{"gene":"TG_321640","gene_symbol":"CDC48AP","run_date":"2026-09-08T15:15:14","timeline":{"discoveries":[{"year":2017,"finding":"CDC48AP, an AAA ATPase, functions to translocate apicoplast proteins across the periplastid membrane during protein import into the apicoplast. Conditional null mutants demonstrate CDC48AP is essential for this translocation process and for parasite survival.","method":"Conditional null mutants, genetic complementation, functional import assays","journal":"mBio","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional null mutants with specific cellular phenotype (failure of periplastid membrane translocation) and genetic complementation, demonstrating essentiality and pathway placement","pmids":["28655825"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2017,"finding":"CDC48AP acts together with the plastid ubiquitin-like protein (PUBL) as part of an apicoplast-specific ERAD-like complex at the periplastid membrane, coupling ubiquitin-like conjugation to protein translocation across this membrane during apicoplast protein import.","method":"Genetic interaction / epistasis via conditional null mutants of both CDC48AP and PUBL, functional complementation","journal":"mBio","confidence":"High","confidence_rationale":"Tier 2 / Strong — both components shown by conditional null mutants to be required for the same translocation step, with mechanistic pathway placement in an apicoplast-specific ERAD complex","pmids":["28655825"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"CDC48AP is an AAA ATPase motor that works together with the plastid ubiquitin-like protein (PUBL) as part of an apicoplast-specific ERAD-like complex to translocate nucleus-encoded proteins across the periplastid membrane during apicoplast protein import, and is essential for parasite survival in Toxoplasma gondii."},"narrative":{"mechanistic_narrative":"CDC48AP is an AAA ATPase motor that drives translocation of nucleus-encoded apicoplast proteins across the periplastid membrane during apicoplast protein import in Toxoplasma gondii [PMID:28655825]. It operates within an apicoplast-specific ERAD-like complex together with the plastid ubiquitin-like protein (PUBL), coupling ubiquitin-like conjugation to the membrane translocation step [PMID:28655825]. Conditional null mutants establish that CDC48AP is essential both for this translocation and for parasite survival [PMID:28655825]. Beyond its role as the translocation motor in the CDC48AP–PUBL ERAD-like complex, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2017,"claim":"It was unknown how nucleus-encoded proteins cross the periplastid membrane into the apicoplast; conditional deletion identified CDC48AP as an essential AAA ATPase driving this translocation step.","evidence":"Conditional null mutants with genetic complementation and functional import assays in Toxoplasma gondii","pmids":["28655825"],"confidence":"High","gaps":["ATPase catalytic mechanism and nucleotide-cycle coupling to translocation not resolved","Full set of translocated substrates not defined","Structural organization of the motor at the periplastid membrane unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2017,"claim":"The question of how translocation is coupled to a ubiquitin-like signal was addressed by showing CDC48AP acts with PUBL in an apicoplast-specific ERAD-like complex at the periplastid membrane.","evidence":"Genetic interaction/epistasis via conditional null mutants of both CDC48AP and PUBL with functional complementation in Toxoplasma gondii","pmids":["28655825"],"confidence":"High","gaps":["Physical composition of the ERAD-like complex and additional subunits not defined","Nature of the ubiquitin-like conjugation events coupled to translocation not detailed","Direct biochemical interaction between CDC48AP and PUBL not shown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The biochemical and structural basis of how CDC48AP recognizes, engages, and unfolds substrates and mechanistically links PUBL conjugation to ATP-driven translocation remains unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No structural model of the CDC48AP motor or ERAD-like complex","No enumerated substrate repertoire","Mechanism of substrate recognition and unfolding uncharacterized"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Apicoplast-specific ERAD-like complex (CDC48AP–PUBL) at the periplastid membrane"],"partners":["PUBL (PLASTID UBIQUITIN-LIKE PROTEIN)"],"other_free_text":["Essential for Toxoplasma gondii survival, as shown by conditional null mutants [#0]","Couples ubiquitin-like conjugation to ATP-driven protein translocation across the periplastid membrane [#1]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"28655825","id":"PMC_28655825","title":"A Plastid Protein That Evolved from Ubiquitin and Is Required for Apicoplast Protein Import in Toxoplasma gondii.","date":"2017","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/28655825","citation_count":28,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3207,"output_tokens":574,"usd":0.009116,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5264,"output_tokens":1642,"usd":0.033685,"stage2_stop_reason":"end_turn"},"total_usd":0.042801,"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\": 2017,\n      \"finding\": \"CDC48AP, an AAA ATPase, functions to translocate apicoplast proteins across the periplastid membrane during protein import into the apicoplast. Conditional null mutants demonstrate CDC48AP is essential for this translocation process and for parasite survival.\",\n      \"method\": \"Conditional null mutants, genetic complementation, functional import assays\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional null mutants with specific cellular phenotype (failure of periplastid membrane translocation) and genetic complementation, demonstrating essentiality and pathway placement\",\n      \"pmids\": [\"28655825\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"CDC48AP acts together with the plastid ubiquitin-like protein (PUBL) as part of an apicoplast-specific ERAD-like complex at the periplastid membrane, coupling ubiquitin-like conjugation to protein translocation across this membrane during apicoplast protein import.\",\n      \"method\": \"Genetic interaction / epistasis via conditional null mutants of both CDC48AP and PUBL, functional complementation\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — both components shown by conditional null mutants to be required for the same translocation step, with mechanistic pathway placement in an apicoplast-specific ERAD complex\",\n      \"pmids\": [\"28655825\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"CDC48AP is an AAA ATPase motor that works together with the plastid ubiquitin-like protein (PUBL) as part of an apicoplast-specific ERAD-like complex to translocate nucleus-encoded proteins across the periplastid membrane during apicoplast protein import, and is essential for parasite survival in Toxoplasma gondii.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CDC48AP is an AAA ATPase motor that drives translocation of nucleus-encoded apicoplast proteins across the periplastid membrane during apicoplast protein import in Toxoplasma gondii [#0]. It operates within an apicoplast-specific ERAD-like complex together with the plastid ubiquitin-like protein (PUBL), coupling ubiquitin-like conjugation to the membrane translocation step [#1]. Conditional null mutants establish that CDC48AP is essential both for this translocation and for parasite survival [#0]. Beyond its role as the translocation motor in the CDC48AP–PUBL ERAD-like complex, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"It was unknown how nucleus-encoded proteins cross the periplastid membrane into the apicoplast; conditional deletion identified CDC48AP as an essential AAA ATPase driving this translocation step.\",\n      \"evidence\": \"Conditional null mutants with genetic complementation and functional import assays in Toxoplasma gondii\",\n      \"pmids\": [\"28655825\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"ATPase catalytic mechanism and nucleotide-cycle coupling to translocation not resolved\",\n        \"Full set of translocated substrates not defined\",\n        \"Structural organization of the motor at the periplastid membrane unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"The question of how translocation is coupled to a ubiquitin-like signal was addressed by showing CDC48AP acts with PUBL in an apicoplast-specific ERAD-like complex at the periplastid membrane.\",\n      \"evidence\": \"Genetic interaction/epistasis via conditional null mutants of both CDC48AP and PUBL with functional complementation in Toxoplasma gondii\",\n      \"pmids\": [\"28655825\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Physical composition of the ERAD-like complex and additional subunits not defined\",\n        \"Nature of the ubiquitin-like conjugation events coupled to translocation not detailed\",\n        \"Direct biochemical interaction between CDC48AP and PUBL not shown\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical and structural basis of how CDC48AP recognizes, engages, and unfolds substrates and mechanistically links PUBL conjugation to ATP-driven translocation remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No structural model of the CDC48AP motor or ERAD-like complex\",\n        \"No enumerated substrate repertoire\",\n        \"Mechanism of substrate recognition and unfolding uncharacterized\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016887\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0015450\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0031972\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0036503\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0045037\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"Apicoplast-specific ERAD-like complex (CDC48AP–PUBL) at the periplastid membrane\"],\n    \"partners\": [\"PUBL (plastid ubiquitin-like protein)\"],\n    \"other_free_text\": [\n      \"Essential for Toxoplasma gondii survival, as shown by conditional null mutants [#0]\",\n      \"Couples ubiquitin-like conjugation to ATP-driven protein translocation across the periplastid membrane [#1]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_321640","name":"CDC48AP","product":"cell division protein CDC48AP","uniprot_acc":"A0A125YJG8","chromosome":"TGME49_chrIb","start_pos":1665247},{"strain":"GT1","gene_id":"TGGT1_321640","name":null,"product":"cell division protein CDC48AP","uniprot_acc":null,"chromosome":"TGGT1_chrIb","start_pos":1672063},{"strain":"RH88","gene_id":"TGRH88_021040","name":null,"product":"cell division protein CDC48AP","uniprot_acc":null,"chromosome":"CM023082","start_pos":294261},{"strain":"VEG","gene_id":"TGVEG_321640","name":null,"product":"cell division protein CDC48AP","uniprot_acc":"V5B144","chromosome":"TGVEG_chrIb","start_pos":1683290}]}