{"gene":"PF3D7_1433600","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2007,"finding":"PF3D7_1433600 (SPC1/PfSP21), the catalytic subunit of the signal peptidase complex in P. falciparum, was shown to cleave a peptide substrate containing the signal peptidase cleavage site in vitro, demonstrating endopeptidase activity responsible for removal of N-terminal signal peptides from secretory preproteins.","method":"In vitro peptide cleavage assay using recombinant PfSP21 with a signal peptidase cleavage site-containing substrate","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro enzymatic activity assay established catalytic function, but single lab, single study with no independent replication","pmids":["18054093"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"finding":"PF3D7_1433600 (SPC1/PfSP21) is phosphorylated by protein kinase C, and this phosphorylation upregulates its signal peptidase enzymatic activity.","method":"In vitro phosphorylation assay with protein kinase C followed by measurement of peptide cleavage activity","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro biochemical assay with PKC establishing PTM and activity modulation, single lab, no independent replication","pmids":["18054093"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"finding":"PF3D7_1433600 (SPC1/PfSP21) localizes to the endoplasmic reticulum of P. falciparum intraerythrocytic stages, consistent with its role in co-translational signal peptide cleavage.","method":"Immunofluorescence assay (IFA) with antibodies against PfSP21","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single IFA experiment in one lab, no functional consequence directly linked to ER localization in the same experiment","pmids":["18054093"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"finding":"PF3D7_1433600 (SPC1/PfSP21) is required for intra-erythrocytic growth of P. falciparum; dsRNA-mediated knockdown of PfSP21 specifically inhibited parasite growth in culture, with a corresponding decrease in endogenous PfSP21 protein levels.","method":"dsRNA-mediated gene silencing followed by parasite growth assay and immunoblot quantification of PfSP21 protein","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean loss-of-function with defined growth phenotype and protein-level confirmation, single lab, no independent replication","pmids":["18054093"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1433600 (SPC1) is the catalytic subunit of the P. falciparum endoplasmic reticulum signal peptidase complex that cleaves N-terminal signal peptides from secretory preproteins; its activity is upregulated by protein kinase C-mediated phosphorylation, it localizes to the parasite ER, and it is required for intra-erythrocytic parasite growth."},"narrative":{"mechanistic_narrative":"PF3D7_1433600 (SPC1/PfSP21) is the catalytic subunit of the Plasmodium falciparum signal peptidase complex that cleaves N-terminal signal peptides from secretory preproteins, an activity demonstrated directly by cleavage of a signal peptidase cleavage site-containing substrate in vitro [PMID:18054093]. Its endopeptidase activity is upregulated by protein kinase C-mediated phosphorylation [PMID:18054093]. Consistent with a role in co-translational signal peptide processing, SPC1 localizes to the parasite endoplasmic reticulum [PMID:18054093], and it is required for intra-erythrocytic growth, since dsRNA-mediated knockdown reducing endogenous SPC1 protein specifically inhibits parasite proliferation in culture [PMID:18054093]. All available characterization derives from a single study; beyond these findings, no further mechanistic detail on SPC1 has been characterized in the available corpus.","teleology":[{"year":2007,"claim":"Whether SPC1/PfSP21 is enzymatically responsible for signal peptide removal was unresolved; demonstrating direct cleavage established it as the catalytic signal peptidase activity in the parasite.","evidence":"in vitro peptide cleavage assay with recombinant PfSP21 on a substrate carrying a signal peptidase cleavage site, in P. falciparum","pmids":["18054093"],"confidence":"Medium","gaps":["no independent replication beyond the single study","cleavage of authentic full-length preprotein substrates not shown","contribution of other complex subunits to catalysis not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"claim":"How SPC1 activity is regulated was unknown; PKC phosphorylation was shown to upregulate its cleavage activity, linking signal peptidase function to a kinase-dependent post-translational control.","evidence":"in vitro phosphorylation by protein kinase C followed by measurement of peptide cleavage activity, in P. falciparum","pmids":["18054093"],"confidence":"Medium","gaps":["phosphorylation sites on SPC1 not mapped","no evidence this regulation operates in vivo","identity of the physiological kinase not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"claim":"The subcellular site of SPC1 action was undefined; ER localization placed its activity at the expected compartment for co-translational signal peptide cleavage.","evidence":"immunofluorescence with anti-PfSP21 antibodies in intraerythrocytic stages, in P. falciparum","pmids":["18054093"],"confidence":"Medium","gaps":["single IFA with no functional consequence linked to localization","membrane topology and complex assembly at the ER not characterized"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"claim":"Whether SPC1 is essential for the parasite was unknown; knockdown-induced growth inhibition established it as required for intra-erythrocytic proliferation.","evidence":"dsRNA-mediated gene silencing with growth assay and immunoblot confirmation of reduced PfSP21, in P. falciparum","pmids":["18054093"],"confidence":"Medium","gaps":["no independent genetic confirmation (e.g. conditional knockout or complementation)","molecular basis of the growth defect (accumulation of unprocessed preproteins) not directly demonstrated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The native composition, stoichiometry, and in vivo substrate repertoire of the SPC1-containing signal peptidase complex remain unestablished.","evidence":"","pmids":[],"confidence":"Medium","gaps":["no interacting subunits of the complex characterized in the corpus","no structural model of SPC1","no endogenous substrate set defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["signal peptidase complex"],"partners":[],"other_free_text":["Endopeptidase activity upregulated by protein kinase C-mediated phosphorylation [#1]","Required for intra-erythrocytic parasite growth by dsRNA knockdown [#3]","All characterization derives from a single 2007 study; complex partners, in vivo substrates, and structure remain uncharacterized in the corpus"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"18054093","id":"PMC_18054093","title":"Plasmodium falciparum signal peptidase is regulated by phosphorylation and required for intra-erythrocytic growth.","date":"2007","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/18054093","citation_count":19,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39631773","id":"","title":"Integral Solvent-Induced Protein Precipitation for Target-Engagement Studies in Plasmodium falciparum.","date":"2024","source":"ACS infectious diseases","url":"https://pubmed.ncbi.nlm.nih.gov/39631773","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPC1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28050233","id":"","title":"Signaling transcript profile of the asexual intraerythrocytic development cycle of Plasmodium falciparum induced by melatonin and cAMP.","date":"2016","source":"Genes & cancer","url":"https://pubmed.ncbi.nlm.nih.gov/28050233","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPC1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5433,"output_tokens":1081,"usd":0.016257,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5855,"output_tokens":1972,"usd":0.039288,"stage2_stop_reason":"end_turn"},"total_usd":0.055545,"stage1_batch_id":"msgbatch_01SRp5hyRc82zNjddxyCCXGk","stage2_batch_id":"msgbatch_01K3BTmBazRo3pRrMvyaPMTY","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2007,\n      \"finding\": \"PF3D7_1433600 (SPC1/PfSP21), the catalytic subunit of the signal peptidase complex in P. falciparum, was shown to cleave a peptide substrate containing the signal peptidase cleavage site in vitro, demonstrating endopeptidase activity responsible for removal of N-terminal signal peptides from secretory preproteins.\",\n      \"method\": \"In vitro peptide cleavage assay using recombinant PfSP21 with a signal peptidase cleavage site-containing substrate\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro enzymatic activity assay established catalytic function, but single lab, single study with no independent replication\",\n      \"pmids\": [\"18054093\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"PF3D7_1433600 (SPC1/PfSP21) is phosphorylated by protein kinase C, and this phosphorylation upregulates its signal peptidase enzymatic activity.\",\n      \"method\": \"In vitro phosphorylation assay with protein kinase C followed by measurement of peptide cleavage activity\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro biochemical assay with PKC establishing PTM and activity modulation, single lab, no independent replication\",\n      \"pmids\": [\"18054093\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"PF3D7_1433600 (SPC1/PfSP21) localizes to the endoplasmic reticulum of P. falciparum intraerythrocytic stages, consistent with its role in co-translational signal peptide cleavage.\",\n      \"method\": \"Immunofluorescence assay (IFA) with antibodies against PfSP21\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single IFA experiment in one lab, no functional consequence directly linked to ER localization in the same experiment\",\n      \"pmids\": [\"18054093\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"PF3D7_1433600 (SPC1/PfSP21) is required for intra-erythrocytic growth of P. falciparum; dsRNA-mediated knockdown of PfSP21 specifically inhibited parasite growth in culture, with a corresponding decrease in endogenous PfSP21 protein levels.\",\n      \"method\": \"dsRNA-mediated gene silencing followed by parasite growth assay and immunoblot quantification of PfSP21 protein\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean loss-of-function with defined growth phenotype and protein-level confirmation, single lab, no independent replication\",\n      \"pmids\": [\"18054093\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1433600 (SPC1) is the catalytic subunit of the P. falciparum endoplasmic reticulum signal peptidase complex that cleaves N-terminal signal peptides from secretory preproteins; its activity is upregulated by protein kinase C-mediated phosphorylation, it localizes to the parasite ER, and it is required for intra-erythrocytic parasite growth.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1433600 (SPC1/PfSP21) is the catalytic subunit of the Plasmodium falciparum signal peptidase complex that cleaves N-terminal signal peptides from secretory preproteins, an activity demonstrated directly by cleavage of a signal peptidase cleavage site-containing substrate in vitro [#0]. Its endopeptidase activity is upregulated by protein kinase C-mediated phosphorylation [#1]. Consistent with a role in co-translational signal peptide processing, SPC1 localizes to the parasite endoplasmic reticulum [#2], and it is required for intra-erythrocytic growth, since dsRNA-mediated knockdown reducing endogenous SPC1 protein specifically inhibits parasite proliferation in culture [#3]. All available characterization derives from a single study; beyond these findings, no further mechanistic detail on SPC1 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"Whether SPC1/PfSP21 is enzymatically responsible for signal peptide removal was unresolved; demonstrating direct cleavage established it as the catalytic signal peptidase activity in the parasite.\",\n      \"evidence\": \"in vitro peptide cleavage assay with recombinant PfSP21 on a substrate carrying a signal peptidase cleavage site, in P. falciparum\",\n      \"pmids\": [\"18054093\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"no independent replication beyond the single study\",\n        \"cleavage of authentic full-length preprotein substrates not shown\",\n        \"contribution of other complex subunits to catalysis not resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"How SPC1 activity is regulated was unknown; PKC phosphorylation was shown to upregulate its cleavage activity, linking signal peptidase function to a kinase-dependent post-translational control.\",\n      \"evidence\": \"in vitro phosphorylation by protein kinase C followed by measurement of peptide cleavage activity, in P. falciparum\",\n      \"pmids\": [\"18054093\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"phosphorylation sites on SPC1 not mapped\",\n        \"no evidence this regulation operates in vivo\",\n        \"identity of the physiological kinase not established\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"The subcellular site of SPC1 action was undefined; ER localization placed its activity at the expected compartment for co-translational signal peptide cleavage.\",\n      \"evidence\": \"immunofluorescence with anti-PfSP21 antibodies in intraerythrocytic stages, in P. falciparum\",\n      \"pmids\": [\"18054093\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"single IFA with no functional consequence linked to localization\",\n        \"membrane topology and complex assembly at the ER not characterized\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Whether SPC1 is essential for the parasite was unknown; knockdown-induced growth inhibition established it as required for intra-erythrocytic proliferation.\",\n      \"evidence\": \"dsRNA-mediated gene silencing with growth assay and immunoblot confirmation of reduced PfSP21, in P. falciparum\",\n      \"pmids\": [\"18054093\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"no independent genetic confirmation (e.g. conditional knockout or complementation)\",\n        \"molecular basis of the growth defect (accumulation of unprocessed preproteins) not directly demonstrated\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The native composition, stoichiometry, and in vivo substrate repertoire of the SPC1-containing signal peptidase complex remain unestablished.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"no interacting subunits of the complex characterized in the corpus\",\n        \"no structural model of SPC1\",\n        \"no endogenous substrate set defined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004252\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0016486\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006465\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0045047\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\"signal peptidase complex\"],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Endopeptidase activity upregulated by protein kinase C-mediated phosphorylation [#1]\",\n      \"Required for intra-erythrocytic parasite growth by dsRNA knockdown [#3]\",\n      \"All characterization derives from a single 2007 study; complex partners, in vivo substrates, and structure remain uncharacterized in the corpus\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1433600","name":null,"product":"signal peptidase complex subunit SPC1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1011300","name":null,"product":"signal peptidase complex subunit SPC1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0420200","name":null,"product":"signal peptidase complex subunit SPC1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SPC1","evaluation":null}