{"gene":"TBCC","run_date":"2026-06-10T10:51:54","timeline":{"discoveries":[{"year":2010,"finding":"TBCC (tubulin binding cofactor C) overexpression increases the non-polymerizable tubulin fraction, decreases polymerizable tubulin dimers and microtubule mass, and reduces microtubule dynamicity in breast cancer cells, establishing its role as a regulator of tubulin dimer content and microtubule dynamics.","method":"Lysate fractionation, time-lapse microscopy of microtubule dynamics, cell cycle analysis by flow cytometry, xenograft tumor growth assays","journal":"BMC cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (fractionation, live imaging, in vivo xenograft) in a single lab study establishing functional consequences of TBCC overexpression","pmids":["20384997"],"is_preprint":false},{"year":2019,"finding":"TBCC overexpression inhibits CDK4 and LC3BII expression while promoting α/β-tubulin and p62 expression, suppressing cell cycle progression and autophagy in ovarian cancer cells; miR-1251-5p targets TBCC to reverse these effects, placing TBCC in a miR-1251-5p/TBCC/α/β-tubulin regulatory axis.","method":"Exogenous TBCC overexpression, miR-1251-5p overexpression/inhibition, western blotting for CDK4, LC3BII, p62, α/β-tubulin, cell cycle analysis, xenograft tumor growth","journal":"Molecular therapy : the journal of the American Society of Gene Therapy","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (western blot, cell cycle, xenograft) in single lab; pathway placement via rescue experiments","pmids":["31278033"],"is_preprint":false},{"year":2009,"finding":"The TBCC-like protein Tbccd1/Asq2p (encoded by ASQ2 in Chlamydomonas) is required for mother-daughter centriole linkage; loss of Tbccd1 causes variable centriole numbers, centriole positioning defects, and mitotic spindle orientation defects, establishing a role for this TBCC family member in centriole linkage and spindle positioning.","method":"Genetic mutant analysis, live-cell imaging of centrioles and mitotic spindles in asq2 mutant Chlamydomonas cells","journal":"Current biology : CB","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean loss-of-function mutant with defined cellular phenotypes (centriole number, spindle orientation) in a model organism; single lab but multiple orthogonal cellular readouts; note this is a TBCC family member (Tbccd1), not canonical TBCC itself","pmids":["19631545"],"is_preprint":false}],"current_model":"TBCC (tubulin binding cofactor C) controls tubulin dimer content and microtubule dynamics by regulating the balance between non-polymerizable and polymerizable tubulin fractions; overexpression reduces microtubule dynamicity and suppresses tumor cell growth, cell cycle progression, and autophagy, in part through regulation of CDK4, α/β-tubulin, and p62 levels, and is targeted post-transcriptionally by miR-1251-5p."},"narrative":{"mechanistic_narrative":"TBCC (tubulin binding cofactor C) is a regulator of tubulin dimer content and microtubule dynamics that constrains microtubule-dependent proliferation programs [PMID:20384997]. Overexpression of TBCC shifts the tubulin pool toward the non-polymerizable fraction, depleting polymerizable tubulin dimers, lowering microtubule mass, and reducing microtubule dynamicity in breast cancer cells, with accompanying suppression of cell cycle progression and tumor growth [PMID:20384997]. In ovarian cancer cells, TBCC suppresses cell cycle progression and autophagy by lowering CDK4 and LC3BII while raising α/β-tubulin and p62; this activity is held in check by miR-1251-5p, which targets TBCC to reverse these effects, defining a miR-1251-5p/TBCC/α/β-tubulin regulatory axis [PMID:31278033]. Beyond these tumor-cell studies and a centriole-linkage role described for the TBCC family member Tbccd1 in Chlamydomonas [PMID:19631545], no further mechanistic detail for canonical TBCC has been characterized in the available corpus.","teleology":[{"year":2009,"claim":"Whether TBCC-family proteins act beyond tubulin folding was unknown; analysis of the TBCC-like protein Tbccd1 established a structural role in linking mother and daughter centrioles and orienting the mitotic spindle.","evidence":"Loss-of-function asq2 mutant analysis with live-cell imaging of centrioles and spindles in Chlamydomonas","pmids":["19631545"],"confidence":"Medium","gaps":["Concerns a TBCC family member (Tbccd1), not canonical TBCC","Molecular mechanism of centriole linkage not defined","No demonstration that human TBCC shares this centriole function"]},{"year":2010,"claim":"Whether TBCC influences the cellular balance of tubulin and microtubule behavior was unresolved; overexpression studies showed it increases non-polymerizable tubulin, depletes polymerizable dimers, and dampens microtubule dynamics, establishing TBCC as a regulator of tubulin dimer content.","evidence":"Lysate fractionation, time-lapse microtubule dynamics imaging, flow cytometry cell cycle analysis, and xenograft growth assays in breast cancer cells","pmids":["20384997"],"confidence":"Medium","gaps":["Relies on overexpression rather than loss-of-function","Single-lab study without independent replication","Biochemical mechanism of partitioning tubulin into a non-polymerizable fraction not defined"]},{"year":2019,"claim":"How TBCC connects to proliferation and autophagy control, and how it is itself regulated, was unknown; TBCC was placed in a miR-1251-5p/TBCC/α/β-tubulin axis modulating CDK4, LC3BII, and p62 to suppress cell cycle and autophagy.","evidence":"TBCC and miR-1251-5p overexpression/inhibition with western blotting, cell cycle analysis, and xenograft growth in ovarian cancer cells","pmids":["31278033"],"confidence":"Medium","gaps":["Direct miR-1251-5p binding to TBCC transcript not biochemically mapped","Mechanistic link between TBCC and CDK4/LC3BII/p62 changes unresolved","Findings confined to overexpression in cancer-cell models"]},{"year":null,"claim":"The biochemical mechanism by which TBCC partitions tubulin into non-polymerizable versus polymerizable pools, and whether human TBCC contributes to centriole or spindle functions, remains undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural or enzymatic mechanism for tubulin dimer regulation","No loss-of-function characterization of endogenous TBCC","Centriole role established only for the family member Tbccd1, not TBCC itself"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0]}],"localization":[],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[0,1]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[1]}],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q15814","full_name":"Tubulin-specific chaperone C","aliases":["Tubulin-folding cofactor C","CFC"],"length_aa":346,"mass_kda":39.2,"function":"Tubulin-folding protein; involved in the final step of the tubulin folding pathway","subcellular_location":"Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q15814/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/TBCC","classification":"Common Essential","n_dependent_lines":1155,"n_total_lines":1208,"dependency_fraction":0.9561258278145696},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"COPB2","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/TBCC","total_profiled":1310},"omim":[{"mim_id":"619848","title":"TBCC DOMAIN-CONTAINING PROTEIN 1; TBCCD1","url":"https://www.omim.org/entry/619848"},{"mim_id":"610451","title":"TUBULIN FOLDING COFACTOR E-LIKE; TBCEL","url":"https://www.omim.org/entry/610451"},{"mim_id":"604934","title":"TUBULIN FOLDING COFACTOR E; TBCE","url":"https://www.omim.org/entry/604934"},{"mim_id":"604695","title":"ADP-RIBOSYLATION FACTOR-LIKE GTPase 3; ARL3","url":"https://www.omim.org/entry/604695"},{"mim_id":"604649","title":"TUBULIN FOLDING COFACTOR D; TBCD","url":"https://www.omim.org/entry/604649"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Cytosol","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/TBCC"},"hgnc":{"alias_symbol":["CFC"],"prev_symbol":[]},"alphafold":{"accession":"Q15814","domains":[{"cath_id":"1.20.58.1250","chopping":"30-132","consensus_level":"high","plddt":86.2196,"start":30,"end":132},{"cath_id":"2.160.20.70","chopping":"184-341","consensus_level":"high","plddt":95.0537,"start":184,"end":341}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q15814","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q15814-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q15814-F1-predicted_aligned_error_v6.png","plddt_mean":81.31},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TBCC","jax_strain_url":"https://www.jax.org/strain/search?query=TBCC"},"sequence":{"accession":"Q15814","fasta_url":"https://rest.uniprot.org/uniprotkb/Q15814.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q15814/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q15814"}},"corpus_meta":[{"pmid":"10199408","id":"PMC_10199408","title":"The EGF-CFC protein one-eyed pinhead is essential for nodal signaling.","date":"1999","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/10199408","citation_count":607,"is_preprint":false},{"pmid":"11062482","id":"PMC_11062482","title":"Loss-of-function mutations in the EGF-CFC gene CFC1 are associated with human left-right laterality defects.","date":"2000","source":"Nature genetics","url":"https://pubmed.ncbi.nlm.nih.gov/11062482","citation_count":255,"is_preprint":false},{"pmid":"10521397","id":"PMC_10521397","title":"Conserved requirement for EGF-CFC genes in vertebrate left-right axis formation.","date":"1999","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/10521397","citation_count":214,"is_preprint":false},{"pmid":"10858660","id":"PMC_10858660","title":"The EGF-CFC gene family in vertebrate development.","date":"2000","source":"Trends in genetics : TIG","url":"https://pubmed.ncbi.nlm.nih.gov/10858660","citation_count":174,"is_preprint":false},{"pmid":"12514096","id":"PMC_12514096","title":"EGF-CFC proteins are essential coreceptors for the TGF-beta signals Vg1 and GDF1.","date":"2003","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/12514096","citation_count":146,"is_preprint":false},{"pmid":"2665850","id":"PMC_2665850","title":"Detection of a human CFC with a high proliferative potential.","date":"1989","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/2665850","citation_count":142,"is_preprint":false},{"pmid":"12925698","id":"PMC_12925698","title":"Antibody blockade of the Cripto CFC domain suppresses tumor cell growth in vivo.","date":"2003","source":"The Journal of clinical investigation","url":"https://pubmed.ncbi.nlm.nih.gov/12925698","citation_count":139,"is_preprint":false},{"pmid":"2189013","id":"PMC_2189013","title":"Colony-forming cells with high proliferative potential (HPP-CFC).","date":"1990","source":"International journal of cell cloning","url":"https://pubmed.ncbi.nlm.nih.gov/2189013","citation_count":132,"is_preprint":false},{"pmid":"11174844","id":"PMC_11174844","title":"The EGF-CFC family: novel epidermal growth factor-related proteins in development and cancer.","date":"2000","source":"Endocrine-related cancer","url":"https://pubmed.ncbi.nlm.nih.gov/11174844","citation_count":113,"is_preprint":false},{"pmid":"17366577","id":"PMC_17366577","title":"Molecular and clinical characterization of cardio-facio-cutaneous (CFC) syndrome: overlapping clinical manifestations with Costello syndrome.","date":"2007","source":"American journal of medical genetics. 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non-polymerizable tubulin fraction, decreases polymerizable tubulin dimers and microtubule mass, and reduces microtubule dynamicity in breast cancer cells, establishing its role as a regulator of tubulin dimer content and microtubule dynamics.\",\n      \"method\": \"Lysate fractionation, time-lapse microscopy of microtubule dynamics, cell cycle analysis by flow cytometry, xenograft tumor growth assays\",\n      \"journal\": \"BMC cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (fractionation, live imaging, in vivo xenograft) in a single lab study establishing functional consequences of TBCC overexpression\",\n      \"pmids\": [\"20384997\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"TBCC overexpression inhibits CDK4 and LC3BII expression while promoting α/β-tubulin and p62 expression, suppressing cell cycle progression and autophagy in ovarian cancer cells; miR-1251-5p targets TBCC to reverse these effects, placing TBCC in a miR-1251-5p/TBCC/α/β-tubulin regulatory axis.\",\n      \"method\": \"Exogenous TBCC overexpression, miR-1251-5p overexpression/inhibition, western blotting for CDK4, LC3BII, p62, α/β-tubulin, cell cycle analysis, xenograft tumor growth\",\n      \"journal\": \"Molecular therapy : the journal of the American Society of Gene Therapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (western blot, cell cycle, xenograft) in single lab; pathway placement via rescue experiments\",\n      \"pmids\": [\"31278033\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"The TBCC-like protein Tbccd1/Asq2p (encoded by ASQ2 in Chlamydomonas) is required for mother-daughter centriole linkage; loss of Tbccd1 causes variable centriole numbers, centriole positioning defects, and mitotic spindle orientation defects, establishing a role for this TBCC family member in centriole linkage and spindle positioning.\",\n      \"method\": \"Genetic mutant analysis, live-cell imaging of centrioles and mitotic spindles in asq2 mutant Chlamydomonas cells\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean loss-of-function mutant with defined cellular phenotypes (centriole number, spindle orientation) in a model organism; single lab but multiple orthogonal cellular readouts; note this is a TBCC family member (Tbccd1), not canonical TBCC itself\",\n      \"pmids\": [\"19631545\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TBCC (tubulin binding cofactor C) controls tubulin dimer content and microtubule dynamics by regulating the balance between non-polymerizable and polymerizable tubulin fractions; overexpression reduces microtubule dynamicity and suppresses tumor cell growth, cell cycle progression, and autophagy, in part through regulation of CDK4, α/β-tubulin, and p62 levels, and is targeted post-transcriptionally by miR-1251-5p.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TBCC (tubulin binding cofactor C) is a regulator of tubulin dimer content and microtubule dynamics that constrains microtubule-dependent proliferation programs [#0]. Overexpression of TBCC shifts the tubulin pool toward the non-polymerizable fraction, depleting polymerizable tubulin dimers, lowering microtubule mass, and reducing microtubule dynamicity in breast cancer cells, with accompanying suppression of cell cycle progression and tumor growth [#0]. In ovarian cancer cells, TBCC suppresses cell cycle progression and autophagy by lowering CDK4 and LC3BII while raising α/β-tubulin and p62; this activity is held in check by miR-1251-5p, which targets TBCC to reverse these effects, defining a miR-1251-5p/TBCC/α/β-tubulin regulatory axis [#1]. Beyond these tumor-cell studies and a centriole-linkage role described for the TBCC family member Tbccd1 in Chlamydomonas [#2], no further mechanistic detail for canonical TBCC has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Whether TBCC-family proteins act beyond tubulin folding was unknown; analysis of the TBCC-like protein Tbccd1 established a structural role in linking mother and daughter centrioles and orienting the mitotic spindle.\",\n      \"evidence\": \"Loss-of-function asq2 mutant analysis with live-cell imaging of centrioles and spindles in Chlamydomonas\",\n      \"pmids\": [\"19631545\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Concerns a TBCC family member (Tbccd1), not canonical TBCC\",\n        \"Molecular mechanism of centriole linkage not defined\",\n        \"No demonstration that human TBCC shares this centriole function\"\n      ]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Whether TBCC influences the cellular balance of tubulin and microtubule behavior was unresolved; overexpression studies showed it increases non-polymerizable tubulin, depletes polymerizable dimers, and dampens microtubule dynamics, establishing TBCC as a regulator of tubulin dimer content.\",\n      \"evidence\": \"Lysate fractionation, time-lapse microtubule dynamics imaging, flow cytometry cell cycle analysis, and xenograft growth assays in breast cancer cells\",\n      \"pmids\": [\"20384997\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Relies on overexpression rather than loss-of-function\",\n        \"Single-lab study without independent replication\",\n        \"Biochemical mechanism of partitioning tubulin into a non-polymerizable fraction not defined\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"How TBCC connects to proliferation and autophagy control, and how it is itself regulated, was unknown; TBCC was placed in a miR-1251-5p/TBCC/α/β-tubulin axis modulating CDK4, LC3BII, and p62 to suppress cell cycle and autophagy.\",\n      \"evidence\": \"TBCC and miR-1251-5p overexpression/inhibition with western blotting, cell cycle analysis, and xenograft growth in ovarian cancer cells\",\n      \"pmids\": [\"31278033\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct miR-1251-5p binding to TBCC transcript not biochemically mapped\",\n        \"Mechanistic link between TBCC and CDK4/LC3BII/p62 changes unresolved\",\n        \"Findings confined to overexpression in cancer-cell models\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical mechanism by which TBCC partitions tubulin into non-polymerizable versus polymerizable pools, and whether human TBCC contributes to centriole or spindle functions, remains undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural or enzymatic mechanism for tubulin dimer regulation\",\n        \"No loss-of-function characterization of endogenous TBCC\",\n        \"Centriole role established only for the family member Tbccd1, not TBCC itself\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}