{"gene":"CEP44","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":2020,"finding":"CEP44 localizes to the centriole lumen where it binds to A-microtubules and interacts with POC1B, affecting centriole wall structure; depletion of CEP44 impairs 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, Co-immunoprecipitation, fluorescence microscopy, electron microscopy","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (depletion, Co-IP, EM structural analysis, epistasis) in a single rigorous study establishing pathway position and molecular interaction","pmids":["32060285"],"is_preprint":false},{"year":2020,"finding":"CEP44 localizes to the proximal end of both mother and daughter centrioles and is required for centrosome cohesion; it associates with rootletin and regulates rootletin's stability and localization to the centrosome, independently of C-Nap1, LRRC45, and Cep215.","method":"siRNA ablation, immunofluorescence, co-immunoprecipitation, centrosome cohesion assays","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal interaction data and loss-of-function phenotype with defined molecular partner (rootletin), single lab","pmids":["31974111"],"is_preprint":false},{"year":2023,"finding":"CEP44 localizes in ninefold symmetry at the centrosome, as determined by nanoscale-resolution imaging, consistent with its association with the centriole microtubule wall.","method":"Expansion microscopy / super-resolution nanoscale imaging","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct high-resolution localization experiment with functional context, single lab","pmids":["37707473"],"is_preprint":false},{"year":2022,"finding":"AlphaFold2 structural predictions for CEP44 were experimentally validated, revealing modular organization and structural features relevant to its function in centriole biogenesis.","method":"AlphaFold2 computational prediction with experimental validation (structural biology approaches)","journal":"Communications biology","confidence":"Low","confidence_rationale":"Tier 4 / Weak — primarily computational with partial experimental validation; abstract does not detail the experimental validation method for CEP44 specifically","pmids":["35383272"],"is_preprint":false},{"year":2025,"finding":"CEP44 contains intrinsically disordered regions (IDRs) that enable liquid-liquid phase separation (LLPS), forming liquid droplets both in vivo and in vitro; CEP44 is O-GlcNAcylated by O-GlcNAc transferase (OGT), and O-GlcNAcylation promotes CEP44 droplet fusion and influences its subcellular localization.","method":"Droplet formation assays (in vivo and in vitro), immunoblotting for O-GlcNAcylation, immunostaining, post-translational modification prediction","journal":"Cytoskeleton (Hoboken, N.J.)","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — multiple methods (LLPS assay, immunoblot, immunostaining) in a single study; interaction with OGT and functional consequence on droplet fusion demonstrated","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 and interacts with POC1B to maintain centriole wall integrity, is required for centriole-to-centrosome conversion downstream of CEP295, stabilizes rootletin to maintain centrosome cohesion, undergoes O-GlcNAcylation by OGT which promotes its liquid-liquid phase separation and droplet fusion, and collectively these activities place CEP44 as a structural scaffold coordinating centriole biogenesis, centrosome cohesion, and centrosomal condensate organization."},"narrative":{"mechanistic_narrative":"CEP44 is a luminal centriole protein that functions as a structural scaffold coordinating centriole biogenesis and centrosome integrity [PMID:32060285, PMID:31974111]. It localizes to the proximal end of both mother and daughter centrioles in ninefold symmetry, binding A-microtubules of the centriole wall and interacting with POC1B to maintain wall structure [PMID:32060285, PMID:37707473]. CEP44 acts downstream of CEP295 in a centriole-to-centrosome conversion pathway (CEP295→CEP44→POC1B→TUBE1/TUBD1) that is required for pericentriolar material recruitment; its depletion blocks conversion even when CEP295 still binds centrioles [PMID:32060285]. Independently of C-Nap1, LRRC45, and Cep215, CEP44 associates with rootletin and regulates its stability and localization to maintain centrosome cohesion [PMID:31974111]. CEP44 also contains intrinsically disordered regions that drive liquid-liquid phase separation into droplets in vitro and in vivo, and it is O-GlcNAcylated by OGT, a modification that promotes droplet fusion and influences its subcellular localization [PMID:40906019].","teleology":[{"year":2020,"claim":"Established CEP44's molecular role in centriole architecture by placing it within an ordered biogenesis pathway and identifying its physical and structural partners.","evidence":"siRNA depletion, Co-IP, and electron microscopy defining the CEP295→CEP44→POC1B→TUBE1/TUBD1 axis in human cells","pmids":["32060285"],"confidence":"High","gaps":["How CEP44 binding to A-microtubules mechanically stabilizes the wall is not resolved at atomic detail","The direct biochemical link between CEP44 and TUBE1/TUBD1 is not demonstrated","Whether CEP44 recruits POC1B directly or via intermediates is unclear"]},{"year":2020,"claim":"Extended CEP44's function beyond biogenesis to centrosome cohesion by linking it to rootletin stability, defining a pathway distinct from canonical cohesion factors.","evidence":"siRNA ablation, Co-IP, and centrosome cohesion assays showing CEP44 regulates rootletin independently of C-Nap1, LRRC45, and Cep215","pmids":["31974111"],"confidence":"Medium","gaps":["Mechanism by which CEP44 stabilizes rootletin is unknown","Single-lab finding without reciprocal structural validation","Relationship between cohesion role and centriole-wall role not integrated"]},{"year":2023,"claim":"Resolved CEP44's precise spatial organization, confirming a ninefold-symmetric arrangement consistent with direct association with the centriole microtubule wall.","evidence":"Expansion/super-resolution nanoscale imaging of the centrosome","pmids":["37707473"],"confidence":"Medium","gaps":["Does not establish stoichiometry of CEP44 per centriole","Single-lab localization without functional perturbation"]},{"year":2025,"claim":"Revealed a biophysical and regulatory dimension to CEP44 function, showing it phase-separates and that O-GlcNAcylation by OGT modulates its condensate behavior and localization.","evidence":"In vitro/in vivo droplet assays, immunoblotting for O-GlcNAcylation, and immunostaining","pmids":["40906019"],"confidence":"Medium","gaps":["Functional consequence of CEP44 LLPS for centriole biogenesis or cohesion is not established","O-GlcNAcylation sites are not mapped","Whether phase separation occurs at the centriole in cells is not shown"]},{"year":null,"claim":"How CEP44's structural scaffolding at the centriole wall, its regulation of centrosome cohesion, and its phase-separation behavior are mechanistically integrated remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model linking wall stabilization, rootletin regulation, and condensate formation","No high-resolution structure of CEP44 bound to microtubules or POC1B","Role of CEP44 LLPS in vivo at the centrosome undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,1]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0,1,2]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0]}],"complexes":[],"partners":["POC1B","CEP295","ROOTLETIN","OGT"],"other_free_text":[]}},"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":43,"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":14,"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":12,"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":5407,"output_tokens":1242,"usd":0.017426,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7837,"output_tokens":1901,"usd":0.043355,"stage2_stop_reason":"end_turn"},"total_usd":0.060781,"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\": 2020,\n      \"finding\": \"CEP44 localizes to the centriole lumen where it binds to A-microtubules and interacts with POC1B, affecting centriole wall structure; depletion of CEP44 impairs 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, Co-immunoprecipitation, fluorescence microscopy, electron microscopy\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (depletion, Co-IP, EM structural analysis, epistasis) in a single rigorous study establishing pathway position and molecular interaction\",\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 and is required for centrosome cohesion; it associates with rootletin and regulates rootletin's stability and localization to the centrosome, independently of C-Nap1, LRRC45, and Cep215.\",\n      \"method\": \"siRNA ablation, immunofluorescence, co-immunoprecipitation, centrosome cohesion assays\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal interaction data and loss-of-function phenotype with defined molecular partner (rootletin), single lab\",\n      \"pmids\": [\"31974111\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"CEP44 localizes in ninefold symmetry at the centrosome, as determined by nanoscale-resolution imaging, consistent with its association with the centriole microtubule wall.\",\n      \"method\": \"Expansion microscopy / super-resolution nanoscale imaging\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct high-resolution localization experiment with functional context, single lab\",\n      \"pmids\": [\"37707473\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"AlphaFold2 structural predictions for CEP44 were experimentally validated, revealing modular organization and structural features relevant to its function in centriole biogenesis.\",\n      \"method\": \"AlphaFold2 computational prediction with experimental validation (structural biology approaches)\",\n      \"journal\": \"Communications biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — primarily computational with partial experimental validation; abstract does not detail the experimental validation method for CEP44 specifically\",\n      \"pmids\": [\"35383272\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CEP44 contains intrinsically disordered regions (IDRs) that enable liquid-liquid phase separation (LLPS), forming liquid droplets both in vivo and in vitro; CEP44 is O-GlcNAcylated by O-GlcNAc transferase (OGT), and O-GlcNAcylation promotes CEP44 droplet fusion and influences its subcellular localization.\",\n      \"method\": \"Droplet formation assays (in vivo and in vitro), immunoblotting for O-GlcNAcylation, immunostaining, post-translational modification prediction\",\n      \"journal\": \"Cytoskeleton (Hoboken, N.J.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — multiple methods (LLPS assay, immunoblot, immunostaining) in a single study; interaction with OGT and functional consequence on droplet fusion demonstrated\",\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 and interacts with POC1B to maintain centriole wall integrity, is required for centriole-to-centrosome conversion downstream of CEP295, stabilizes rootletin to maintain centrosome cohesion, undergoes O-GlcNAcylation by OGT which promotes its liquid-liquid phase separation and droplet fusion, and collectively these activities place CEP44 as a structural scaffold coordinating centriole biogenesis, centrosome cohesion, and centrosomal condensate organization.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CEP44 is a luminal centriole protein that functions as a structural scaffold coordinating centriole biogenesis and centrosome integrity [#0, #1]. It localizes to the proximal end of both mother and daughter centrioles in ninefold symmetry, binding A-microtubules of the centriole wall and interacting with POC1B to maintain wall structure [#0, #2]. CEP44 acts downstream of CEP295 in a centriole-to-centrosome conversion pathway (CEP295→CEP44→POC1B→TUBE1/TUBD1) that is required for pericentriolar material recruitment; its depletion blocks conversion even when CEP295 still binds centrioles [#0]. Independently of C-Nap1, LRRC45, and Cep215, CEP44 associates with rootletin and regulates its stability and localization to maintain centrosome cohesion [#1]. CEP44 also contains intrinsically disordered regions that drive liquid-liquid phase separation into droplets in vitro and in vivo, and it is O-GlcNAcylated by OGT, a modification that promotes droplet fusion and influences its subcellular localization [#4].\",\n  \"teleology\": [\n    {\n      \"year\": 2020,\n      \"claim\": \"Established CEP44's molecular role in centriole architecture by placing it within an ordered biogenesis pathway and identifying its physical and structural partners.\",\n      \"evidence\": \"siRNA depletion, Co-IP, and electron microscopy defining the CEP295→CEP44→POC1B→TUBE1/TUBD1 axis in human cells\",\n      \"pmids\": [\"32060285\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"How CEP44 binding to A-microtubules mechanically stabilizes the wall is not resolved at atomic detail\",\n        \"The direct biochemical link between CEP44 and TUBE1/TUBD1 is not demonstrated\",\n        \"Whether CEP44 recruits POC1B directly or via intermediates is unclear\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Extended CEP44's function beyond biogenesis to centrosome cohesion by linking it to rootletin stability, defining a pathway distinct from canonical cohesion factors.\",\n      \"evidence\": \"siRNA ablation, Co-IP, and centrosome cohesion assays showing CEP44 regulates rootletin independently of C-Nap1, LRRC45, and Cep215\",\n      \"pmids\": [\"31974111\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism by which CEP44 stabilizes rootletin is unknown\",\n        \"Single-lab finding without reciprocal structural validation\",\n        \"Relationship between cohesion role and centriole-wall role not integrated\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Resolved CEP44's precise spatial organization, confirming a ninefold-symmetric arrangement consistent with direct association with the centriole microtubule wall.\",\n      \"evidence\": \"Expansion/super-resolution nanoscale imaging of the centrosome\",\n      \"pmids\": [\"37707473\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Does not establish stoichiometry of CEP44 per centriole\",\n        \"Single-lab localization without functional perturbation\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Revealed a biophysical and regulatory dimension to CEP44 function, showing it phase-separates and that O-GlcNAcylation by OGT modulates its condensate behavior and localization.\",\n      \"evidence\": \"In vitro/in vivo droplet assays, immunoblotting for O-GlcNAcylation, and immunostaining\",\n      \"pmids\": [\"40906019\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Functional consequence of CEP44 LLPS for centriole biogenesis or cohesion is not established\",\n        \"O-GlcNAcylation sites are not mapped\",\n        \"Whether phase separation occurs at the centriole in cells is not shown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CEP44's structural scaffolding at the centriole wall, its regulation of centrosome cohesion, and its phase-separation behavior are mechanistically integrated remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No unified model linking wall stabilization, rootletin regulation, and condensate formation\",\n        \"No high-resolution structure of CEP44 bound to microtubules or POC1B\",\n        \"Role of CEP44 LLPS in vivo at the centrosome undefined\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"POC1B\", \"CEP295\", \"rootletin\", \"OGT\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":5,"faith_total":5,"faith_pct":100.0}}