{"gene":"CEP44","run_date":"2026-04-28T17:28:52","timeline":{"discoveries":[{"year":2020,"finding":"CEP44 is a luminal centriole protein that binds to A-microtubules of centrioles and interacts with POC1B, and its depletion disrupts centriole wall structure and prevents centriole-to-centrosome conversion despite CEP295 still binding to centrioles, placing CEP44 in a centriole biogenesis pathway (CEP295→CEP44→POC1B→TUBE1/TUBD1) required for pericentriolar material recruitment.","method":"siRNA depletion with immunofluorescence, electron microscopy, co-immunoprecipitation, epistasis analysis in human cells","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (EM, Co-IP, epistasis, KD phenotype) in a single study with clear pathway placement","pmids":["32060285"],"is_preprint":false},{"year":2020,"finding":"CEP44 localizes to the proximal end of both mother and daughter centrioles in human cells, associates with rootletin, stabilizes rootletin and promotes its centrosomal localization, and is required for centrosome cohesion (linker assembly); its ablation causes premature centrosome separation without affecting C-Nap1, LRRC45, or Cep215 stability.","method":"siRNA depletion, immunofluorescence, co-immunoprecipitation, centrosome cohesion assays in human cells","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 — reciprocal Co-IP plus KD with defined cohesion phenotype and pathway dissection across multiple linker components","pmids":["31974111"],"is_preprint":false},{"year":2023,"finding":"Super-resolution imaging reveals that CEP44 localizes in ninefold symmetry at centrioles, providing a precise nanoscale distribution map that distinguishes it from the more complex patterning of CEP152 during centriole maturation.","method":"Expansion microscopy / super-resolution fluorescence imaging in human cells","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 — direct high-resolution localization experiment, single study, no functional perturbation of CEP44 specifically","pmids":["37707473"],"is_preprint":false},{"year":2022,"finding":"AlphaFold2 structural predictions for CEP44 were experimentally validated and provided insights into the modular organization of CEP44 within the context of centriole biogenesis complexes.","method":"Computational structure prediction (AlphaFold2) with experimental structural validation","journal":"Communications biology","confidence":"Low","confidence_rationale":"Tier 4/1 hybrid — AF2 models validated structurally but functional consequences of CEP44 domain organization not directly tested experimentally in this paper","pmids":["35383272"],"is_preprint":false},{"year":2025,"finding":"CEP44 contains intrinsically disordered regions (IDRs) enabling liquid-liquid phase separation (LLPS) and droplet formation in vivo and in vitro; CEP44 is O-GlcNAcylated by OGT, and O-GlcNAcylation promotes CEP44 droplet fusion and influences its subcellular localization, with a predicted interplay between O-GlcNAcylation and phosphorylation modulating CEP44 structural dynamics.","method":"Droplet formation assays (in vitro and in vivo), immunoblotting for O-GlcNAc, co-immunoprecipitation with OGT, immunostaining, PTM prediction analysis","journal":"Cytoskeleton (Hoboken, N.J.)","confidence":"Medium","confidence_rationale":"Tier 2/3 — multiple methods (LLPS assay, IP, immunostaining) from a single lab, moderate mechanistic follow-up on the PTM","pmids":["40906019"],"is_preprint":false}],"current_model":"CEP44 is a luminal centriole protein that localizes in ninefold symmetry at the proximal end of centrioles, where it binds A-microtubules, interacts with POC1B to maintain centriole wall integrity, and functions in a CEP295-dependent pathway essential for centriole-to-centrosome conversion; independently, it associates with rootletin to stabilize the centrosome linker and maintain centrosome cohesion; additionally, CEP44 undergoes O-GlcNAcylation by OGT, which promotes its liquid-liquid phase separation and influences its centrosomal localization."},"narrative":{"teleology":[{"year":2020,"claim":"Establishing that CEP44 functions as a luminal centriole structural component acting downstream of CEP295 to recruit POC1B, maintain centriole wall integrity, and enable centriole-to-centrosome conversion resolved where CEP44 fits in the centriole biogenesis hierarchy.","evidence":"siRNA depletion with electron microscopy, co-immunoprecipitation, epistasis analysis, and immunofluorescence in human cells","pmids":["32060285"],"confidence":"High","gaps":["Direct binding interface between CEP44 and A-microtubules not structurally resolved","Whether CEP44 has catalytic activity or acts purely as a scaffold is unknown","Mechanism by which CEP44 loss prevents PCM recruitment despite CEP295 presence is unclear"]},{"year":2020,"claim":"Demonstrating that CEP44 associates with rootletin and is required for centrosome linker stability and cohesion revealed a second, distinct function for CEP44 at the proximal centriole end, separable from its centriole biogenesis role.","evidence":"siRNA depletion, reciprocal co-immunoprecipitation, centrosome cohesion assays, and immunofluorescence in human cells","pmids":["31974111"],"confidence":"High","gaps":["Whether the rootletin-binding and POC1B-binding functions of CEP44 are mediated by distinct domains is unknown","How CEP44 stabilizes rootletin at a molecular level has not been determined"]},{"year":2023,"claim":"Super-resolution mapping of CEP44 in ninefold symmetry at centrioles provided a precise nanoscale framework for its structural role, distinguishing it from outer centriole components like CEP152.","evidence":"Expansion microscopy and super-resolution fluorescence imaging in human cells","pmids":["37707473"],"confidence":"Medium","gaps":["No functional perturbation of CEP44 was performed in this study","Whether the ninefold pattern reflects direct microtubule attachment stoichiometry is unresolved"]},{"year":2025,"claim":"Discovery that CEP44 undergoes liquid–liquid phase separation via intrinsically disordered regions and that OGT-mediated O-GlcNAcylation promotes droplet fusion and modulates centrosomal localization introduced a post-translational regulatory layer to CEP44 function.","evidence":"In vitro and in vivo droplet formation assays, co-immunoprecipitation with OGT, immunoblotting for O-GlcNAc, immunostaining, and PTM prediction analysis","pmids":["40906019"],"confidence":"Medium","gaps":["Specific O-GlcNAcylation sites on CEP44 have not been mapped by mutagenesis","Functional consequence of LLPS for centriole biogenesis or centrosome cohesion not tested","Interplay between O-GlcNAcylation and phosphorylation is based on prediction, not direct experimental validation"]},{"year":null,"claim":"The relationship between CEP44 phase separation properties and its two established functions — centriole-to-centrosome conversion and centrosome linker maintenance — remains unconnected, as does the structural basis of its interactions with POC1B and rootletin.","evidence":"","pmids":[],"confidence":"High","gaps":["No high-resolution structure of CEP44 or its complexes exists","Whether LLPS contributes to PCM recruitment or linker assembly is untested","In vivo relevance of CEP44 loss in animal models has not been reported"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,2]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0,1,2,4]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0,1]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[0]}],"complexes":[],"partners":["POC1B","CEP295","CROCC","OGT"],"other_free_text":[]},"mechanistic_narrative":"CEP44 is a luminal centriole protein that localizes in ninefold symmetry at the proximal end of both mother and daughter centrioles, where it binds A-microtubules and interacts with POC1B to maintain centriole wall integrity and enable centriole-to-centrosome conversion through a CEP295→CEP44→POC1B→TUBE1/TUBD1 pathway required for pericentriolar material recruitment [PMID:32060285, PMID:37707473]. Independently of its role in centriole biogenesis, CEP44 associates with rootletin to stabilize the centrosome linker and maintain centrosome cohesion; its depletion causes premature centrosome separation without affecting C-Nap1 or LRRC45 levels [PMID:31974111]. CEP44 contains intrinsically disordered regions that drive liquid–liquid phase separation, and O-GlcNAcylation by OGT promotes CEP44 droplet fusion and modulates its centrosomal localization [PMID:40906019]."},"prefetch_data":{"uniprot":{"accession":"Q9C0F1","full_name":"Centrosomal protein of 44 kDa","aliases":["HBV PreS1-transactivated protein 3","PS1TP3"],"length_aa":390,"mass_kda":44.1,"function":"Centriole-enriched microtubule-binding protein involved in centriole biogenesis. In collaboration with CEP295 and POC1B, is required for the centriole-to-centrosome conversion by ensuring the formation of bona fide centriole wall (PubMed:32060285). Functions as a linker component that maintains centrosome cohesion. Associates with CROCC and regulates its stability and localization to the centrosome (PubMed:31974111)","subcellular_location":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole; Cytoplasm, cytoskeleton, spindle pole; Midbody","url":"https://www.uniprot.org/uniprotkb/Q9C0F1/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CEP44","classification":"Not Classified","n_dependent_lines":52,"n_total_lines":1208,"dependency_fraction":0.04304635761589404},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CEP44","total_profiled":1310},"omim":[{"mim_id":"620217","title":"CENTROSOMAL PROTEIN, 44-KD; CEP44","url":"https://www.omim.org/entry/620217"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Basal body","reliability":"Approved"},{"location":"Cytosol","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/CEP44"},"hgnc":{"alias_symbol":[],"prev_symbol":["KIAA1712"]},"alphafold":{"accession":"Q9C0F1","domains":[{"cath_id":"1.10.418","chopping":"7-127","consensus_level":"high","plddt":89.1199,"start":7,"end":127}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9C0F1","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9C0F1-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9C0F1-F1-predicted_aligned_error_v6.png","plddt_mean":67.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CEP44","jax_strain_url":"https://www.jax.org/strain/search?query=CEP44"},"sequence":{"accession":"Q9C0F1","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9C0F1.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9C0F1/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9C0F1"}},"corpus_meta":[{"pmid":"35383272","id":"PMC_35383272","title":"Structural validation and assessment of AlphaFold2 predictions for centrosomal and centriolar proteins and their complexes.","date":"2022","source":"Communications biology","url":"https://pubmed.ncbi.nlm.nih.gov/35383272","citation_count":41,"is_preprint":false},{"pmid":"32060285","id":"PMC_32060285","title":"CEP44 ensures the formation of bona fide centriole wall, a requirement for the centriole-to-centrosome conversion.","date":"2020","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/32060285","citation_count":40,"is_preprint":false},{"pmid":"31974111","id":"PMC_31974111","title":"Cep44 functions in centrosome cohesion by stabilizing rootletin.","date":"2020","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/31974111","citation_count":13,"is_preprint":false},{"pmid":"37707473","id":"PMC_37707473","title":"Centrosomal organization of Cep152 provides flexibility in Plk4 and procentriole positioning.","date":"2023","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/37707473","citation_count":10,"is_preprint":false},{"pmid":"30988073","id":"PMC_30988073","title":"A gene signature predicts response to neoadjuvant chemotherapy in triple-negative breast cancer patients.","date":"2019","source":"Bioscience reports","url":"https://pubmed.ncbi.nlm.nih.gov/30988073","citation_count":10,"is_preprint":false},{"pmid":"39667359","id":"PMC_39667359","title":"Dramatic Response to Ensartinib in Metastatic Neuroendocrine Tumors With a Novel CEP44-ALK Fusion: A Case Report and Literature Review.","date":"2024","source":"The clinical respiratory journal","url":"https://pubmed.ncbi.nlm.nih.gov/39667359","citation_count":2,"is_preprint":false},{"pmid":"40906019","id":"PMC_40906019","title":"O-GlcNAcylation of CEP44 Promotes Its Droplet Formation and Regulates Its Localization.","date":"2025","source":"Cytoskeleton (Hoboken, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/40906019","citation_count":1,"is_preprint":false},{"pmid":"40606991","id":"PMC_40606991","title":"Case Report: Metastatic colorectal cancer with ALK-CEP44 fusion and rapid resistance development.","date":"2025","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/40606991","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4650,"output_tokens":1299,"usd":0.016717},"stage2":{"model":"claude-opus-4-6","input_tokens":4524,"output_tokens":1521,"usd":0.090968},"total_usd":0.107685,"stage1_batch_id":"msgbatch_011kfMfE81o6CTcyhVUqumuW","stage2_batch_id":"msgbatch_01DTputS6WNkH745x1nVSoBo","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2020,\n      \"finding\": \"CEP44 is a luminal centriole protein that binds to A-microtubules of centrioles and interacts with POC1B, and its depletion disrupts centriole wall structure and prevents centriole-to-centrosome conversion despite CEP295 still binding to centrioles, placing CEP44 in a centriole biogenesis pathway (CEP295→CEP44→POC1B→TUBE1/TUBD1) required for pericentriolar material recruitment.\",\n      \"method\": \"siRNA depletion with immunofluorescence, electron microscopy, co-immunoprecipitation, epistasis analysis in human cells\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (EM, Co-IP, epistasis, KD phenotype) in a single study with clear pathway placement\",\n      \"pmids\": [\"32060285\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"CEP44 localizes to the proximal end of both mother and daughter centrioles in human cells, associates with rootletin, stabilizes rootletin and promotes its centrosomal localization, and is required for centrosome cohesion (linker assembly); its ablation causes premature centrosome separation without affecting C-Nap1, LRRC45, or Cep215 stability.\",\n      \"method\": \"siRNA depletion, immunofluorescence, co-immunoprecipitation, centrosome cohesion assays in human cells\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP plus KD with defined cohesion phenotype and pathway dissection across multiple linker components\",\n      \"pmids\": [\"31974111\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Super-resolution imaging reveals that CEP44 localizes in ninefold symmetry at centrioles, providing a precise nanoscale distribution map that distinguishes it from the more complex patterning of CEP152 during centriole maturation.\",\n      \"method\": \"Expansion microscopy / super-resolution fluorescence imaging in human cells\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct high-resolution localization experiment, single study, no functional perturbation of CEP44 specifically\",\n      \"pmids\": [\"37707473\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"AlphaFold2 structural predictions for CEP44 were experimentally validated and provided insights into the modular organization of CEP44 within the context of centriole biogenesis complexes.\",\n      \"method\": \"Computational structure prediction (AlphaFold2) with experimental structural validation\",\n      \"journal\": \"Communications biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4/1 hybrid — AF2 models validated structurally but functional consequences of CEP44 domain organization not directly tested experimentally in this paper\",\n      \"pmids\": [\"35383272\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CEP44 contains intrinsically disordered regions (IDRs) enabling liquid-liquid phase separation (LLPS) and droplet formation in vivo and in vitro; CEP44 is O-GlcNAcylated by OGT, and O-GlcNAcylation promotes CEP44 droplet fusion and influences its subcellular localization, with a predicted interplay between O-GlcNAcylation and phosphorylation modulating CEP44 structural dynamics.\",\n      \"method\": \"Droplet formation assays (in vitro and in vivo), immunoblotting for O-GlcNAc, co-immunoprecipitation with OGT, immunostaining, PTM prediction analysis\",\n      \"journal\": \"Cytoskeleton (Hoboken, N.J.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2/3 — multiple methods (LLPS assay, IP, immunostaining) from a single lab, moderate mechanistic follow-up on the PTM\",\n      \"pmids\": [\"40906019\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CEP44 is a luminal centriole protein that localizes in ninefold symmetry at the proximal end of centrioles, where it binds A-microtubules, interacts with POC1B to maintain centriole wall integrity, and functions in a CEP295-dependent pathway essential for centriole-to-centrosome conversion; independently, it associates with rootletin to stabilize the centrosome linker and maintain centrosome cohesion; additionally, CEP44 undergoes O-GlcNAcylation by OGT, which promotes its liquid-liquid phase separation and influences its centrosomal localization.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"CEP44 is a luminal centriole protein that localizes in ninefold symmetry at the proximal end of both mother and daughter centrioles, where it binds A-microtubules and interacts with POC1B to maintain centriole wall integrity and enable centriole-to-centrosome conversion through a CEP295→CEP44→POC1B→TUBE1/TUBD1 pathway required for pericentriolar material recruitment [PMID:32060285, PMID:37707473]. Independently of its role in centriole biogenesis, CEP44 associates with rootletin to stabilize the centrosome linker and maintain centrosome cohesion; its depletion causes premature centrosome separation without affecting C-Nap1 or LRRC45 levels [PMID:31974111]. CEP44 contains intrinsically disordered regions that drive liquid–liquid phase separation, and O-GlcNAcylation by OGT promotes CEP44 droplet fusion and modulates its centrosomal localization [PMID:40906019].\",\n  \"teleology\": [\n    {\n      \"year\": 2020,\n      \"claim\": \"Establishing that CEP44 functions as a luminal centriole structural component acting downstream of CEP295 to recruit POC1B, maintain centriole wall integrity, and enable centriole-to-centrosome conversion resolved where CEP44 fits in the centriole biogenesis hierarchy.\",\n      \"evidence\": \"siRNA depletion with electron microscopy, co-immunoprecipitation, epistasis analysis, and immunofluorescence in human cells\",\n      \"pmids\": [\"32060285\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct binding interface between CEP44 and A-microtubules not structurally resolved\",\n        \"Whether CEP44 has catalytic activity or acts purely as a scaffold is unknown\",\n        \"Mechanism by which CEP44 loss prevents PCM recruitment despite CEP295 presence is unclear\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Demonstrating that CEP44 associates with rootletin and is required for centrosome linker stability and cohesion revealed a second, distinct function for CEP44 at the proximal centriole end, separable from its centriole biogenesis role.\",\n      \"evidence\": \"siRNA depletion, reciprocal co-immunoprecipitation, centrosome cohesion assays, and immunofluorescence in human cells\",\n      \"pmids\": [\"31974111\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether the rootletin-binding and POC1B-binding functions of CEP44 are mediated by distinct domains is unknown\",\n        \"How CEP44 stabilizes rootletin at a molecular level has not been determined\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Super-resolution mapping of CEP44 in ninefold symmetry at centrioles provided a precise nanoscale framework for its structural role, distinguishing it from outer centriole components like CEP152.\",\n      \"evidence\": \"Expansion microscopy and super-resolution fluorescence imaging in human cells\",\n      \"pmids\": [\"37707473\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional perturbation of CEP44 was performed in this study\",\n        \"Whether the ninefold pattern reflects direct microtubule attachment stoichiometry is unresolved\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Discovery that CEP44 undergoes liquid–liquid phase separation via intrinsically disordered regions and that OGT-mediated O-GlcNAcylation promotes droplet fusion and modulates centrosomal localization introduced a post-translational regulatory layer to CEP44 function.\",\n      \"evidence\": \"In vitro and in vivo droplet formation assays, co-immunoprecipitation with OGT, immunoblotting for O-GlcNAc, immunostaining, and PTM prediction analysis\",\n      \"pmids\": [\"40906019\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Specific O-GlcNAcylation sites on CEP44 have not been mapped by mutagenesis\",\n        \"Functional consequence of LLPS for centriole biogenesis or centrosome cohesion not tested\",\n        \"Interplay between O-GlcNAcylation and phosphorylation is based on prediction, not direct experimental validation\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The relationship between CEP44 phase separation properties and its two established functions — centriole-to-centrosome conversion and centrosome linker maintenance — remains unconnected, as does the structural basis of its interactions with POC1B and rootletin.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No high-resolution structure of CEP44 or its complexes exists\",\n        \"Whether LLPS contributes to PCM recruitment or linker assembly is untested\",\n        \"In vivo relevance of CEP44 loss in animal models has not been reported\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0, 1, 2, 4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"POC1B\",\n      \"CEP295\",\n      \"CROCC\",\n      \"OGT\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}