{"gene":"PF3D7_0527500","run_date":"2026-09-07T10:55:52","timeline":{"discoveries":[{"year":2006,"finding":"PF3D7_0527500 (PfHip, Hsp70-interacting protein) was cloned, overexpressed, and shown to enhance the chaperone activity of PfHsp70-1 (which carries the C-terminal EEVD motif) and PfHsp70-2 in an ATP-dependent manner. Binding of protein substrates to PfHip was unaffected by the antimalarial compound 15-deoxyspergualin (DSG).","method":"Cloning, overexpression, and in vitro chaperone activity assay with and without ATP and DSG","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro biochemical reconstitution of chaperone activity with defined substrates, single lab, single study","pmids":["16884692"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1998,"finding":"A complex of HSC70 with 32/34-kDa proteins (co-purifying from F-actin affinity and ATP-agarose columns, and co-eluting by gel filtration) from Plasmodium knowlesi merozoites inhibited actin polymerization in vitro in a calcium-independent, phosphatidylinositol-4,5-bisphosphate-sensitive manner, consistent with filament-capping activity. The identity of the 32/34-kDa proteins as PF3D7_0527500 (HIP) is not explicitly stated in this abstract; the finding is attributed to the HSC70/32/34-kDa complex.","method":"F-actin affinity chromatography, ATP-agarose chromatography, gel filtration, in vitro actin polymerization assay, Western blotting, tryptic peptide microsequencing","journal":"Molecular and biochemical parasitology","confidence":"Low","confidence_rationale":"Tier 2 / Weak — multiple orthogonal biochemical methods but identity of 32/34-kDa proteins as HIP/PF3D7_0527500 is not confirmed in the abstract; attribution to this gene is uncertain","pmids":["9662713"],"is_preprint":false,"attribution":[{"species":"Plasmodium knowlesi","strain":""}]}],"current_model":"PF3D7_0527500 (HIP, Hsp70-interacting protein) enhances the ATP-dependent chaperone activity of PfHsp70-1 and PfHsp70-2 in P. falciparum, and its substrate-binding activity is unaffected by the antimalarial compound 15-deoxyspergualin; it may also participate, as part of an HSC70-associated complex, in regulation of actin polymerization in Plasmodium merozoites, though the latter role requires further confirmation of the complex's protein identity."},"narrative":{"mechanistic_narrative":"PF3D7_0527500 (HIP) is a Plasmodium falciparum Hsp70-interacting co-chaperone that enhances the ATP-dependent chaperone activity of the Hsp70 chaperones PfHsp70-1 (which carries the C-terminal EEVD motif) and PfHsp70-2 [PMID:16884692]. Its substrate-binding activity is not blocked by the antimalarial compound 15-deoxyspergualin (DSG) [PMID:16884692]. A separate HSC70-associated complex containing 32/34-kDa proteins from P. knowlesi merozoites caps actin filaments and inhibits actin polymerization in a calcium-independent, PIP2-sensitive manner, but the identity of those 32/34-kDa proteins as PF3D7_0527500 was not established, so this activity cannot be assigned to HIP itself [PMID:9662713]. Beyond its role as an Hsp70 co-chaperone [PMID:16884692], no further mechanistic detail for PF3D7_0527500 has been characterized in the available corpus.","teleology":[{"year":2006,"claim":"To establish what PF3D7_0527500 does biochemically, it was tested for direct effects on Hsp70 function, showing it is a co-chaperone that potentiates Hsp70 chaperone activity in P. falciparum.","evidence":"cloning, overexpression, and in vitro chaperone activity assay with defined Hsp70 substrates, +/- ATP and DSG","pmids":["16884692"],"confidence":"Medium","gaps":["single-lab in vitro reconstitution not confirmed in cellulo or in vivo","structural basis of the HIP-Hsp70 interaction not defined","physiological substrates handed off by the HIP/Hsp70 pair not identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1998,"claim":"Whether an HSC70-associated 32/34-kDa protein complex regulates the merozoite actin cytoskeleton was tested, showing filament-capping and polymerization-inhibiting activity, but the complex was not confirmed to contain PF3D7_0527500.","evidence":"F-actin affinity and ATP-agarose chromatography, gel filtration, in vitro actin polymerization assay, and tryptic peptide microsequencing in P. knowlesi merozoites","pmids":["9662713"],"confidence":"Low","gaps":["identity of the 32/34-kDa proteins as PF3D7_0527500 not confirmed in the source","activity is attributed to the HSC70/32-34-kDa complex, not to HIP individually","shown in P. knowlesi, not P. falciparum"],"attribution":[{"species":"Plasmodium knowlesi","strain":""}]},{"year":null,"claim":"Whether PF3D7_0527500 physically participates in the actin-regulating HSC70 complex, and what its role is in intact parasites, remains unresolved.","evidence":"no direct evidence in the available corpus linking PF3D7_0527500 to the actin complex or to an in vivo phenotype","pmids":[],"confidence":"Low","gaps":["no genetic knockout or knockdown phenotype for PF3D7_0527500 reported","no confirmed link between the biochemically characterized co-chaperone and the actin-capping complex"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFHSP70-1 (EEVD MOTIF HSP70) [#0]","PFHSP70-2 [#0]"],"other_free_text":["Enhances PfHsp70-1/PfHsp70-2 chaperone activity in an ATP-dependent manner [#0].","Substrate binding by PF3D7_0527500 is unaffected by the antimalarial 15-deoxyspergualin (DSG) [#0].","An HSC70/32-34-kDa complex in P. knowlesi merozoites caps actin filaments (Ca2+-independent, PIP2-sensitive), but the 32/34-kDa proteins were not confirmed to be PF3D7_0527500 [#1]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"2659668","id":"PMC_2659668","title":"Heat shock cognate 70 is a prominent immunogen in Brugian filariasis.","date":"1989","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/2659668","citation_count":81,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Hsc70"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"11581168","id":"PMC_11581168","title":"Generation of cytotoxic T lymphocytes by MHC class I ligands fused to heat shock cognate protein 70.","date":"2001","source":"International immunology","url":"https://pubmed.ncbi.nlm.nih.gov/11581168","citation_count":70,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Hsc70"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"16884692","id":"PMC_16884692","title":"15-Deoxyspergualin modulates Plasmodium falciparum heat shock protein function.","date":"2006","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/16884692","citation_count":51,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"9662713","id":"PMC_9662713","title":"Actin-binding proteins of invasive malaria parasites and the regulation of actin polymerization by a complex of 32/34-kDa proteins associated with heat shock protein 70kDa.","date":"1998","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/9662713","citation_count":33,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Hsc70"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"12379684","id":"PMC_12379684","title":"Merozoite surface protein 1-specific immune response is protective against exoerythrocytic forms of Plasmodium yoelii.","date":"2002","source":"Infection and immunity","url":"https://pubmed.ncbi.nlm.nih.gov/12379684","citation_count":26,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Hsc70"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5485,"output_tokens":817,"usd":0.014355,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5439,"output_tokens":1693,"usd":0.03476,"stage2_stop_reason":"end_turn"},"total_usd":0.049115,"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\": 2006,\n      \"finding\": \"PF3D7_0527500 (PfHip, Hsp70-interacting protein) was cloned, overexpressed, and shown to enhance the chaperone activity of PfHsp70-1 (which carries the C-terminal EEVD motif) and PfHsp70-2 in an ATP-dependent manner. Binding of protein substrates to PfHip was unaffected by the antimalarial compound 15-deoxyspergualin (DSG).\",\n      \"method\": \"Cloning, overexpression, and in vitro chaperone activity assay with and without ATP and DSG\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro biochemical reconstitution of chaperone activity with defined substrates, single lab, single study\",\n      \"pmids\": [\"16884692\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"A complex of HSC70 with 32/34-kDa proteins (co-purifying from F-actin affinity and ATP-agarose columns, and co-eluting by gel filtration) from Plasmodium knowlesi merozoites inhibited actin polymerization in vitro in a calcium-independent, phosphatidylinositol-4,5-bisphosphate-sensitive manner, consistent with filament-capping activity. The identity of the 32/34-kDa proteins as PF3D7_0527500 (HIP) is not explicitly stated in this abstract; the finding is attributed to the HSC70/32/34-kDa complex.\",\n      \"method\": \"F-actin affinity chromatography, ATP-agarose chromatography, gel filtration, in vitro actin polymerization assay, Western blotting, tryptic peptide microsequencing\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 2 / Weak — multiple orthogonal biochemical methods but identity of 32/34-kDa proteins as HIP/PF3D7_0527500 is not confirmed in the abstract; attribution to this gene is uncertain\",\n      \"pmids\": [\"9662713\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium knowlesi\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_0527500 (HIP, Hsp70-interacting protein) enhances the ATP-dependent chaperone activity of PfHsp70-1 and PfHsp70-2 in P. falciparum, and its substrate-binding activity is unaffected by the antimalarial compound 15-deoxyspergualin; it may also participate, as part of an HSC70-associated complex, in regulation of actin polymerization in Plasmodium merozoites, though the latter role requires further confirmation of the complex's protein identity.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0527500 (HIP) is a Plasmodium falciparum Hsp70-interacting co-chaperone that enhances the ATP-dependent chaperone activity of the Hsp70 chaperones PfHsp70-1 (which carries the C-terminal EEVD motif) and PfHsp70-2 [#0]. Its substrate-binding activity is not blocked by the antimalarial compound 15-deoxyspergualin (DSG) [#0]. A separate HSC70-associated complex containing 32/34-kDa proteins from P. knowlesi merozoites caps actin filaments and inhibits actin polymerization in a calcium-independent, PIP2-sensitive manner, but the identity of those 32/34-kDa proteins as PF3D7_0527500 was not established, so this activity cannot be assigned to HIP itself [#1]. Beyond its role as an Hsp70 co-chaperone [#0], no further mechanistic detail for PF3D7_0527500 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"To establish what PF3D7_0527500 does biochemically, it was tested for direct effects on Hsp70 function, showing it is a co-chaperone that potentiates Hsp70 chaperone activity in P. falciparum.\",\n      \"evidence\": \"cloning, overexpression, and in vitro chaperone activity assay with defined Hsp70 substrates, +/- ATP and DSG\",\n      \"pmids\": [\"16884692\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"single-lab in vitro reconstitution not confirmed in cellulo or in vivo\",\n        \"structural basis of the HIP-Hsp70 interaction not defined\",\n        \"physiological substrates handed off by the HIP/Hsp70 pair not identified\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"Whether an HSC70-associated 32/34-kDa protein complex regulates the merozoite actin cytoskeleton was tested, showing filament-capping and polymerization-inhibiting activity, but the complex was not confirmed to contain PF3D7_0527500.\",\n      \"evidence\": \"F-actin affinity and ATP-agarose chromatography, gel filtration, in vitro actin polymerization assay, and tryptic peptide microsequencing in P. knowlesi merozoites\",\n      \"pmids\": [\"9662713\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"identity of the 32/34-kDa proteins as PF3D7_0527500 not confirmed in the source\",\n        \"activity is attributed to the HSC70/32-34-kDa complex, not to HIP individually\",\n        \"shown in P. knowlesi, not P. falciparum\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium knowlesi\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether PF3D7_0527500 physically participates in the actin-regulating HSC70 complex, and what its role is in intact parasites, remains unresolved.\",\n      \"evidence\": \"no direct evidence in the available corpus linking PF3D7_0527500 to the actin complex or to an in vivo phenotype\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"no genetic knockout or knockdown phenotype for PF3D7_0527500 reported\",\n        \"no confirmed link between the biochemically characterized co-chaperone and the actin-capping complex\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0051087\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0030674\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006457\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"PfHsp70-1 (EEVD motif Hsp70) [#0]\",\n      \"PfHsp70-2 [#0]\"\n    ],\n    \"other_free_text\": [\n      \"Enhances PfHsp70-1/PfHsp70-2 chaperone activity in an ATP-dependent manner [#0].\",\n      \"Substrate binding by PF3D7_0527500 is unaffected by the antimalarial 15-deoxyspergualin (DSG) [#0].\",\n      \"An HSC70/32-34-kDa complex in P. knowlesi merozoites caps actin filaments (Ca2+-independent, PIP2-sensitive), but the 32/34-kDa proteins were not confirmed to be PF3D7_0527500 [#1].\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_0527500","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 1 of 2 cited papers name other catalogue genes (PF3D7_0818900). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0527500","name":null,"product":"Hsc70-interacting protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1242300","name":null,"product":"Hsc70-interacting protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1005200","name":null,"product":"Hsc70-interacting protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"HIP","evaluation":null}