{"gene":"PF3D7_1016900","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":2003,"finding":"ETRAMP10.3 (a member of the ETRAMP family) is associated with membrane fractions and localizes to the parasitophorous vacuole membrane (PVM) of P. falciparum, including tubovesicular extensions of the PVM, as demonstrated by colocalization, selective permeabilization, and immunoelectron microscopy.","method":"Western blot fractionation, colocalization and selective permeabilization studies, immunoelectron microscopy","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by immunoelectron microscopy and selective permeabilization, multiple orthogonal methods in a single lab study; ETRAMP10.3 is one of thirteen family members described collectively","pmids":["12686607"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2003,"finding":"ETRAMP10.3, as part of the ETRAMP family, shows stage-specific expression; certain ETRAMPs (including members identified as ring-stage specific) define separate PVM domains that are distinct from those occupied by the negatively charged integral PVM protein EXP-1, suggesting functionally different PVM microdomains.","method":"Northern blot, Western blot (stage-specific expression); colocalization studies comparing ETRAMP and EXP-1 distribution","journal":"Molecular biology of the cell","confidence":"Low","confidence_rationale":"Tier 3 / Weak — domain separation inferred from colocalization comparisons in a single study; ETRAMP10.3-specific data not individually resolved from family-level data","pmids":["12686607"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"finding":"ETRAMP family members (including those forming oligomeric arrays at the PVM) form complexes of oligomeric arrays at the parasite-host cell interface, with each ETRAMP member occupying a separate non-random array/microdomain; recombinant ETRAMPs oligomerize in bacterial membranes independently of other Plasmodium proteins, confirmed by in vivo cross-linking.","method":"In vivo chemical cross-linking, recombinant expression in bacterial membranes (oligomerization assay)","journal":"Molecular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo cross-linking plus bacterial reconstitution of oligomerization; ETRAMP10.3 is one of the family members studied but not all members are individually distinguished in the abstract","pmids":["16420351"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"finding":"ETRAMP10.3 (PF10_0164) localizes to the parasitophorous vacuole membrane and is also exported to the host erythrocyte in asexual blood stages of P. falciparum, as shown by localization studies; it is refractory to gene disruption, establishing that it is essential in asexual blood stages.","method":"Subcellular localization (immunofluorescence/fractionation), attempted gene disruption (refractory to knockout)","journal":"Eukaryotic cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment plus essentiality demonstrated by failed gene disruption with controls; single lab, two orthogonal approaches","pmids":["20228203"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"finding":"ETRAMP10.3 (PF10_0164) localizes to the parasitophorous vacuole membrane of liver stages in P. yoelii when expressed transgenically, but does not functionally complement the loss of P. yoelii UIS4 (transgenic parasites fail to complete liver-stage development), indicating ETRAMP10.3 is not a functional ortholog of UIS4.","method":"Transgenic complementation in P. yoelii uis4(-) background; immunolocalization in liver stages; mouse infection assay","journal":"Eukaryotic cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional complementation experiment with localization and phenotypic readout in a rodent malaria model; single lab study","pmids":["20228203"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii","strain":""}]}],"current_model":"ETRAMP10.3 (PF3D7_1016900) is an integral membrane protein that localizes to the parasitophorous vacuole membrane (PVM) of P. falciparum during asexual blood stages and sporozoite stages, is also exported to the host erythrocyte, forms oligomeric arrays at the PVM independently of other parasite proteins, and is essential for asexual blood-stage parasite survival; it localizes to the PVM in liver stages but does not functionally complement the rodent malaria UIS4 ortholog."},"narrative":{"mechanistic_narrative":"ETRAMP10.3 (PF3D7_1016900) is an integral membrane protein of the Plasmodium falciparum parasitophorous vacuole membrane (PVM) that contributes to organizing the parasite-host cell interface during blood- and liver-stage infection [PMID:12686607, PMID:20228203]. In asexual blood stages it associates with membrane fractions and localizes to the PVM, including its tubovesicular extensions, and is additionally exported to the host erythrocyte [PMID:12686607, PMID:20228203]. As a member of the ETRAMP family, ETRAMP10.3 self-assembles into oligomeric arrays at the PVM; recombinant ETRAMPs oligomerize when expressed in bacterial membranes, showing that array formation is intrinsic and does not require other Plasmodium proteins [PMID:16420351]. ETRAMP10.3 is refractory to gene disruption, establishing that it is essential for asexual blood-stage survival [PMID:20228203]. When expressed transgenically in Plasmodium yoelii it localizes to the liver-stage PVM but fails to complement loss of the rodent UIS4 protein, indicating it is not a functional ortholog of UIS4 [PMID:20228203]. Beyond its PVM localization, oligomerization, export, and essentiality, the molecular activity and binding partners of ETRAMP10.3 have not been characterized in the available corpus; several findings resolve the ETRAMP family collectively rather than PF3D7_1016900 individually.","teleology":[{"year":2003,"claim":"Establishing where an uncharacterized ETRAMP family member resides addressed whether it acts at the parasite-host interface; ETRAMP10.3 was localized to the PVM and its tubovesicular extensions.","evidence":"Membrane fractionation, colocalization with selective permeabilization, and immunoelectron microscopy in P. falciparum","pmids":["12686607"],"confidence":"Medium","gaps":["ETRAMP10.3 is described as one of thirteen family members and not fully resolved from family-level data","no molecular function or binding partner identified","topology within the PVM not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2003,"claim":"Whether different ETRAMPs occupy the same or distinct PVM regions was tested to ask if the PVM is compartmentalized; certain ETRAMPs defined microdomains distinct from EXP-1.","evidence":"Northern/Western stage-specific expression and colocalization comparisons of ETRAMP versus EXP-1 distribution in P. falciparum","pmids":["12686607"],"confidence":"Low","gaps":["domain separation inferred from colocalization and ETRAMP10.3-specific data not individually resolved","functional significance of separate microdomains unknown","no mechanism for microdomain establishment"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"claim":"How ETRAMPs organize at the PVM was addressed by testing whether they oligomerize and whether this depends on other parasite factors; ETRAMPs form non-random oligomeric arrays and oligomerize intrinsically.","evidence":"In vivo chemical cross-linking and recombinant expression/oligomerization assay in bacterial membranes","pmids":["16420351"],"confidence":"Medium","gaps":["individual contribution of ETRAMP10.3 not fully distinguished from other family members","structural basis of array formation unresolved","functional consequence of oligomerization not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"claim":"Whether ETRAMP10.3 is dispensable and confined to the PVM was tested to gauge its importance and trafficking; it proved essential in asexual blood stages and is also exported to the host erythrocyte.","evidence":"Subcellular localization plus attempted gene disruption (refractory to knockout) in P. falciparum","pmids":["20228203"],"confidence":"Medium","gaps":["essentiality inferred from failed disruption rather than conditional knockdown","molecular basis of essential function unknown","export mechanism to the erythrocyte not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"claim":"Whether ETRAMP10.3 is functionally equivalent to the liver-stage-critical UIS4 was tested by cross-species complementation; it localized correctly to the liver-stage PVM but did not rescue UIS4 loss.","evidence":"Transgenic complementation in a P. yoelii uis4(-) background with liver-stage immunolocalization and mouse infection readout","pmids":["20228203"],"confidence":"Medium","gaps":["reason for failure to complement (missing interactions or motifs) not identified","native role of ETRAMP10.3 in P. falciparum liver stages not directly assessed","single rodent-model study"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":null,"claim":"The molecular activity of ETRAMP10.3 and the identity of its binding partners or transport role at the PVM remain undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["no biochemical function assigned","no direct protein interaction partners identified for PF3D7_1016900","essential function in blood stages not mechanistically explained"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["ETRAMP oligomeric arrays at the parasitophorous vacuole membrane"],"partners":[],"other_free_text":["Integral membrane protein essential for asexual blood-stage survival (refractory to gene disruption) [#3]","Exported to the host erythrocyte in addition to PVM localization [#3]","Occupies a distinct PVM microdomain separate from EXP-1 (family-level inference) [#1]","Localizes to the liver-stage PVM in transgenic P. yoelii but does not functionally complement UIS4 [#4]","Several findings resolve the ETRAMP family collectively rather than PF3D7_1016900 individually [#0, #1, #2]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"12686607","id":"PMC_12686607","title":"etramps, a new Plasmodium falciparum gene family coding for developmentally regulated and highly charged membrane proteins located at the parasite-host cell interface.","date":"2003","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/12686607","citation_count":141,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"16420351","id":"PMC_16420351","title":"Organization of ETRAMPs and EXP-1 at the parasite-host cell interface of malaria parasites.","date":"2006","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/16420351","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":"20228203","id":"PMC_20228203","title":"Plasmodium falciparum PF10_0164 (ETRAMP10.3) is an essential parasitophorous vacuole and exported protein in blood stages.","date":"2010","source":"Eukaryotic cell","url":"https://pubmed.ncbi.nlm.nih.gov/20228203","citation_count":40,"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":4184,"output_tokens":1454,"usd":0.017181,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6436,"output_tokens":2528,"usd":0.04769,"stage2_stop_reason":"end_turn"},"total_usd":0.064871,"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\": 2003,\n      \"finding\": \"ETRAMP10.3 (a member of the ETRAMP family) is associated with membrane fractions and localizes to the parasitophorous vacuole membrane (PVM) of P. falciparum, including tubovesicular extensions of the PVM, as demonstrated by colocalization, selective permeabilization, and immunoelectron microscopy.\",\n      \"method\": \"Western blot fractionation, colocalization and selective permeabilization studies, immunoelectron microscopy\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by immunoelectron microscopy and selective permeabilization, multiple orthogonal methods in a single lab study; ETRAMP10.3 is one of thirteen family members described collectively\",\n      \"pmids\": [\"12686607\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"ETRAMP10.3, as part of the ETRAMP family, shows stage-specific expression; certain ETRAMPs (including members identified as ring-stage specific) define separate PVM domains that are distinct from those occupied by the negatively charged integral PVM protein EXP-1, suggesting functionally different PVM microdomains.\",\n      \"method\": \"Northern blot, Western blot (stage-specific expression); colocalization studies comparing ETRAMP and EXP-1 distribution\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — domain separation inferred from colocalization comparisons in a single study; ETRAMP10.3-specific data not individually resolved from family-level data\",\n      \"pmids\": [\"12686607\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"ETRAMP family members (including those forming oligomeric arrays at the PVM) form complexes of oligomeric arrays at the parasite-host cell interface, with each ETRAMP member occupying a separate non-random array/microdomain; recombinant ETRAMPs oligomerize in bacterial membranes independently of other Plasmodium proteins, confirmed by in vivo cross-linking.\",\n      \"method\": \"In vivo chemical cross-linking, recombinant expression in bacterial membranes (oligomerization assay)\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo cross-linking plus bacterial reconstitution of oligomerization; ETRAMP10.3 is one of the family members studied but not all members are individually distinguished in the abstract\",\n      \"pmids\": [\"16420351\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"ETRAMP10.3 (PF10_0164) localizes to the parasitophorous vacuole membrane and is also exported to the host erythrocyte in asexual blood stages of P. falciparum, as shown by localization studies; it is refractory to gene disruption, establishing that it is essential in asexual blood stages.\",\n      \"method\": \"Subcellular localization (immunofluorescence/fractionation), attempted gene disruption (refractory to knockout)\",\n      \"journal\": \"Eukaryotic cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment plus essentiality demonstrated by failed gene disruption with controls; single lab, two orthogonal approaches\",\n      \"pmids\": [\"20228203\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"ETRAMP10.3 (PF10_0164) localizes to the parasitophorous vacuole membrane of liver stages in P. yoelii when expressed transgenically, but does not functionally complement the loss of P. yoelii UIS4 (transgenic parasites fail to complete liver-stage development), indicating ETRAMP10.3 is not a functional ortholog of UIS4.\",\n      \"method\": \"Transgenic complementation in P. yoelii uis4(-) background; immunolocalization in liver stages; mouse infection assay\",\n      \"journal\": \"Eukaryotic cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional complementation experiment with localization and phenotypic readout in a rodent malaria model; single lab study\",\n      \"pmids\": [\"20228203\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"ETRAMP10.3 (PF3D7_1016900) is an integral membrane protein that localizes to the parasitophorous vacuole membrane (PVM) of P. falciparum during asexual blood stages and sporozoite stages, is also exported to the host erythrocyte, forms oligomeric arrays at the PVM independently of other parasite proteins, and is essential for asexual blood-stage parasite survival; it localizes to the PVM in liver stages but does not functionally complement the rodent malaria UIS4 ortholog.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ETRAMP10.3 (PF3D7_1016900) is an integral membrane protein of the Plasmodium falciparum parasitophorous vacuole membrane (PVM) that contributes to organizing the parasite-host cell interface during blood- and liver-stage infection [#0, #3]. In asexual blood stages it associates with membrane fractions and localizes to the PVM, including its tubovesicular extensions, and is additionally exported to the host erythrocyte [#0, #3]. As a member of the ETRAMP family, ETRAMP10.3 self-assembles into oligomeric arrays at the PVM; recombinant ETRAMPs oligomerize when expressed in bacterial membranes, showing that array formation is intrinsic and does not require other Plasmodium proteins [#2]. ETRAMP10.3 is refractory to gene disruption, establishing that it is essential for asexual blood-stage survival [#3]. When expressed transgenically in Plasmodium yoelii it localizes to the liver-stage PVM but fails to complement loss of the rodent UIS4 protein, indicating it is not a functional ortholog of UIS4 [#4]. Beyond its PVM localization, oligomerization, export, and essentiality, the molecular activity and binding partners of ETRAMP10.3 have not been characterized in the available corpus; several findings resolve the ETRAMP family collectively rather than PF3D7_1016900 individually.\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Establishing where an uncharacterized ETRAMP family member resides addressed whether it acts at the parasite-host interface; ETRAMP10.3 was localized to the PVM and its tubovesicular extensions.\",\n      \"evidence\": \"Membrane fractionation, colocalization with selective permeabilization, and immunoelectron microscopy in P. falciparum\",\n      \"pmids\": [\"12686607\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"ETRAMP10.3 is described as one of thirteen family members and not fully resolved from family-level data\",\n        \"no molecular function or binding partner identified\",\n        \"topology within the PVM not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Whether different ETRAMPs occupy the same or distinct PVM regions was tested to ask if the PVM is compartmentalized; certain ETRAMPs defined microdomains distinct from EXP-1.\",\n      \"evidence\": \"Northern/Western stage-specific expression and colocalization comparisons of ETRAMP versus EXP-1 distribution in P. falciparum\",\n      \"pmids\": [\"12686607\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"domain separation inferred from colocalization and ETRAMP10.3-specific data not individually resolved\",\n        \"functional significance of separate microdomains unknown\",\n        \"no mechanism for microdomain establishment\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"How ETRAMPs organize at the PVM was addressed by testing whether they oligomerize and whether this depends on other parasite factors; ETRAMPs form non-random oligomeric arrays and oligomerize intrinsically.\",\n      \"evidence\": \"In vivo chemical cross-linking and recombinant expression/oligomerization assay in bacterial membranes\",\n      \"pmids\": [\"16420351\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"individual contribution of ETRAMP10.3 not fully distinguished from other family members\",\n        \"structural basis of array formation unresolved\",\n        \"functional consequence of oligomerization not established\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Whether ETRAMP10.3 is dispensable and confined to the PVM was tested to gauge its importance and trafficking; it proved essential in asexual blood stages and is also exported to the host erythrocyte.\",\n      \"evidence\": \"Subcellular localization plus attempted gene disruption (refractory to knockout) in P. falciparum\",\n      \"pmids\": [\"20228203\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"essentiality inferred from failed disruption rather than conditional knockdown\",\n        \"molecular basis of essential function unknown\",\n        \"export mechanism to the erythrocyte not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Whether ETRAMP10.3 is functionally equivalent to the liver-stage-critical UIS4 was tested by cross-species complementation; it localized correctly to the liver-stage PVM but did not rescue UIS4 loss.\",\n      \"evidence\": \"Transgenic complementation in a P. yoelii uis4(-) background with liver-stage immunolocalization and mouse infection readout\",\n      \"pmids\": [\"20228203\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"reason for failure to complement (missing interactions or motifs) not identified\",\n        \"native role of ETRAMP10.3 in P. falciparum liver stages not directly assessed\",\n        \"single rodent-model study\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular activity of ETRAMP10.3 and the identity of its binding partners or transport role at the PVM remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"no biochemical function assigned\",\n        \"no direct protein interaction partners identified for PF3D7_1016900\",\n        \"essential function in blood stages not mechanistically explained\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0042803\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020005\", \"supporting_discovery_ids\": [0, 3, 4]},\n      {\"term_id\": \"GO:0020036\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [\"ETRAMP oligomeric arrays at the parasitophorous vacuole membrane\"],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Integral membrane protein essential for asexual blood-stage survival (refractory to gene disruption) [#3]\",\n      \"Exported to the host erythrocyte in addition to PVM localization [#3]\",\n      \"Occupies a distinct PVM microdomain separate from EXP-1 (family-level inference) [#1]\",\n      \"Localizes to the liver-stage PVM in transgenic P. yoelii but does not functionally complement UIS4 [#4]\",\n      \"Several findings resolve the ETRAMP family collectively rather than PF3D7_1016900 individually [#0, #1, #2]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1016900","name":null,"product":"early transcribed membrane protein 10.3","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}