into a multi-protein complex containing all six PfCCp proteins through direct binding between distinct adhesion domains, and this assembly is mutually stabilizing, such that loss of any one member — or of the WD40-repeat partner PfWLP1 — reduces CCp2 protein levels without affecting its transcript [PMID:16388802, PMID:19304662, PMID:35923798]. Functionally, targeted disruption of CCp2 permits oocyst sporozoite formation but blocks the transition to salivary-gland invasion, defining a mosquito-stage developmental checkpoint [PMID:15184503], and its surface exposure on gametocytes renders it a target for complement-mediated inhibition of exflagellation by domain-specific antibodies [PMID:17950739]. In the rodent malaria P. yoelii, the ccp2 locus drives female-gametocyte-specific expression [PMID:30040976]. The molecular activity of CCp2 beyond adhesion-mediated complex assembly has not been characterized in the available corpus.","teleology":[{"year":2004,"claim":"Establishing whether CCp2 has a non-redundant role in the parasite life cycle, the first knockout defined a specific mosquito-stage transmission checkpoint downstream of oocyst sporozoite formation.","evidence":"Targeted gene disruption by homologous recombination with phenotypic analysis of mosquito-stage development in P. falciparum","pmids":["15184503"],"confidence":"High","gaps":["Molecular basis of the salivary-gland invasion block not identified","Does not define which molecular interaction of CCp2 is required for the transition"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2004,"claim":"Defining when and where CCp2 acts, expression and localization studies placed the protein at the gametocyte plasma membrane within the parasitophorous vacuole and showed its release around emerging gamete complexes during gametogenesis.","evidence":"Transcript/protein expression analysis and immunofluorescence localization in P. falciparum sexual stages","pmids":["15184503","17950739","16388802"],"confidence":"Medium","gaps":["Mechanism of extracellular release during gametogenesis unknown","Functional consequence of the surrounding of gamete complexes not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"claim":"Testing whether CCp proteins act independently, disruption of PfCCp3 was found to eliminate CCp2 protein but not its transcript, providing the first evidence of post-transcriptional co-dependence indicative of complex formation.","evidence":"Gene disruption with Western blot versus RT-PCR comparison of CCp2 protein and mRNA in disruptant lines","pmids":["16388802"],"confidence":"Medium","gaps":["Does not demonstrate direct physical interaction between CCp2 and CCp3","Single lab"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"claim":"Resolving the stage and cell-type distribution of CCp2 and confirming its transmission role, the protein was mapped to the surface of both sexes of gametocytes and macrogametes but not exflagellating microgametes, with knockout again blocking mosquito-stage development.","evidence":"Immunofluorescence, targeted gene disruption, and mosquito infection assays in P. falciparum","pmids":["17950739"],"confidence":"High","gaps":["Why CCp2 is lost from exflagellating microgametes is unexplained","Surface anchoring mechanism not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"claim":"Probing whether surface-exposed CCp2 is functionally accessible, domain-specific antibodies were shown to reduce exflagellation in a complement-dependent manner, marking CCp2 as a transmission-blocking-relevant surface antigen.","evidence":"Exflagellation assay with domain-specific antibodies in the presence of complement in P. falciparum","pmids":["17950739"],"confidence":"Medium","gaps":["Inhibition inferred rather than direct binding demonstrated","Which specific domain mediates the effect not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"claim":"Determining the physical architecture behind the co-dependence, reciprocal Co-IP and recombinant-domain binding assays demonstrated that CCp2 engages in direct adhesion-domain interactions within a six-member PfCCp complex whose members mutually stabilize one another.","evidence":"Co-immunoprecipitation from gametocyte lysates, affinity chromatography co-elution with recombinant domains, and five gene-disruptant lines in P. falciparum","pmids":["19304662"],"confidence":"High","gaps":["Stoichiometry and spatial organization of the complex not resolved","No structural model of the CCp2 domain interfaces","Single lab"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Extending the stability network beyond the CCp family, knockdown of the WD40-repeat protein PfWLP1 reduced CCp2 levels, identifying an additional partner required to maintain CCp2 within the adhesion complex.","evidence":"Reverse-genetic knockdown with Western blot quantification of CCp2 in P. falciparum gametocytes","pmids":["35923798"],"confidence":"Medium","gaps":["Whether PfWLP1 binds CCp2 directly not shown","Single lab"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Assessing conservation of expression pattern across species, tagging of the ccp2 locus in P. yoelii confirmed female-gametocyte-specific expression in a rodent malaria parasite.","evidence":"CRISPR/Cas9 knockin of mCherry downstream of ccp2 with fluorescence imaging in P. yoelii","pmids":["30040976"],"confidence":"Medium","gaps":["Does not test the function of ccp2 in P. yoelii","P. falciparum expression is reported in both sexes, so cross-species divergence in sex-specificity is unresolved"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":null,"claim":"The biochemical activity of CCp2 and the mechanistic reason its loss blocks the sporozoite-to-salivary-gland transition remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No enzymatic or ligand-binding activity assigned to CCp2 itself","The downstream event dependent on CCp2/the CCp complex at the salivary-gland step is unknown","No structural characterization of CCp2 domains"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfCCp six-member adhesion complex (all six PfCCp proteins) [#5]","PfCCp complex stabilized by PfWLP1 [#6]"],"partners":["PFCCP1 [#5]","PFCCP3 [#2, #5]","OTHER PFCCP FAMILY PROTEINS [#5]","PFWLP1 (WD40-REPEAT PROTEIN) [#6]"],"other_free_text":["Sexual-stage-specific expression across gametocyte stages II–V and early gametes; released during gametogenesis to surround gamete complexes and downregulated after zygote formation [#1, #3]","Knockout permits oocyst sporozoite formation but blocks salivary-gland transition in the mosquito [#0]","Surface exposure makes CCp2 a target for complement-mediated, antibody-dependent inhibition of exflagellation [#4]","In P. yoelii, ccp2 is female-gametocyte-specific [#7], whereas in P. falciparum CCp2 is detected on both male and female gametocytes [#3]"]}},"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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CCp2 in mosquito-stage parasite development beyond oocyst sporozoite formation.\",\n      \"method\": \"Targeted gene disruption by homologous recombination; phenotypic analysis of transgenic parasites\",\n      \"journal\": \"The Journal of experimental medicine\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean knockout with defined developmental phenotype, replicated in sibling study (PMID:17950739)\",\n      \"pmids\": [\"15184503\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"CCp2 (PfCCp2) protein is expressed in a sexual stage-specific manner, localizes to the plasma membrane of mature gametocytes within the parasitophorous vacuole, is released during gametogenesis to surround complexes of newly emerged microgametes and macrogametes, and its expression markedly decreases after zygote formation.\",\n      \"method\": \"Transcript and protein expression analysis; cellular localization studies (immunofluorescence)\",\n      \"journal\": \"The Journal of experimental medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — immunofluorescence localization replicated across multiple papers (PMIDs 15184503, 17950739, 16388802)\",\n      \"pmids\": [\"15184503\", \"17950739\", \"16388802\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Abrogation of PfCCp3 in gene-disruptant parasites leads to loss of CCp2 (PfCCp2) protein but not its transcript, indicating co-dependent protein expression among PfCCp1, PfCCp2, and PfCCp3 consistent with protein complex formation during gametocytogenesis.\",\n      \"method\": \"Gene disruption; Western blot and RT-PCR comparison of protein vs. mRNA levels in disruptant lines\",\n      \"journal\": \"Experimental parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic loss-of-function with orthogonal protein and transcript readouts, single lab\",\n      \"pmids\": [\"16388802\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"CCp2 (PfCCp2) is expressed in stages II–V of gametocytogenesis and during early gamete formation, is present on the surface of both male and female gametocytes and macrogametes but absent from exflagellating microgametes; targeted gene disruption of CCp2 inhibits parasite development in the mosquito vector.\",\n      \"method\": \"Immunofluorescence; targeted gene disruption; mosquito infection assays\",\n      \"journal\": \"International journal for parasitology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct localization experiments combined with genetic knockout and functional mosquito-stage phenotype, replicated across labs\",\n      \"pmids\": [\"17950739\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Antibodies directed against distinct domains of CCp2 (PfCCp2) support a complement-mediated decrease in gametocyte exflagellation, implicating CCp2 surface exposure in complement-mediated inhibition.\",\n      \"method\": \"Exflagellation assay with domain-specific antibodies in the presence of complement\",\n      \"journal\": \"International journal for parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — functional antibody inhibition assay, single lab, mechanism inferred from inhibition rather than direct binding\",\n      \"pmids\": [\"17950739\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Co-immunoprecipitation of gametocyte lysates and affinity chromatography co-elution binding assays with recombinant PfCCp domains demonstrated that CCp2 (PfCCp2) participates in multi-protein complexes involving all six PfCCp proteins, with direct binding between distinct adhesion domains; loss of any single PfCCp protein leads to loss of others at the protein level, consistent with complex-dependent stabilization.\",\n      \"method\": \"Co-immunoprecipitation from gametocyte lysates; affinity chromatography co-elution with recombinant domains; five gene-disruptant parasite lines\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP plus recombinant domain binding assay plus multiple genetic knockouts, single lab but orthogonal methods\",\n      \"pmids\": [\"19304662\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Knockdown of the WD40-repeat protein PfWLP1 led to reduced protein levels of CCp2 (PfCCp2) in P. falciparum gametocytes, indicating that PfWLP1 interaction with the PfCCp-based adhesion complex is required for the stability of CCp2 within that complex.\",\n      \"method\": \"Reverse genetics (knockdown); Western blot quantification of CCp2 protein levels\",\n      \"journal\": \"Frontiers in cellular and infection microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — genetic knockdown with protein-level readout for CCp2, single lab\",\n      \"pmids\": [\"35923798\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"In Plasmodium yoelii, the ccp2 locus was used as a genomic insertion site to drive mCherry expression specifically in female gametocytes, confirming that ccp2 expression is female gametocyte-specific in this rodent malaria species.\",\n      \"method\": \"CRISPR/Cas9-mediated knockin of mCherry downstream of the ccp2 coding region; fluorescence imaging\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct genetic tagging experiment confirming female-specific expression, single lab\",\n      \"pmids\": [\"30040976\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"CCp2 (PF3D7_1455800) is a secreted, multi-adhesion-domain protein expressed exclusively in sexual-stage P. falciparum (stages II–V gametocytes and early gametes) that localizes to the parasitophorous vacuole membrane of gametocytes, is released extracellularly during gametogenesis to surround gamete complexes, participates as a member of a multi-protein complex with the other five PfCCp family proteins (stabilized in part by PfWLP1), and is essential for parasite development in the mosquito vector at a step after oocyst sporozoite formation but before salivary gland invasion; its surface exposure on gametocytes also renders it susceptible to complement-mediated inhibition of exflagellation by domain-specific antibodies.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CCp2 (PF3D7_1455800) is a sexual-stage-specific adhesion-domain protein of Plasmodium falciparum that is essential for parasite transmission through the mosquito vector [#0, #3]. It is expressed across gametocyte stages II–V and during early gamete formation, localizing to the plasma membrane of mature gametocytes within the parasitophorous vacuole and being released during gametogenesis to surround complexes of newly emerged micro- and macrogametes, with expression falling sharply after zygote formation [#1, #3]. CCp2 does not act in isolation: it assembles into a multi-protein complex containing all six PfCCp proteins through direct binding between distinct adhesion domains, and this assembly is mutually stabilizing, such that loss of any one member — or of the WD40-repeat partner PfWLP1 — reduces CCp2 protein levels without affecting its transcript [#2, #5, #6]. Functionally, targeted disruption of CCp2 permits oocyst sporozoite formation but blocks the transition to salivary-gland invasion, defining a mosquito-stage developmental checkpoint [#0], and its surface exposure on gametocytes renders it a target for complement-mediated inhibition of exflagellation by domain-specific antibodies [#4]. In the rodent malaria P. yoelii, the ccp2 locus drives female-gametocyte-specific expression [#7]. The molecular activity of CCp2 beyond adhesion-mediated complex assembly has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"Establishing whether CCp2 has a non-redundant role in the parasite life cycle, the first knockout defined a specific mosquito-stage transmission checkpoint downstream of oocyst sporozoite formation.\",\n      \"evidence\": \"Targeted gene disruption by homologous recombination with phenotypic analysis of mosquito-stage development in P. falciparum\",\n      \"pmids\": [\"15184503\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular basis of the salivary-gland invasion block not identified\", \"Does not define which molecular interaction of CCp2 is required for the transition\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Defining when and where CCp2 acts, expression and localization studies placed the protein at the gametocyte plasma membrane within the parasitophorous vacuole and showed its release around emerging gamete complexes during gametogenesis.\",\n      \"evidence\": \"Transcript/protein expression analysis and immunofluorescence localization in P. falciparum sexual stages\",\n      \"pmids\": [\"15184503\", \"17950739\", \"16388802\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of extracellular release during gametogenesis unknown\", \"Functional consequence of the surrounding of gamete complexes not established\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Testing whether CCp proteins act independently, disruption of PfCCp3 was found to eliminate CCp2 protein but not its transcript, providing the first evidence of post-transcriptional co-dependence indicative of complex formation.\",\n      \"evidence\": \"Gene disruption with Western blot versus RT-PCR comparison of CCp2 protein and mRNA in disruptant lines\",\n      \"pmids\": [\"16388802\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not demonstrate direct physical interaction between CCp2 and CCp3\", \"Single lab\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Resolving the stage and cell-type distribution of CCp2 and confirming its transmission role, the protein was mapped to the surface of both sexes of gametocytes and macrogametes but not exflagellating microgametes, with knockout again blocking mosquito-stage development.\",\n      \"evidence\": \"Immunofluorescence, targeted gene disruption, and mosquito infection assays in P. falciparum\",\n      \"pmids\": [\"17950739\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Why CCp2 is lost from exflagellating microgametes is unexplained\", \"Surface anchoring mechanism not defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Probing whether surface-exposed CCp2 is functionally accessible, domain-specific antibodies were shown to reduce exflagellation in a complement-dependent manner, marking CCp2 as a transmission-blocking-relevant surface antigen.\",\n      \"evidence\": \"Exflagellation assay with domain-specific antibodies in the presence of complement in P. falciparum\",\n      \"pmids\": [\"17950739\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Inhibition inferred rather than direct binding demonstrated\", \"Which specific domain mediates the effect not resolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Determining the physical architecture behind the co-dependence, reciprocal Co-IP and recombinant-domain binding assays demonstrated that CCp2 engages in direct adhesion-domain interactions within a six-member PfCCp complex whose members mutually stabilize one another.\",\n      \"evidence\": \"Co-immunoprecipitation from gametocyte lysates, affinity chromatography co-elution with recombinant domains, and five gene-disruptant lines in P. falciparum\",\n      \"pmids\": [\"19304662\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Stoichiometry and spatial organization of the complex not resolved\", \"No structural model of the CCp2 domain interfaces\", \"Single lab\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Extending the stability network beyond the CCp family, knockdown of the WD40-repeat protein PfWLP1 reduced CCp2 levels, identifying an additional partner required to maintain CCp2 within the adhesion complex.\",\n      \"evidence\": \"Reverse-genetic knockdown with Western blot quantification of CCp2 in P. falciparum gametocytes\",\n      \"pmids\": [\"35923798\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether PfWLP1 binds CCp2 directly not shown\", \"Single lab\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Assessing conservation of expression pattern across species, tagging of the ccp2 locus in P. yoelii confirmed female-gametocyte-specific expression in a rodent malaria parasite.\",\n      \"evidence\": \"CRISPR/Cas9 knockin of mCherry downstream of ccp2 with fluorescence imaging in P. yoelii\",\n      \"pmids\": [\"30040976\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not test the function of ccp2 in P. yoelii\", \"P. falciparum expression is reported in both sexes, so cross-species divergence in sex-specificity is unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical activity of CCp2 and the mechanistic reason its loss blocks the sporozoite-to-salivary-gland transition remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No enzymatic or ligand-binding activity assigned to CCp2 itself\", \"The downstream event dependent on CCp2/the CCp complex at the salivary-gland step is unknown\", \"No structural characterization of CCp2 domains\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005515\", \"supporting_discovery_ids\": [2, 5, 6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020002\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0009986\", \"supporting_discovery_ids\": [1, 3]},\n      {\"term_id\": \"GO:0005576\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0030437\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"complexes\": [\n      \"PfCCp six-member adhesion complex (all six PfCCp proteins) [#5]\",\n      \"PfCCp complex stabilized by PfWLP1 [#6]\"\n    ],\n    \"partners\": [\n      \"PfCCp1 [#5]\",\n      \"PfCCp3 [#2, #5]\",\n      \"other PfCCp family proteins [#5]\",\n      \"PfWLP1 (WD40-repeat protein) [#6]\"\n    ],\n    \"other_free_text\": [\n      \"Sexual-stage-specific expression across gametocyte stages II–V and early gametes; released during gametogenesis to surround gamete complexes and downregulated after zygote formation [#1, #3]\",\n      \"Knockout permits oocyst sporozoite formation but blocks salivary-gland transition in the mosquito [#0]\",\n      \"Surface exposure makes CCp2 a target for complement-mediated, antibody-dependent inhibition of exflagellation [#4]\",\n      \"In P. yoelii, ccp2 is female-gametocyte-specific [#7], whereas in P. falciparum CCp2 is detected on both male and female gametocytes [#3]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1455800","name":null,"product":"LCCL domain-containing protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1319500","name":null,"product":"LCCL domain-containing protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1226000","name":null,"product":"LCCL domain-containing protein","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"CCP2","evaluation":null}