{"gene":"PKNH_1324800","run_date":"2026-09-08T15:24:05","timeline":{"discoveries":[{"year":2015,"finding":"PKNH_1324800 (PkTRAg38.3) binds to human erythrocytes, as demonstrated by cell-ELISA with recombinant protein expressed in E. coli and in mammalian CHO-K1 cells, and by in vitro rosetting assay. PkTRAg38.3 cross-competes for erythrocyte receptor binding with PkTRAg40.1 and with previously described P. vivax tryptophan-rich antigens (PvTRAgs), indicating shared receptor usage. Additionally, recombinant PkTRAg38.3 inhibited P. falciparum parasite growth in in vitro culture, further supporting a role in receptor-ligand interactions at the erythrocyte surface.","method":"Cell-ELISA with recombinant protein (E. coli and CHO-K1 expression), in vitro rosetting assay, cross-competition binding assay, in vitro P. falciparum growth inhibition assay","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — multiple orthogonal binding assays (cell-ELISA, rosetting, competition) in a single study, single lab, no mutagenesis or structural validation","pmids":["26393350"],"is_preprint":false,"attribution":[{"species":"Plasmodium knowlesi","strain":""}]}],"current_model":"PKNH_1324800 (TRAG38.3/PkTRAg38.3) is a P. knowlesi tryptophan-rich antigen that binds to human erythrocytes via receptor(s) shared with PkTRAg40.1 and P. vivax TRAg orthologues, and whose recombinant form inhibits P. falciparum growth in vitro, implicating it in host erythrocyte recognition during zoonotic infection."},"narrative":{"mechanistic_narrative":"PKNH_1324800 (TRAG38.3/PkTRAg38.3) is a Plasmodium knowlesi tryptophan-rich antigen implicated in host erythrocyte recognition during zoonotic infection [PMID:26393350]. Recombinant PKNH_1324800, expressed in both E. coli and CHO-K1 cells, binds human erythrocytes as shown by cell-ELISA and in vitro rosetting, and cross-competes for erythrocyte receptor binding with PkTRAg40.1 and with P. vivax tryptophan-rich antigens (PvTRAgs), indicating shared receptor usage among these antigens [PMID:26393350]. Recombinant PKNH_1324800 also inhibits P. falciparum growth in vitro, consistent with a receptor-ligand function at the erythrocyte surface [PMID:26393350]. Beyond this erythrocyte-binding activity established in a single study [PMID:26393350], no further mechanistic detail — including the identity of its erythrocyte receptor, structural basis of binding, or in vivo function — has been characterized in the available corpus.","teleology":[{"year":2015,"claim":"Whether PKNH_1324800 engages the host erythrocyte surface was unknown; demonstrating direct erythrocyte binding and shared receptor usage established it as a candidate ligand in P. knowlesi host-cell recognition.","evidence":"Cell-ELISA with recombinant protein (E. coli and CHO-K1), in vitro rosetting, cross-competition binding, and in vitro P. falciparum growth inhibition in Plasmodium knowlesi","pmids":["26393350"],"confidence":"Medium","gaps":["The human erythrocyte receptor bound by PKNH_1324800 is not identified","No mutagenesis or structural analysis defines the binding domain or specificity","In vivo role during P. knowlesi infection and function distinct from PkTRAg40.1/PvTRAgs are not established"],"attribution":[{"species":"Plasmodium knowlesi","strain":""}]},{"year":null,"claim":"The identity of the erythrocyte receptor, the structural basis of binding, and the native function of PKNH_1324800 during P. knowlesi blood-stage infection remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No receptor has been molecularly identified","No structural or mutagenesis data on the binding interface","No genetic or in vivo evidence for the antigen's role in invasion or sequestration"],"attribution":[{"species":"Plasmodium knowlesi","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PKTRAG40.1 (SHARED ERYTHROCYTE RECEPTOR USAGE, BY CROSS-COMPETITION) [#0]","P. VIVAX TRYPTOPHAN-RICH ANTIGENS / PVTRAGS (SHARED ERYTHROCYTE RECEPTOR USAGE, BY CROSS-COMPETITION) [#0]"],"other_free_text":["PKNH_1324800 (TRAG38.3/PkTRAg38.3) binds human erythrocytes; recombinant protein inhibits P. falciparum growth in vitro [#0]","Erythrocyte binding demonstrated with recombinant protein from both E. coli and CHO-K1 expression systems [#0]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"11704272","id":"PMC_11704272","title":"Properties of the Plasmodium falciparum homologue of a protective vaccine candidate of Plasmodium yoelii.","date":"2001","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/11704272","citation_count":22,"is_preprint":false,"source_species":["Pk"],"role":"primary","match_terms":["tryptophan-rich protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25960542","id":"PMC_25960542","title":"A Sporozoite- and Liver Stage-expressed Tryptophan-rich Protein Plays an Auxiliary Role in Plasmodium Liver Stage Development and Is a Potential Vaccine Candidate.","date":"2015","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/25960542","citation_count":19,"is_preprint":false,"source_species":["Pk"],"role":"primary","match_terms":["tryptophan-rich protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"18603013","id":"PMC_18603013","title":"Immunological responses to a 39.8kDa Plasmodium vivax tryptophan-rich antigen (PvTRAg39.8) among humans.","date":"2008","source":"Microbes and infection","url":"https://pubmed.ncbi.nlm.nih.gov/18603013","citation_count":16,"is_preprint":false,"source_species":["Pk"],"role":"primary","match_terms":["tryptophan-rich protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21464256","id":"PMC_21464256","title":"Artesunate tolerance in transgenic Plasmodium falciparum parasites overexpressing a tryptophan-rich protein.","date":"2011","source":"Antimicrobial agents and chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/21464256","citation_count":15,"is_preprint":false,"source_species":["Pk"],"role":"primary","match_terms":["tryptophan-rich protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21283717","id":"PMC_21283717","title":"Plasmodium vivax tryptophan-rich antigen PvTRAg33.5 contains alpha helical structure and multidomain architecture.","date":"2011","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/21283717","citation_count":10,"is_preprint":false,"source_species":["Pk"],"role":"primary","match_terms":["tryptophan-rich protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26393350","id":"PMC_26393350","title":"Recognition of Human Erythrocyte Receptors by the Tryptophan-Rich Antigens of Monkey Malaria Parasite Plasmodium knowlesi.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/26393350","citation_count":9,"is_preprint":false,"source_species":["Pk"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36126089","id":"PMC_36126089","title":"A member of the tryptophan-rich protein family is required for efficient sequestration of Plasmodium berghei schizonts.","date":"2022","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/36126089","citation_count":8,"is_preprint":false,"source_species":["Pk"],"role":"primary","match_terms":["tryptophan-rich protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35744665","id":"PMC_35744665","title":"Genetic Diversity and Phylogenetic Relatedness of Plasmodium ovale curtisi and Plasmodium ovale wallikeri in sub-Saharan Africa.","date":"2022","source":"Microorganisms","url":"https://pubmed.ncbi.nlm.nih.gov/35744665","citation_count":1,"is_preprint":false,"source_species":["Pk"],"role":"primary","match_terms":["tryptophan-rich protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41810678","id":"PMC_41810678","title":"Transcriptomics of Plasmodium vivax rosetting.","date":"2026","source":"Memorias do Instituto Oswaldo Cruz","url":"https://pubmed.ncbi.nlm.nih.gov/41810678","citation_count":0,"is_preprint":false,"source_species":["Pk"],"role":"primary","match_terms":["tryptophan-rich protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41983137","id":"PMC_41983137","title":"Poly(I:C) and R848 adjuvants elicit sizeable humoral immunity to liver stage malaria antigens.","date":"2026","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/41983137","citation_count":0,"is_preprint":false,"source_species":["Pk"],"role":"primary","match_terms":["tryptophan-rich protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8079,"output_tokens":1176,"usd":0.020938,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5041,"output_tokens":1270,"usd":0.028477,"stage2_stop_reason":"end_turn"},"total_usd":0.049415,"stage1_batch_id":"msgbatch_01S4WrhSkksYHeZXxqf3za3o","stage2_batch_id":"msgbatch_019VBBeuW6G52X8gZfsFDfb5","note":"batch pricing = 50% of standard"},"stage1_raw":"I need to carefully identify which papers are about PKNH_1324800 (TRAG38.3), a P. knowlesi tryptophan-rich protein.\n\n**Paper-by-paper classification:**\n\n1. [PMID:11704272] — P. falciparum tryptophan-rich protein (Pf homologue). Not P. knowlesi TRAG38.3. SKIP.\n\n2. [PMID:25960542] — SLTRiP, a sporozoite/liver stage tryptophan-rich protein in P. berghei/falciparum context. Not TRAG38.3. SKIP.\n\n3. [PMID:18603013] — PvTRAg39.8, a P. vivax tryptophan-rich antigen. Not TRAG38.3. SKIP.\n\n4. [PMID:21464256] — PArt (Pf10_0026), a P. falciparum tryptophan-rich protein. Not TRAG38.3. SKIP.\n\n5. [PMID:21283717] — PvTRAg33.5, a P. vivax tryptophan-rich protein. Not TRAG38.3. SKIP.\n\n6. [PMID:26393350] — This describes **PkTRAg38.3** from P. knowlesi — this is PKNH_1324800/TRAG38.3! INCLUDE.\n\n7. [PMID:36126089] — P. berghei IPIS2/IPIS3 tryptophan-rich domain proteins. Not TRAG38.3. SKIP.\n\n8. [PMID:35744665] — P. ovale tryptophan-rich protein for phylogenetics. Not TRAG38.3. SKIP.\n\n9. [PMID:41810678] — P. vivax TRAG16 mentioned, not TRAG38.3. SKIP.\n\n10. [PMID:41983137] — PbSLTRiP (P. berghei). Not TRAG38.3. SKIP.\n\n**Paper 6 [PMID:26393350]** is the only paper directly about PKNH_1324800 (PkTRAg38.3). It shows:\n- PkTRAg38.3 binds to human erythrocytes (cell-ELISA, rosetting assay)\n- PkTRAg38.3 cross-competes with PkTRAg40.1 and PvTRAgs for human erythrocyte receptors\n- PkTRAg38.3 inhibits P. falciparum growth in vitro\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2015,\n      \"finding\": \"PKNH_1324800 (PkTRAg38.3) binds to human erythrocytes, as demonstrated by cell-ELISA with recombinant protein expressed in E. coli and in mammalian CHO-K1 cells, and by in vitro rosetting assay. PkTRAg38.3 cross-competes for erythrocyte receptor binding with PkTRAg40.1 and with previously described P. vivax tryptophan-rich antigens (PvTRAgs), indicating shared receptor usage. Additionally, recombinant PkTRAg38.3 inhibited P. falciparum parasite growth in in vitro culture, further supporting a role in receptor-ligand interactions at the erythrocyte surface.\",\n      \"method\": \"Cell-ELISA with recombinant protein (E. coli and CHO-K1 expression), in vitro rosetting assay, cross-competition binding assay, in vitro P. falciparum growth inhibition assay\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — multiple orthogonal binding assays (cell-ELISA, rosetting, competition) in a single study, single lab, no mutagenesis or structural validation\",\n      \"pmids\": [\"26393350\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium knowlesi\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PKNH_1324800 (TRAG38.3/PkTRAg38.3) is a P. knowlesi tryptophan-rich antigen that binds to human erythrocytes via receptor(s) shared with PkTRAg40.1 and P. vivax TRAg orthologues, and whose recombinant form inhibits P. falciparum growth in vitro, implicating it in host erythrocyte recognition during zoonotic infection.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PKNH_1324800 (TRAG38.3/PkTRAg38.3) is a Plasmodium knowlesi tryptophan-rich antigen implicated in host erythrocyte recognition during zoonotic infection [#0]. Recombinant PKNH_1324800, expressed in both E. coli and CHO-K1 cells, binds human erythrocytes as shown by cell-ELISA and in vitro rosetting, and cross-competes for erythrocyte receptor binding with PkTRAg40.1 and with P. vivax tryptophan-rich antigens (PvTRAgs), indicating shared receptor usage among these antigens [#0]. Recombinant PKNH_1324800 also inhibits P. falciparum growth in vitro, consistent with a receptor-ligand function at the erythrocyte surface [#0]. Beyond this erythrocyte-binding activity established in a single study [#0], no further mechanistic detail — including the identity of its erythrocyte receptor, structural basis of binding, or in vivo function — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"Whether PKNH_1324800 engages the host erythrocyte surface was unknown; demonstrating direct erythrocyte binding and shared receptor usage established it as a candidate ligand in P. knowlesi host-cell recognition.\",\n      \"evidence\": \"Cell-ELISA with recombinant protein (E. coli and CHO-K1), in vitro rosetting, cross-competition binding, and in vitro P. falciparum growth inhibition in Plasmodium knowlesi\",\n      \"pmids\": [\"26393350\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The human erythrocyte receptor bound by PKNH_1324800 is not identified\",\n        \"No mutagenesis or structural analysis defines the binding domain or specificity\",\n        \"In vivo role during P. knowlesi infection and function distinct from PkTRAg40.1/PvTRAgs are not established\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium knowlesi\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The identity of the erythrocyte receptor, the structural basis of binding, and the native function of PKNH_1324800 during P. knowlesi blood-stage infection remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No receptor has been molecularly identified\",\n        \"No structural or mutagenesis data on the binding interface\",\n        \"No genetic or in vivo evidence for the antigen's role in invasion or sequestration\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium knowlesi\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\n      \"PkTRAg40.1 (shared erythrocyte receptor usage, by cross-competition) [#0]\",\n      \"P. vivax tryptophan-rich antigens / PvTRAgs (shared erythrocyte receptor usage, by cross-competition) [#0]\"\n    ],\n    \"other_free_text\": [\n      \"PKNH_1324800 (TRAG38.3/PkTRAg38.3) binds human erythrocytes; recombinant protein inhibits P. falciparum growth in vitro [#0]\",\n      \"Erythrocyte binding demonstrated with recombinant protein from both E. coli and CHO-K1 expression systems [#0]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"PkH","gene_id":"PKNH_1324800","name":null,"product":"tryptophan-rich protein","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}