{"gene":"PF3D7_0314000","run_date":"2026-09-07T10:55:51","timeline":{"discoveries":[{"year":2011,"finding":"Genetic ablation of HSP20 (PF3D7_0314000) in Plasmodium sporozoites profoundly impairs sporozoite-substrate adhesion, resulting in aberrant speed and directionality in vitro and impaired migration in the host, establishing HSP20 as a critical regulator of actin/myosin-based gliding motility.","method":"Genetic knockout (HSP20 ablation) in Plasmodium berghei with in vitro motility assays and in vivo migration assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean genetic knockout with defined cellular phenotype (adhesion, speed, directionality) measured by multiple orthogonal assays (in vitro gliding, in vivo migration), single lab but rigorous multi-readout study","pmids":["22139844"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2012,"finding":"HSP20 (PF3D7_0314000) is proposed to regulate actin microfilament turnover in Plasmodium sporozoites, either directly (competing with myosin) or indirectly (modulating actin depolymerizing factor/cofilin activity), based on the phenotype of genetic ablation; the study frames HSP20 function within the HSPB family's known biochemical roles in microfilament regulation.","method":"Review/discussion of prior genetic ablation data combined with biochemical framework from model systems","journal":"Cell adhesion & migration","confidence":"Low","confidence_rationale":"Tier 4 / Weak — mechanistic model is proposed based on analogy to other systems; no new direct biochemical experiment in Plasmodium is reported in this abstract","pmids":["22568951"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2019,"finding":"In HSP20 (PF3D7_0314000)-null Plasmodium berghei sporozoites, the polarized apical distribution of MTIP (Myosin A-tail interacting protein) observed during gliding locomotion in wild-type sporozoites is abrogated, linking HSP20 function to proper subcellular organization of the glideosome motor complex.","method":"Immunofluorescence/subcellular localization of MTIP in HSP20 knockout Plasmodium berghei sporozoites compared to wild-type","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization experiment in genetic mutant with functional consequence (loss of MTIP polarization correlates with aberrant locomotion), single lab, single method","pmids":["31874192"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"HSP20 (PF3D7_0314000) is a small heat shock protein expressed in Plasmodium sporozoites that is required for normal substrate adhesion, speed, and directionality of gliding motility by regulating actin-based motility and maintaining the polarized apical distribution of the glideosome component MTIP; its loss impairs sporozoite migration in the host and natural malaria transmission."},"narrative":{"mechanistic_narrative":"HSP20 (PF3D7_0314000) is a small heat shock protein-like chaperone required for productive gliding motility of Plasmodium sporozoites, functioning as a critical regulator of actin/myosin-based locomotion [PMID:22139844]. Genetic ablation of HSP20 in P. berghei sporozoites profoundly impairs sporozoite-substrate adhesion and produces aberrant gliding speed and directionality in vitro together with impaired migration in the host [PMID:22139844]. This motility defect is accompanied by loss of the normal polarized apical distribution of the glideosome component MTIP, linking HSP20 to proper subcellular organization of the motor complex during locomotion [PMID:31874192]. Beyond these genetic and localization phenotypes, the direct biochemical activity of HSP20 in Plasmodium — including any physical substrate or partner interaction — has not been characterized in the available corpus.","teleology":[{"year":2011,"claim":"To establish whether HSP20 has any role in the parasite, its gene was ablated, revealing that HSP20 is required for sporozoite adhesion and normal gliding motility rather than being dispensable.","evidence":"Genetic knockout of HSP20 in P. berghei with in vitro gliding motility assays and in vivo host migration assays","pmids":["22139844"],"confidence":"High","gaps":["No direct biochemical activity or substrate demonstrated for HSP20","Whether the adhesion defect is primary or secondary to a motor/cytoskeletal defect is unresolved","No structural characterization of the protein"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2012,"claim":"To interpret the motility phenotype mechanistically, a model was framed in which HSP20 regulates actin microfilament turnover, but this rested on analogy rather than direct Plasmodium biochemistry.","evidence":"Review/discussion combining the prior knockout phenotype with the biochemical framework of HSPB-family microfilament regulators","pmids":["22568951"],"confidence":"Low","gaps":["Proposed actin-turnover mechanism was not tested by any new direct biochemical experiment in Plasmodium","Whether HSP20 competes with myosin or modulates cofilin/ADF activity is not distinguished experimentally","No demonstrated physical interaction between HSP20 and actin or actin regulators"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2019,"claim":"To connect HSP20 to the glideosome, MTIP localization was examined in knockout sporozoites, showing that HSP20 loss abrogates the polarized apical distribution of MTIP and thereby links HSP20 to spatial organization of the motor complex.","evidence":"Immunofluorescence/subcellular localization of MTIP in HSP20-null versus wild-type P. berghei sporozoites","pmids":["31874192"],"confidence":"Medium","gaps":["Single-method, single-lab correlation; no reciprocal validation","Whether HSP20 physically interacts with MTIP or the glideosome is unknown","Mechanism by which HSP20 maintains MTIP polarization is not defined"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"The direct molecular activity of HSP20 — whether it acts as a chaperone on a defined substrate, physically engages actin or MTIP, and how it maintains glideosome polarization — remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No demonstrated binding partner or substrate for HSP20 in Plasmodium","No biochemical reconstitution of any proposed actin-regulatory activity","No evidence in P. falciparum itself; all functional data derive from the P. berghei ortholog"],"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["MTIP (LOCALIZATION DEPENDENCY IN HSP20-NULL SPOROZOITES; NO DEMONSTRATED PHYSICAL INTERACTION) [#2]"],"other_free_text":["HSP20 ablation impairs sporozoite-substrate adhesion, gliding speed, and directionality, and reduces host migration [#0].","HSP20 loss abrogates the polarized apical distribution of the glideosome component MTIP [#2].","A model in which HSP20 regulates actin microfilament turnover was proposed by analogy to HSPB-family proteins, without direct Plasmodium biochemistry [#1].","All functional evidence derives from the P. berghei ortholog; the subject gene is PF3D7_0314000."]}},"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":945,"usd":0.013097,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5673,"output_tokens":1849,"usd":0.037295,"stage2_stop_reason":"end_turn"},"total_usd":0.050392,"stage1_batch_id":"msgbatch_01DbiymDmubkPpYvdbAu5a7V","stage2_batch_id":"msgbatch_012TbrWvMRH129T7PQ4SmvrJ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2011,\n      \"finding\": \"Genetic ablation of HSP20 (PF3D7_0314000) in Plasmodium sporozoites profoundly impairs sporozoite-substrate adhesion, resulting in aberrant speed and directionality in vitro and impaired migration in the host, establishing HSP20 as a critical regulator of actin/myosin-based gliding motility.\",\n      \"method\": \"Genetic knockout (HSP20 ablation) in Plasmodium berghei with in vitro motility assays and in vivo migration assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean genetic knockout with defined cellular phenotype (adhesion, speed, directionality) measured by multiple orthogonal assays (in vitro gliding, in vivo migration), single lab but rigorous multi-readout study\",\n      \"pmids\": [\"22139844\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"HSP20 (PF3D7_0314000) is proposed to regulate actin microfilament turnover in Plasmodium sporozoites, either directly (competing with myosin) or indirectly (modulating actin depolymerizing factor/cofilin activity), based on the phenotype of genetic ablation; the study frames HSP20 function within the HSPB family's known biochemical roles in microfilament regulation.\",\n      \"method\": \"Review/discussion of prior genetic ablation data combined with biochemical framework from model systems\",\n      \"journal\": \"Cell adhesion & migration\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — mechanistic model is proposed based on analogy to other systems; no new direct biochemical experiment in Plasmodium is reported in this abstract\",\n      \"pmids\": [\"22568951\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"In HSP20 (PF3D7_0314000)-null Plasmodium berghei sporozoites, the polarized apical distribution of MTIP (Myosin A-tail interacting protein) observed during gliding locomotion in wild-type sporozoites is abrogated, linking HSP20 function to proper subcellular organization of the glideosome motor complex.\",\n      \"method\": \"Immunofluorescence/subcellular localization of MTIP in HSP20 knockout Plasmodium berghei sporozoites compared to wild-type\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization experiment in genetic mutant with functional consequence (loss of MTIP polarization correlates with 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_0314000) is a small heat shock protein expressed in Plasmodium sporozoites that is required for normal substrate adhesion, speed, and directionality of gliding motility by regulating actin-based motility and maintaining the polarized apical distribution of the glideosome component MTIP; its loss impairs sporozoite migration in the host and natural malaria transmission.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"HSP20 (PF3D7_0314000) is a small heat shock protein-like chaperone required for productive gliding motility of Plasmodium sporozoites, functioning as a critical regulator of actin/myosin-based locomotion [#0]. Genetic ablation of HSP20 in P. berghei sporozoites profoundly impairs sporozoite-substrate adhesion and produces aberrant gliding speed and directionality in vitro together with impaired migration in the host [#0]. This motility defect is accompanied by loss of the normal polarized apical distribution of the glideosome component MTIP, linking HSP20 to proper subcellular organization of the motor complex during locomotion [#2]. Beyond these genetic and localization phenotypes, the direct biochemical activity of HSP20 in Plasmodium — including any physical substrate or partner interaction — has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2011,\n      \"claim\": \"To establish whether HSP20 has any role in the parasite, its gene was ablated, revealing that HSP20 is required for sporozoite adhesion and normal gliding motility rather than being dispensable.\",\n      \"evidence\": \"Genetic knockout of HSP20 in P. berghei with in vitro gliding motility assays and in vivo host migration assays\",\n      \"pmids\": [\"22139844\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No direct biochemical activity or substrate demonstrated for HSP20\",\n        \"Whether the adhesion defect is primary or secondary to a motor/cytoskeletal defect is unresolved\",\n        \"No structural characterization of the protein\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"To interpret the motility phenotype mechanistically, a model was framed in which HSP20 regulates actin microfilament turnover, but this rested on analogy rather than direct Plasmodium biochemistry.\",\n      \"evidence\": \"Review/discussion combining the prior knockout phenotype with the biochemical framework of HSPB-family microfilament regulators\",\n      \"pmids\": [\"22568951\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Proposed actin-turnover mechanism was not tested by any new direct biochemical experiment in Plasmodium\",\n        \"Whether HSP20 competes with myosin or modulates cofilin/ADF activity is not distinguished experimentally\",\n        \"No demonstrated physical interaction between HSP20 and actin or actin regulators\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"To connect HSP20 to the glideosome, MTIP localization was examined in knockout sporozoites, showing that HSP20 loss abrogates the polarized apical distribution of MTIP and thereby links HSP20 to spatial organization of the motor complex.\",\n      \"evidence\": \"Immunofluorescence/subcellular localization of MTIP in HSP20-null versus wild-type P. berghei sporozoites\",\n      \"pmids\": [\"31874192\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single-method, single-lab correlation; no reciprocal validation\",\n        \"Whether HSP20 physically interacts with MTIP or the glideosome is unknown\",\n        \"Mechanism by which HSP20 maintains MTIP polarization is not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct molecular activity of HSP20 — whether it acts as a chaperone on a defined substrate, physically engages actin or MTIP, and how it maintains glideosome polarization — remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No demonstrated binding partner or substrate for HSP20 in Plasmodium\",\n        \"No biochemical reconstitution of any proposed actin-regulatory activity\",\n        \"No evidence in P. falciparum itself; all functional data derive from the P. berghei ortholog\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0071976\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"MTIP (localization dependency in HSP20-null sporozoites; no demonstrated physical interaction) [#2]\"],\n    \"other_free_text\": [\n      \"HSP20 ablation impairs sporozoite-substrate adhesion, gliding speed, and directionality, and reduces host migration [#0].\",\n      \"HSP20 loss abrogates the polarized apical distribution of the glideosome component MTIP [#2].\",\n      \"A model in which HSP20 regulates actin microfilament turnover was proposed by analogy to HSPB-family proteins, without direct Plasmodium biochemistry [#1].\",\n      \"All functional evidence derives from the P. berghei ortholog; the subject gene is PF3D7_0314000.\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_0314000","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 3 of 3 cited papers name other catalogue genes (PF3D7_0816500, PF3D7_1246400). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0314000","name":null,"product":"HSP20-like chaperone, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0411700","name":null,"product":"HSP20-like chaperone, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0828200","name":null,"product":"HSP20-like chaperone, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}