{"gene":"TG_222370","gene_symbol":"SRS13","run_date":"2026-09-10T21:09:19","timeline":{"discoveries":[{"year":2018,"finding":"SRS13 is a novel mucin domain-containing SRS protein that localizes to the cyst wall of Toxoplasma gondii bradyzoites. It contains two SRS domains flanking a threonine-rich tandem repeat mucin-like domain (similar to CST1/SRS44), is upregulated in bradyzoites, is O-GalNAc glycosylated by ppGalNAc-T2 and T3, and localizes to the cyst wall. Unlike CST1, SRS13 is dispensable for normal cyst wall formation as shown by loss-of-function experiments.","method":"Glycoepitope-specific antibody identification, immunofluorescence localization, stage-specific expression analysis, O-GalNAc glycosylation assay with ppGalNAc-T2/T3, gene knockout with cyst wall phenotype readout","journal":"Parasitology research","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods in a single focused study: biochemical glycosylation assay, direct localization, loss-of-function with defined phenotypic readout, structural domain characterization","pmids":["29911257"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"finding":"SRS13 DNA vaccine administered by intramuscular or intradermal electroporation induces high-level anti-SRS13 IgG antibody responses and IFN-γ production, with the electroporation route eliciting significantly higher CD8+ IFN-γ-secreting T cells, and confers significant reduction in tissue cyst number and T. gondii DNA load in mouse brains following oral challenge with PRU strain tissue cysts.","method":"DNA vaccination with pVAX1-SRS13 in BALB/c mice, ELISA, Western blot, cytokine ELISA, flow cytometry, oral challenge with PRU strain, qPCR quantification of brain cyst burden","journal":"Vaccine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean in vivo loss-of-function challenge model with multiple orthogonal immune readouts, single lab","pmids":["38880692"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"PRU"}]}],"current_model":"SRS13 is a bradyzoite-upregulated, cyst wall-localized SRS protein in Toxoplasma gondii that contains two SRS domains flanking a threonine-rich mucin-like repeat domain, is O-GalNAc glycosylated by ppGalNAc-T2 and T3, and localizes to the cyst wall similarly to CST1/SRS44 but is dispensable for normal cyst wall formation; its immunogenicity makes it a functional vaccine antigen capable of conferring protection against chronic toxoplasmosis in mouse models."},"narrative":{"mechanistic_narrative":"SRS13 is a bradyzoite-upregulated, cyst wall-localized member of the SRS protein family in Toxoplasma gondii that contributes to the bradyzoite cyst surface but is dispensable for cyst wall formation, while serving as a protective vaccine antigen against chronic infection [PMID:29911257, PMID:38880692]. Structurally, it comprises two SRS domains flanking a threonine-rich tandem-repeat mucin-like domain resembling CST1/SRS44, and is O-GalNAc glycosylated by the polypeptide GalNAc-transferases ppGalNAc-T2 and T3, consistent with its localization to the cyst wall [PMID:29911257]. Loss-of-function experiments show that, unlike CST1, SRS13 is not required for normal cyst wall formation [PMID:29911257]. Its immunogenicity underlies a functional role as a vaccine target: a SRS13 DNA vaccine delivered by electroporation elicits anti-SRS13 IgG, IFN-γ production and CD8+ IFN-γ-secreting T cells, and reduces brain tissue cyst burden after oral challenge with PRU strain cysts [PMID:38880692]. Beyond its cyst wall localization, glycosylation, and antigenic properties, no additional molecular function of SRS13 has been characterized in the available corpus.","teleology":[{"year":2018,"claim":"Whether a mucin-domain SRS protein participates in the bradyzoite cyst wall was unknown; identifying SRS13 established a glycosylated, cyst wall-localized SRS protein that, unlike CST1, is not essential for cyst wall integrity.","evidence":"Glycoepitope antibody identification, immunofluorescence localization, stage-specific expression, O-GalNAc glycosylation assay with ppGalNAc-T2/T3, and gene knockout with cyst wall phenotype readout in T. gondii","pmids":["29911257"],"confidence":"High","gaps":["The molecular function of SRS13 at the cyst wall and any binding partners are undefined","The consequence of its dispensability for bradyzoite persistence in vivo is not established","No structural model beyond domain architecture is available"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"claim":"Whether SRS13 could be exploited immunologically was untested; a SRS13 DNA vaccine showed it is an immunogenic antigen that mobilizes humoral and CD8+ T-cell responses and reduces chronic-stage cyst burden.","evidence":"pVAX1-SRS13 DNA vaccination by intramuscular or intradermal electroporation in BALB/c mice with ELISA, Western blot, cytokine ELISA, flow cytometry, and oral PRU-strain challenge quantified by brain-cyst qPCR","pmids":["38880692"],"confidence":"Medium","gaps":["Protection was shown in a single lab and mouse model; durability and cross-strain protection are not established","The relative contribution of antibody versus CD8+ T-cell responses to protection is not resolved","Whether native SRS13 is a target during natural infection immunity is untested"],"attribution":[{"species":"Toxoplasma gondii","strain":"PRU"}]},{"year":null,"claim":"The biochemical role of SRS13 at the cyst wall and its binding partners or host-interaction function remain unknown.","evidence":"","pmids":[],"confidence":"Low","gaps":["No molecular activity or ligand has been identified for SRS13","The functional significance of its mucin-like O-GalNAc glycosylation is uncharacterized"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PPGALNAC-T2 (O-GALNAC GLYCOSYLATION ENZYME)","PPGALNAC-T3 (O-GALNAC GLYCOSYLATION ENZYME)"],"other_free_text":["Bradyzoite-upregulated SRS family protein with two SRS domains flanking a threonine-rich mucin-like tandem-repeat domain, similar to CST1/SRS44 [#0]","O-GalNAc glycosylated by ppGalNAc-T2 and T3 [#0]","Dispensable for normal cyst wall formation, unlike CST1 [#0]","Functional DNA vaccine antigen conferring protection against chronic toxoplasmosis in mice [#1]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"15664946","id":"PMC_15664946","title":"Sarcocystis neurona merozoites express a family of immunogenic surface antigens that are orthologues of the Toxoplasma gondii surface antigens (SAGs) and SAG-related sequences.","date":"2005","source":"Infection and immunity","url":"https://pubmed.ncbi.nlm.nih.gov/15664946","citation_count":37,"is_preprint":false},{"pmid":"29973272","id":"PMC_29973272","title":"Discovery of new Toxoplasma gondii antigenic proteins using a high throughput protein microarray approach screening sera of murine model infected orally with oocysts and tissue cysts.","date":"2018","source":"Parasites & vectors","url":"https://pubmed.ncbi.nlm.nih.gov/29973272","citation_count":24,"is_preprint":false},{"pmid":"24496792","id":"PMC_24496792","title":"Differential locus expansion distinguishes Toxoplasmatinae species and closely related strains of Toxoplasma gondii.","date":"2014","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/24496792","citation_count":19,"is_preprint":false},{"pmid":"29911257","id":"PMC_29911257","title":"Characterization of a SRS13: a new cyst wall mucin-like domain containing protein.","date":"2018","source":"Parasitology research","url":"https://pubmed.ncbi.nlm.nih.gov/29911257","citation_count":12,"is_preprint":false},{"pmid":"32365814","id":"PMC_32365814","title":"Epidemiologic Survey on Toxoplasma gondii and Trichinella pseudospiralis Infection in Corvids from Central Italy.","date":"2020","source":"Pathogens (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/32365814","citation_count":12,"is_preprint":false},{"pmid":"38880692","id":"PMC_38880692","title":"A novel DNA vaccine encoding the SRS13 protein administered by electroporation confers protection against chronic toxoplasmosis.","date":"2024","source":"Vaccine","url":"https://pubmed.ncbi.nlm.nih.gov/38880692","citation_count":6,"is_preprint":false},{"pmid":"36871500","id":"PMC_36871500","title":"In vitro anti-Toxoplasma gondii effects of a coccidiostat dinitolmide.","date":"2023","source":"Veterinary parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/36871500","citation_count":2,"is_preprint":false},{"pmid":"39160342","id":"PMC_39160342","title":"First Report on the Molecular Detection and Genetic Characterization of Toxoplasma gondii From Donkeys in Kenya.","date":"2024","source":"Acta parasitologica","url":"https://pubmed.ncbi.nlm.nih.gov/39160342","citation_count":1,"is_preprint":false},{"pmid":"24505177","id":"PMC_24505177","title":"Polymerase chain reaction based detection of Toxoplasma gondii from lymph node aspirates of dogs.","date":"2012","source":"Journal of parasitic diseases : official organ of the Indian Society for Parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/24505177","citation_count":1,"is_preprint":false},{"pmid":"33387894","id":"PMC_33387894","title":"The activity of the diaminopyrimidine dihydrofolate reducatase inhibitor, iclaprim, against Toxoplasma gondii in an in vitro model: a pilot study.","date":"2020","source":"Diagnostic microbiology and infectious disease","url":"https://pubmed.ncbi.nlm.nih.gov/33387894","citation_count":1,"is_preprint":false},{"pmid":"42188907","id":"PMC_42188907","title":"Advances and Translational Challenges in Toxoplasma gondii Vaccine Development: From Antigen Discovery to mRNA and One Health Strategies.","date":"2026","source":"Veterinary sciences","url":"https://pubmed.ncbi.nlm.nih.gov/42188907","citation_count":0,"is_preprint":false},{"pmid":"42347660","id":"PMC_42347660","title":"Protective Effect Against Acute Experimental Toxoplasmosis Conferred by Intranasal Immunisation with Toxoplasma gondii Membrane Proteins Plus CpG Adjuvant.","date":"2026","source":"Vaccines","url":"https://pubmed.ncbi.nlm.nih.gov/42347660","citation_count":0,"is_preprint":false},{"pmid":"24822344","id":"PMC_24822344","title":"[Stable green fluorescent protein expression in Toxoplasma gondii mutant].","date":"2011","source":"Zhongguo ji sheng chong xue yu ji sheng chong bing za zhi = Chinese journal of parasitology & parasitic diseases","url":"https://pubmed.ncbi.nlm.nih.gov/24822344","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":25166,"output_tokens":824,"usd":0.043929,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5597,"output_tokens":1803,"usd":0.03653,"stage2_stop_reason":"end_turn"},"total_usd":0.080459,"stage1_batch_id":"msgbatch_01WokvBYTB6JLnYrpD4rXnyV","stage2_batch_id":"msgbatch_01M7hsQDvz6AqVC9DLVjQzzc","note":"batch pricing = 50% of standard","corrective_rerun":"2026-09-10 wrong-gene rerun (round-4 rules)","corrective_reason":"paper list: removed papers about other genes"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"SRS13 is a novel mucin domain-containing SRS protein that localizes to the cyst wall of Toxoplasma gondii bradyzoites. It contains two SRS domains flanking a threonine-rich tandem repeat mucin-like domain (similar to CST1/SRS44), is upregulated in bradyzoites, is O-GalNAc glycosylated by ppGalNAc-T2 and T3, and localizes to the cyst wall. Unlike CST1, SRS13 is dispensable for normal cyst wall formation as shown by loss-of-function experiments.\",\n      \"method\": \"Glycoepitope-specific antibody identification, immunofluorescence localization, stage-specific expression analysis, O-GalNAc glycosylation assay with ppGalNAc-T2/T3, gene knockout with cyst wall phenotype readout\",\n      \"journal\": \"Parasitology research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods in a single focused study: biochemical glycosylation assay, direct localization, loss-of-function with defined phenotypic readout, structural domain characterization\",\n      \"pmids\": [\"29911257\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"SRS13 DNA vaccine administered by intramuscular or intradermal electroporation induces high-level anti-SRS13 IgG antibody responses and IFN-γ production, with the electroporation route eliciting significantly higher CD8+ IFN-γ-secreting T cells, and confers significant reduction in tissue cyst number and T. gondii DNA load in mouse brains following oral challenge with PRU strain tissue cysts.\",\n      \"method\": \"DNA vaccination with pVAX1-SRS13 in BALB/c mice, ELISA, Western blot, cytokine ELISA, flow cytometry, oral challenge with PRU strain, qPCR quantification of brain cyst burden\",\n      \"journal\": \"Vaccine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean in vivo loss-of-function challenge model with multiple orthogonal immune readouts, single lab\",\n      \"pmids\": [\"38880692\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"PRU\"}\n      ]\n    }\n  ],\n  \"current_model\": \"SRS13 is a bradyzoite-upregulated, cyst wall-localized SRS protein in Toxoplasma gondii that contains two SRS domains flanking a threonine-rich mucin-like repeat domain, is O-GalNAc glycosylated by ppGalNAc-T2 and T3, and localizes to the cyst wall similarly to CST1/SRS44 but is dispensable for normal cyst wall formation; its immunogenicity makes it a functional vaccine antigen capable of conferring protection against chronic toxoplasmosis in mouse models.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SRS13 is a bradyzoite-upregulated, cyst wall-localized member of the SRS protein family in Toxoplasma gondii that contributes to the bradyzoite cyst surface but is dispensable for cyst wall formation, while serving as a protective vaccine antigen against chronic infection [#0, #1]. Structurally, it comprises two SRS domains flanking a threonine-rich tandem-repeat mucin-like domain resembling CST1/SRS44, and is O-GalNAc glycosylated by the polypeptide GalNAc-transferases ppGalNAc-T2 and T3, consistent with its localization to the cyst wall [#0]. Loss-of-function experiments show that, unlike CST1, SRS13 is not required for normal cyst wall formation [#0]. Its immunogenicity underlies a functional role as a vaccine target: a SRS13 DNA vaccine delivered by electroporation elicits anti-SRS13 IgG, IFN-\\u03b3 production and CD8+ IFN-\\u03b3-secreting T cells, and reduces brain tissue cyst burden after oral challenge with PRU strain cysts [#1]. Beyond its cyst wall localization, glycosylation, and antigenic properties, no additional molecular function of SRS13 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether a mucin-domain SRS protein participates in the bradyzoite cyst wall was unknown; identifying SRS13 established a glycosylated, cyst wall-localized SRS protein that, unlike CST1, is not essential for cyst wall integrity.\",\n      \"evidence\": \"Glycoepitope antibody identification, immunofluorescence localization, stage-specific expression, O-GalNAc glycosylation assay with ppGalNAc-T2/T3, and gene knockout with cyst wall phenotype readout in T. gondii\",\n      \"pmids\": [\"29911257\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The molecular function of SRS13 at the cyst wall and any binding partners are undefined\",\n        \"The consequence of its dispensability for bradyzoite persistence in vivo is not established\",\n        \"No structural model beyond domain architecture is available\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Whether SRS13 could be exploited immunologically was untested; a SRS13 DNA vaccine showed it is an immunogenic antigen that mobilizes humoral and CD8+ T-cell responses and reduces chronic-stage cyst burden.\",\n      \"evidence\": \"pVAX1-SRS13 DNA vaccination by intramuscular or intradermal electroporation in BALB/c mice with ELISA, Western blot, cytokine ELISA, flow cytometry, and oral PRU-strain challenge quantified by brain-cyst qPCR\",\n      \"pmids\": [\"38880692\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Protection was shown in a single lab and mouse model; durability and cross-strain protection are not established\",\n        \"The relative contribution of antibody versus CD8+ T-cell responses to protection is not resolved\",\n        \"Whether native SRS13 is a target during natural infection immunity is untested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"PRU\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical role of SRS13 at the cyst wall and its binding partners or host-interaction function remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No molecular activity or ligand has been identified for SRS13\",\n        \"The functional significance of its mucin-like O-GalNAc glycosylation is uncharacterized\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"cyst wall\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"ppGalNAc-T2 (O-GalNAc glycosylation enzyme)\", \"ppGalNAc-T3 (O-GalNAc glycosylation enzyme)\"],\n    \"other_free_text\": [\n      \"Bradyzoite-upregulated SRS family protein with two SRS domains flanking a threonine-rich mucin-like tandem-repeat domain, similar to CST1/SRS44 [#0]\",\n      \"O-GalNAc glycosylated by ppGalNAc-T2 and T3 [#0]\",\n      \"Dispensable for normal cyst wall formation, unlike CST1 [#0]\",\n      \"Functional DNA vaccine antigen conferring protection against chronic toxoplasmosis in mice [#1]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_222370","name":"SRS13","product":"SAG-related sequence SRS13","uniprot_acc":"S8F856","chromosome":"TGME49_chrII","start_pos":1078765},{"strain":"GT1","gene_id":"TGGT1_222370","name":null,"product":"SAG-related sequence SRS13","uniprot_acc":null,"chromosome":"TGGT1_chrII","start_pos":1060771},{"strain":"RH88","gene_id":"TGRH88_001410","name":null,"product":"SAG-related sequence SRS13","uniprot_acc":null,"chromosome":"CM023083","start_pos":1233769}]}