{"gene":"PF3D7_1141800","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":2024,"finding":"PF3D7_1141800 (EELM2/PfEELM2) was identified as a binding partner of PfMORC (PF3D7_1468100) in a nuclear protein complex in P. falciparum, placing it among chromatin remodelers that interact with the MORC-centered complex involved in epigenetic control of asexual blood stage transcriptional regulation.","method":"Co-immunoprecipitation / multi-omic analysis (proteomics of PfMORC interactome)","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single Co-IP/proteomics identification in one study; no direct functional follow-up specific to PF3D7_1141800 itself, but part of a multi-omic study with broader validation of the complex","pmids":["39412522"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"finding":"PF3D7_1141800 (EELM2) was detected in the experimentally determined core nuclear proteome of P. falciparum, and its nuclear localization was confirmed by transgenic cell line validation using tagging approaches.","method":"Nuclear fractionation followed by high-accuracy mass spectrometry; validation by transgenic GFP/epitope-tagged cell lines","journal":"Genome biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct subcellular fractionation with mass spectrometry plus independent transgenic fluorescence validation, single lab","pmids":["23181666"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"finding":"PF3D7_1141800 (EELM2) was identified as a putative nuclear protein with a specific sub-nuclear localization pattern in P. falciparum, detected via bioinformatic prediction and confirmed by GFP or HA epitope tagging; it localizes to a distinct area of the nucleus consistent with a role in transcriptional regulation.","method":"Bioinformatic identification followed by GFP/HA epitope tagging and fluorescence microscopy in transgenic P. falciparum","journal":"International journal for parasitology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — localization confirmed by fluorescence tagging in a single study but no direct functional consequence established for this specific protein","pmids":["19765590"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1141800 (EELM2) is a nuclear-localized chromatin-associated protein in P. falciparum that physically interacts with the PfMORC complex (including ApiAP2 transcription factors and other chromatin remodelers), implicating it in epigenetic control of asexual blood stage gene expression, though its specific molecular function within the complex has not yet been directly established."},"narrative":{"mechanistic_narrative":"PF3D7_1141800 (EELM2) is a nuclear-localized protein of Plasmodium falciparum implicated in the epigenetic control of asexual blood stage transcription through its association with the PfMORC-centered chromatin complex [PMID:39412522, PMID:23181666]. It was recovered in the experimentally determined core nuclear proteome, with transgenic tagging confirming a distinct sub-nuclear localization pattern consistent with a transcriptional regulatory role [PMID:23181666, PMID:19765590]. It physically associates with PfMORC (PF3D7_1468100) as a binding partner within a nuclear complex that includes chromatin remodelers implicated in asexual blood stage transcriptional regulation [PMID:39412522]. Beyond this complex membership and its nuclear localization, no molecular function specific to EELM2 itself has been characterized in the available corpus.","teleology":[{"year":2009,"claim":"The first question was whether EELM2 is a nuclear protein at all; bioinformatic prediction plus epitope tagging established that it localizes to a discrete sub-nuclear region, hinting at a transcriptional regulatory role.","evidence":"Bioinformatic identification with GFP/HA tagging and fluorescence microscopy in transgenic P. falciparum","pmids":["19765590"],"confidence":"Low","gaps":["No direct functional consequence established for the protein","The sub-nuclear compartment was not molecularly defined","No interaction partners identified at this stage"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"claim":"To move beyond prediction, the protein's nuclear residence was independently verified as part of the experimentally determined core nuclear proteome, corroborating the localization by fractionation and transgenic validation.","evidence":"Nuclear fractionation with high-accuracy mass spectrometry plus GFP/epitope-tagged transgenic validation","pmids":["23181666"],"confidence":"Medium","gaps":["Establishes localization but not molecular activity","No binding partners or substrates identified","Single-lab validation"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"The key advance was placing EELM2 within a functional context: it was identified as a binding partner of PfMORC in a nuclear complex, connecting it to chromatin remodeling and epigenetic control of asexual blood stage transcription.","evidence":"Co-immunoprecipitation and proteomics of the PfMORC interactome in a multi-omic study","pmids":["39412522"],"confidence":"Medium","gaps":["Single Co-IP/proteomics identification without direct functional follow-up specific to EELM2","EELM2's own molecular activity within the complex is undefined","Whether EELM2 is required for complex integrity or MORC function is unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The central open question is what specific molecular function EELM2 contributes within the PfMORC complex and whether its loss perturbs epigenetic control of blood stage gene expression.","evidence":"","pmids":[],"confidence":"Low","gaps":["No knockout, knockdown, or conditional depletion of EELM2 reported","No enzymatic or DNA/chromatin-binding activity assigned to the protein","No structural or domain-function characterization of the EELM2 domain in this protein"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfMORC-centered nuclear chromatin complex"],"partners":["PFMORC (PF3D7_1468100)"],"other_free_text":["Recovered in the P. falciparum core nuclear proteome with a distinct sub-nuclear localization pattern.","Implicated in epigenetic control of asexual blood stage transcription solely through its association with the PfMORC complex; no molecular function specific to EELM2 itself has been established in the corpus."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"23181666","id":"PMC_23181666","title":"Organellar proteomics reveals hundreds of novel nuclear proteins in the malaria parasite Plasmodium falciparum.","date":"2012","source":"Genome biology","url":"https://pubmed.ncbi.nlm.nih.gov/23181666","citation_count":119,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19765590","id":"PMC_19765590","title":"Potential epigenetic regulatory proteins localise to distinct nuclear sub-compartments in Plasmodium falciparum.","date":"2009","source":"International journal for parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/19765590","citation_count":64,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39412522","id":"PMC_39412522","title":"A Plasmodium falciparum MORC protein complex modulates epigenetic control of gene expression through interaction with heterochromatin.","date":"2024","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/39412522","citation_count":12,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfEELM2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4363,"output_tokens":884,"usd":0.013175,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5570,"output_tokens":1655,"usd":0.034612,"stage2_stop_reason":"end_turn"},"total_usd":0.047787,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2024,\n      \"finding\": \"PF3D7_1141800 (EELM2/PfEELM2) was identified as a binding partner of PfMORC (PF3D7_1468100) in a nuclear protein complex in P. falciparum, placing it among chromatin remodelers that interact with the MORC-centered complex involved in epigenetic control of asexual blood stage transcriptional regulation.\",\n      \"method\": \"Co-immunoprecipitation / multi-omic analysis (proteomics of PfMORC interactome)\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single Co-IP/proteomics identification in one study; no direct functional follow-up specific to PF3D7_1141800 itself, but part of a multi-omic study with broader validation of the complex\",\n      \"pmids\": [\"39412522\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"PF3D7_1141800 (EELM2) was detected in the experimentally determined core nuclear proteome of P. falciparum, and its nuclear localization was confirmed by transgenic cell line validation using tagging approaches.\",\n      \"method\": \"Nuclear fractionation followed by high-accuracy mass spectrometry; validation by transgenic GFP/epitope-tagged cell lines\",\n      \"journal\": \"Genome biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct subcellular fractionation with mass spectrometry plus independent transgenic fluorescence validation, single lab\",\n      \"pmids\": [\"23181666\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"PF3D7_1141800 (EELM2) was identified as a putative nuclear protein with a specific sub-nuclear localization pattern in P. falciparum, detected via bioinformatic prediction and confirmed by GFP or HA epitope tagging; it localizes to a distinct area of the nucleus consistent with a role in transcriptional regulation.\",\n      \"method\": \"Bioinformatic identification followed by GFP/HA epitope tagging and fluorescence microscopy in transgenic P. falciparum\",\n      \"journal\": \"International journal for parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — localization confirmed by fluorescence tagging in a single study but no direct functional consequence established for this specific protein\",\n      \"pmids\": [\"19765590\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_1141800 (EELM2) is a nuclear-localized chromatin-associated protein in P. falciparum that physically interacts with the PfMORC complex (including ApiAP2 transcription factors and other chromatin remodelers), implicating it in epigenetic control of asexual blood stage gene expression, though its specific molecular function within the complex has not yet been directly established.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1141800 (EELM2) is a nuclear-localized protein of Plasmodium falciparum implicated in the epigenetic control of asexual blood stage transcription through its association with the PfMORC-centered chromatin complex [#0, #1]. It was recovered in the experimentally determined core nuclear proteome, with transgenic tagging confirming a distinct sub-nuclear localization pattern consistent with a transcriptional regulatory role [#1, #2]. It physically associates with PfMORC (PF3D7_1468100) as a binding partner within a nuclear complex that includes chromatin remodelers implicated in asexual blood stage transcriptional regulation [#0]. Beyond this complex membership and its nuclear localization, no molecular function specific to EELM2 itself has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"The first question was whether EELM2 is a nuclear protein at all; bioinformatic prediction plus epitope tagging established that it localizes to a discrete sub-nuclear region, hinting at a transcriptional regulatory role.\",\n      \"evidence\": \"Bioinformatic identification with GFP/HA tagging and fluorescence microscopy in transgenic P. falciparum\",\n      \"pmids\": [\"19765590\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct functional consequence established for the protein\",\n        \"The sub-nuclear compartment was not molecularly defined\",\n        \"No interaction partners identified at this stage\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"To move beyond prediction, the protein's nuclear residence was independently verified as part of the experimentally determined core nuclear proteome, corroborating the localization by fractionation and transgenic validation.\",\n      \"evidence\": \"Nuclear fractionation with high-accuracy mass spectrometry plus GFP/epitope-tagged transgenic validation\",\n      \"pmids\": [\"23181666\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Establishes localization but not molecular activity\",\n        \"No binding partners or substrates identified\",\n        \"Single-lab validation\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"The key advance was placing EELM2 within a functional context: it was identified as a binding partner of PfMORC in a nuclear complex, connecting it to chromatin remodeling and epigenetic control of asexual blood stage transcription.\",\n      \"evidence\": \"Co-immunoprecipitation and proteomics of the PfMORC interactome in a multi-omic study\",\n      \"pmids\": [\"39412522\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single Co-IP/proteomics identification without direct functional follow-up specific to EELM2\",\n        \"EELM2's own molecular activity within the complex is undefined\",\n        \"Whether EELM2 is required for complex integrity or MORC function is unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The central open question is what specific molecular function EELM2 contributes within the PfMORC complex and whether its loss perturbs epigenetic control of blood stage gene expression.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No knockout, knockdown, or conditional depletion of EELM2 reported\",\n        \"No enzymatic or DNA/chromatin-binding activity assigned to the protein\",\n        \"No structural or domain-function characterization of the EELM2 domain in this protein\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006325\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"PfMORC-centered nuclear chromatin complex\"],\n    \"partners\": [\"PfMORC (PF3D7_1468100)\"],\n    \"other_free_text\": [\n      \"Recovered in the P. falciparum core nuclear proteome with a distinct sub-nuclear localization pattern.\",\n      \"Implicated in epigenetic control of asexual blood stage transcription solely through its association with the PfMORC complex; no molecular function specific to EELM2 itself has been established in the corpus.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1141800","name":null,"product":"EELM2 domain-containing protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0907200","name":null,"product":"EELM2 domain-containing protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0939600","name":null,"product":"EELM2 domain-containing protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}