{"gene":"PF3D7_1434300","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2011,"finding":"Recombinant PfHop (HOP/PF3D7_1434300) was produced in E. coli, and using specific anti-PfHop antisera, PfHop was shown to co-localize with PfHsp70 and PfHsp90 in trophozoite-stage parasites. Gel filtration and co-immunoprecipitation experiments demonstrated that PfHop is present in a complex together with PfHsp70 and PfHsp90, suggesting it mediates the functional interaction between the two chaperones.","method":"Recombinant protein production, indirect immunofluorescence (co-localization), gel filtration chromatography, co-immunoprecipitation","journal":"Cell stress & chaperones","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-localization and co-IP in a single lab with two orthogonal methods (gel filtration + co-IP), no in vitro reconstitution or mutagenesis","pmids":["22005844"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"PfHop (HOP/PF3D7_1434300) directly associates with PfHsp70-1 in a nucleotide-dependent manner: ADP promotes the association more than ATP, as demonstrated by far Western and surface plasmon resonance analyses, further validated by co-immunoprecipitation. The TPR1 and TPR2B subdomains of PfHop bind preferentially to the C-terminus of PfHsp70-1, whereas the TPR2A motif preferentially interacts with the C-terminus of PfHsp90, as shown by a split-GFP approach. PfHop also exhibits self-association (dimerization) detected by SPR. PfHop expression is stress-inducible.","method":"Far Western blot, surface plasmon resonance (SPR), co-immunoprecipitation, split-GFP domain-binding assay, size exclusion chromatography","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — multiple orthogonal methods (SPR, far Western, co-IP, split-GFP) in a single rigorous study establishing direct binding, nucleotide dependence, and subdomain specificity","pmids":["26267894"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"Human Hop (hHop) interacts with PfHsp70-x via the EEVN motif at the C-terminus of PfHsp70-x in vitro, as demonstrated by structural and biochemical characterization. This finding implies that HOP-type proteins recognize the C-terminal motif of Hsp70 family members. The result is directly relevant to HOP/PF3D7_1434300 because it establishes the binding interface through which Hop proteins engage Hsp70 partners in P. falciparum biology.","method":"Recombinant protein biochemistry, in vitro binding assays between PfHsp70-x (EEVN motif) and human Hop","journal":"Proteins","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single in vitro binding assay using human Hop (not PfHop/PF3D7_1434300 itself) interacting with PfHsp70-x; mechanistic inference for PF3D7_1434300 is indirect","pmids":["30183110"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PfHop (HOP/PF3D7_1434300) is a stress-inducible adaptor protein that physically bridges PfHsp70-1 and PfHsp90 in the P. falciparum trophozoite cytosol: its TPR1 and TPR2B subdomains bind the C-terminus of PfHsp70-1 (preferentially in the ADP-bound state), its TPR2A subdomain binds the C-terminus of PfHsp90, and the protein can self-associate, consistent with its proposed role as a scaffold that brings the two major chaperones into a functional complex."},"narrative":{"mechanistic_narrative":"PfHop (HOP/PF3D7_1434300) is a stress-inducible adaptor protein that bridges the two major cytosolic chaperones of Plasmodium falciparum, PfHsp70-1 and PfHsp90, within a functional complex in trophozoite-stage parasites [PMID:22005844, PMID:26267894]. It co-localizes with both chaperones and co-fractionates with them, and it uses distinct TPR subdomains to engage each partner: the TPR1 and TPR2B subdomains bind the C-terminus of PfHsp70-1 while the TPR2A motif binds the C-terminus of PfHsp90 [PMID:26267894]. The PfHop–PfHsp70-1 association is nucleotide-dependent, favored by the ADP-bound state of Hsp70, and PfHop can self-associate, consistent with a scaffolding role that assembles the chaperone complex [PMID:26267894]. Beyond this adaptor function, no further mechanistic role for PF3D7_1434300 has been characterized in the available corpus.","teleology":[{"year":2011,"claim":"Establishing whether P. falciparum possesses a physical link between its two principal chaperones addressed whether Hsp70 and Hsp90 could act coordinately; the finding placed PfHop in a complex with both.","evidence":"Recombinant protein production with anti-PfHop antisera, immunofluorescence co-localization, gel filtration and co-immunoprecipitation in trophozoite-stage parasites","pmids":["22005844"],"confidence":"Medium","gaps":["Interaction shown at the complex level without direct binding measurement or defined interfaces","No mutagenesis or in vitro reconstitution to prove PfHop is the bridging factor","Functional consequence for parasite biology not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"The prior complex-level observation left open how PfHop engages each chaperone; mapping subdomain-specific, nucleotide-dependent binding established PfHop as a direct scaffold with defined interfaces.","evidence":"Far Western, surface plasmon resonance, co-immunoprecipitation, split-GFP subdomain-binding assays, and size exclusion chromatography","pmids":["26267894"],"confidence":"High","gaps":["No structural model of the assembled PfHop–PfHsp70-1–PfHsp90 complex","Functional/client-processing consequences of the interaction not demonstrated","In vivo requirement of PfHop for parasite viability or stress survival untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Whether Hop-type proteins recognize a conserved Hsp70 C-terminal motif was tested using human Hop against PfHsp70-x, implying the interface through which Hop proteins engage Hsp70 partners in P. falciparum.","evidence":"Recombinant protein biochemistry and in vitro binding assays between the PfHsp70-x EEVN motif and human Hop (not PfHop itself)","pmids":["30183110"],"confidence":"Low","gaps":["Used human Hop, not PfHop/PF3D7_1434300, so the inference for this gene is indirect","Did not test PfHop binding to PfHsp70-x directly","Single in vitro binding assay without cellular validation"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The functional consequences of PfHop-mediated chaperone assembly for parasite growth, stress survival, and client protein maturation remain unaddressed.","evidence":"","pmids":[],"confidence":"Low","gaps":["No loss-of-function or knockdown phenotype for PF3D7_1434300","No identified chaperone clients dependent on PfHop","No structural model of the ternary complex"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfHop–PfHsp70-1–PfHsp90 chaperone complex"],"partners":["PFHSP70-1 (NUCLEOTIDE-DEPENDENT, ADP-FAVORED; VIA TPR1 AND TPR2B BINDING HSP70 C-TERMINUS)","PFHSP90 (VIA TPR2A BINDING HSP90 C-TERMINUS)","PFHOP SELF-ASSOCIATION (DIMERIZATION)"],"other_free_text":["PfHop expression is stress-inducible [#1].","Human Hop binds the C-terminal EEVN motif of PfHsp70-x in vitro, implying Hop-type proteins recognize the Hsp70 C-terminal motif; this was shown with human Hop, not PfHop/PF3D7_1434300 itself [#2]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"12560551","id":"PMC_12560551","title":"Dissecting apicoplast targeting in the malaria parasite Plasmodium falciparum.","date":"2003","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/12560551","citation_count":370,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Hsp70"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"12584193","id":"PMC_12584193","title":"Heat shock protein 90 function is essential for Plasmodium falciparum growth in human 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Gel filtration and co-immunoprecipitation experiments demonstrated that PfHop is present in a complex together with PfHsp70 and PfHsp90, suggesting it mediates the functional interaction between the two chaperones.\",\n      \"method\": \"Recombinant protein production, indirect immunofluorescence (co-localization), gel filtration chromatography, co-immunoprecipitation\",\n      \"journal\": \"Cell stress & chaperones\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-localization and co-IP in a single lab with two orthogonal methods (gel filtration + co-IP), no in vitro reconstitution or mutagenesis\",\n      \"pmids\": [\"22005844\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"PfHop (HOP/PF3D7_1434300) directly associates with PfHsp70-1 in a nucleotide-dependent manner: ADP promotes the association more than ATP, as demonstrated by far Western and surface plasmon resonance analyses, further validated by co-immunoprecipitation. The TPR1 and TPR2B subdomains of PfHop bind preferentially to the C-terminus of PfHsp70-1, whereas the TPR2A motif preferentially interacts with the C-terminus of PfHsp90, as shown by a split-GFP approach. PfHop also exhibits self-association (dimerization) detected by SPR. PfHop expression is stress-inducible.\",\n      \"method\": \"Far Western blot, surface plasmon resonance (SPR), co-immunoprecipitation, split-GFP domain-binding assay, size exclusion chromatography\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — multiple orthogonal methods (SPR, far Western, co-IP, split-GFP) in a single rigorous study establishing direct binding, nucleotide dependence, and subdomain specificity\",\n      \"pmids\": [\"26267894\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Human Hop (hHop) interacts with PfHsp70-x via the EEVN motif at the C-terminus of PfHsp70-x in vitro, as demonstrated by structural and biochemical characterization. This finding implies that HOP-type proteins recognize the C-terminal motif of Hsp70 family members. The result is directly relevant to HOP/PF3D7_1434300 because it establishes the binding interface through which Hop proteins engage Hsp70 partners in P. falciparum biology.\",\n      \"method\": \"Recombinant protein biochemistry, in vitro binding assays between PfHsp70-x (EEVN motif) and human Hop\",\n      \"journal\": \"Proteins\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single in vitro binding assay using human Hop (not PfHop/PF3D7_1434300 itself) interacting with PfHsp70-x; mechanistic inference for PF3D7_1434300 is indirect\",\n      \"pmids\": [\"30183110\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PfHop (HOP/PF3D7_1434300) is a stress-inducible adaptor protein that physically bridges PfHsp70-1 and PfHsp90 in the P. falciparum trophozoite cytosol: its TPR1 and TPR2B subdomains bind the C-terminus of PfHsp70-1 (preferentially in the ADP-bound state), its TPR2A subdomain binds the C-terminus of PfHsp90, and the protein can self-associate, consistent with its proposed role as a scaffold that brings the two major chaperones into a functional complex.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PfHop (HOP/PF3D7_1434300) is a stress-inducible adaptor protein that bridges the two major cytosolic chaperones of Plasmodium falciparum, PfHsp70-1 and PfHsp90, within a functional complex in trophozoite-stage parasites [#0, #1]. It co-localizes with both chaperones and co-fractionates with them, and it uses distinct TPR subdomains to engage each partner: the TPR1 and TPR2B subdomains bind the C-terminus of PfHsp70-1 while the TPR2A motif binds the C-terminus of PfHsp90 [#1]. The PfHop–PfHsp70-1 association is nucleotide-dependent, favored by the ADP-bound state of Hsp70, and PfHop can self-associate, consistent with a scaffolding role that assembles the chaperone complex [#1]. Beyond this adaptor function, no further mechanistic role for PF3D7_1434300 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2011,\n      \"claim\": \"Establishing whether P. falciparum possesses a physical link between its two principal chaperones addressed whether Hsp70 and Hsp90 could act coordinately; the finding placed PfHop in a complex with both.\",\n      \"evidence\": \"Recombinant protein production with anti-PfHop antisera, immunofluorescence co-localization, gel filtration and co-immunoprecipitation in trophozoite-stage parasites\",\n      \"pmids\": [\"22005844\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Interaction shown at the complex level without direct binding measurement or defined interfaces\",\n        \"No mutagenesis or in vitro reconstitution to prove PfHop is the bridging factor\",\n        \"Functional consequence for parasite biology not tested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"The prior complex-level observation left open how PfHop engages each chaperone; mapping subdomain-specific, nucleotide-dependent binding established PfHop as a direct scaffold with defined interfaces.\",\n      \"evidence\": \"Far Western, surface plasmon resonance, co-immunoprecipitation, split-GFP subdomain-binding assays, and size exclusion chromatography\",\n      \"pmids\": [\"26267894\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No structural model of the assembled PfHop–PfHsp70-1–PfHsp90 complex\",\n        \"Functional/client-processing consequences of the interaction not demonstrated\",\n        \"In vivo requirement of PfHop for parasite viability or stress survival untested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether Hop-type proteins recognize a conserved Hsp70 C-terminal motif was tested using human Hop against PfHsp70-x, implying the interface through which Hop proteins engage Hsp70 partners in P. falciparum.\",\n      \"evidence\": \"Recombinant protein biochemistry and in vitro binding assays between the PfHsp70-x EEVN motif and human Hop (not PfHop itself)\",\n      \"pmids\": [\"30183110\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Used human Hop, not PfHop/PF3D7_1434300, so the inference for this gene is indirect\",\n        \"Did not test PfHop binding to PfHsp70-x directly\",\n        \"Single in vitro binding assay without cellular validation\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The functional consequences of PfHop-mediated chaperone assembly for parasite growth, stress survival, and client protein maturation remain unaddressed.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No loss-of-function or knockdown phenotype for PF3D7_1434300\",\n        \"No identified chaperone clients dependent on PfHop\",\n        \"No structural model of the ternary complex\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0051087\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0042803\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0030544\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0061077\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0006950\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\n      \"PfHop–PfHsp70-1–PfHsp90 chaperone complex\"\n    ],\n    \"partners\": [\n      \"PfHsp70-1 (nucleotide-dependent, ADP-favored; via TPR1 and TPR2B binding Hsp70 C-terminus)\",\n      \"PfHsp90 (via TPR2A binding Hsp90 C-terminus)\",\n      \"PfHop self-association (dimerization)\"\n    ],\n    \"other_free_text\": [\n      \"PfHop expression is stress-inducible [#1].\",\n      \"Human Hop binds the C-terminal EEVN motif of PfHsp70-x in vitro, implying Hop-type proteins recognize the Hsp70 C-terminal motif; this was shown with human Hop, not PfHop/PF3D7_1434300 itself [#2].\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1434300","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_0708400, PF3D7_0818900, PF3D7_0831700). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1434300","name":null,"product":"Hsp70/Hsp90 organizing protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1010500","name":null,"product":"Hsp70/Hsp90 organizing protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0420900","name":null,"product":"Hsp70/Hsp90 organizing protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"HOP","evaluation":null}