{"gene":"PF3D7_1448700","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2011,"finding":"Genetic ablation of HSP20 (PF3D7_1448700) in Plasmodium sporozoites profoundly disrupts substrate adhesion and results in aberrant speed and directionality of gliding motility in vitro, demonstrating a critical role for this small heat shock protein in actin-based cell traction and motility.","method":"Molecular genetics / loss-of-function (gene knockout) with in vitro gliding motility and adhesion assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean genetic knockout with defined cellular phenotypes (speed, directionality, adhesion) measured by multiple orthogonal assays in a single rigorous study, replicated in follow-up review","pmids":["22139844"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2011,"finding":"HSP20 (PF3D7_1448700) loss-of-function impairs sporozoite migration in the mammalian host (skin-to-liver), establishing that HSP20-dependent motility is required for natural malaria transmission.","method":"Molecular genetics / loss-of-function (gene knockout) with in vivo host migration assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean genetic knockout with defined in vivo phenotype (impaired host migration and transmission), supported by in vitro corroboration","pmids":["22139844"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2019,"finding":"In HSP20 (PF3D7_1448700)-null mutant sporozoites, the polarized apical distribution of MTIP (Myosin A-tail interacting protein) observed during gliding is abrogated, indicating that HSP20 is required for correct spatial organization of the acto-myosin motor complex during locomotion.","method":"Subcellular localization by immunofluorescence/microscopy of MTIP in HSP20 knockout parasites compared to wild-type","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — localization experiment in genetic mutant background with functional consequence (aberrant locomotion), single lab, single method","pmids":["31874192"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"HSP20 (PF3D7_1448700) is a small heat shock protein that is essential for sporozoite gliding motility and host migration: its loss abolishes normal substrate adhesion, speed, and directionality in vitro, impairs skin-to-liver migration in vivo, and disrupts the polarized apical localization of the acto-myosin motor component MTIP, placing HSP20 as a regulator of actin-based motility and motor complex organization in Plasmodium infectious stages."},"narrative":{"mechanistic_narrative":"HSP20 (PF3D7_1448700) is a small heat shock protein required for the gliding motility and host migration of Plasmodium sporozoites [PMID:22139844]. Genetic ablation of HSP20 in P. berghei sporozoites disrupts substrate adhesion and produces aberrant gliding speed and directionality in vitro, identifying HSP20 as a positive regulator of actin-based cell traction [PMID:22139844], and in vivo this defect impairs skin-to-liver migration and thereby the transmission-relevant steps of infection [PMID:22139844]. Mechanistically, loss of HSP20 abrogates the polarized apical distribution of the acto-myosin motor component MTIP during gliding, indicating that HSP20 is needed for correct spatial organization of the motor complex during locomotion [PMID:31874192]. Beyond these motility and MTIP-organization phenotypes established in P. berghei, no biochemical chaperone activity, direct binding partner, or substrate has been characterized for HSP20 in the available corpus.","teleology":[{"year":2011,"claim":"Whether this small heat shock protein contributes to parasite motility was unknown; knockout established that HSP20 is required for normal substrate adhesion and for the speed and directionality of sporozoite gliding.","evidence":"gene knockout with in vitro gliding motility and adhesion assays in P. berghei sporozoites","pmids":["22139844"],"confidence":"High","gaps":["does not identify the molecular partners or substrates of HSP20","does not establish whether the defect reflects chaperone activity or a structural role","no biochemical demonstration of small heat shock protein function"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2011,"claim":"It was unclear whether the in vitro motility defect had consequences for infection; the knockout showed impaired sporozoite skin-to-liver migration, linking HSP20-dependent motility to natural transmission.","evidence":"gene knockout with in vivo host migration assays in P. berghei","pmids":["22139844"],"confidence":"High","gaps":["does not resolve the molecular step at which migration fails","does not quantify contribution to overall infectivity beyond migration"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2019,"claim":"The mechanistic basis of the motility defect was unknown; comparison of MTIP localization in null versus wild-type sporozoites showed HSP20 is required for the polarized apical distribution of the acto-myosin motor component.","evidence":"immunofluorescence/microscopy of MTIP in HSP20 knockout versus wild-type P. berghei sporozoites","pmids":["31874192"],"confidence":"Medium","gaps":["single lab, single method (localization only), no reciprocal or biochemical validation","does not show direct interaction between HSP20 and MTIP or motor components","does not establish whether HSP20 acts as a chaperone for motor assembly"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"Whether HSP20 possesses chaperone activity and which client proteins or motor complex components it directly binds remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["no direct binding partner or substrate identified","no structural or biochemical characterization of chaperone function","no data in P. falciparum despite the PF3D7 identifier; all phenotypes derive from P. berghei"],"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["MTIP (SPATIAL ORGANIZATION DEPENDENT ON HSP20; NO DIRECT INTERACTION DEMONSTRATED)"],"other_free_text":["Genetic ablation in P. berghei sporozoites disrupts substrate adhesion and gliding speed/directionality in vitro [#0].","Knockout impairs sporozoite skin-to-liver migration in the mammalian host [#1].","Loss of HSP20 abrogates polarized apical distribution of the acto-myosin motor component MTIP [#2].","No biochemical chaperone activity, direct partner, or client substrate has been characterized in the available corpus."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"22139844","id":"PMC_22139844","title":"Critical role for heat shock protein 20 (HSP20) in migration of malarial sporozoites.","date":"2011","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/22139844","citation_count":54,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["HSP20"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22568951","id":"PMC_22568951","title":"Small heat shock proteins in cellular adhesion and migration: evidence from Plasmodium genetics.","date":"2012","source":"Cell adhesion & migration","url":"https://pubmed.ncbi.nlm.nih.gov/22568951","citation_count":12,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["HSP20"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31874192","id":"PMC_31874192","title":"Polarization of MTIP is a signature of gliding locomotion in Plasmodium ookinetes and sporozoites.","date":"2019","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/31874192","citation_count":3,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["HSP20"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4006,"output_tokens":877,"usd":0.012587,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5583,"output_tokens":1699,"usd":0.035195,"stage2_stop_reason":"end_turn"},"total_usd":0.047782,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2011,\n      \"finding\": \"Genetic ablation of HSP20 (PF3D7_1448700) in Plasmodium sporozoites profoundly disrupts substrate adhesion and results in aberrant speed and directionality of gliding motility in vitro, demonstrating a critical role for this small heat shock protein in actin-based cell traction and motility.\",\n      \"method\": \"Molecular genetics / loss-of-function (gene knockout) with in vitro gliding motility and adhesion assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean genetic knockout with defined cellular phenotypes (speed, directionality, adhesion) measured by multiple orthogonal assays in a single rigorous study, replicated in follow-up review\",\n      \"pmids\": [\"22139844\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"HSP20 (PF3D7_1448700) loss-of-function impairs sporozoite migration in the mammalian host (skin-to-liver), establishing that HSP20-dependent motility is required for natural malaria transmission.\",\n      \"method\": \"Molecular genetics / loss-of-function (gene knockout) with in vivo host migration assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean genetic knockout with defined in vivo phenotype (impaired host migration and transmission), supported by in vitro corroboration\",\n      \"pmids\": [\"22139844\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"In HSP20 (PF3D7_1448700)-null mutant sporozoites, the polarized apical distribution of MTIP (Myosin A-tail interacting protein) observed during gliding is abrogated, indicating that HSP20 is required for correct spatial organization of the acto-myosin motor complex during locomotion.\",\n      \"method\": \"Subcellular localization by immunofluorescence/microscopy of MTIP in HSP20 knockout parasites compared to wild-type\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — localization experiment in genetic mutant background with functional consequence (aberrant locomotion), single lab, single method\",\n      \"pmids\": [\"31874192\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"HSP20 (PF3D7_1448700) is a small heat shock protein that is essential for sporozoite gliding motility and host migration: its loss abolishes normal substrate adhesion, speed, and directionality in vitro, impairs skin-to-liver migration in vivo, and disrupts the polarized apical localization of the acto-myosin motor component MTIP, placing HSP20 as a regulator of actin-based motility and motor complex organization in Plasmodium infectious stages.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"HSP20 (PF3D7_1448700) is a small heat shock protein required for the gliding motility and host migration of Plasmodium sporozoites [#0, #1]. Genetic ablation of HSP20 in P. berghei sporozoites disrupts substrate adhesion and produces aberrant gliding speed and directionality in vitro, identifying HSP20 as a positive regulator of actin-based cell traction [#0], and in vivo this defect impairs skin-to-liver migration and thereby the transmission-relevant steps of infection [#1]. Mechanistically, loss of HSP20 abrogates the polarized apical distribution of the acto-myosin motor component MTIP during gliding, indicating that HSP20 is needed for correct spatial organization of the motor complex during locomotion [#2]. Beyond these motility and MTIP-organization phenotypes established in P. berghei, no biochemical chaperone activity, direct binding partner, or substrate has been characterized for HSP20 in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2011,\n      \"claim\": \"Whether this small heat shock protein contributes to parasite motility was unknown; knockout established that HSP20 is required for normal substrate adhesion and for the speed and directionality of sporozoite gliding.\",\n      \"evidence\": \"gene knockout with in vitro gliding motility and adhesion assays in P. berghei sporozoites\",\n      \"pmids\": [\"22139844\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"does not identify the molecular partners or substrates of HSP20\",\n        \"does not establish whether the defect reflects chaperone activity or a structural role\",\n        \"no biochemical demonstration of small heat shock protein function\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"It was unclear whether the in vitro motility defect had consequences for infection; the knockout showed impaired sporozoite skin-to-liver migration, linking HSP20-dependent motility to natural transmission.\",\n      \"evidence\": \"gene knockout with in vivo host migration assays in P. berghei\",\n      \"pmids\": [\"22139844\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"does not resolve the molecular step at which migration fails\",\n        \"does not quantify contribution to overall infectivity beyond migration\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"The mechanistic basis of the motility defect was unknown; comparison of MTIP localization in null versus wild-type sporozoites showed HSP20 is required for the polarized apical distribution of the acto-myosin motor component.\",\n      \"evidence\": \"immunofluorescence/microscopy of MTIP in HSP20 knockout versus wild-type P. berghei sporozoites\",\n      \"pmids\": [\"31874192\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"single lab, single method (localization only), no reciprocal or biochemical validation\",\n        \"does not show direct interaction between HSP20 and MTIP or motor components\",\n        \"does not establish whether HSP20 acts as a chaperone for motor assembly\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether HSP20 possesses chaperone activity and which client proteins or motor complex components it directly binds remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"no direct binding partner or substrate identified\",\n        \"no structural or biochemical characterization of chaperone function\",\n        \"no data in P. falciparum despite the PF3D7 identifier; all phenotypes derive from P. berghei\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0071973\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"MTIP (spatial organization dependent on HSP20; no direct interaction demonstrated)\"],\n    \"other_free_text\": [\n      \"Genetic ablation in P. berghei sporozoites disrupts substrate adhesion and gliding speed/directionality in vitro [#0].\",\n      \"Knockout impairs sporozoite skin-to-liver migration in the mammalian host [#1].\",\n      \"Loss of HSP20 abrogates polarized apical distribution of the acto-myosin motor component MTIP [#2].\",\n      \"No biochemical chaperone activity, direct partner, or client substrate has been characterized in the available corpus.\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1448700","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 2 of 2 cited papers name other catalogue genes (PF3D7_0816500, PF3D7_1246400). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1448700","name":null,"product":"HSP20-like chaperone, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1312400","name":null,"product":"HSP20-like chaperone, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1233400","name":null,"product":"HSP20-like chaperone, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}