{"gene":"TG_300130","gene_symbol":"AMA2","run_date":"2026-09-08T15:15:12","timeline":{"discoveries":[{"year":2014,"finding":"AMA1 interacts with RON2 to maintain moving junction (MJ) structural integrity in T. gondii and is required for parasite internalization; disruption of AMA1 gene results in upregulation of AMA2 and RON2 homologues that cooperate to support residual invasion, demonstrating molecular plasticity and redundancy among AMA-RON pairs.","method":"Reverse genetics (AMA1 gene disruption), upregulation analysis of homologues, functional invasion assays","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic epistasis via reverse genetics with defined phenotypic readout (MJ integrity, internalization), with functional follow-up on AMA2 upregulation and residual invasion","pmids":["24934579"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"finding":"In bradyzoites, the moving junction relies on AMA2 and AMA4 (instead of tachyzoite AMA1), indicating that AMA2 is a paralog used specifically in bradyzoite-stage host cell invasion via an MJ-dependent mechanism.","method":"Molecular characterization of bradyzoite MJ protein composition; functional characterization of AMA4 by loss-of-function; stage-specific invasion assays","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct functional characterization of bradyzoite MJ composition using genetic and biochemical approaches in a single study; AMA2 role inferred from MJ composition data, with detailed functional analysis focused on AMA4","pmids":["36693095"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"AMA2 is a paralog of AMA1 in Toxoplasma gondii that is upregulated and cooperates with RON2 homologues to support residual host cell invasion when AMA1 is disrupted in tachyzoites, and is specifically deployed as a component of the moving junction during bradyzoite-stage invasion, highlighting its role in stage-specific and redundant invasion machinery."},"narrative":{"mechanistic_narrative":"AMA2 is a paralog of the invasion adhesin AMA1 in Toxoplasma gondii that functions within the moving junction (MJ) machinery to support host cell invasion [PMID:24934579, PMID:36693095]. When AMA1 is genetically disrupted in tachyzoites, AMA2 is upregulated together with RON2 homologues and cooperates with them to sustain residual parasite internalization, revealing functional plasticity and redundancy among AMA–RON invasion pairs [PMID:24934579]. AMA2 additionally serves a stage-specific role: in bradyzoites, the MJ is built from AMA2 and AMA4 rather than the tachyzoite adhesin AMA1, indicating that AMA2 is deployed as a dedicated MJ component for bradyzoite-stage invasion [PMID:36693095]. Beyond its participation in MJ assembly and its cooperation with RON2 homologues, no further mechanistic detail on AMA2 — including direct binding partners, structural basis, or regulation — has been characterized in the available corpus.","teleology":[{"year":2014,"claim":"Whether Toxoplasma invasion depends strictly on AMA1 or can proceed through alternative adhesins was unknown; disrupting AMA1 revealed a compensatory system in which AMA2 is upregulated and cooperates with RON2 homologues to preserve residual invasion.","evidence":"Reverse genetics disruption of AMA1 with homologue upregulation analysis and functional invasion assays in T. gondii","pmids":["24934579"],"confidence":"High","gaps":["Direct binding of AMA2 to specific RON2 homologues not biochemically defined","Contribution of AMA2 to invasion in the presence of intact AMA1 not established","Structural basis of AMA2 function within the MJ not determined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"claim":"Whether the same MJ adhesins operate across parasite life stages was unresolved; characterization of the bradyzoite MJ showed that AMA2 and AMA4 replace tachyzoite AMA1, establishing AMA2 as a stage-specific invasion component.","evidence":"Molecular and biochemical characterization of bradyzoite MJ composition with stage-specific invasion assays; loss-of-function analysis focused on AMA4 in T. gondii","pmids":["36693095"],"confidence":"Medium","gaps":["AMA2 role inferred from MJ composition data rather than direct AMA2 loss-of-function","RON partner of AMA2 in bradyzoites not defined","Mechanism regulating stage-specific AMA2 deployment unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"Whether AMA2 has a distinct, non-redundant function and which specific RON partners and structural interfaces mediate its role in the moving junction remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No direct AMA2 loss-of-function phenotype reported","No structural model of AMA2–RON interactions","Transcriptional/regulatory control of AMA2 expression uncharacterized"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Moving junction (MJ) complex with RON2 homologues"],"partners":["RON2 HOMOLOGUES","AMA4"],"other_free_text":["Paralog of AMA1; upregulated upon AMA1 disruption to support residual tachyzoite invasion [#0]","Stage-specific: forms the bradyzoite moving junction with AMA4 in place of tachyzoite AMA1 [#1]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"24934579","id":"PMC_24934579","title":"Plasticity and redundancy among AMA-RON pairs ensure host cell entry of Toxoplasma parasites.","date":"2014","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/24934579","citation_count":128,"is_preprint":false},{"pmid":"36693095","id":"PMC_36693095","title":"Invasion of Toxoplasma gondii bradyzoites: Molecular dissection of the moving junction proteins and effective vaccination targets.","date":"2023","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/36693095","citation_count":24,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3346,"output_tokens":648,"usd":0.009879,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5377,"output_tokens":1637,"usd":0.033905,"stage2_stop_reason":"end_turn"},"total_usd":0.043784,"stage1_batch_id":"msgbatch_01S6GjoYQm8LTPUsdhASdqag","stage2_batch_id":"msgbatch_01VX63RTMdBJqsG6gQMqoCjz","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2014,\n      \"finding\": \"AMA1 interacts with RON2 to maintain moving junction (MJ) structural integrity in T. gondii and is required for parasite internalization; disruption of AMA1 gene results in upregulation of AMA2 and RON2 homologues that cooperate to support residual invasion, demonstrating molecular plasticity and redundancy among AMA-RON pairs.\",\n      \"method\": \"Reverse genetics (AMA1 gene disruption), upregulation analysis of homologues, functional invasion assays\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic epistasis via reverse genetics with defined phenotypic readout (MJ integrity, internalization), with functional follow-up on AMA2 upregulation and residual invasion\",\n      \"pmids\": [\"24934579\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"In bradyzoites, the moving junction relies on AMA2 and AMA4 (instead of tachyzoite AMA1), indicating that AMA2 is a paralog used specifically in bradyzoite-stage host cell invasion via an MJ-dependent mechanism.\",\n      \"method\": \"Molecular characterization of bradyzoite MJ protein composition; functional characterization of AMA4 by loss-of-function; stage-specific invasion assays\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct functional characterization of bradyzoite MJ composition using genetic and biochemical approaches in a single study; AMA2 role inferred from MJ composition data, with detailed functional analysis focused on AMA4\",\n      \"pmids\": [\"36693095\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"AMA2 is a paralog of AMA1 in Toxoplasma gondii that is upregulated and cooperates with RON2 homologues to support residual host cell invasion when AMA1 is disrupted in tachyzoites, and is specifically deployed as a component of the moving junction during bradyzoite-stage invasion, highlighting its role in stage-specific and redundant invasion machinery.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"AMA2 is a paralog of the invasion adhesin AMA1 in Toxoplasma gondii that functions within the moving junction (MJ) machinery to support host cell invasion [#0, #1]. When AMA1 is genetically disrupted in tachyzoites, AMA2 is upregulated together with RON2 homologues and cooperates with them to sustain residual parasite internalization, revealing functional plasticity and redundancy among AMA–RON invasion pairs [#0]. AMA2 additionally serves a stage-specific role: in bradyzoites, the MJ is built from AMA2 and AMA4 rather than the tachyzoite adhesin AMA1, indicating that AMA2 is deployed as a dedicated MJ component for bradyzoite-stage invasion [#1]. Beyond its participation in MJ assembly and its cooperation with RON2 homologues, no further mechanistic detail on AMA2 — including direct binding partners, structural basis, or regulation — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Whether Toxoplasma invasion depends strictly on AMA1 or can proceed through alternative adhesins was unknown; disrupting AMA1 revealed a compensatory system in which AMA2 is upregulated and cooperates with RON2 homologues to preserve residual invasion.\",\n      \"evidence\": \"Reverse genetics disruption of AMA1 with homologue upregulation analysis and functional invasion assays in T. gondii\",\n      \"pmids\": [\"24934579\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct binding of AMA2 to specific RON2 homologues not biochemically defined\",\n        \"Contribution of AMA2 to invasion in the presence of intact AMA1 not established\",\n        \"Structural basis of AMA2 function within the MJ not determined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Whether the same MJ adhesins operate across parasite life stages was unresolved; characterization of the bradyzoite MJ showed that AMA2 and AMA4 replace tachyzoite AMA1, establishing AMA2 as a stage-specific invasion component.\",\n      \"evidence\": \"Molecular and biochemical characterization of bradyzoite MJ composition with stage-specific invasion assays; loss-of-function analysis focused on AMA4 in T. gondii\",\n      \"pmids\": [\"36693095\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"AMA2 role inferred from MJ composition data rather than direct AMA2 loss-of-function\",\n        \"RON partner of AMA2 in bradyzoites not defined\",\n        \"Mechanism regulating stage-specific AMA2 deployment unknown\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether AMA2 has a distinct, non-redundant function and which specific RON partners and structural interfaces mediate its role in the moving junction remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct AMA2 loss-of-function phenotype reported\",\n        \"No structural model of AMA2–RON interactions\",\n        \"Transcriptional/regulatory control of AMA2 expression uncharacterized\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"moving junction\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"host cell invasion\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\n      \"Moving junction (MJ) complex with RON2 homologues\"\n    ],\n    \"partners\": [\n      \"RON2 homologues\",\n      \"AMA4\"\n    ],\n    \"other_free_text\": [\n      \"Paralog of AMA1; upregulated upon AMA1 disruption to support residual tachyzoite invasion [#0]\",\n      \"Stage-specific: forms the bradyzoite moving junction with AMA4 in place of tachyzoite AMA1 [#1]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_300130","name":"AMA2","product":"apical membrane antigen AMA2","uniprot_acc":"S8GAW3","chromosome":"TGME49_chrXII","start_pos":189278},{"strain":"GT1","gene_id":"TGGT1_300130","name":null,"product":"apical membrane antigen 1 domain-containing protein","uniprot_acc":null,"chromosome":"TGGT1_chrXII","start_pos":150753},{"strain":"RH88","gene_id":"TGRH88_057230","name":null,"product":"apical membrane antigen 1 domain-containing protein","uniprot_acc":null,"chromosome":"CM023093","start_pos":180130},{"strain":"VEG","gene_id":"TGVEG_300130","name":null,"product":"apical membrane antigen 1 domain-containing protein","uniprot_acc":"V4Z337","chromosome":"TGVEG_chrXII","start_pos":180476}]}