{"gene":"PF3D7_0303400","run_date":"2026-09-07T12:57:13+00:00","timeline":{"discoveries":[{"year":2014,"finding":"PfDHHC1 (PF3D7_0303400) is exclusively localized to the inner membrane complex (IMC) of P. falciparum, where it co-distributes with dual-acylated IMC-localized proteins PfISP1 and PfISP3 during schizogony, identifying it as an IMC-resident palmitoyl acyltransferase (PAT) involved in recruiting palmitoylated proteins to the IMC.","method":"Subcellular localization by direct imaging/fractionation; phylogenetic analysis; identification of co-distribution with IMC marker proteins; probing sequence requirements for IMC membrane recruitment","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization experiment with functional context (IMC-specific PAT activity implied), single lab, multiple approaches (localization, phylogenetics, co-distribution), but no in vitro enzymatic reconstitution or KO phenotype reported in abstract","pmids":["25425642"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"Genome-wide analysis of DHHC-CRD palmitoyl acyltransferases in Plasmodium berghei and Toxoplasma gondii established that some apicomplexan-specific DHHC enzymes are essential for parasite growth and are targeted to apicomplexan-specific organelles; the family member DHHC7 (not DHHC1/PF3D7_0303400) was identified as essential for invasion via rhoptry positioning. PF3D7_0303400 is catalogued as a member of this PAT family but no specific functional experiment was performed on it in this study.","method":"Global repertoire analysis of DHHC-CRD PATs; essentiality assessment in P. berghei; localization studies","journal":"Traffic (Copenhagen, Denmark)","confidence":"Low","confidence_rationale":"Tier 4 / Weak — PF3D7_0303400 is only catalogued as a family member; no specific experiment targets DHHC1 itself in this paper","pmids":["23638681"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2005,"finding":"A P. falciparum protein containing a DHHC domain (described as a Golgi-localized protein with ankyrin domains expressed in late schizonts) was characterized; its Golgi localization and late-schizont expression timing suggest a role in sorting proteins to apical organelles. NOTE: this paper describes a DHHC-domain-containing protein localized to the Golgi, which may or may not correspond to PF3D7_0303400; the abstract does not provide a gene identifier confirming identity with PF3D7_0303400.","method":"Subcellular localization (Golgi); expression timing analysis in asexual stages","journal":"Experimental parasitology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single localization experiment, no gene identifier confirmed in abstract, no functional loss-of-function or enzymatic assay performed","pmids":["15882865"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0303400 (PfDHHC1) is a palmitoyl acyltransferase that localizes exclusively to the inner membrane complex (IMC) of P. falciparum during schizogony, where it co-distributes with dual-acylated IMC proteins (PfISP1 and PfISP3) and is implicated in the palmitoylation-dependent recruitment of proteins to the IMC, though direct enzymatic activity and loss-of-function phenotypes have not been reported in the available literature."},"narrative":{"mechanistic_narrative":"PF3D7_0303400 (DHHC1) is a DHHC-family palmitoyl acyltransferase of Plasmodium falciparum that resides exclusively in the inner membrane complex (IMC) during schizogony, where it co-distributes with the dual-acylated IMC proteins PfISP1 and PfISP3, implicating it in the palmitoylation-dependent recruitment of proteins to the IMC [PMID:25425642]. Beyond this IMC localization and co-distribution, no direct enzymatic reconstitution, substrate assignment, or loss-of-function phenotype for PF3D7_0303400 has been characterized in the available corpus; genome-wide DHHC-family analyses catalogue it as a family member but attribute the invasion/rhoptry-positioning essential functions to a distinct sibling (DHHC7), not to DHHC1 [PMID:23638681].","teleology":[{"year":2014,"claim":"To place a specific parasite palmitoyltransferase within a defined organelle, imaging established that PF3D7_0303400 localizes exclusively to the IMC alongside dual-acylated markers, framing it as the candidate enzyme for IMC protein acylation.","evidence":"Subcellular localization by imaging/fractionation with co-distribution against IMC markers PfISP1/PfISP3 and phylogenetic analysis in P. falciparum","pmids":["25425642"],"confidence":"Medium","gaps":["No in vitro or in vivo demonstration of palmitoyltransferase catalytic activity by PF3D7_0303400","No identified physiological palmitoylation substrate","No loss-of-function or knockout phenotype reported"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"claim":"A genome-wide survey of apicomplexan DHHC-CRD enzymes addressed which family members are essential, but resolved this only for siblings (e.g. DHHC7 for rhoptry positioning), leaving PF3D7_0303400 catalogued without a dedicated functional test.","evidence":"Global repertoire and essentiality analysis of DHHC-CRD PATs in P. berghei and T. gondii; PF3D7_0303400 listed only as a family member","pmids":["23638681"],"confidence":"Low","gaps":["No experiment in this study targeted PF3D7_0303400 itself; essentiality was assessed for other family members","Essentiality and organellar targeting of DHHC1 specifically remain undetermined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether PF3D7_0303400 is catalytically active, which IMC proteins it palmitoylates, and whether its function is essential for schizogony or invasion remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No enzymatic reconstitution establishing DHHC1 acyltransferase activity","No direct substrate identification linking DHHC1 to PfISP1/PfISP3 acylation","No genetic loss-of-function phenotype for PF3D7_0303400"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFISP1 (CO-DISTRIBUTES AT THE IMC) [#0]","PFISP3 (CO-DISTRIBUTES AT THE IMC) [#0]"],"other_free_text":["PF3D7_0303400 is a member of the DHHC-CRD palmitoyl acyltransferase family; genome-wide family analyses attribute essential invasion/rhoptry-positioning roles to the sibling DHHC7, not to DHHC1 [#1].","A 2005 report of a Golgi-localized, ankyrin-domain DHHC-domain protein expressed in late schizonts is not confirmed by gene identifier to correspond to PF3D7_0303400 [#2]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"23638681","id":"PMC_23638681","title":"Global analysis of apicomplexan protein S-acyl transferases reveals an enzyme essential for invasion.","date":"2013","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/23638681","citation_count":62,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25425642","id":"PMC_25425642","title":"The role of palmitoylation for protein recruitment to the inner membrane complex of the malaria parasite.","date":"2014","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/25425642","citation_count":40,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfDHHC1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"15882865","id":"PMC_15882865","title":"Plasmodium falciparum: characterization of a late asexual stage golgi protein containing both ankyrin and DHHC domains.","date":"2005","source":"Experimental parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/15882865","citation_count":12,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4137,"output_tokens":1086,"usd":0.014351,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5859,"output_tokens":1640,"usd":0.035147,"stage2_stop_reason":"end_turn"},"total_usd":0.0,"stage1_batch_id":"msgbatch_01FCDwJBogPrvFL5RpW1bgoz","stage2_batch_id":"msgbatch_017MJf5R7pwT6SSC5ZnYgqis","note":"batch pricing = 50% of standard","skipped":true},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2014,\n      \"finding\": \"PfDHHC1 (PF3D7_0303400) is exclusively localized to the inner membrane complex (IMC) of P. falciparum, where it co-distributes with dual-acylated IMC-localized proteins PfISP1 and PfISP3 during schizogony, identifying it as an IMC-resident palmitoyl acyltransferase (PAT) involved in recruiting palmitoylated proteins to the IMC.\",\n      \"method\": \"Subcellular localization by direct imaging/fractionation; phylogenetic analysis; identification of co-distribution with IMC marker proteins; probing sequence requirements for IMC membrane recruitment\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization experiment with functional context (IMC-specific PAT activity implied), single lab, multiple approaches (localization, phylogenetics, co-distribution), but no in vitro enzymatic reconstitution or KO phenotype reported in abstract\",\n      \"pmids\": [\"25425642\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Genome-wide analysis of DHHC-CRD palmitoyl acyltransferases in Plasmodium berghei and Toxoplasma gondii established that some apicomplexan-specific DHHC enzymes are essential for parasite growth and are targeted to apicomplexan-specific organelles; the family member DHHC7 (not DHHC1/PF3D7_0303400) was identified as essential for invasion via rhoptry positioning. PF3D7_0303400 is catalogued as a member of this PAT family but no specific functional experiment was performed on it in this study.\",\n      \"method\": \"Global repertoire analysis of DHHC-CRD PATs; essentiality assessment in P. berghei; localization studies\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — PF3D7_0303400 is only catalogued as a family member; no specific experiment targets DHHC1 itself in this paper\",\n      \"pmids\": [\"23638681\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"A P. falciparum protein containing a DHHC domain (described as a Golgi-localized protein with ankyrin domains expressed in late schizonts) was characterized; its Golgi localization and late-schizont expression timing suggest a role in sorting proteins to apical organelles. NOTE: this paper describes a DHHC-domain-containing protein localized to the Golgi, which may or may not correspond to PF3D7_0303400; the abstract does not provide a gene identifier confirming identity with PF3D7_0303400.\",\n      \"method\": \"Subcellular localization (Golgi); expression timing analysis in asexual stages\",\n      \"journal\": \"Experimental parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single localization experiment, no gene identifier confirmed in abstract, no functional loss-of-function or enzymatic assay performed\",\n      \"pmids\": [\"15882865\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_0303400 (PfDHHC1) is a palmitoyl acyltransferase that localizes exclusively to the inner membrane complex (IMC) of P. falciparum during schizogony, where it co-distributes with dual-acylated IMC proteins (PfISP1 and PfISP3) and is implicated in the palmitoylation-dependent recruitment of proteins to the IMC, though direct enzymatic activity and loss-of-function phenotypes have not been reported in the available literature.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0303400 (DHHC1) is a DHHC-family palmitoyl acyltransferase of Plasmodium falciparum that resides exclusively in the inner membrane complex (IMC) during schizogony, where it co-distributes with the dual-acylated IMC proteins PfISP1 and PfISP3, implicating it in the palmitoylation-dependent recruitment of proteins to the IMC [#0]. Beyond this IMC localization and co-distribution, no direct enzymatic reconstitution, substrate assignment, or loss-of-function phenotype for PF3D7_0303400 has been characterized in the available corpus; genome-wide DHHC-family analyses catalogue it as a family member but attribute the invasion/rhoptry-positioning essential functions to a distinct sibling (DHHC7), not to DHHC1 [#1].\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"To place a specific parasite palmitoyltransferase within a defined organelle, imaging established that PF3D7_0303400 localizes exclusively to the IMC alongside dual-acylated markers, framing it as the candidate enzyme for IMC protein acylation.\",\n      \"evidence\": \"Subcellular localization by imaging/fractionation with co-distribution against IMC markers PfISP1/PfISP3 and phylogenetic analysis in P. falciparum\",\n      \"pmids\": [\"25425642\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No in vitro or in vivo demonstration of palmitoyltransferase catalytic activity by PF3D7_0303400\",\n        \"No identified physiological palmitoylation substrate\",\n        \"No loss-of-function or knockout phenotype reported\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"A genome-wide survey of apicomplexan DHHC-CRD enzymes addressed which family members are essential, but resolved this only for siblings (e.g. DHHC7 for rhoptry positioning), leaving PF3D7_0303400 catalogued without a dedicated functional test.\",\n      \"evidence\": \"Global repertoire and essentiality analysis of DHHC-CRD PATs in P. berghei and T. gondii; PF3D7_0303400 listed only as a family member\",\n      \"pmids\": [\"23638681\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No experiment in this study targeted PF3D7_0303400 itself; essentiality was assessed for other family members\",\n        \"Essentiality and organellar targeting of DHHC1 specifically remain undetermined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether PF3D7_0303400 is catalytically active, which IMC proteins it palmitoylates, and whether its function is essential for schizogony or invasion remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No enzymatic reconstitution establishing DHHC1 acyltransferase activity\",\n        \"No direct substrate identification linking DHHC1 to PfISP1/PfISP3 acylation\",\n        \"No genetic loss-of-function phenotype for PF3D7_0303400\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0019706\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020039\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0018345\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"PfISP1 (co-distributes at the IMC) [#0]\",\n      \"PfISP3 (co-distributes at the IMC) [#0]\"\n    ],\n    \"other_free_text\": [\n      \"PF3D7_0303400 is a member of the DHHC-CRD palmitoyl acyltransferase family; genome-wide family analyses attribute essential invasion/rhoptry-positioning roles to the sibling DHHC7, not to DHHC1 [#1].\",\n      \"A 2005 report of a Golgi-localized, ankyrin-domain DHHC-domain protein expressed in late schizonts is not confirmed by gene identifier to correspond to PF3D7_0303400 [#2].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0303400","name":null,"product":"palmitoyltransferase DHHC1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0402000","name":null,"product":"palmitoyltransferase DHHC1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0839700","name":null,"product":"palmitoyltransferase DHHC1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"DHHC1","evaluation":null}