CEP104

Summary: CEP104 localizes to spindle poles during mitosis.

Reason: The UniProt subcellular-location mapping is consistent with human RPE1 immunofluorescence in PMID:23970417, supplementary Figure S1D/E. This is a genuine cell-cycle-dependent localization; it does not establish a separate spindle-organizing molecular activity and is retained outside the ciliary microtubule-stabilization core.

Summary: Human CEP104 fragments interact with the SF1 bait in yeast two-hybrid screens.

Reason: PMID:26420826 explicitly identifies KIAA0562/CEP104 among SF1 prey proteins. Exact positive IntAct records connect human O60308 fragments to human Q15637 residues 1–441 in yeast. The interaction is retained under the explicit ClinGen project instruction; neither the fragment assays nor SF1 identity establish a splicing activity for CEP104.

Summary: CEP104 is proximal to CCDC66 in the centrosome-cilium BioID screen.

Reason: The exact PMID:26638075 IntAct record is positive proximity-dependent biotin identification with human CEP104 bait in HEK293 cells, not a purified binary-binding assay. Independently, PMID:32453716 targeted co-immunoprecipitation supports the corresponding CCDC66 association. Retain the biologically supported association as non-core under the project instruction, preserving the original BioID source and its lower spatial resolution. Separately, PMID:39856351 Figure 3 reconstitutes recruitment of purified CEP104 to microtubules by purified CCDC66, enhancing end blocking/stabilization; loss of the CEP104 jelly-roll region abolishes this recruitment. This stronger functional interaction evidence is distinguished from the original cellular assay and does not define an atomic contact interface or transfer CCDC66 activity to CEP104.

Summary: CEP104 is proximal to CSPP1 in the centrosome-cilium BioID screen.

Reason: The exact PMID:26638075 IntAct record is positive proximity-dependent biotin identification with human CEP104 bait in HEK293 cells, not a purified binary-binding assay. Independently, PMID:32453716 targeted co-immunoprecipitation supports the corresponding CSPP1 association. Retain the biologically supported association as non-core under the project instruction, preserving the original BioID source and its lower spatial resolution. Separately, PMID:39856351 Figure 3 reconstitutes recruitment of purified CEP104 to microtubules by purified CSPP1, enhancing end blocking/stabilization; loss of the CEP104 jelly-roll region abolishes this recruitment. This stronger functional interaction evidence is distinguished from the original cellular assay and does not define an atomic contact interface or transfer CSPP1 activity to CEP104.

Summary: CEP104 is proximal to TOGARAM1 in the centrosome-cilium BioID screen.

Reason: The exact PMID:26638075 IntAct record is positive proximity-dependent biotin identification with human CEP104 bait in HEK293 cells, not a purified binary-binding assay. Independently, PMID:32453716 targeted co-immunoprecipitation supports the corresponding TOGARAM1 association. Retain the biologically supported association as non-core under the project instruction, preserving the original BioID source and its lower spatial resolution.

Summary: CEP104 associates with CCDC66 in targeted co-immunoprecipitation.

Reason: PMID:32453716 supplementary Figure S1B/E tests tagged human CEP104 (NM_014704.4) and CCDC66 in HEK293T cells with mRFP controls and reciprocal precipitation. These cellular precipitations support complex association. Keep the generic association non-core under the explicit project instruction. Separately, PMID:39856351 Figure 3 reconstitutes recruitment of purified CEP104 to microtubules by purified CCDC66, enhancing end blocking/stabilization; loss of the CEP104 jelly-roll region abolishes this recruitment. This stronger functional interaction evidence is distinguished from the original cellular assay and does not define an atomic contact interface or transfer CCDC66 activity to CEP104.

Summary: CEP104 associates with CSPP1 in targeted co-immunoprecipitation.

Reason: PMID:32453716 supplementary Figure S1C/F tests tagged human CEP104 (NM_014704.4) and CSPP1 in HEK293T cells with mRFP controls and reciprocal precipitation. These cellular precipitations support complex association. Keep the generic association non-core under the explicit project instruction. Separately, PMID:39856351 Figure 3 reconstitutes recruitment of purified CEP104 to microtubules by purified CSPP1, enhancing end blocking/stabilization; loss of the CEP104 jelly-roll region abolishes this recruitment. This stronger functional interaction evidence is distinguished from the original cellular assay and does not define an atomic contact interface or transfer CSPP1 activity to CEP104.

Summary: The reported weak ARMC9–CEP104 association has conflicting replication evidence.

Reason: PMID:32453716 Figure 1F and supplementary Figure S1G report weak tagged-protein co-immunoprecipitation. PMID:39856351 explicitly reports failure to reproduce this association in Extended Data Figure 4c. The positive original result is preserved, but the conditions and reproducibility of the association remain unresolved; neither a direct interface nor an erroneous source assertion is inferred.

Summary: CEP104 associates with TOGARAM1 in targeted co-immunoprecipitation.

Reason: PMID:32453716 supplementary Figure S1A/D tests tagged human CEP104 (NM_014704.4) and TOGARAM1 in HEK293T cells with mRFP controls and reciprocal precipitation. This supports complex association without establishing a purified direct interface or transferring the partner’s activity to CEP104. Keep the generic association non-core under the explicit project instruction.

Summary: CEP104 associates with CCDC66.

Reason: The published PMID:36606424 abstract explicitly identifies this interaction. Selected primary preprint Results and Figure 5/S4 describe controlled co-immunoprecipitation, and independent PMID:39856351 Extended Data Figure 2c corroborates the association through the CEP104 jelly-roll region. The final 2023 article body was not recovered; the preprint is not represented as that final version. Retain the supported association non-core without assigning CCDC66 activity to CEP104. Separately, PMID:39856351 Figure 3 reconstitutes recruitment of purified CEP104 to microtubules by purified CCDC66, enhancing end blocking/stabilization; loss of the CEP104 jelly-roll region abolishes this recruitment. This stronger functional interaction evidence is distinguished from the original cellular assay and does not define an atomic contact interface or transfer CCDC66 activity to CEP104.

Summary: CEP104 occupies the centrosome in non-ciliated and dividing cells.

Reason: The UniProt location mapping is consistent with human RPE1 observations in PMID:23970417. CEP104 is present at distal centrioles and mitotic centrosomes, then redistributes from the mother centriole to the ciliary tip during ciliogenesis. The broad centrosomal location is retained as supporting context outside the ciliary activity core. The independent human centrosome study PMID:21399614 also lists KIAA0562 among cell-cycle-varying centrosomal proteins; that observation is broader than the resolved distal-centriolar position.

Summary: CEP104 is a distal centriolar component.

Reason: The original human centrosome-proteomics/localization study identifies KIAA0562/CEP104. Its centriolar localization is independently resolved in PMID:23970417 Figures 5–7: both distal centrioles in non-ciliated RPE1 cells and the daughter centriole after ciliation. Retain this location without equating localization with an independently established centriolar catalytic activity.

Summary: The centriolar UniProt location mapping is biologically supported.

Reason: Human RPE1 imaging establishes distal centriolar CEP104, with ciliation-dependent redistribution described in PMID:23970417. This supports the original controlled-vocabulary mapping; the current activity core is allocated to the ciliary location.

Summary: The PAINT-inferred active ciliary location agrees with CEP104’s own function.

Reason: This IBA is an ancestral-node inference, not a donor-count argument. Its inclusion of human O60308 among descendant evidence is legitimate. Human ciliary-tip localization and functional depletion/rescue studies, together with direct microtubule-regulatory activity, support a ciliary site of action. No loss or divergence contradicting the inference is identified; no uninspected ancestral placement is invented.

Summary: Ciliary localization is part of CEP104’s core biological context.

Reason: The source’s primary preprint examines fluorescent CEP104 in ciliated RPE1 cells; the final PMID:36606424 body remained inaccessible. Independent full primary PMID:23970417 Figures 5–7 directly localizes endogenous CEP104 to ciliary tips in human RPE1 cells and tracheal cilia. This well-supported location is retained while preserving the original IDA source.

Summary: The UniProt cilium mapping agrees with the ciliary activity core.

Reason: The curated location mapping is supported by direct human ciliary-tip imaging and by CEP104’s own microtubule-regulatory function. Preserve the original broad cilium term and location qualifier rather than inventing an isoform-specific localization.

Summary: Tagged CEP104 molecules co-immunoprecipitate.

Reason: PMID:32453716 supplementary Figure S1H/I specifically tests differently tagged CEP104 molecules, with mRFP controls and reciprocal precipitation. This supports the original self-association term in the tested cellular context, without specifying native oligomer stoichiometry or obligate dimerization.

Summary: Full-length human CEP104 stabilizes microtubule plus ends.

Reason: Purified full-length CEP104 directly suppresses microtubule shortening and persistently blocks plus ends in single-filament reconstitution assays (Figures 1–3). Recruitment partners enhance its activity; TOGARAM1 can overcome growth inhibition. This measured stabilizing activity is distinct from the isolated TOG-domain bulk-polymerization assay and is not an ancestor or descendant of the existing binding terms. The separate ciliary-process proposal is grounded in mapped cellular rescue plus this physical work, not inferred from the activity label alone.

Summary: CEP104 regulates the elongation phase of cilium assembly through its microtubule-interacting machinery.

Reason: Selected full PMID:32820051 Figure 2D–F shows that siRNA-resistant full-length CEP104 rescues cilium shortening after endogenous CEP104 depletion in human RPE1 cells, whereas the TOG tubulin-contact mutant W448A/V493D/R626A does not; both constructs are reported at the ciliary base/axoneme. The inspected cloning Methods do not resolve the rescue construct species/accession. Independent human TOG binding (PMID:28017521) and full-length human end-stabilization reconstitution (PMID:39856351) identify work performed by CEP104 itself, rather than relying only on necessity. This supports regulation of the extent of ciliary elongation, not initiation, an intrinsic full-length polymerase activity, or every downstream Hedgehog effect. Same-role ciliary microtubule proteins have experimental assembly annotations; ontology parents and the exact-head GO-CAM index reveal no redundant existing process assertion or contrary modeled role. Only this broad regulatory process is proposed.