{"gene":"SNAPC5","run_date":"2026-04-28T20:42:08","timeline":{"discoveries":[{"year":1998,"finding":"SNAP19 (SNAPC5) is an essential subunit of SNAPc; reconstitution of the five-subunit complex (SNAP43, SNAP45, SNAP50, SNAP190, and SNAP19) produces a fully functional SNAPc that binds specifically to the PSE and directs both RNA polymerase II and III snRNA gene transcription.","method":"Reconstitution of recombinant five-subunit SNAPc from baculovirus-expressed subunits; PSE-binding assay; in vitro transcription assay","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 1 — reconstitution of defined recombinant complex with functional validation in transcription and DNA-binding assays","pmids":["9732265"],"is_preprint":false},{"year":2000,"finding":"SNAP19 (SNAPC5) participates in a defined network of subunit-subunit contacts within SNAPc; domains required for SNAP19's association with other subunits were mapped, and complexes retaining these minimal contact domains were sufficient for specific PSE binding.","method":"Systematic deletion analysis of subunit interaction domains; GST pulldown / co-immunoprecipitation of recombinant subunits; PSE electrophoretic mobility shift assay (EMSA)","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1-2 — systematic domain mapping with multiple interaction assays and functional (DNA-binding) validation","pmids":["11056176"],"is_preprint":false},{"year":2006,"finding":"A partial SNAPc containing SNAP190 (1-505), SNAP50, SNAP43, and SNAP19 (SNAPC5) co-expressed in E. coli binds PSE DNA specifically, recruits TBP to U6 promoter DNA, and supports reconstituted transcription of both U1 (Pol II) and U6 (Pol III) snRNA genes.","method":"Co-expression in E. coli; PSE-binding EMSA; TBP recruitment assay; in vitro reconstituted transcription assay","journal":"Protein expression and purification","confidence":"High","confidence_rationale":"Tier 1 — reconstitution in a defined biochemical system with multiple functional readouts","pmids":["16603380"],"is_preprint":false},{"year":2025,"finding":"Cryo-EM structures of the full-length SNAPc-containing RNA Pol III pre-initiation complex on the U6 snRNA promoter (open and melting states, 3.2–4.2 Å) reveal that SNAPC5 (along with SNAPC2) localizes near the promoter DNA, and crosslinking mass spectrometry confirms this positioning; structural comparison with the Pol II PIC explains the basis for selective SNAPc engagement with each polymerase.","method":"Cryo-EM structure determination; crosslinking mass spectrometry (XL-MS); structural comparison with yeast Pol III PIC and human Pol II PIC","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1 — near-atomic resolution cryo-EM structures combined with XL-MS, multiple states resolved","pmids":["39747245"],"is_preprint":false}],"current_model":"SNAPC5 (SNAP19) is an integral subunit of the five-subunit SNAPc complex that binds the PSE core promoter element of human snRNA genes; it participates in a defined network of inter-subunit contacts, localizes near promoter DNA as revealed by cryo-EM and crosslinking MS, and is required for the assembly of functional SNAPc that nucleates both RNA polymerase II and III pre-initiation complexes at snRNA gene promoters."},"narrative":{"teleology":[{"year":1998,"claim":"Establishing that SNAP19 is a bona fide SNAPc subunit resolved the complete composition of the complex and demonstrated that all five subunits are needed for PSE binding and for directing both Pol II and Pol III snRNA gene transcription in vitro.","evidence":"Reconstitution of recombinant five-subunit SNAPc from baculovirus-expressed proteins with PSE-binding EMSA and in vitro transcription assays","pmids":["9732265"],"confidence":"High","gaps":["The specific contacts SNAP19 makes with other subunits were not yet mapped","Whether SNAP19 directly contacts DNA was unknown","Structural basis for how a single complex directs two different polymerases remained unresolved"]},{"year":2000,"claim":"Systematic domain mapping revealed the inter-subunit interaction network through which SNAPC5 integrates into SNAPc, showing that minimal contact domains are sufficient for specific PSE binding and thereby delineating the architectural logic of the complex.","evidence":"Deletion analysis with GST pulldowns, co-immunoprecipitation of recombinant subunits, and PSE EMSA","pmids":["11056176"],"confidence":"High","gaps":["Atomic-level structure of SNAPC5 and its interfaces remained unknown","Whether SNAPC5 has a direct role in TBP recruitment was not tested","Functional contribution of individual interaction surfaces in a transcription assay was not dissected"]},{"year":2006,"claim":"Demonstrating that a mini-SNAPc including SNAPC5 co-expressed in E. coli retains PSE binding, TBP recruitment, and transcription activity confirmed that SNAPC5 participates in a functionally sufficient core and enabled simpler reconstitution strategies.","evidence":"Co-expression of four-subunit partial SNAPc in E. coli; PSE-binding EMSA; TBP recruitment assay; reconstituted in vitro transcription of U1 and U6 genes","pmids":["16603380"],"confidence":"High","gaps":["The role of SNAPC5 in TBP recruitment versus PSE binding was not individually separated","Structural positioning of SNAPC5 relative to DNA was still unknown","In vivo relevance of the minimal complex was not assessed"]},{"year":2025,"claim":"Cryo-EM structures of the complete SNAPc-containing Pol III PIC at near-atomic resolution placed SNAPC5 near the promoter DNA and, by structural comparison with the Pol II PIC, provided the first mechanistic explanation for how SNAPc selectively engages each polymerase.","evidence":"Cryo-EM at 3.2–4.2 Å resolution of open and melting states on the U6 snRNA promoter; crosslinking mass spectrometry; structural comparison with Pol II PIC","pmids":["39747245"],"confidence":"High","gaps":["Whether SNAPC5 directly contacts promoter DNA or acts only through other subunits is not fully resolved","Dynamics of SNAPC5 during PIC remodeling and promoter opening have not been characterized","Loss-of-function studies in vivo assessing individual SNAPC5 contributions to Pol II versus Pol III transcription are lacking"]},{"year":null,"claim":"It remains unknown whether SNAPC5 has functions independent of SNAPc, whether it directly contacts DNA, and what regulatory inputs modulate its incorporation into the complex.","evidence":"","pmids":[],"confidence":"High","gaps":["No post-translational modifications of SNAPC5 with functional consequences have been identified","No disease-associated mutations in SNAPC5 have been described","Whether SNAPC5 participates in non-snRNA transcription programs is untested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[0,1,2,3]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[3]}],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[0,2,3]}],"complexes":["SNAPc"],"partners":["SNAPC1","SNAPC2","SNAPC3","SNAPC4"],"other_free_text":[]},"mechanistic_narrative":"SNAPC5 (SNAP19) is an integral subunit of the five-subunit small nuclear RNA-activating protein complex (SNAPc), which binds the proximal sequence element (PSE) of snRNA gene promoters and nucleates pre-initiation complex assembly for both RNA polymerase II- and RNA polymerase III-dependent snRNA transcription [PMID:9732265]. Within SNAPc, SNAPC5 participates in a defined network of inter-subunit contacts that are essential for complex assembly and specific PSE recognition [PMID:11056176]. Cryo-EM structures of the SNAPc-containing RNA Pol III pre-initiation complex on the U6 snRNA promoter place SNAPC5 near the promoter DNA, a positioning confirmed by crosslinking mass spectrometry, and structural comparisons reveal the basis for selective SNAPc engagement with Pol II versus Pol III [PMID:39747245]."},"prefetch_data":{"uniprot":{"accession":"O75971","full_name":"snRNA-activating protein complex subunit 5","aliases":["Small nuclear RNA-activating complex polypeptide 5","snRNA-activating protein complex 19 kDa subunit","SNAPc 19 kDa subunit"],"length_aa":98,"mass_kda":11.3,"function":"Part of the SNAPc complex required for the transcription of both RNA polymerase II and III small-nuclear RNA genes. Binds to the proximal sequence element (PSE), a non-TATA-box basal promoter element common to these 2 types of genes. Recruits TBP and BRF2 to the U6 snRNA TATA box","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/O75971/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/SNAPC5","classification":"Common Essential","n_dependent_lines":1190,"n_total_lines":1208,"dependency_fraction":0.9850993377483444},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/SNAPC5","total_profiled":1310},"omim":[{"mim_id":"605979","title":"SMALL NUCLEAR RNA-ACTIVATING PROTEIN COMPLEX, POLYPEPTIDE 5; SNAPC5","url":"https://www.omim.org/entry/605979"},{"mim_id":"600591","title":"SMALL NUCLEAR RNA-ACTIVATING PROTEIN COMPLEX, POLYPEPTIDE 1; SNAPC1","url":"https://www.omim.org/entry/600591"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SNAPC5"},"hgnc":{"alias_symbol":["SNAP19"],"prev_symbol":[]},"alphafold":{"accession":"O75971","domains":[{"cath_id":"1.20.5","chopping":"1-51","consensus_level":"medium","plddt":91.13,"start":1,"end":51}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O75971","model_url":"https://alphafold.ebi.ac.uk/files/AF-O75971-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O75971-F1-predicted_aligned_error_v6.png","plddt_mean":76.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SNAPC5","jax_strain_url":"https://www.jax.org/strain/search?query=SNAPC5"},"sequence":{"accession":"O75971","fasta_url":"https://rest.uniprot.org/uniprotkb/O75971.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O75971/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O75971"}},"corpus_meta":[{"pmid":"9732265","id":"PMC_9732265","title":"SNAP19 mediates the assembly of a functional core promoter complex (SNAPc) shared by RNA polymerases II and III.","date":"1998","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/9732265","citation_count":73,"is_preprint":false},{"pmid":"11056176","id":"PMC_11056176","title":"A map of protein-protein contacts within the small nuclear RNA-activating protein complex SNAPc.","date":"2000","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11056176","citation_count":41,"is_preprint":false},{"pmid":"12391172","id":"PMC_12391172","title":"Redundant cooperative interactions for assembly of a human U6 transcription initiation complex.","date":"2002","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/12391172","citation_count":34,"is_preprint":false},{"pmid":"35672525","id":"PMC_35672525","title":"The role of plasma exosomal lnc-SNAPC5-3:4 in monitoring the efficacy of anlotinib in the treatment of advanced non-small cell lung cancer.","date":"2022","source":"Journal of cancer research and clinical oncology","url":"https://pubmed.ncbi.nlm.nih.gov/35672525","citation_count":19,"is_preprint":false},{"pmid":"37441804","id":"PMC_37441804","title":"Exploring Cancer Dependency Map genes and immune subtypes in colon cancer, in which TIGD1 contributes to colon cancer progression.","date":"2023","source":"Aging","url":"https://pubmed.ncbi.nlm.nih.gov/37441804","citation_count":9,"is_preprint":false},{"pmid":"16603380","id":"PMC_16603380","title":"Co-expression of multiple subunits enables recombinant SNAPC assembly and function for transcription by human RNA polymerases II and III.","date":"2006","source":"Protein expression and purification","url":"https://pubmed.ncbi.nlm.nih.gov/16603380","citation_count":6,"is_preprint":false},{"pmid":"39747245","id":"PMC_39747245","title":"Structural insights into distinct mechanisms of RNA polymerase II and III recruitment to snRNA promoters.","date":"2025","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/39747245","citation_count":4,"is_preprint":false},{"pmid":"39833228","id":"PMC_39833228","title":"Brain gliomas new transcriptomic discoveries from differentially expressed genes to therapeutic targets.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/39833228","citation_count":3,"is_preprint":false},{"pmid":"38312596","id":"PMC_38312596","title":"Long noncoding RNA lnc-SNAPC5-3:4 inhibits malignancy by directly upregulating miR-224-3p in non-small cell lung cancer.","date":"2024","source":"Heliyon","url":"https://pubmed.ncbi.nlm.nih.gov/38312596","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5697,"output_tokens":1054,"usd":0.01645},"stage2":{"model":"claude-opus-4-6","input_tokens":4258,"output_tokens":1480,"usd":0.087435},"total_usd":0.103885,"stage1_batch_id":"msgbatch_011rkcQdVV1RaFq9XhcG6df6","stage2_batch_id":"msgbatch_01RzgrJafdF4EWHhj5mNi6dh","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1998,\n      \"finding\": \"SNAP19 (SNAPC5) is an essential subunit of SNAPc; reconstitution of the five-subunit complex (SNAP43, SNAP45, SNAP50, SNAP190, and SNAP19) produces a fully functional SNAPc that binds specifically to the PSE and directs both RNA polymerase II and III snRNA gene transcription.\",\n      \"method\": \"Reconstitution of recombinant five-subunit SNAPc from baculovirus-expressed subunits; PSE-binding assay; in vitro transcription assay\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — reconstitution of defined recombinant complex with functional validation in transcription and DNA-binding assays\",\n      \"pmids\": [\"9732265\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"SNAP19 (SNAPC5) participates in a defined network of subunit-subunit contacts within SNAPc; domains required for SNAP19's association with other subunits were mapped, and complexes retaining these minimal contact domains were sufficient for specific PSE binding.\",\n      \"method\": \"Systematic deletion analysis of subunit interaction domains; GST pulldown / co-immunoprecipitation of recombinant subunits; PSE electrophoretic mobility shift assay (EMSA)\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — systematic domain mapping with multiple interaction assays and functional (DNA-binding) validation\",\n      \"pmids\": [\"11056176\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"A partial SNAPc containing SNAP190 (1-505), SNAP50, SNAP43, and SNAP19 (SNAPC5) co-expressed in E. coli binds PSE DNA specifically, recruits TBP to U6 promoter DNA, and supports reconstituted transcription of both U1 (Pol II) and U6 (Pol III) snRNA genes.\",\n      \"method\": \"Co-expression in E. coli; PSE-binding EMSA; TBP recruitment assay; in vitro reconstituted transcription assay\",\n      \"journal\": \"Protein expression and purification\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — reconstitution in a defined biochemical system with multiple functional readouts\",\n      \"pmids\": [\"16603380\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Cryo-EM structures of the full-length SNAPc-containing RNA Pol III pre-initiation complex on the U6 snRNA promoter (open and melting states, 3.2–4.2 Å) reveal that SNAPC5 (along with SNAPC2) localizes near the promoter DNA, and crosslinking mass spectrometry confirms this positioning; structural comparison with the Pol II PIC explains the basis for selective SNAPc engagement with each polymerase.\",\n      \"method\": \"Cryo-EM structure determination; crosslinking mass spectrometry (XL-MS); structural comparison with yeast Pol III PIC and human Pol II PIC\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — near-atomic resolution cryo-EM structures combined with XL-MS, multiple states resolved\",\n      \"pmids\": [\"39747245\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SNAPC5 (SNAP19) is an integral subunit of the five-subunit SNAPc complex that binds the PSE core promoter element of human snRNA genes; it participates in a defined network of inter-subunit contacts, localizes near promoter DNA as revealed by cryo-EM and crosslinking MS, and is required for the assembly of functional SNAPc that nucleates both RNA polymerase II and III pre-initiation complexes at snRNA gene promoters.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"SNAPC5 (SNAP19) is an integral subunit of the five-subunit small nuclear RNA-activating protein complex (SNAPc), which binds the proximal sequence element (PSE) of snRNA gene promoters and nucleates pre-initiation complex assembly for both RNA polymerase II- and RNA polymerase III-dependent snRNA transcription [PMID:9732265]. Within SNAPc, SNAPC5 participates in a defined network of inter-subunit contacts that are essential for complex assembly and specific PSE recognition [PMID:11056176]. Cryo-EM structures of the SNAPc-containing RNA Pol III pre-initiation complex on the U6 snRNA promoter place SNAPC5 near the promoter DNA, a positioning confirmed by crosslinking mass spectrometry, and structural comparisons reveal the basis for selective SNAPc engagement with Pol II versus Pol III [PMID:39747245].\",\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"Establishing that SNAP19 is a bona fide SNAPc subunit resolved the complete composition of the complex and demonstrated that all five subunits are needed for PSE binding and for directing both Pol II and Pol III snRNA gene transcription in vitro.\",\n      \"evidence\": \"Reconstitution of recombinant five-subunit SNAPc from baculovirus-expressed proteins with PSE-binding EMSA and in vitro transcription assays\",\n      \"pmids\": [\"9732265\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The specific contacts SNAP19 makes with other subunits were not yet mapped\",\n        \"Whether SNAP19 directly contacts DNA was unknown\",\n        \"Structural basis for how a single complex directs two different polymerases remained unresolved\"\n      ]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Systematic domain mapping revealed the inter-subunit interaction network through which SNAPC5 integrates into SNAPc, showing that minimal contact domains are sufficient for specific PSE binding and thereby delineating the architectural logic of the complex.\",\n      \"evidence\": \"Deletion analysis with GST pulldowns, co-immunoprecipitation of recombinant subunits, and PSE EMSA\",\n      \"pmids\": [\"11056176\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Atomic-level structure of SNAPC5 and its interfaces remained unknown\",\n        \"Whether SNAPC5 has a direct role in TBP recruitment was not tested\",\n        \"Functional contribution of individual interaction surfaces in a transcription assay was not dissected\"\n      ]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Demonstrating that a mini-SNAPc including SNAPC5 co-expressed in E. coli retains PSE binding, TBP recruitment, and transcription activity confirmed that SNAPC5 participates in a functionally sufficient core and enabled simpler reconstitution strategies.\",\n      \"evidence\": \"Co-expression of four-subunit partial SNAPc in E. coli; PSE-binding EMSA; TBP recruitment assay; reconstituted in vitro transcription of U1 and U6 genes\",\n      \"pmids\": [\"16603380\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The role of SNAPC5 in TBP recruitment versus PSE binding was not individually separated\",\n        \"Structural positioning of SNAPC5 relative to DNA was still unknown\",\n        \"In vivo relevance of the minimal complex was not assessed\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Cryo-EM structures of the complete SNAPc-containing Pol III PIC at near-atomic resolution placed SNAPC5 near the promoter DNA and, by structural comparison with the Pol II PIC, provided the first mechanistic explanation for how SNAPc selectively engages each polymerase.\",\n      \"evidence\": \"Cryo-EM at 3.2–4.2 Å resolution of open and melting states on the U6 snRNA promoter; crosslinking mass spectrometry; structural comparison with Pol II PIC\",\n      \"pmids\": [\"39747245\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether SNAPC5 directly contacts promoter DNA or acts only through other subunits is not fully resolved\",\n        \"Dynamics of SNAPC5 during PIC remodeling and promoter opening have not been characterized\",\n        \"Loss-of-function studies in vivo assessing individual SNAPC5 contributions to Pol II versus Pol III transcription are lacking\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether SNAPC5 has functions independent of SNAPc, whether it directly contacts DNA, and what regulatory inputs modulate its incorporation into the complex.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No post-translational modifications of SNAPC5 with functional consequences have been identified\",\n        \"No disease-associated mutations in SNAPC5 have been described\",\n        \"Whether SNAPC5 participates in non-snRNA transcription programs is untested\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [0, 1, 2, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0, 2, 3]}\n    ],\n    \"complexes\": [\"SNAPc\"],\n    \"partners\": [\"SNAPC1\", \"SNAPC2\", \"SNAPC3\", \"SNAPC4\"],\n    \"other_free_text\": []\n  }\n}\n```"}