{"gene":"PF3D7_1027900","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2016,"finding":"DHHC10 is translationally repressed in female Plasmodium berghei gametocytes and is activated translationally during ookinete formation, where it localizes to the crystalloid organelle and is essential for crystalloid biogenesis, correct targeting of the crystalloid-resident protein LAP2, and malaria parasite transmission to mosquitoes.","method":"Reverse genetics (gene knockout/null mutant), fluorescence localization, translational repression analysis","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean knockout with defined cellular and transmission phenotype, localization experiment, and LAP2 mistargeting readout; published in peer-reviewed journal","pmids":["27303037"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2013,"finding":"A global survey of Plasmodium and Toxoplasma DHHC-CRD palmitoyltransferases established that viable knockout mutants could be obtained for DHHC10 in Plasmodium berghei, indicating it is dispensable for asexual blood-stage growth, unlike several other family members.","method":"Genome-wide reverse genetic screen (knockout generation), localization analysis","journal":"Traffic (Copenhagen, Denmark)","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — systematic screen confirmed dispensability for blood-stage growth via viable KO, single study; specific mechanistic details for DHHC10 are secondary to the broader screen","pmids":["23638681"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2016,"finding":"DHHC10 transcript is present among translationally repressed maternal mRNAs in P. falciparum female gametocytes (protein not detected despite mRNA expression), consistent with storage for post-fertilization translation.","method":"Integrated transcriptomics and proteomics (transcriptome + proteome comparison of male and female gametocytes)","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — multi-omic dataset from single lab showing mRNA/protein discordance; indirect mechanistic inference about translational repression","pmids":["27298255"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"In Plasmodium berghei, DHHC10 is a palmitoyl-S-acyltransferase whose mRNA is translationally repressed in female gametocytes and activated during ookinete formation; the protein localizes to the crystalloid organelle and is essential for crystalloid biogenesis, proper targeting of the crystalloid cargo protein LAP2, and subsequent sporogony and mosquito transmission, while being dispensable for asexual blood-stage growth."},"narrative":{"mechanistic_narrative":"DHHC10 (PF3D7_1027900) is a putative DHHC-CRD palmitoyl-S-acyltransferase that functions in the sexual and mosquito-transmission stages of the malaria parasite rather than in asexual blood-stage growth [PMID:27303037, PMID:23638681]. In Plasmodium berghei, its mRNA is translationally repressed in female gametocytes and translationally activated during ookinete formation, after which the protein localizes to the crystalloid organelle and is required for crystalloid biogenesis, for correct targeting of the crystalloid-resident cargo protein LAP2, and for parasite transmission to mosquitoes [PMID:27303037]. Consistent with this stage-specific role, DHHC10 knockout is viable and dispensable for asexual blood-stage growth in P. berghei, unlike several other DHHC family members [PMID:23638681]. In P. falciparum, the DHHC10 transcript is likewise present among translationally repressed maternal mRNAs in female gametocytes with no detectable protein, indicating conservation of its storage-for-post-fertilization regulatory pattern [PMID:27298255]. Beyond its localization and the LAP2 mistargeting phenotype, the direct palmitoylation substrates and enzymatic mechanism of DHHC10 have not been characterized in the available corpus.","teleology":[{"year":2013,"claim":"Whether DHHC10 is required for parasite survival was unknown; establishing that a viable knockout could be generated defined it as dispensable for asexual proliferation and pointed toward a stage-restricted role.","evidence":"Genome-wide reverse genetic knockout screen of Plasmodium and Toxoplasma DHHC-CRD palmitoyltransferases with localization analysis in P. berghei","pmids":["23638681"],"confidence":"Medium","gaps":["Does not identify the stage or process in which DHHC10 is required","No substrate or enzymatic activity assigned","Mechanistic details secondary to the broader family screen"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2016,"claim":"The functional role of DHHC10 was resolved by showing it is translationally repressed in female gametocytes, activated during ookinete formation, localizes to the crystalloid organelle, and is required for crystalloid biogenesis, LAP2 targeting, and mosquito transmission.","evidence":"Reverse genetics (null mutant), fluorescence localization, and translational repression analysis in P. berghei","pmids":["27303037"],"confidence":"High","gaps":["Direct palmitoylation substrates of DHHC10 not identified","Whether LAP2 mistargeting is a direct or indirect consequence unresolved","Enzymatic mechanism and acyl-CoA specificity not tested"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2016,"claim":"Whether the translational-repression regulation extends to human-infective parasites was addressed by detecting DHHC10 mRNA but not protein among stored maternal transcripts in P. falciparum female gametocytes.","evidence":"Integrated transcriptomic and proteomic comparison of male and female P. falciparum gametocytes","pmids":["27298255"],"confidence":"Medium","gaps":["Indirect inference of translational repression from mRNA/protein discordance","Post-fertilization localization and function not tested in P. falciparum","No functional knockout in P. falciparum"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The direct palmitoylation substrates of DHHC10 and the biochemical basis by which it drives crystalloid biogenesis and LAP2 targeting remain unidentified.","evidence":"","pmids":[],"confidence":"Low","gaps":["No demonstrated acyltransferase activity or palmitoylated substrate for DHHC10","Whether LAP2 or crystalloid cargo are direct substrates is untested","No structural or catalytic-mutant analysis"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["LAP2 (CRYSTALLOID CARGO PROTEIN MISTARGETED IN DHHC10 KNOCKOUT)"],"other_free_text":["Dispensable for asexual blood-stage growth in P. berghei [#1]","mRNA translationally repressed in female gametocytes and activated during ookinete formation in P. berghei [#0]","Transcript stored as translationally repressed maternal mRNA in P. falciparum female gametocytes [#2]","Required for crystalloid organelle biogenesis and mosquito transmission in P. berghei [#0]","Member of the DHHC-CRD palmitoyltransferase family [#1]"]}},"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":"27303037","id":"PMC_27303037","title":"Maternally supplied S-acyl-transferase is required for crystalloid organelle formation and transmission of the malaria parasite.","date":"2016","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/27303037","citation_count":28,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DHHC10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42233156","id":"","title":"A pleckstrin homology domain protein is involved in crystalloid formation in Plasmodium ookinetes and affects the maturation of infective sporozoites.","date":"2026","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/42233156","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DHHC10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38399683","id":"","title":"The Multiple Roles of LCCL Domain-Containing Proteins for Malaria Parasite Transmission.","date":"2024","source":"Microorganisms","url":"https://pubmed.ncbi.nlm.nih.gov/38399683","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DHHC10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35638735","id":"","title":"PfARID Regulates P. falciparum Malaria Parasite Male Gametogenesis and Female Fertility and Is Critical for Parasite Transmission to the Mosquito Vector.","date":"2022","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/35638735","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DHHC10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37708854","id":"","title":"Identification of genes required for Plasmodium gametocyte-to-sporozoite development in the mosquito vector.","date":"2023","source":"Cell host & microbe","url":"https://pubmed.ncbi.nlm.nih.gov/37708854","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DHHC10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32736136","id":"","title":"Plasmodium berghei LAPs form an extended protein complex that facilitates crystalloid targeting and biogenesis.","date":"2020","source":"Journal of proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/32736136","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DHHC10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35775739","id":"","title":"Inner membrane complex proteomics reveals a palmitoylation regulation critical for intraerythrocytic development of malaria parasite.","date":"2022","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/35775739","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DHHC10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31951090","id":"","title":"NAD(P) transhydrogenase has vital non-mitochondrial functions in malaria parasite transmission.","date":"2020","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/31951090","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DHHC10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30367865","id":"","title":"The Plasmodium LAP complex affects crystalloid biogenesis and oocyst cell division.","date":"2018","source":"International journal for parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/30367865","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DHHC10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27298255","id":"","title":"Integrated transcriptomic and proteomic analyses of P. falciparum gametocytes: molecular insight into sex-specific processes and translational repression.","date":"2016","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/27298255","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DHHC10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":12220,"output_tokens":854,"usd":0.024735,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5588,"output_tokens":1945,"usd":0.038282,"stage2_stop_reason":"end_turn"},"total_usd":0.063017,"stage1_batch_id":"msgbatch_01SRp5hyRc82zNjddxyCCXGk","stage2_batch_id":"msgbatch_01K3BTmBazRo3pRrMvyaPMTY","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2016,\n      \"finding\": \"DHHC10 is translationally repressed in female Plasmodium berghei gametocytes and is activated translationally during ookinete formation, where it localizes to the crystalloid organelle and is essential for crystalloid biogenesis, correct targeting of the crystalloid-resident protein LAP2, and malaria parasite transmission to mosquitoes.\",\n      \"method\": \"Reverse genetics (gene knockout/null mutant), fluorescence localization, translational repression analysis\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean knockout with defined cellular and transmission phenotype, localization experiment, and LAP2 mistargeting readout; published in peer-reviewed journal\",\n      \"pmids\": [\"27303037\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"A global survey of Plasmodium and Toxoplasma DHHC-CRD palmitoyltransferases established that viable knockout mutants could be obtained for DHHC10 in Plasmodium berghei, indicating it is dispensable for asexual blood-stage growth, unlike several other family members.\",\n      \"method\": \"Genome-wide reverse genetic screen (knockout generation), localization analysis\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — systematic screen confirmed dispensability for blood-stage growth via viable KO, single study; specific mechanistic details for DHHC10 are secondary to the broader screen\",\n      \"pmids\": [\"23638681\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"DHHC10 transcript is present among translationally repressed maternal mRNAs in P. falciparum female gametocytes (protein not detected despite mRNA expression), consistent with storage for post-fertilization translation.\",\n      \"method\": \"Integrated transcriptomics and proteomics (transcriptome + proteome comparison of male and female gametocytes)\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — multi-omic dataset from single lab showing mRNA/protein discordance; indirect mechanistic inference about translational repression\",\n      \"pmids\": [\"27298255\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"In Plasmodium berghei, DHHC10 is a palmitoyl-S-acyltransferase whose mRNA is translationally repressed in female gametocytes and activated during ookinete formation; the protein localizes to the crystalloid organelle and is essential for crystalloid biogenesis, proper targeting of the crystalloid cargo protein LAP2, and subsequent sporogony and mosquito transmission, while being dispensable for asexual blood-stage growth.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DHHC10 (PF3D7_1027900) is a putative DHHC-CRD palmitoyl-S-acyltransferase that functions in the sexual and mosquito-transmission stages of the malaria parasite rather than in asexual blood-stage growth [#0, #1]. In Plasmodium berghei, its mRNA is translationally repressed in female gametocytes and translationally activated during ookinete formation, after which the protein localizes to the crystalloid organelle and is required for crystalloid biogenesis, for correct targeting of the crystalloid-resident cargo protein LAP2, and for parasite transmission to mosquitoes [#0]. Consistent with this stage-specific role, DHHC10 knockout is viable and dispensable for asexual blood-stage growth in P. berghei, unlike several other DHHC family members [#1]. In P. falciparum, the DHHC10 transcript is likewise present among translationally repressed maternal mRNAs in female gametocytes with no detectable protein, indicating conservation of its storage-for-post-fertilization regulatory pattern [#2]. Beyond its localization and the LAP2 mistargeting phenotype, the direct palmitoylation substrates and enzymatic mechanism of DHHC10 have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Whether DHHC10 is required for parasite survival was unknown; establishing that a viable knockout could be generated defined it as dispensable for asexual proliferation and pointed toward a stage-restricted role.\",\n      \"evidence\": \"Genome-wide reverse genetic knockout screen of Plasmodium and Toxoplasma DHHC-CRD palmitoyltransferases with localization analysis in P. berghei\",\n      \"pmids\": [\"23638681\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Does not identify the stage or process in which DHHC10 is required\",\n        \"No substrate or enzymatic activity assigned\",\n        \"Mechanistic details secondary to the broader family screen\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"The functional role of DHHC10 was resolved by showing it is translationally repressed in female gametocytes, activated during ookinete formation, localizes to the crystalloid organelle, and is required for crystalloid biogenesis, LAP2 targeting, and mosquito transmission.\",\n      \"evidence\": \"Reverse genetics (null mutant), fluorescence localization, and translational repression analysis in P. berghei\",\n      \"pmids\": [\"27303037\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct palmitoylation substrates of DHHC10 not identified\",\n        \"Whether LAP2 mistargeting is a direct or indirect consequence unresolved\",\n        \"Enzymatic mechanism and acyl-CoA specificity not tested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Whether the translational-repression regulation extends to human-infective parasites was addressed by detecting DHHC10 mRNA but not protein among stored maternal transcripts in P. falciparum female gametocytes.\",\n      \"evidence\": \"Integrated transcriptomic and proteomic comparison of male and female P. falciparum gametocytes\",\n      \"pmids\": [\"27298255\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Indirect inference of translational repression from mRNA/protein discordance\",\n        \"Post-fertilization localization and function not tested in P. falciparum\",\n        \"No functional knockout in P. falciparum\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct palmitoylation substrates of DHHC10 and the biochemical basis by which it drives crystalloid biogenesis and LAP2 targeting remain unidentified.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No demonstrated acyltransferase activity or palmitoylated substrate for DHHC10\",\n        \"Whether LAP2 or crystalloid cargo are direct substrates is untested\",\n        \"No structural or catalytic-mutant analysis\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0019706\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020030\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0018345\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"LAP2 (crystalloid cargo protein mistargeted in DHHC10 knockout)\"],\n    \"other_free_text\": [\n      \"Dispensable for asexual blood-stage growth in P. berghei [#1]\",\n      \"mRNA translationally repressed in female gametocytes and activated during ookinete formation in P. berghei [#0]\",\n      \"Transcript stored as translationally repressed maternal mRNA in P. falciparum female gametocytes [#2]\",\n      \"Required for crystalloid organelle biogenesis and mosquito transmission in P. berghei [#0]\",\n      \"Member of the DHHC-CRD palmitoyltransferase family [#1]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1027900","name":null,"product":"palmitoyltransferase DHHC10, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0512000","name":null,"product":"palmitoyltransferase DHHC10","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0612300","name":null,"product":"palmitoyltransferase DHHC10, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"DHHC10","evaluation":null}