CEP290 is a large coiled-coil protein at the ciliary transition zone, centriolar satellites and photoreceptor connecting cilium. Its microtubule-binding and membrane-binding domains support ciliary organization and compartmentalization. CEP290 associates with PCM1, CEP131 and CCDC66 at centriolar satellites and helps recruit proteins needed for primary-cilium formation. Its interaction with CP110 contributes to the restraint of ciliogenesis. Conserved transition-zone assembly involves a hierarchy in which the Caenorhabditis elegans RPGRIP1L/RPGRIP1 ortholog MKS-5 recruits CEP-290, which organizes MKS-module proteins. CEP290 also modulates ATF4-dependent transcription in human cells. Biallelic pathogenic variants cause a spectrum including Joubert, Meckel, Senior-Loken and Bardet-Biedl syndromes and Leber congenital amaurosis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001822 kidney development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Conserved contribution to kidney development. Reason: Retain the PAINT inference at PTN002706047. Zebrafish morpholino experiments in PMID:16682973 produce pronephric cysts; this supports a developmental contribution compatible with the conserved ciliary role, without making CEP290 a kidney-specific developmental regulator. The historical node reconstruction was not independently recovered; the extant evidence count is not a reason to reject the phylogenetic judgment. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16682973 The centrosomal protein nephrocystin-6 is mutated in Joubert... | KEEP AS NON CORE | Summary: ATF4 association Reason: PMID:16682973 reports CEP290/ATF4 yeast two-hybrid interaction with human library constructs, reciprocal bait/prey testing and co-immunoprecipitation from bovine retina. These are positive association data with mixed assay species; the human transcriptional reporter is separate evidence, not a purified binary-binding measurement. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18694559 CP110 suppresses primary cilia formation through its interac... | KEEP AS NON CORE | Summary: CP110 association Reason: PMID:18694559 reports endogenous CP110βCEP290 co-immunoprecipitation, shared biochemical fractions and tagged construct mapping in human cells. Retain this physical association without treating CEP290 as the enzyme or the CP110-dependent suppressor in every cell state. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. Supporting Evidence: PMID:18694559 physical association of CEP290 with CP110 |
| GO:0005515 protein binding | IPI PMID:18723859 Genetic and physical interaction between the NPHP5 and NPHP6... | KEEP AS NON CORE | Summary: NPHP5/IQCB1 association Reason: PMID:18723859 tests human CEP290 fragments with human NPHP5 in HEK293T co-immunoprecipitation and lysate-based GST pull-downs. Full-length CEP290 expression was limiting. Retain the measured fragment association without claiming a purified full-length binary interface. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21565611 Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy... | KEEP AS NON CORE | Summary: NPHP5/IQCB1 association Reason: The exact human RPE-cell anti-tag co-immunoprecipitation record matches this pair and PMID:21565611. The paper additionally maps association using translated proteins. Retain the physical association; disease-network membership alone is not the evidence. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. |
| GO:0005515 protein binding | IPI PMID:21620453 Centriolar kinesin Kif24 interacts with CP110 to remodel mic... | KEEP AS NON CORE | Summary: CP110 association Reason: The exact PMID:21620453 anti-bait co-immunoprecipitation record identifies the human CEP290βCP110 pair in HEK293 cells. The abstract foregrounds KIF24, but the curated target record is positive; no KIF24 motor activity is transferred to CEP290. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. |
| GO:0005515 protein binding | IPI PMID:22441691 Neurl4, a novel daughter centriole protein, prevents formati... | KEEP AS NON CORE | Summary: CP110 association Reason: The recovered full PMID:22441691 Figure 1C legend specifies endogenous proteins immunoprecipitated from 293T extracts. Visual inspection of the bottom CEP290 blot shows signal in the CP110 IP lane; the Neurl4 IP comparison is negative and is not the pair asserted here. This supports CP110 co-complex recovery, not a purified binary interface. Retain the supported generic assertion as non-core under the ClinGen project instruction. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22446187 Combining Cep290 and Mkks ciliopathy alleles in mice rescues... | KEEP AS NON CORE | Summary: MKKS association Reason: PMID:22446187 Figure 1 reports a CEP290-domain/MKKS yeast two-hybrid interaction, tagged full-length association in HEK293 cells and retinal co-immunoprecipitation. The study combines human-cell assays with mouse constructs/genetics and bovine retina. Retain the reported association without assigning every construct or mutant phenotype to human CEP290. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22797915 The centriolar satellite protein Cep131 is important for gen... | KEEP AS NON CORE | Summary: Pericentrin association Reason: The full Results and Figure 3E of PMID:22797915 report CEP290βpericentrin co-purification from human HEK293 lysates. This supports a physical complex association; it does not isolate a binary interface. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22797915 The centriolar satellite protein Cep131 is important for gen... | KEEP AS NON CORE | Summary: CEP131 association Reason: PMID:22797915 Figure 3C reports endogenous CEP131βCEP290 co-immunoprecipitation in human HEK293 cells. Retain the association separately from the paperβs CEP131 genome-stability phenotypes. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22863007 Exome capture reveals ZNF423 and CEP164 mutations, linking r... | KEEP AS NON CORE | Summary: ZNF423 association Reason: The exact records and PMID:22863007 Figure 2FβG test CEP290 residues 1917β2479 against ZNF423 residues 178β406 by two-hybrid and tagged co-immunoprecipitation. Retain fragment-supported binding without transferring CEP164/ZNF423 DNA-damage functions to CEP290. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. Supporting Evidence: PMID:22863007 we identified ZNF423 as a direct interaction partner of CEP290/NPHP6 file:human/CEP290/CEP290-source-evidence.json intact:EBI-6267390 |
| GO:0005515 protein binding | IPI PMID:23446637 Pathogenic NPHP5 mutations impair protein interaction with C... | KEEP AS NON CORE | Summary: NPHP5/IQCB1 association Reason: PMID:23446637 reports reciprocal endogenous NPHP5βCEP290 co-immunoprecipitation in human HEK293 cells and maps interaction-sensitive regions. This is positive target-specific evidence; a broad binding term remains appropriate without inventing an adaptor activity. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23644468 CEP162 is an axoneme-recognition protein promoting ciliary t... | KEEP AS NON CORE | Summary: CEP162 association Reason: PMID:23644468 Figure 5A reports reciprocal endogenous CEP162βCEP290 co-immunoprecipitation. The cellular dependence of CEP290 microtubule association on CEP162 does not make this a purified binary assay or negate the later direct CEP290-fragment microtubule result. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23943788 BBS mutations modify phenotypic expression of CEP290-related... | KEEP AS NON CORE | Summary: BBS4 association Reason: The recovered indexed full Results of PMID:23943788 report FLAG-BBS4 co-immunoprecipitation of endogenous CEP290 and endogenous CEP290 immunoprecipitation from human HEK293T lysates. Retain BBSome-associated binding without treating CEP290 as an obligate BBSome subunit or asserting purified binary contact. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24421332 The CP110-interacting proteins Talpid3 and Cep290 play overl... | KEEP AS NON CORE | Summary: CP110 association Reason: PMID:24421332 tests human-cell endogenous and tagged CP110-associated complexes containing CEP290. This supports the CP110 interaction while leaving the complexβs direct contacts and stoichiometry unresolved. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24550735 The centriolar satellite protein AZI1 interacts with BBS4 an... | KEEP AS NON CORE | Summary: CEP131/AZI1 association Reason: The recovered full PMID:24550735 Figure S2A legend and Results describe CEP290 in FLAG/S-AZI1 precipitates from stable human 293T cells. Retain that tagged-complex association; proximity or colocalization alone is not being substituted for the biochemical assay. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24816561 Ccdc13 is a novel human centriolar satellite protein require... | KEEP AS NON CORE | Summary: CCDC13 association Reason: Exact positive records for PMID:24816561 show CEP290 associated with tagged CCDC13 in human HEK293/HeLa co-immunoprecipitation assays. These establish complex association, not a purified binary interface or CEP290 genome-stability activity. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. Supporting Evidence: file:human/CEP290/CEP290-source-evidence.json intact:EBI-10961247 |
| GO:0005515 protein binding | IPI PMID:24816561 Ccdc13 is a novel human centriolar satellite protein require... | KEEP AS NON CORE | Summary: CEP131 association Reason: Exact positive PMID:24816561 records recover the human CEP290βCEP131 pair in co-immunoprecipitation experiments, including complex-expanded records. Retain the association with the actual assay scope; do not infer direct contact from a spoke-expanded complex. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. Supporting Evidence: file:human/CEP290/CEP290-source-evidence.json intact:EBI-11170590 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Screened Q9BUW7 interaction Reason: The exact positive PMID:25416956 records use a CEP290 fragment spanning residues 941β1104 in human-protein yeast two-hybrid screening and validation. Retain the tested fragment interaction without claiming endogenous or full-length confirmation. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. Supporting Evidence: file:human/CEP290/CEP290-source-evidence.json intact:EBI-10182070 |
| GO:0005515 protein binding | IPI PMID:25552655 Nephrocystin proteins NPHP5 and Cep290 regulate BBSome integ... | KEEP AS NON CORE | Summary: NPHP5/IQCB1 association Reason: PMID:25552655 reports tagged NPHP5 C-terminal constructs co-precipitating endogenous CEP290 in HEK293 cells, with binding-defective controls. Proximity ligation is corroborative and is not treated as a purified binary assay. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26638075 A Dynamic Protein Interaction Landscape of the Human Centros... | KEEP AS NON CORE | Summary: CP110 centrosomal-network association Reason: The exact PMID:26638075 pair is present in positive anti-tag affinity-purification records from human HEK293 cells. BioID records also exist but are not used alone to infer binding; retain the co-complex association with tagging and expansion limits. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. The cited shared IntAct complex is expanded into this specific participant pair; the pair-specific source-line anchor identifies the record without implying a separate binary-interface experiment. Supporting Evidence: file:human/CEP290/CEP290-source-evidence.json uniprotkb:O15078 / uniprotkb:O43303; pubmed:26638075; intact:EBI-11362224; spoke expansion; source line 62 |
| GO:0005515 protein binding | IPI PMID:26638075 A Dynamic Protein Interaction Landscape of the Human Centros... | KEEP AS NON CORE | Summary: NPHP5 centrosomal-network association Reason: The exact PMID:26638075 pair is supported by positive anti-tag affinity-purification records from human HEK293 cells, separately from the studyβs BioID proximity layer. This supports association, not an isolated binary interface. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. The cited shared IntAct complex is expanded into this specific participant pair; the pair-specific source-line anchor identifies the record without implying a separate binary-interface experiment. Supporting Evidence: file:human/CEP290/CEP290-source-evidence.json uniprotkb:O15078 / uniprotkb:Q15051; pubmed:26638075; intact:EBI-11362224; spoke expansion; source line 68 |
| GO:0005515 protein binding | IPI PMID:26638075 A Dynamic Protein Interaction Landscape of the Human Centros... | KEEP AS NON CORE | Summary: CEP162 centrosomal-network association Reason: The exact PMID:26638075 pair has positive anti-tag co-immunoprecipitation records in human HEK293 cells. Retain that tagged-complex evidence, distinguishing it from BioID proximity records and from a direct purified interaction. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. The cited shared IntAct complex is expanded into this specific participant pair; the pair-specific source-line anchor identifies the record without implying a separate binary-interface experiment. Supporting Evidence: file:human/CEP290/CEP290-source-evidence.json uniprotkb:O15078 / uniprotkb:Q5TB80; pubmed:26638075; intact:EBI-11362224; spoke expansion; source line 56 |
| GO:0005515 protein binding | IPI PMID:26638075 A Dynamic Protein Interaction Landscape of the Human Centros... | KEEP AS NON CORE | Summary: CEP131 centrosomal-network association Reason: The exact PMID:26638075 pair has positive affinity-purification records in human HEK293 cells. The network includes both biochemical association and proximity measurements; the former supports this binding decision. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. The cited shared IntAct complex is expanded into this specific participant pair; the pair-specific source-line anchor identifies the record without implying a separate binary-interface experiment. Supporting Evidence: file:human/CEP290/CEP290-source-evidence.json uniprotkb:O15078 / uniprotkb:Q9UPN4; pubmed:26638075; intact:EBI-11362224; spoke expansion; source line 73 |
| GO:0005515 protein binding | IPI PMID:28235840 The centriolar satellite protein CCDC66 interacts with CEP29... | KEEP AS NON CORE | Summary: CCDC66 association Reason: PMID:28235840 Figure 5D and its Methods report anti-GFP co-immunoprecipitation of tagged CCDC66/CEP290 constructs in HEK293T cells. Retain the biochemical association rather than relying only on the paperβs BioID layer. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. Supporting Evidence: PMID:28235840 CCDC66 interacted with both CEP290 and PCM1 |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: BioPlex NPHP5 association Reason: The exact PMID:28514442 BioPlex record is a positive human HEK293T affinity-purification pair with a C-terminally tagged bait and spoke-expanded complex representation. Retain complex association without claiming purified binary or physiological contact in every tissue. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. Supporting Evidence: file:human/CEP290/CEP290-source-evidence.json intact:EBI-21720472 |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Screened Q86T90 interaction Reason: Exact positive PMID:32296183 records test human participants in a yeast host using CEP290 residues 941β1104 and fusion tags. Retain the validated fragment interaction; pooled and array records are not independent endogenous confirmation. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. Supporting Evidence: file:human/CEP290/CEP290-source-evidence.json intact:EBI-22817394 |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Screened Q9BUW7 interaction Reason: Exact positive PMID:32296183 records match the human Q9BUW7 pair and the CEP290 941β1104 fragment in yeast two-hybrid assays. Retain the actual construct-supported interaction without a whole-protein or native-cell inference. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. Supporting Evidence: file:human/CEP290/CEP290-source-evidence.json intact:EBI-22871453 |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Screened Q9NRD5 interaction Reason: Exact positive PMID:32296183 records identify the human Q9NRD5 pair tested against CEP290 residues 941β1104 in yeast two-hybrid assays. This supports the screened interaction with construct and host limits. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. Supporting Evidence: file:human/CEP290/CEP290-source-evidence.json intact:EBI-24396419 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BioPlex NPHP5 association Reason: The exact PMID:33961781 record is a positive affinity-purification pair in human HEK293T cells with a C-terminally tagged bait and spoke-expanded complex representation. Retain this association without treating it as a purified direct interface. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. Supporting Evidence: file:human/CEP290/CEP290-source-evidence.json intact:EBI-54651309 |
| GO:0005515 protein binding | IPI PMID:36606424 CCDC66 regulates primary cilium length and signaling via int... | KEEP AS NON CORE | Summary: CCDC66 association Reason: The full publisher Results and Figure 5A of PMID:36606424 show endogenous CEP290 co-pelleting with GFPβCCDC66 from human HEK293T cells, with GFP-only and truncation controls. This supports physical association, independently of the mouse-cell miniTurbo screen in the same paper. The supported generic binding assertion is retained as non-core under the ClinGen project instruction; no better molecular activity is established by this partner assay. Supporting Evidence: |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6798749 | UNDECIDED | Summary: Reactome extracellular CEP290 location remains unresolved. Reason: Reactome directly includes human O15078 chain 1β2479 as R-HSA-6806291 in the extracellular output set of R-HSA-6798749. The source is neutrophil fraction proteomics (PMID:23650620); the exact target peptide/fraction evidence and secretion of CEP290 were not independently established. Absence of a signal peptide or a ciliary role does not refute the curated location. Retain uncertainty rather than the previous biological-impossibility removal. Supporting Evidence: Reactome:R-HSA-6798749 file:human/CEP290/CEP290-source-evidence.json |
| GO:0005634 nucleus | IDA PMID:16682973 The centrosomal protein nephrocystin-6 is mutated in Joubert... | KEEP AS NON CORE | Summary: Contextual nuclear localization. Reason: PMID:16682973 Figure 5g detects CEP290 in human HEK293T nuclear and cytoplasmic fractions; its cell-cycle-dependent imaging also uses renal epithelial models. This is a supported location, but the ATF4-related nuclear context is distinct from the dominant ciliary structural role. Supporting Evidence: |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Broad nuclear localization mapping. Reason: The UniProt subcellular-location mapping is compatible with the directly observed human nuclear fraction in PMID:16682973. Retain this contextual location without making the nucleus the principal ciliary site. Supporting Evidence: |
| GO:0005634 nucleus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog-supported nuclear localization. Reason: Preserve the mouse Q6A078 transfer. Independently, human HEK293T fractionation in PMID:16682973 supports nuclear presence. This is contextual localization rather than a claim that every CEP290 function acts in the nucleus. Supporting Evidence: |
| GO:0005737 cytoplasm | IDA PMID:14654843 Proteomic characterization of the human centrosome by protei... | KEEP AS NON CORE | Summary: Broad cytoplasmic localization. Reason: The original human centrosome-proteomics assignment is consistent with independent human fractionation and cytoplasmic satellite imaging. Retain the broad cytoplasmic compartment as non-core; the specific functional sites are centrosomes, satellites and the ciliary transition zone. |
| GO:0005813 centrosome | IDA PMID:14654843 Proteomic characterization of the human centrosome by protei... | ACCEPT | Summary: Centrosomal CEP290. Reason: Preserve the human centrosome-proteomics IDA. Independent target immunofluorescence in human RPE cells places CEP290 at the pericentrin-marked centrosome and surrounding satellites, supporting this core location. |
| GO:0005813 centrosome | IDA PMID:16682973 The centrosomal protein nephrocystin-6 is mutated in Joubert... | ACCEPT | Summary: Centrosomal localization. Reason: The original paper images endogenous CEP290 at centrosomes in IMCD3/COS7 models; independent human-cell work confirms the same location. Preserve the human GOA assertion while keeping the original assay-species scope explicit. |
| GO:0005813 centrosome | IDA PMID:21399614 Novel asymmetrically localizing components of human centroso... | ACCEPT | Summary: Centrosomal proteomics/localization assignment. Reason: PMID:21399614 describes human centrosome proteomics and imaging; its exact CEP290 target table was not reconstructed here. The location is independently verified in human cells by PMID:24648492, so retain the correct core assignment without claiming to have inspected the original target panel. |
| GO:0005813 centrosome | IDA PMID:24550735 The centriolar satellite protein AZI1 interacts with BBS4 an... | ACCEPT | Summary: Centrosomal CEP290 in the AZI1 study. Reason: The recovered full PMID:24550735 and Figure S2C describe centrosomal CEP290 in human RPE1 cells. Retain the core location; the AZI1 trafficking mechanism is not transferred wholesale to CEP290. Supporting Evidence: |
| GO:0005813 centrosome | IDA PMID:24648492 Casein kinase 1Ξ΄ functions at the centrosome and Golgi to pr... | ACCEPT | Summary: Centrosomal CEP290 in human RPE cells. Reason: PMID:24648492 Figure 4AβE directly detects CEP290 at the pericentrin-marked centrosome and satellites in hTERT-RPE cells. CK1Ξ΄ perturbation redistributes these pools, but the control localization itself supports this annotation. Supporting Evidence: PMID:24648492 CEP290 punctae coincided with the centrosomal marker pericentrin |
| GO:0005813 centrosome | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt centrosome location. Reason: The conservative subcellular-location mapping agrees with direct human CEP290 centrosomal imaging and its cilium-assembly role. |
| GO:0005814 centriole | IDA PMID:27623382 A Conserved Role for Girdin in Basal Body Positioning and Ci... | ACCEPT | Summary: Centriole-associated CEP290. Reason: The recovered full PMID:27623382 Figure 6C examines endogenous CEP290 at the basal-body/transition-zone region in human RPE1 cells. This supports centriole association; Girdin-specific positioning functions are not assigned to CEP290. Supporting Evidence: |
| GO:0005814 centriole | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt centriole location. Reason: Retain the mapped centriole-associated location, consistent with human basal-body imaging. It does not imply that CEP290 is confined to the centriole barrel. Supporting Evidence: |
| GO:0005829 cytosol | IDA PMID:16682973 The centrosomal protein nephrocystin-6 is mutated in Joubert... | KEEP AS NON CORE | Summary: Human cytosolic CEP290 fraction. Reason: PMID:16682973 Figure 5g detects CEP290 in the human HEK293T cytoplasmic fraction as well as the nuclear fraction. Retain the broad cytosolic location without using it as a separate core activity. Supporting Evidence: |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2574840 | KEEP AS NON CORE | Summary: CEP290 location in the cytosolic centrosome entity used by this Reactome event. Reason: This location is inherited from the CEP290-containing centrosome entity used in the Reactome event. The repeated event annotations share entity provenance and are not independent localization experiments. Retain the broad compartment without assigning the eventβs kinase, exchange-factor or transport activity to CEP290. The separate PMID:16682973 cytosol annotation records the independent human fractionation evidence. Supporting Evidence: Reactome:R-HSA-2574840 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2574845 | KEEP AS NON CORE | Summary: CEP290 location in the cytosolic centrosome entity used by this Reactome event. Reason: This location is inherited from the CEP290-containing centrosome entity used in the Reactome event. The repeated event annotations share entity provenance and are not independent localization experiments. Retain the broad compartment without assigning the eventβs kinase, exchange-factor or transport activity to CEP290. The separate PMID:16682973 cytosol annotation records the independent human fractionation evidence. Supporting Evidence: Reactome:R-HSA-2574845 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3000310 | KEEP AS NON CORE | Summary: CEP290 location in the cytosolic centrosome entity used by this Reactome event. Reason: This location is inherited from the CEP290-containing centrosome entity used in the Reactome event. The repeated event annotations share entity provenance and are not independent localization experiments. Retain the broad compartment without assigning the eventβs kinase, exchange-factor or transport activity to CEP290. The separate PMID:16682973 cytosol annotation records the independent human fractionation evidence. Supporting Evidence: Reactome:R-HSA-3000310 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3000319 | KEEP AS NON CORE | Summary: CEP290 location in the cytosolic centrosome entity used by this Reactome event. Reason: This location is inherited from the CEP290-containing centrosome entity used in the Reactome event. The repeated event annotations share entity provenance and are not independent localization experiments. Retain the broad compartment without assigning the eventβs kinase, exchange-factor or transport activity to CEP290. The separate PMID:16682973 cytosol annotation records the independent human fractionation evidence. Supporting Evidence: Reactome:R-HSA-3000319 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380272 | KEEP AS NON CORE | Summary: CEP290 location in the cytosolic centrosome entity used by this Reactome event. Reason: This location is inherited from the CEP290-containing centrosome entity used in the Reactome event. The repeated event annotations share entity provenance and are not independent localization experiments. Retain the broad compartment without assigning the eventβs kinase, exchange-factor or transport activity to CEP290. The separate PMID:16682973 cytosol annotation records the independent human fractionation evidence. Supporting Evidence: Reactome:R-HSA-380272 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380283 | KEEP AS NON CORE | Summary: CEP290 location in the cytosolic centrosome entity used by this Reactome event. Reason: This location is inherited from the CEP290-containing centrosome entity used in the Reactome event. The repeated event annotations share entity provenance and are not independent localization experiments. Retain the broad compartment without assigning the eventβs kinase, exchange-factor or transport activity to CEP290. The separate PMID:16682973 cytosol annotation records the independent human fractionation evidence. Supporting Evidence: Reactome:R-HSA-380283 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380294 | KEEP AS NON CORE | Summary: CEP290 location in the cytosolic centrosome entity used by this Reactome event. Reason: This location is inherited from the CEP290-containing centrosome entity used in the Reactome event. The repeated event annotations share entity provenance and are not independent localization experiments. Retain the broad compartment without assigning the eventβs kinase, exchange-factor or transport activity to CEP290. The separate PMID:16682973 cytosol annotation records the independent human fractionation evidence. Supporting Evidence: Reactome:R-HSA-380294 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380303 | KEEP AS NON CORE | Summary: CEP290 location in the cytosolic centrosome entity used by this Reactome event. Reason: This location is inherited from the CEP290-containing centrosome entity used in the Reactome event. The repeated event annotations share entity provenance and are not independent localization experiments. Retain the broad compartment without assigning the eventβs kinase, exchange-factor or transport activity to CEP290. The separate PMID:16682973 cytosol annotation records the independent human fractionation evidence. Supporting Evidence: Reactome:R-HSA-380303 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380311 | KEEP AS NON CORE | Summary: CEP290 location in the cytosolic centrosome entity used by this Reactome event. Reason: This location is inherited from the CEP290-containing centrosome entity used in the Reactome event. The repeated event annotations share entity provenance and are not independent localization experiments. Retain the broad compartment without assigning the eventβs kinase, exchange-factor or transport activity to CEP290. The separate PMID:16682973 cytosol annotation records the independent human fractionation evidence. Supporting Evidence: Reactome:R-HSA-380311 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380316 | KEEP AS NON CORE | Summary: CEP290 location in the cytosolic centrosome entity used by this Reactome event. Reason: This location is inherited from the CEP290-containing centrosome entity used in the Reactome event. The repeated event annotations share entity provenance and are not independent localization experiments. Retain the broad compartment without assigning the eventβs kinase, exchange-factor or transport activity to CEP290. The separate PMID:16682973 cytosol annotation records the independent human fractionation evidence. Supporting Evidence: Reactome:R-HSA-380316 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380455 | KEEP AS NON CORE | Summary: CEP290 location in the cytosolic centrosome entity used by this Reactome event. Reason: This location is inherited from the CEP290-containing centrosome entity used in the Reactome event. The repeated event annotations share entity provenance and are not independent localization experiments. Retain the broad compartment without assigning the eventβs kinase, exchange-factor or transport activity to CEP290. The separate PMID:16682973 cytosol annotation records the independent human fractionation evidence. Supporting Evidence: Reactome:R-HSA-380455 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380508 | KEEP AS NON CORE | Summary: CEP290 location in the cytosolic centrosome entity used by this Reactome event. Reason: This location is inherited from the CEP290-containing centrosome entity used in the Reactome event. The repeated event annotations share entity provenance and are not independent localization experiments. Retain the broad compartment without assigning the eventβs kinase, exchange-factor or transport activity to CEP290. The separate PMID:16682973 cytosol annotation records the independent human fractionation evidence. Supporting Evidence: Reactome:R-HSA-380508 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5617816 | KEEP AS NON CORE | Summary: CEP290 location in the cytosolic centrosome entity used by this Reactome event. Reason: This location is inherited from the CEP290-containing centrosome entity used in the Reactome event. The repeated event annotations share entity provenance and are not independent localization experiments. Retain the broad compartment without assigning the eventβs kinase, exchange-factor or transport activity to CEP290. The separate PMID:16682973 cytosol annotation records the independent human fractionation evidence. Supporting Evidence: Reactome:R-HSA-5617816 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626220 | KEEP AS NON CORE | Summary: CEP290 location in the cytosolic centrosome entity used by this Reactome event. Reason: This location is inherited from the CEP290-containing centrosome entity used in the Reactome event. The repeated event annotations share entity provenance and are not independent localization experiments. Retain the broad compartment without assigning the eventβs kinase, exchange-factor or transport activity to CEP290. The separate PMID:16682973 cytosol annotation records the independent human fractionation evidence. Supporting Evidence: Reactome:R-HSA-5626220 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626223 | KEEP AS NON CORE | Summary: CEP290 location in the cytosolic centrosome entity used by this Reactome event. Reason: This location is inherited from the CEP290-containing centrosome entity used in the Reactome event. The repeated event annotations share entity provenance and are not independent localization experiments. Retain the broad compartment without assigning the eventβs kinase, exchange-factor or transport activity to CEP290. The separate PMID:16682973 cytosol annotation records the independent human fractionation evidence. Supporting Evidence: Reactome:R-HSA-5626223 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626227 | KEEP AS NON CORE | Summary: CEP290 location in the cytosolic centrosome entity used by this Reactome event. Reason: This location is inherited from the CEP290-containing centrosome entity used in the Reactome event. The repeated event annotations share entity provenance and are not independent localization experiments. Retain the broad compartment without assigning the eventβs kinase, exchange-factor or transport activity to CEP290. The separate PMID:16682973 cytosol annotation records the independent human fractionation evidence. Supporting Evidence: Reactome:R-HSA-5626227 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626228 | KEEP AS NON CORE | Summary: CEP290 location in the cytosolic centrosome entity used by this Reactome event. Reason: This location is inherited from the CEP290-containing centrosome entity used in the Reactome event. The repeated event annotations share entity provenance and are not independent localization experiments. Retain the broad compartment without assigning the eventβs kinase, exchange-factor or transport activity to CEP290. The separate PMID:16682973 cytosol annotation records the independent human fractionation evidence. Supporting Evidence: Reactome:R-HSA-5626228 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626681 | KEEP AS NON CORE | Summary: CEP290 location in the cytosolic centrosome entity used by this Reactome event. Reason: This location is inherited from the CEP290-containing centrosome entity used in the Reactome event. The repeated event annotations share entity provenance and are not independent localization experiments. Retain the broad compartment without assigning the eventβs kinase, exchange-factor or transport activity to CEP290. The separate PMID:16682973 cytosol annotation records the independent human fractionation evidence. Supporting Evidence: Reactome:R-HSA-5626681 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626699 | KEEP AS NON CORE | Summary: CEP290 location in the cytosolic centrosome entity used by this Reactome event. Reason: This location is inherited from the CEP290-containing centrosome entity used in the Reactome event. The repeated event annotations share entity provenance and are not independent localization experiments. Retain the broad compartment without assigning the eventβs kinase, exchange-factor or transport activity to CEP290. The separate PMID:16682973 cytosol annotation records the independent human fractionation evidence. Supporting Evidence: Reactome:R-HSA-5626699 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5638009 | KEEP AS NON CORE | Summary: CEP290 location in the cytosolic centrosome entity used by this Reactome event. Reason: This location is inherited from the CEP290-containing centrosome entity used in the Reactome event. The repeated event annotations share entity provenance and are not independent localization experiments. Retain the broad compartment without assigning the eventβs kinase, exchange-factor or transport activity to CEP290. The separate PMID:16682973 cytosol annotation records the independent human fractionation evidence. Supporting Evidence: Reactome:R-HSA-5638009 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8853405 | KEEP AS NON CORE | Summary: CEP290 location in the cytosolic centrosome entity used by this Reactome event. Reason: This location is inherited from the CEP290-containing centrosome entity used in the Reactome event. The repeated event annotations share entity provenance and are not independent localization experiments. Retain the broad compartment without assigning the eventβs kinase, exchange-factor or transport activity to CEP290. The separate PMID:16682973 cytosol annotation records the independent human fractionation evidence. Supporting Evidence: Reactome:R-HSA-8853405 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8853419 | KEEP AS NON CORE | Summary: CEP290 location in the cytosolic centrosome entity used by this Reactome event. Reason: This location is inherited from the CEP290-containing centrosome entity used in the Reactome event. The repeated event annotations share entity provenance and are not independent localization experiments. Retain the broad compartment without assigning the eventβs kinase, exchange-factor or transport activity to CEP290. The separate PMID:16682973 cytosol annotation records the independent human fractionation evidence. Supporting Evidence: Reactome:R-HSA-8853419 |
| GO:0005929 cilium | IEA GO_REF:0000044 | ACCEPT | Summary: Ciliary location. Reason: The UniProt cilium mapping is supported by CEP290 localization at the transition zone and photoreceptor connecting cilium. This broader anatomical compartment remains correct even though CEP290 is not distributed uniformly along the axoneme. |
| GO:0015031 protein transport | ISS GO_REF:0000024 | MODIFY | Summary: Ciliary protein localization is the specific conserved role. Reason: The mouse Q6A078 donor includes PMID:16632484, which shows altered photoreceptor protein localization in rd16 mice. Human CEP290 depletion affects Rab8a targeting and BBSome integrity/ciliary entry (PMIDs:18694559,25552655). Protein localization to cilium captures this performed structural/organizational contribution more precisely than unrestricted protein transport; it does not assert motor activity or that structural participants cannot contribute to transport. Proposed replacements: protein localization to cilium |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | KEEP AS NON CORE | Summary: Membrane-associated CEP290. Reason: The original NK-cell membrane-proteomics target measurement was not independently recovered. Separate human CEP290 fractionation and purified N-terminal liposome binding in PMID:24051377 support membrane association broadly. Retain the broad location without asserting an integral membrane topology, plasma-membrane specificity or a demonstrated essential amphipathic helix. |
| GO:0030902 hindbrain development | ISS PMID:16682973 The centrosomal protein nephrocystin-6 is mutated in Joubert... | KEEP AS NON CORE | Summary: Ortholog-supported hindbrain development. Reason: PMID:16682973 reports cerebellar developmental abnormalities after zebrafish cep290 morpholino perturbation. Preserve that ortholog-supported developmental role, distinct from a human hindbrain assay or a tissue-specific regulatory molecular activity. Supporting Evidence: |
| GO:0030916 otic vesicle formation | ISS PMID:16682973 The centrosomal protein nephrocystin-6 is mutated in Joubert... | KEEP AS NON CORE | Summary: Ortholog-supported otic vesicle formation. Reason: The zebrafish morpholino study in PMID:16682973 includes otic-vesicle abnormalities. Retain the developmental contribution with that perturbation and species scope rather than treating CEP290 as a dedicated otic-patterning factor. Supporting Evidence: |
| GO:0031410 cytoplasmic vesicle | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Mapped vesicle-associated location. Reason: Human CEP290 N-terminal constructs associate with cellular membrane fractions and ARL13B-positive vesicular structures in PMID:24051377. This supports a contextual vesicle-associated pool; the ciliary-vesicle maturation phenotype alone would not establish localization. Supporting Evidence: |
| GO:0031410 cytoplasmic vesicle | NAS PMID:24051377 Disruption of CEP290 microtubule/membrane-binding domains ca... | KEEP AS NON CORE | Summary: Vesicle-associated CEP290 pool. Reason: PMID:24051377 reports human CEP290 N-terminal construct association with membranes and ARL13B-positive vesicles. Retain the NAS location with this construct scope, without claiming the purified liposome experiment defines a physiological vesicle subtype. Supporting Evidence: |
| GO:0032391 photoreceptor connecting cilium | ISS PMID:16682973 The centrosomal protein nephrocystin-6 is mutated in Joubert... | ACCEPT | Summary: Photoreceptor connecting-cilium localization. Reason: Preserve the mouse ortholog evidence: immunogold/localization in PMID:16682973 and independent mouse retinal analysis in PMID:16632484 place CEP290 at the connecting cilium. This is a specialized site of its conserved ciliary role, not an unreported human retinal experiment. |
| GO:0032991 protein-containing complex | IDA PMID:24421332 The CP110-interacting proteins Talpid3 and Cep290 play overl... | KEEP AS NON CORE | Summary: CP110/Talpid3-associated protein complex. Reason: Human-cell co-immunoprecipitation in PMID:24421332 supports a CEP290-containing complex with CP110/Talpid3-associated components. Retain broad complex membership; weak associations do not define all direct interfaces or a single obligate stoichiometry. Supporting Evidence: |
| GO:0034451 centriolar satellite | IBA GO_REF:0000033 | ACCEPT | Summary: Conserved activity at centriolar satellites. Reason: The PAINT node PTN001051325 is consistent with human CEP290 satellite localization and its requirement for redistribution/recruitment of ciliary components. This combines localization with functional perturbation rather than treating imaging alone as proof of activity. No donor-count or self-donor criticism is warranted. |
| GO:0034451 centriolar satellite | IDA PMID:22797915 The centriolar satellite protein Cep131 is important for gen... | ACCEPT | Summary: Centriolar satellite localization. Reason: The full PMID:22797915 images CEP290 in the satellite network and uses human-cell endogenous complexes and depletion experiments. Retain this core functional location without assigning CEP131βs DNA-damage phenotype to CEP290. Supporting Evidence: |
| GO:0034451 centriolar satellite | IDA PMID:23943788 BBS mutations modify phenotypic expression of CEP290-related... | ACCEPT | Summary: Human centriolar satellite localization. Reason: PMID:23943788 Results and Figure 2A explicitly localize CEP290 to satellites in hTERT-RPE1 cells. BBSome perturbation affects that pool; the annotation records the observed location, not an obligate BBSome-complex identity. Supporting Evidence: |
| GO:0034451 centriolar satellite | IEA GO_REF:0000044 | ACCEPT | Summary: Mapped satellite location. Reason: The UniProt mapping agrees with directly observed human centriolar satellites and their role in organizing CEP290-dependent ciliary recruitment. |
| GO:0035580 specific granule lumen | TAS Reactome:R-HSA-6798749 | UNDECIDED | Summary: Reactome specific-granule lumen location remains unresolved. Reason: The official event explicitly contains O15078 chain 1β2479 as R-HSA-6799524 in input set R-HSA-6799354. Its source is human neutrophil fraction proteomics (PMID:23650620). Exact target peptide/fraction identification and luminal topology were not independently established. A cytoplasmic structural role and absent signal peptide do not justify rejecting a genuine curated proteomic assignment. Supporting Evidence: Reactome:R-HSA-6798749 file:human/CEP290/CEP290-source-evidence.json |
| GO:0035869 ciliary transition zone | IBA GO_REF:0000033 | ACCEPT | Summary: Conserved transition-zone activity. Reason: The PAINT inference is consistent with human CEP290 transition-zone localization, direct domain binding and conserved structural assembly/gating evidence. The C. elegans loss/rescue and ultrastructural work in PMID:26982032 supports active assembly, not just residence. Human native Y-link bridging remains a model rather than a reconstituted full-length mechanism. |
| GO:0035869 ciliary transition zone | IDA PMID:23943788 BBS mutations modify phenotypic expression of CEP290-related... | ACCEPT | Summary: Human transition-zone localization. Reason: PMID:23943788 Figure 2A and Results place CEP290 at the primary-cilium base/transition zone in hTERT-RPE1 cells. Retain this core location; the mouse retinal assays are separately scoped. Supporting Evidence: |
| GO:0035869 ciliary transition zone | IDA PMID:36606424 CCDC66 regulates primary cilium length and signaling via int... | ACCEPT | Summary: CEP290 at the human ciliary transition zone. Reason: PMID:36606424 Figure 3IβJ measures CEP290 signal distal to basal-body markers in human RPE1 cells. CCDC66 depletion changes its recruitment, while the control images establish the annotated location. Supporting Evidence: |
| GO:0035869 ciliary transition zone | NAS PMID:28401750 The Ciliary Transition Zone: Finding the Pieces and Assembli... | ACCEPT | Summary: Transition-zone location summarized by the review. Reason: PMID:28401750 synthesizes CEP290βs transition-zone position; independent human primary imaging supports it. Preserve NAS provenance rather than relabeling the review as an original localization experiment. |
| GO:0036038 MKS complex | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Contextual MKS/Tectonic-complex association. Reason: The mouse donor source PMID:21725307 recovers CEP290 in Tctn1-LAP affinity purification and co-fractionation from NIH3T3 cells. The same paper reports failure to reproduce tagged Tctn1βCEP290 co-immunoprecipitation and allows peripheral/substoichiometric association. Retain the transferred complex assignment with this context; do not turn a worm MKS-module assembly role into proof of an obligate human MKS subunit. PMID:28401750 distinguishes MKS, NPHP and CEP290 transition-zone modules; this module framework explains why contextual MKS association is retained outside the core rather than equated with obligate membership in a single stable human complex. Supporting Evidence: PMID:28401750 three main TZ modules, MKS, NPHP and CEP290 |
| GO:0042462 eye photoreceptor cell development | ISS PMID:16682973 The centrosomal protein nephrocystin-6 is mutated in Joubert... | KEEP AS NON CORE | Summary: Ortholog-supported photoreceptor development. Reason: The zebrafish perturbation in PMID:16682973 affects retinal development. Preserve this developmental contribution with the species and morpholino scope, separately from the directly assayed ciliary molecular functions. Supporting Evidence: |
| GO:0042802 identical protein binding | IPI PMID:18723859 Genetic and physical interaction between the NPHP5 and NPHP6... | KEEP AS NON CORE | Summary: CEP290 fragment self-association. Reason: PMID:18723859 reports tagged CEP290 N-terminal and C-terminal fragments co-immunoprecipitating with themselves and one another in HEK293T cells. Retain measured self-association without asserting a defined native full-length oligomer or stoichiometry. Supporting Evidence: |
| GO:0043010 camera-type eye development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Conserved eye-development contribution. Reason: Retain the PAINT developmental inference at PTN002706047, consistent with fish retinal phenotypes and mammalian photoreceptor dependence. This is a contextual developmental consequence of CEP290βs ciliary work, not a new eye-specific catalytic or transcription-factor activity. |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:16682973 The centrosomal protein nephrocystin-6 is mutated in Joubert... | KEEP AS NON CORE | Summary: ATF4-dependent transcriptional enhancement. Reason: PMID:16682973 tests human full-length CEP290 overexpression and human CEP290 siRNA in an ATF4-dependent CRE reporter in HEK293T cells. The reciprocal perturbations support positive transcriptional regulation in that assay. They do not establish direct DNA binding or a universal transcription-factor function. Supporting Evidence: PMID:16682973 activates transcription factor ATF4 |
| GO:0048793 pronephros development | ISS PMID:16682973 The centrosomal protein nephrocystin-6 is mutated in Joubert... | KEEP AS NON CORE | Summary: Ortholog-supported pronephros development. Reason: The original zebrafish morpholino experiments produce pronephric cysts and other developmental abnormalities. Retain the source-specific ortholog inference without claiming a human pronephros assay or replacing ciliary work with a dedicated renal regulator. Supporting Evidence: |
| GO:0051011 microtubule minus-end binding | IDA NOT PMID:16682973 The centrosomal protein nephrocystin-6 is mutated in Joubert... | ACCEPT | Summary: Preserved negative minus-end-binding assertion. Reason: Accept the explicitly negated assertion in its curated experimental context. Later binding of a purified human CEP290 domain to polymerized microtubules (PMID:24051377) does not demonstrate minus-end selectivity or contradict this NOT annotation from PMID:16682973. Nocodazole-resistant centrosomal localization does not test minus-end specificity and is not used as evidence for this negative assertion; neither study establishes a universal absence under every condition. |
| GO:0060271 cilium assembly | IDA PMID:26386044 Mutations in human homologue of chicken talpid3 gene (KIAA05... | ACCEPT | Summary: CEP290 contribution to cilium assembly. Reason: The function is directly supported by CEP290 depletion and target-specific cellular studies in PMIDs:18694559 and 24421332. The inspected full PMID:26386044 principally assays KIAA0586 and cites prior CEP290 work; the exact original CEP290 IDA linkage was not independently resolved. Preserve the assertion and source while citing independent evidence for the correct core function, rather than removing it from the paperβs main-gene focus. Supporting Evidence: PMID:18694559 Ablation of CEP290 prevents ciliogenesis |
| GO:0060271 cilium assembly | ISS GO_REF:0000024 | ACCEPT | Summary: Conserved cilium-assembly role. Reason: The mouse donor Q6A078 includes experimentally supported ciliogenesis annotations, and independent human CEP290 depletion establishes the same function. Retain the ortholog transfer as core without inventing a new direct-human evidence code. Supporting Evidence: PMID:18694559 Ablation of CEP290 prevents ciliogenesis |
| GO:0070201 regulation of establishment of protein localization | IMP PMID:24421332 The CP110-interacting proteins Talpid3 and Cep290 play overl... | KEEP AS NON CORE | Summary: Regulation of ciliary protein localization. Reason: PMID:24421332 directly measures altered Rab8a and satellite-protein targeting after CEP290 depletion in human RPE1 cells. Retain the broad regulatory annotation; active Rab8a/Rabin8 rescue does not make CEP290 a nucleotide-exchange enzyme or prove direct membrane fusion. Supporting Evidence: PMID:24421332 Cep290 depletion affects localization of centriolar satellite proteins |
| GO:0090316 positive regulation of intracellular protein transport | IMP PMID:22797915 The centriolar satellite protein Cep131 is important for gen... | KEEP AS NON CORE | Summary: CEP131 localization depends on CEP290 in nonciliated cells. Reason: PMID:22797915 reports CEP131 mislocalization after CEP290 depletion in nonciliated human HeLa cells. Retain the positive intracellular-transport contribution with that context. These endpoint localization assays do not measure transport speed or establish a motor activity, and ciliated-cell responses need not be identical. Supporting Evidence: |
| GO:1904491 protein localization to ciliary transition zone | NAS PMID:28401750 The Ciliary Transition Zone: Finding the Pieces and Assembli... | ACCEPT | Summary: Assembly-dependent localization of transition-zone proteins. Reason: The review PMID:28401750 summarizes CEP290-dependent TZ organization. Primary C. elegans work in PMID:26982032 maps CEP-290-dependent recruitment of MKS-module and other TZ proteins with functional rescue and ultrastructure. This supports the conserved assembly role, with the detailed hierarchy explicitly an ortholog experiment rather than a fully reconstructed human pathway. |
| GO:1905349 ciliary transition zone assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Conserved transition-zone assembly. Reason: Retain the PAINT node inference. C. elegans loss/rescue and ultrastructure show CEP-290-dependent TZ organization, while human localization, interaction and domain-function studies support conserved structural participation. The exact human Y-link tether geometry is not established by isolated-domain binding. |
| GO:1905515 non-motile cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Non-motile cilium assembly. Reason: The conserved PAINT inference agrees with direct primary-cilium assembly defects after CEP290 depletion in human cells. Structural organization and component recruitment provide performed work beyond a disease association alone. |
| GO:0008017 microtubule binding | IDA PMID:24051377 Disruption of CEP290 microtubule/membrane-binding domains ca... | NEW | Summary: Direct microtubule binding by the human CEP290 region M domain. Reason: Purified bacterially expressed human CEP290 residues 1695β1966 directly co-sediment with prepolymerized bovine microtubules in a concentration-dependent assay (PMID:24051377, Figure 7CβD and recombinant-protein/microtubule-binding Methods). This is an intrinsic binding capability demonstrated for the isolated domain, not a claim that purified native full-length CEP290 simultaneously bridges membranes and microtubules. Cellular recruitment of full-length CEP290 can depend on CEP162 (PMID:23644468); that context does not negate the purified-domain result. Restore this evidence-backed molecular-function proposal alongside the retained lipid-binding proposal. The instruction whose hierarchy restriction was previously invoked is explicitly scoped to NEW biological-process terms. Existing partner-specific source assertions and the separate NOT minus-end-binding assertion remain unchanged. |
| GO:0008289 lipid binding | IDA PMID:24051377 Disruption of CEP290 microtubule/membrane-binding domains ca... | NEW | Summary: Purified human CEP290 N-terminal lipid binding. Reason: Purified bacterially expressed human CEP290 residues 1β580 co-float with 100-nm phosphatidylserine/cholesterol liposomes, with no-liposome and BSA controls. This establishes broad lipid binding; no headgroup selectivity or necessity of the predicted 257β292 amphipathic helix was tested. The positive GO:0005515 annotations cover protein binding, not this nonredundant lipid activity. The separate microtubule- and lipid-binding capabilities support a tether model without reconstituting native full-length bridging. Supporting Evidence: PMID:24051377 CEP290 aa 1β580 associated with liposomes robustly |
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Download this section (compressed HTML)Q: How do full-length human CEP290 conformation and CEP162/other partners regulate access to the separately measured microtubule- and lipid-binding regions, and do native Y-links use simultaneous binding by one molecule?
Q: Can the neutrophil proteomic CEP290 peptides and fraction assignment be reproduced, and do they establish specific-granule lumen residence and extracellular release rather than another granule-associated pool?
Q: Which direct target experiment underlies the CEP290 cilium-assembly IDA linked to PMID:26386044, whose inspected main experiments focus on KIAA0586?
Experiment: Reconstitute full-length human CEP290 with defined membranes, microtubules and recruitment partners to distinguish simultaneous bridging from separate domain capabilities; measure accessibility and test the predicted amphipathic segment by targeted mutations.
Experiment: Use targeted peptide confirmation, granule subfractionation and topology/release assays in primary human neutrophils to test the precise Reactome granule-lumen and extracellular CEP290 assignments.
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