CHAMP1 is a nuclear and mitotic chromosome-associated protein with repeat motifs and zinc-finger regions. It supports stable kinetochore–microtubule attachment and sister-chromatid biorientation, with phosphorylation-sensitive functions in chromosome alignment and kinetochore protein localization. CHAMP1 also binds REV7/MAD2L2 and competes with SHLD3, favoring DNA end resection and homologous-recombination repair. A distinct CHAMP1–POGZ–HP1α complex contributes to heterochromatin organization and recruitment of repair-associated proteins at damaged telomeres in human ALT cells. At stalled replication forks, the chromatin complex supports SETDB1-dependent histone methylation and protects nascent DNA from excessive MRE11-dependent degradation. In differentiating human myoblasts, CHAMP1 cooperates with MyoD at the MYMK enhancer to activate fusogen expression and enable myoblast fusion. Pathogenic CHAMP1 variants cause a neurodevelopmental disorder with intellectual disability and prominent speech impairment.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005654 nucleoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: CHAMP1 acts in the nucleoplasm. Reason: The preserved PAINT inference is independently consistent with nuclear CHAMP1 complexes and direct human REV7-dependent repair regulation. Current GOA identifies ancestral node PTN002204446, while historical node placement was not independently reconstructed. Nucleoplasm is retained as a core location. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002204446 SUPPORTS TRANSFER The authenticated current GOA records curated propagation from PANTHER:PTN002204446 and includes UniProtKB:Q96JM3 experimental self-evidence. SUPPORTS_TRANSFER retains deference to that curated propagation together with the independently verified target experiments; it does not claim independent reconstruction or validation of the ancestral node placement. Historical PAINT node history was not inspected. Neither donor count nor target self-evidence is treated as a failure. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: CHAMP1 acts in the nucleoplasm. Reason: The preserved HPA immunofluorescence assertion is positively resolved by two enhanced-validation antibodies: HPA006623 in HeLa, U2OS and HAP1, and HPA008900 in A-431, U-251MG and U2OS. Actual HeLa and A-431 images were inspected. This localization is coherent with nuclear complex activity. Nucleoplasm is retained as a core location. |
| GO:0005819 spindle | IBA GO_REF:0000033 | ACCEPT | Summary: CHAMP1 localizes to the mitotic spindle. Reason: Human endogenous CHAMP1 and GFP-tagged CHAMP1 were visualized on the spindle in PMID:21063390; depletion reduced the target signal and the FPE region was sufficient for spindle localization. This supports the original IBA assertion independently of a claim that CHAMP1 directly binds purified microtubules. The source reports an unpublished negative microtubule-binding assay, which is not a negated source annotation. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002204446 SUPPORTS TRANSFER The authenticated current GOA records curated propagation from PANTHER:PTN002204446 and includes UniProtKB:Q96JM3 experimental self-evidence. SUPPORTS_TRANSFER retains deference to that curated propagation together with the independently verified target experiments; it does not claim independent reconstruction or validation of the ancestral node placement. Historical PAINT node history was not inspected. Neither donor count nor target self-evidence is treated as a failure. |
| GO:0005819 spindle | IEA GO_REF:0000044 | ACCEPT | Summary: CHAMP1 localizes to the mitotic spindle. Reason: Human endogenous CHAMP1 and GFP-tagged CHAMP1 were visualized on the spindle in PMID:21063390; depletion reduced the target signal and the FPE region was sufficient for spindle localization. This supports the original IEA assertion independently of a claim that CHAMP1 directly binds purified microtubules. The source reports an unpublished negative microtubule-binding assay, which is not a negated source annotation. |
| GO:0005819 spindle | IDA PMID:21063390 CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-m... | ACCEPT | Summary: CHAMP1 localizes to the mitotic spindle. Reason: Human endogenous CHAMP1 and GFP-tagged CHAMP1 were visualized on the spindle in PMID:21063390; depletion reduced the target signal and the FPE region was sufficient for spindle localization. This supports the original IDA assertion independently of a claim that CHAMP1 directly binds purified microtubules. The source reports an unpublished negative microtubule-binding assay, which is not a negated source annotation. |
| GO:0000776 kinetochore | IEA GO_REF:0000043 | ACCEPT | Summary: CHAMP1 localizes to kinetochores during mitosis. Reason: Endogenous CHAMP1 colocalized with CREST on chromosome spreads, and the FPE fragment localized to kinetochores most clearly in prometaphase and after nocodazole treatment. Retain the original location assertion. Localization and the functional depletion/rescue experiments do not by themselves identify the physical kinetochore-binding interface. Supporting Evidence: |
| GO:0000776 kinetochore | IDA PMID:21063390 CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-m... | ACCEPT | Summary: CHAMP1 localizes to kinetochores during mitosis. Reason: Endogenous CHAMP1 colocalized with CREST on chromosome spreads, and the FPE fragment localized to kinetochores most clearly in prometaphase and after nocodazole treatment. Retain the original location assertion. Localization and the functional depletion/rescue experiments do not by themselves identify the physical kinetochore-binding interface. Supporting Evidence: |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: The nucleus is a principal CHAMP1 compartment. Reason: The source mapping and human primary imaging are consistent with the nuclear CHAMP1–REV7 and CHAMP1–POGZ complexes. The broad nuclear term remains correct alongside the more precise nucleoplasm assertion; no activity is inferred merely from a nuclear localization signal. |
| GO:0005634 nucleus | IDA PMID:21063390 CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-m... | ACCEPT | Summary: The nucleus is a principal CHAMP1 compartment. Reason: The source mapping and human primary imaging are consistent with the nuclear CHAMP1–REV7 and CHAMP1–POGZ complexes. The broad nuclear term remains correct alongside the more precise nucleoplasm assertion; no activity is inferred merely from a nuclear localization signal. |
| GO:0005694 chromosome | IEA GO_REF:0000044 | ACCEPT | Summary: CHAMP1 associates with chromosomes. Reason: The conservative UniProt location mapping is supported by human mitotic chromosome imaging and independent chromatin-associated complexes. The broader chromosome location is compatible with, rather than contradicted by, the more precise condensed-chromosome annotation. |
| GO:0000793 condensed chromosome | IDA PMID:21063390 CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-m... | ACCEPT | Summary: CHAMP1 localizes to condensed mitotic chromosomes. Reason: Human endogenous protein and tagged constructs were observed on prometaphase-to-anaphase chromosomes and on chromosome spreads. The C-terminal region contributed to chromosome localization; the FPE fragment alone did not reproduce that arm localization. This is localization evidence, not a claim of sequence-specific DNA recognition. Supporting Evidence: |
| GO:0016604 nuclear body | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: HPA detects a nuclear-body pool in specific cell contexts. Reason: The literal HPA data report nuclear bodies with HPA006623 in HAP1 and HPA008900 in A-431; the A-431 image was visually inspected. Other tested lines principally show nucleoplasm. Retain the experimentally reported subnuclear pool without assigning it to a particular body type or equating it with the independently studied damage-induced heterochromatin foci. Supporting Evidence: file:human/CHAMP1/CHAMP1-source-evidence.json |
| GO:0008270 zinc ion binding | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Zinc-finger architecture supports structural zinc binding. Reason: The preserved UniProt keyword inference is biologically compatible with C2H2 domains. PMID:21063390 describes two N-terminal and three C-terminal predicted zinc fingers, whereas the current UniProt feature set explicitly lists one C2H2 feature; neither establishes a zinc titration assay for every predicted site. Retain this structural property without making it a separate defining molecular core or placing all five domains at the C terminus. |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | MODIFY | Summary: The supported metal-binding class is zinc. Reason: The original broad metal-ion-binding keyword assertion is not false merely because a zinc-binding annotation also exists. C2H2 architecture supplies the supported metal class, so refine this existing assertion to zinc ion binding while retaining its original electronic source and acknowledging the domain-inference scope. Proposed replacements: zinc ion binding |
| GO:0005515 protein binding | IPI PMID:21063390 CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-m... | MODIFY | Summary: CHAMP1 sequesters REV7 from an alternative binding partner. Reason: The original human study establishes direct WK-region binding to MAD2L2/REV7. Independent human fragment crystallography and full-length interaction-mutant assays verify the binding interface. PMID:36044844 then measures CHAMP1-dependent competition with SHLD3 for REV7, limiting Shieldin assembly. Protein sequestering activity describes this performed molecular work more precisely than generic association; it does not assign kinase, recombinase or ATPase activity to CHAMP1. The original PMID:21063390 source object is unchanged. Proposed replacements: protein sequestering activity |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | KEEP AS NON CORE | Summary: The quantitative interaction screen supports REV7 association. Reason: Exact human CHAMP1–MAD2L2 IntAct record and anti-tag coimmunoprecipitation method resolve the source-linked interaction. Retain this screen observation as non-core under the explicit ClinGen project binding instruction. The screen alone does not demonstrate competitive sequestration, and it is not treated as an independent binary-interface assay. |
| GO:0005515 protein binding | IPI PMID:29656893 DNA Repair Network Analysis Reveals Shieldin as a Key Regula... | UNDECIDED | Summary: The exact CHAMP1–REV7 result in this screen remains unresolved. Reason: The original selected cache contains only partial article sections; a genuine fresh normal full variant and full primary HTML were recovered and inspected, but the exact CHAMP1–REV7 target result was not located in the main text. Linked supplementary files returned challenge pages, not usable spreadsheets, and the current target IntAct query returned no matching record for this publication. Preserve the experimental IPI assertion without substituting a different REV7 paper for its source-specific evidence; these retrieval gaps are not negative interaction evidence. |
| GO:0005515 protein binding | IPI PMID:29789392 FAM35A associates with REV7 and modulates DNA damage respons... | KEEP AS NON CORE | Summary: CHAMP1 co-purifies with the REV7 complex. Reason: The actual primary Table 1 explicitly identifies CAMP, UniProt Q96JM3, with 127 spectral counts and 29 unique peptides in sequential FLAG/HA purification of tagged REV7 from human HeLa S3 nuclear extracts. This is strong target-linked complex association, not proof that every copurified subunit directly contacts CHAMP1. Retain non-core under the standing project instruction. |
| GO:0005515 protein binding | IPI PMID:20850016 Quantitative interaction proteomics and genome-wide profilin... | KEEP AS NON CORE | Summary: The chromatin interaction study supports CHAMP1-containing complexes. Reason: Authentic source-linked BioGRID records 1056800 and 1056822 identify human CBX5–CHAMP1 and POGZ–CHAMP1 affinity-capture/MS associations from PMID:20850016. Current GOA also records CBX1 and CBX3 partners, but their exact original target tables were not independently recovered. The preserved original annotation has no partner field and is supported by the verified associations. Keep its low-resolution binding claim under the project instruction; no histone-reader activity, direct HP1 interface or enzymatic activity is transferred from its partners. |
| GO:1905168 positive regulation of double-strand break repair via homologous recombination | IMP PMID:36044844 CHAMP1 binds to REV7/FANCV and promotes homologous recombina... | NEW | Summary: CHAMP1 positively regulates homologous-recombination repair through competitive REV7 binding. Reason: Replace the prior authored recombinational-repair proposal with the more precise regulatory process. CHAMP1 itself occupies REV7 and reduces its SHLD3 association; human CHAMP1 loss and binding-defective rescue experiments connect that performed molecular step to DSB end resection and HR output. This is more than necessity alone, but does not identify CHAMP1 as the strand-exchange catalyst. Complete comparator queries show related regulators are annotated using broader repair terms or positive-effect relationships, not uniformly GO:1905168; no annotation gap is inferred from their absence. Official bidirectional ancestry checks exclude redundancy with the four existing machine biological processes, and the authenticated GO-CAM index contains no target activity. The additional REV7-independent heterochromatin mechanism is not treated as identical to competitive sequestration. Supporting Evidence: PMID:36044844 decreased DSB end resection file:human/CHAMP1/CHAMP1-source-evidence.json |
| GO:0031134 sister chromatid biorientation | IBA GO_REF:0000033 | ACCEPT | Summary: CHAMP1 supports stable sister-kinetochore biorientation. Reason: Human depletion, RNAi-resistant rescue and live kinetochore/microtubule imaging show that sister kinetochores can establish amphitelic attachments but fail to maintain robust attachment under tension. Reduced inter-kinetochore distance and cold-stable K-fibres support the original biorientation assertion; precocious sister separation was not observed. The PAINT version remains consistent with target evidence without a donor-count or self-reference objection. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002204446 SUPPORTS TRANSFER The authenticated current GOA records curated propagation from PANTHER:PTN002204446 and includes UniProtKB:Q96JM3 experimental self-evidence. SUPPORTS_TRANSFER retains deference to that curated propagation together with the independently verified target experiments; it does not claim independent reconstruction or validation of the ancestral node placement. Historical PAINT node history was not inspected. Neither donor count nor target self-evidence is treated as a failure. Supporting Evidence: |
| GO:0031134 sister chromatid biorientation | IMP PMID:21063390 CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-m... | ACCEPT | Summary: CHAMP1 supports stable sister-kinetochore biorientation. Reason: Human depletion, RNAi-resistant rescue and live kinetochore/microtubule imaging show that sister kinetochores can establish amphitelic attachments but fail to maintain robust attachment under tension. Reduced inter-kinetochore distance and cold-stable K-fibres support the original biorientation assertion; precocious sister separation was not observed. The PAINT version remains consistent with target evidence without a donor-count or self-reference objection. Supporting Evidence: |
| GO:0034501 protein localization to kinetochore | IBA GO_REF:0000033 | ACCEPT | Summary: CHAMP1 supports CENP-E and CENP-F localization to kinetochores. Reason: The primary study measures reduced kinetochore CENP-E/CENP-F after human CHAMP1 depletion without a corresponding loss of total protein. Functional CHAMP1 constructs restore their localization, whereas alignment-defective mutants do not. Retain the existing localization process, while distinguishing this demonstrated upstream contribution from an unproven direct CHAMP1–CENP-E/F recruitment bridge. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002204446 SUPPORTS TRANSFER The authenticated current GOA records curated propagation from PANTHER:PTN002204446 and includes UniProtKB:Q96JM3 experimental self-evidence. SUPPORTS_TRANSFER retains deference to that curated propagation together with the independently verified target experiments; it does not claim independent reconstruction or validation of the ancestral node placement. Historical PAINT node history was not inspected. Neither donor count nor target self-evidence is treated as a failure. Supporting Evidence: |
| GO:0034501 protein localization to kinetochore | IMP PMID:21063390 CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-m... | ACCEPT | Summary: CHAMP1 supports CENP-E and CENP-F localization to kinetochores. Reason: The primary study measures reduced kinetochore CENP-E/CENP-F after human CHAMP1 depletion without a corresponding loss of total protein. Functional CHAMP1 constructs restore their localization, whereas alignment-defective mutants do not. Retain the existing localization process, while distinguishing this demonstrated upstream contribution from an unproven direct CHAMP1–CENP-E/F recruitment bridge. Supporting Evidence: |
| GO:0035372 protein localization to microtubule | IBA GO_REF:0000033 | ACCEPT | Summary: CHAMP1 contributes to spindle localization of MAD2L2. Reason: The original human depletion experiment reports loss of spindle-localized MAD2L2 without altered total abundance. That supports the existing protein-localization process. The WK interaction is separable from CHAMP1’s chromosome-alignment function, and later binding-site mutants of MAD2L2 can retain spindle localization through other partners; neither study establishes that CHAMP1 is its exclusive spindle anchor. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002204446 SUPPORTS TRANSFER The authenticated current GOA records curated propagation from PANTHER:PTN002204446 and includes UniProtKB:Q96JM3 experimental self-evidence. SUPPORTS_TRANSFER retains deference to that curated propagation together with the independently verified target experiments; it does not claim independent reconstruction or validation of the ancestral node placement. Historical PAINT node history was not inspected. Neither donor count nor target self-evidence is treated as a failure. |
| GO:0035372 protein localization to microtubule | IMP PMID:21063390 CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-m... | ACCEPT | Summary: CHAMP1 contributes to spindle localization of MAD2L2. Reason: The original human depletion experiment reports loss of spindle-localized MAD2L2 without altered total abundance. That supports the existing protein-localization process. The WK interaction is separable from CHAMP1’s chromosome-alignment function, and later binding-site mutants of MAD2L2 can retain spindle localization through other partners; neither study establishes that CHAMP1 is its exclusive spindle anchor. |
| GO:0051315 attachment of mitotic spindle microtubules to kinetochore | IBA GO_REF:0000033 | ACCEPT | Summary: CHAMP1 maintains kinetochore–microtubule attachments. Reason: The human primary study combines depletion, RNAi-resistant rescue, cold-stable K-fibre analysis and live kinetochore tracking. Attachments become unstable during biorientation, while monopolar K-fibre maturation remains possible. This establishes CHAMP1’s own local functional contribution and corroborates the preserved IBA assertion. Direct microtubule binding or a physical CHAMP1–CENP-E/F bridge is not required by this process term and is not claimed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002204446 SUPPORTS TRANSFER The authenticated current GOA records curated propagation from PANTHER:PTN002204446 and includes UniProtKB:Q96JM3 experimental self-evidence. SUPPORTS_TRANSFER retains deference to that curated propagation together with the independently verified target experiments; it does not claim independent reconstruction or validation of the ancestral node placement. Historical PAINT node history was not inspected. Neither donor count nor target self-evidence is treated as a failure. |
| GO:0051315 attachment of mitotic spindle microtubules to kinetochore | IEA GO_REF:0000002 | ACCEPT | Summary: CHAMP1 maintains kinetochore–microtubule attachments. Reason: The human primary study combines depletion, RNAi-resistant rescue, cold-stable K-fibre analysis and live kinetochore tracking. Attachments become unstable during biorientation, while monopolar K-fibre maturation remains possible. This establishes CHAMP1’s own local functional contribution and corroborates the preserved IEA assertion. Direct microtubule binding or a physical CHAMP1–CENP-E/F bridge is not required by this process term and is not claimed. |
| GO:0051315 attachment of mitotic spindle microtubules to kinetochore | IMP PMID:21063390 CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-m... | ACCEPT | Summary: CHAMP1 maintains kinetochore–microtubule attachments. Reason: The human primary study combines depletion, RNAi-resistant rescue, cold-stable K-fibre analysis and live kinetochore tracking. Attachments become unstable during biorientation, while monopolar K-fibre maturation remains possible. This establishes CHAMP1’s own local functional contribution and corroborates the preserved IMP assertion. Direct microtubule binding or a physical CHAMP1–CENP-E/F bridge is not required by this process term and is not claimed. Supporting Evidence: PMID:21063390 poor resistance of K-fibres to the tension file:human/CHAMP1/CHAMP1-source-evidence.json |
| GO:0003713 transcription coactivator activity | IDA PMID:41540007 CHAMP1 is an essential regulator for human myoblast fusion a... | NEW | Summary: CHAMP1 coactivates MyoD-dependent transcription in human myoblasts. Reason: Human CHAMP1 and MyoD associate by reported co-IP and controlled endogenous proximity ligation, co-occupy the MYMK enhancer and require each other for enhancer occupancy despite preserved nuclear expression. CHAMP1 loss reduces MYMK transcription; re-expression restores it, and MYMK expression bypasses the fusion defect. Interaction-sensitive zinc-finger mutants connect this association to function. Together these experiments support transcription coactivator activity, not autonomous sequence-specific DNA binding or a purified binary interface. CHAMP1 regulates the fusogen transcriptionally rather than performing membrane fusion, and no new fusion process is proposed. Supporting Evidence: PMID:41540007 a key cofactor for MyoD |
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Download this section (compressed HTML)Q: Which physical partner or molecular activity links the CHAMP1 FPE region to stable kinetochore–microtubule attachment, separately from its direct WK-region REV7 interaction?
Q: Can the exact CHAMP1–REV7 source result in the PMID:29656893 supplementary interaction dataset be recovered and its bait, prey and experimental context verified?
Q: How do CHAMP1 interaction regions organize the POGZ–HP1α chromatin complex: through direct chromatin bridging, stabilization of partner assemblies, or recruitment of additional factors? Which contacts explain SETDB1-dependent chromatin changes and restriction of MRE11 at stressed forks, separately from the established heterochromatin localization and POGZ-mediated SETDB1 recruitment? Does CHAMP1 itself recognize modified histones, or does the observed H3K9me3 association depend on the established HP1α reader and other complex contacts?
Q: How do cell type, mitotic phosphorylation and CHAMP1 variant dosage distinguish chromosome-alignment, competitive REV7-binding and heterochromatin-associated functions?
Experiment: Test separation-of-function FPE and WK mutants at endogenous expression for attachment stability, CENP-E/F localization, REV7 competition and repair readouts, controlling cell-cycle distribution.
Experiment: Reconstitute defined CHAMP1–POGZ–HP1α assemblies to determine direct contacts and chromatin-bridging capacity, separately from SETDB1 catalytic activity.
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