{"gene":"CEP170B","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":2023,"finding":"CEP170B is a microtubule minus-end-binding protein that autonomously tracks growing MT minus ends and blocks minus-end growth; in complex with the kinesin KIF2A, it acts as a potent MT minus-end depolymerase capable of antagonizing the stabilizing effect of CAMSAP family proteins.","method":"Reconstitution experiments (in vitro), live imaging, loss-of-function assays in HeLa and human epithelial cells","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution plus multiple orthogonal cellular assays (live imaging, KO phenotype, 3D cyst formation) in a single rigorous study","pmids":["37014312"],"is_preprint":false},{"year":2023,"finding":"CEP170B localizes to cortical patches in a manner dependent on the scaffold protein liprin-α1 and requires liprin-α1-bound PP2A phosphatase for its MT localization; cortical CEP170B excludes CAMSAP-stabilized MT minus ends from the cell periphery and the basal cortex, and is required for directional vesicle trafficking and cyst formation in 3D culture.","method":"Co-localization, knockdown/knockout with functional readouts (vesicle trafficking, 3D cyst formation), fractionation/localization experiments","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (localization, KO phenotype, reconstitution) in one rigorous study","pmids":["37014312"],"is_preprint":false},{"year":2012,"finding":"CEP170R (KIAA0284/CEP170B) specifically associates with the kinesin-13 depolymerase Kif2b via its C-terminus, and the related protein Cep170 binds microtubules in vitro to provide Kif2b with a second microtubule-binding site for spindle targeting.","method":"Co-immunoprecipitation/pulldown, in vitro microtubule-binding assay","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single Co-IP/pulldown identifying the association; in vitro MT-binding shown for Cep170 but the mechanistic detail for CEP170B/KIAA0284 specifically is less fully resolved in the abstract","pmids":["23087211"],"is_preprint":false}],"current_model":"CEP170B is a microtubule minus-end-binding protein that, dependent on the liprin-α1/PP2A scaffold for cortical targeting, autonomously tracks and blocks growing MT minus ends, and in complex with kinesin KIF2A acts as a potent MT minus-end depolymerase that antagonizes CAMSAP-mediated stabilization, thereby excluding MT minus ends from the cell periphery to establish a polarized microtubule network and cell polarity; CEP170B also associates with the kinesin-13 Kif2b at the mitotic spindle."},"narrative":{"mechanistic_narrative":"CEP170B is a microtubule minus-end-binding protein that shapes a polarized microtubule network to establish cell polarity [PMID:37014312]. It autonomously tracks growing microtubule minus ends and blocks their growth, and in complex with the kinesin KIF2A acts as a potent minus-end depolymerase that antagonizes the stabilizing activity of CAMSAP-family proteins [PMID:37014312]. Its cortical deployment is scaffold-dependent: localization to cortical patches requires liprin-α1, and its microtubule-localizing activity requires liprin-α1-bound PP2A phosphatase, allowing cortical CEP170B to exclude CAMSAP-stabilized minus ends from the cell periphery and basal cortex and thereby support directional vesicle trafficking and 3D cyst formation [PMID:37014312]. CEP170B also associates with the kinesin-13 depolymerase Kif2b through its C-terminus, providing an additional microtubule-binding context at the mitotic spindle [PMID:23087211].","teleology":[{"year":2012,"claim":"Before this work it was unclear how CEP170B engaged the microtubule cytoskeleton; the finding established a physical link to a kinesin-13 depolymerase and a microtubule-binding role.","evidence":"Co-immunoprecipitation/pulldown and in vitro microtubule-binding assay","pmids":["23087211"],"confidence":"Medium","gaps":["single Co-IP/pulldown without reciprocal validation for CEP170B specifically","in vitro MT-binding was shown for Cep170, not fully resolved for CEP170B/KIAA0284","functional consequence of the Kif2b association at the spindle not directly tested"]},{"year":2023,"claim":"It was unknown whether CEP170B had intrinsic minus-end activity; reconstitution showed it autonomously tracks and blocks MT minus ends and, with KIF2A, depolymerizes them to counter CAMSAP stabilization.","evidence":"In vitro reconstitution, live imaging, and loss-of-function assays in HeLa and human epithelial cells","pmids":["37014312"],"confidence":"High","gaps":["structural basis of minus-end recognition not defined","how KIF2A and CEP170B are co-regulated at minus ends not established"]},{"year":2023,"claim":"The mechanism of CEP170B cortical targeting was unknown; it was shown to depend on liprin-α1 and liprin-α1-bound PP2A, linking cortical positioning to exclusion of minus ends and to polarized trafficking and morphogenesis.","evidence":"Co-localization, knockdown/knockout with vesicle trafficking and 3D cyst formation readouts, and fractionation","pmids":["37014312"],"confidence":"High","gaps":["PP2A substrate/dephosphorylation event controlling CEP170B localization not identified","molecular nature of the cortical patches not resolved"]},{"year":null,"claim":"How the spindle-associated Kif2b role and the cortical minus-end-exclusion role of CEP170B are integrated, and whether they operate in distinct cellular contexts, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["no unified model linking mitotic and interphase functions","regulation distinguishing KIF2A versus Kif2b partnerships unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,2]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0,2]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[1]}],"pathway":[],"complexes":[],"partners":["KIF2A","KIF2B","PPP2","LIPRIN-Α1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9Y4F5","full_name":"Centrosomal protein of 170 kDa protein B","aliases":["Centrosomal protein 170B","Cep170B"],"length_aa":1589,"mass_kda":171.7,"function":"Plays a role in microtubule organization","subcellular_location":"Cytoplasm, cytoskeleton","url":"https://www.uniprot.org/uniprotkb/Q9Y4F5/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CEP170B","classification":"Not Classified","n_dependent_lines":4,"n_total_lines":1208,"dependency_fraction":0.0033112582781456954},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"TUBB4B","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/CEP170B","total_profiled":1310},"omim":[{"mim_id":"620251","title":"CENTROSOMAL PROTEIN 170B; CEP170B","url":"https://www.omim.org/entry/620251"},{"mim_id":"615142","title":"KINESIN FAMILY MEMBER 2B; KIF2B","url":"https://www.omim.org/entry/615142"},{"mim_id":"613023","title":"CENTROSOMAL PROTEIN, 170-KD; CEP170","url":"https://www.omim.org/entry/613023"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Microtubule ends","reliability":"Approved"},{"location":"Centrosome","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/CEP170B"},"hgnc":{"alias_symbol":["FAM68C","Cep170R"],"prev_symbol":["KIAA0284"]},"alphafold":{"accession":"Q9Y4F5","domains":[{"cath_id":"2.60.200.20","chopping":"2-109","consensus_level":"medium","plddt":89.6671,"start":2,"end":109},{"cath_id":"-","chopping":"1432-1465_1490-1514","consensus_level":"medium","plddt":80.0975,"start":1432,"end":1514}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y4F5","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y4F5-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y4F5-F1-predicted_aligned_error_v6.png","plddt_mean":46.69},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CEP170B","jax_strain_url":"https://www.jax.org/strain/search?query=CEP170B"},"sequence":{"accession":"Q9Y4F5","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9Y4F5.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9Y4F5/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y4F5"}},"corpus_meta":[{"pmid":"23087211","id":"PMC_23087211","title":"The microtubule-binding protein Cep170 promotes the targeting of the kinesin-13 depolymerase Kif2b to the mitotic spindle.","date":"2012","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/23087211","citation_count":47,"is_preprint":false},{"pmid":"21900057","id":"PMC_21900057","title":"Identification of MLL partner genes in 27 patients with acute leukemia from a single cytogenetic laboratory.","date":"2011","source":"Molecular oncology","url":"https://pubmed.ncbi.nlm.nih.gov/21900057","citation_count":25,"is_preprint":false},{"pmid":"37014312","id":"PMC_37014312","title":"The CEP170B-KIF2A complex destabilizes microtubule minus ends to generate polarized microtubule network.","date":"2023","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/37014312","citation_count":12,"is_preprint":false},{"pmid":"33933146","id":"PMC_33933146","title":"Weight loss after Roux-En-Y gastric bypass surgery reveals skeletal muscle DNA methylation changes.","date":"2021","source":"Clinical epigenetics","url":"https://pubmed.ncbi.nlm.nih.gov/33933146","citation_count":11,"is_preprint":false},{"pmid":"37192718","id":"PMC_37192718","title":"Insight on the hub gene associated signatures and potential therapeutic agents in epilepsy and glioma.","date":"2023","source":"Brain research bulletin","url":"https://pubmed.ncbi.nlm.nih.gov/37192718","citation_count":9,"is_preprint":false},{"pmid":"34722763","id":"PMC_34722763","title":"Identification and Validation of a Dysregulated miRNA-Associated mRNA Network in Temporal Lobe Epilepsy.","date":"2021","source":"BioMed research international","url":"https://pubmed.ncbi.nlm.nih.gov/34722763","citation_count":8,"is_preprint":false},{"pmid":"18640063","id":"PMC_18640063","title":"A MLL-KIAA0284 fusion gene in a patient with secondary acute myeloid leukemia and t(11;14)(q23;q32).","date":"2008","source":"Blood cells, molecules & diseases","url":"https://pubmed.ncbi.nlm.nih.gov/18640063","citation_count":3,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6228,"output_tokens":867,"usd":0.015845,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7310,"output_tokens":1544,"usd":0.037575,"stage2_stop_reason":"end_turn"},"total_usd":0.05342,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"CEP170B is a microtubule minus-end-binding protein that autonomously tracks growing MT minus ends and blocks minus-end growth; in complex with the kinesin KIF2A, it acts as a potent MT minus-end depolymerase capable of antagonizing the stabilizing effect of CAMSAP family proteins.\",\n      \"method\": \"Reconstitution experiments (in vitro), live imaging, loss-of-function assays in HeLa and human epithelial cells\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution plus multiple orthogonal cellular assays (live imaging, KO phenotype, 3D cyst formation) in a single rigorous study\",\n      \"pmids\": [\"37014312\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"CEP170B localizes to cortical patches in a manner dependent on the scaffold protein liprin-α1 and requires liprin-α1-bound PP2A phosphatase for its MT localization; cortical CEP170B excludes CAMSAP-stabilized MT minus ends from the cell periphery and the basal cortex, and is required for directional vesicle trafficking and cyst formation in 3D culture.\",\n      \"method\": \"Co-localization, knockdown/knockout with functional readouts (vesicle trafficking, 3D cyst formation), fractionation/localization experiments\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (localization, KO phenotype, reconstitution) in one rigorous study\",\n      \"pmids\": [\"37014312\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"CEP170R (KIAA0284/CEP170B) specifically associates with the kinesin-13 depolymerase Kif2b via its C-terminus, and the related protein Cep170 binds microtubules in vitro to provide Kif2b with a second microtubule-binding site for spindle targeting.\",\n      \"method\": \"Co-immunoprecipitation/pulldown, in vitro microtubule-binding assay\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single Co-IP/pulldown identifying the association; in vitro MT-binding shown for Cep170 but the mechanistic detail for CEP170B/KIAA0284 specifically is less fully resolved in the abstract\",\n      \"pmids\": [\"23087211\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CEP170B is a microtubule minus-end-binding protein that, dependent on the liprin-α1/PP2A scaffold for cortical targeting, autonomously tracks and blocks growing MT minus ends, and in complex with kinesin KIF2A acts as a potent MT minus-end depolymerase that antagonizes CAMSAP-mediated stabilization, thereby excluding MT minus ends from the cell periphery to establish a polarized microtubule network and cell polarity; CEP170B also associates with the kinesin-13 Kif2b at the mitotic spindle.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CEP170B is a microtubule minus-end-binding protein that shapes a polarized microtubule network to establish cell polarity [#0]. It autonomously tracks growing microtubule minus ends and blocks their growth, and in complex with the kinesin KIF2A acts as a potent minus-end depolymerase that antagonizes the stabilizing activity of CAMSAP-family proteins [#0]. Its cortical deployment is scaffold-dependent: localization to cortical patches requires liprin-\\u03b11, and its microtubule-localizing activity requires liprin-\\u03b11-bound PP2A phosphatase, allowing cortical CEP170B to exclude CAMSAP-stabilized minus ends from the cell periphery and basal cortex and thereby support directional vesicle trafficking and 3D cyst formation [#1]. CEP170B also associates with the kinesin-13 depolymerase Kif2b through its C-terminus, providing an additional microtubule-binding context at the mitotic spindle [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Before this work it was unclear how CEP170B engaged the microtubule cytoskeleton; the finding established a physical link to a kinesin-13 depolymerase and a microtubule-binding role.\",\n      \"evidence\": \"Co-immunoprecipitation/pulldown and in vitro microtubule-binding assay\",\n      \"pmids\": [\"23087211\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"single Co-IP/pulldown without reciprocal validation for CEP170B specifically\",\n        \"in vitro MT-binding was shown for Cep170, not fully resolved for CEP170B/KIAA0284\",\n        \"functional consequence of the Kif2b association at the spindle not directly tested\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"It was unknown whether CEP170B had intrinsic minus-end activity; reconstitution showed it autonomously tracks and blocks MT minus ends and, with KIF2A, depolymerizes them to counter CAMSAP stabilization.\",\n      \"evidence\": \"In vitro reconstitution, live imaging, and loss-of-function assays in HeLa and human epithelial cells\",\n      \"pmids\": [\"37014312\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"structural basis of minus-end recognition not defined\",\n        \"how KIF2A and CEP170B are co-regulated at minus ends not established\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"The mechanism of CEP170B cortical targeting was unknown; it was shown to depend on liprin-\\u03b11 and liprin-\\u03b11-bound PP2A, linking cortical positioning to exclusion of minus ends and to polarized trafficking and morphogenesis.\",\n      \"evidence\": \"Co-localization, knockdown/knockout with vesicle trafficking and 3D cyst formation readouts, and fractionation\",\n      \"pmids\": [\"37014312\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"PP2A substrate/dephosphorylation event controlling CEP170B localization not identified\",\n        \"molecular nature of the cortical patches not resolved\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the spindle-associated Kif2b role and the cortical minus-end-exclusion role of CEP170B are integrated, and whether they operate in distinct cellular contexts, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"no unified model linking mitotic and interphase functions\",\n        \"regulation distinguishing KIF2A versus Kif2b partnerships unknown\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"KIF2A\", \"KIF2B\", \"PPP2\", \"liprin-\\u03b11\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":4,"faith_total":4,"faith_pct":100.0}}