CHAMP1 (Chromosome Alignment-Maintaining Phosphoprotein 1) is a vertebrate-specific zinc finger protein that regulates kinetochore-microtubule attachment during mitosis and promotes homologous recombination DNA repair. The protein localizes to chromosomes and spindle structures during mitosis, where it ensures proper chromosome alignment at metaphase by maintaining stable kinetochore-microtubule attachments. CHAMP1 recruits CENP-E and CENP-F to kinetochores as downstream effectors. Through its WK motif, CHAMP1 binds REV7/MAD2L2 to promote homologous recombination by inhibiting the Shieldin complex. CHAMP1 also functions as part of a heterochromatin assembly complex with POGZ and HP1 proteins. De novo mutations in CHAMP1 cause an intellectual disability syndrome with severe speech impairment.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005654 nucleoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference supported by direct immunofluorescence evidence from HPA |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Direct immunofluorescence from Human Protein Atlas confirms nucleoplasm localization |
| GO:0005819 spindle | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference consistent with experimental data showing spindle localization during mitosis |
| GO:0005819 spindle | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic annotation from UniProt subcellular location, consistent with experimental evidence |
| GO:0005819 spindle | IDA PMID:21063390 CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-m... | ACCEPT | Summary: Direct experimental evidence showing spindle localization from prometaphase through anaphase Supporting Evidence: PMID:21063390 CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-microtubule attachment. |
| GO:0000776 kinetochore | IEA GO_REF:0000043 | ACCEPT | Summary: Electronic annotation consistent with experimental evidence; kinetochore localization is a core function |
| GO:0000776 kinetochore | IDA PMID:21063390 CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-m... | ACCEPT | Summary: Direct evidence from Itoh et al. showing CHAMP1 localizes to kinetochores via the FPE region; this is essential for its function in kinetochore-microtubule attachment Supporting Evidence: PMID:21063390 CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-microtubule attachment. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic annotation consistent with experimental evidence for nuclear localization during interphase |
| GO:0005634 nucleus | IDA PMID:21063390 CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-m... | ACCEPT | Summary: Direct evidence showing nuclear localization during interphase Supporting Evidence: PMID:21063390 CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-microtubule attachment. |
| GO:0005694 chromosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic annotation consistent with experimental evidence for chromosome association |
| GO:0000793 condensed chromosome | IDA PMID:21063390 CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-m... | ACCEPT | Summary: Direct evidence from Itoh et al. showing CHAMP1 associates with condensed chromosomes throughout their length during mitosis Supporting Evidence: PMID:21063390 CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-microtubule attachment. |
| GO:0016604 nuclear body | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Immunofluorescence data from Human Protein Atlas showing nuclear body localization |
| GO:0008270 zinc ion binding | IEA GO_REF:0000043 | ACCEPT | Summary: CHAMP1 contains five C2H2-type zinc finger domains that are essential for its function. The C-terminal zinc fingers negatively regulate chromosome alignment and bind chromatin. |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | REMOVE | Summary: Redundant with the more specific GO:0008270 zinc ion binding annotation. The zinc fingers specifically bind zinc ions. |
| GO:0005515 protein binding | IPI PMID:21063390 CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-m... | KEEP AS NON CORE | Summary: Interaction with MAD2L2/REV7 demonstrated by immunoprecipitation in Itoh et al. The WK motif (aa 271-490) mediates this interaction. This interaction is functionally important for both mitotic and DNA repair functions. Supporting Evidence: PMID:21063390 CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-microtubule attachment. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | KEEP AS NON CORE | Summary: Protein interaction study (BioPlex network) Supporting Evidence: PMID:26496610 Oct 22. A human interactome in three quantitative dimensions organized by stoichiometries and abundances. |
| GO:0005515 protein binding | IPI PMID:29656893 DNA Repair Network Analysis Reveals Shieldin as a Key Regula... | KEEP AS NON CORE | Summary: DNA repair network analysis showing CHAMP1 interactions Supporting Evidence: PMID:29656893 2018 Apr 12. DNA Repair Network Analysis Reveals Shieldin as a Key Regulator of NHEJ and PARP Inhibitor Sensitivity. |
| GO:0005515 protein binding | IPI PMID:29789392 FAM35A associates with REV7 and modulates DNA damage respons... | KEEP AS NON CORE | Summary: Study on FAM35A/SHLD2 and REV7 interactions in DNA repair Supporting Evidence: PMID:29789392 FAM35A associates with REV7 and modulates DNA damage responses of normal and BRCA1-defective cells. |
| GO:0005515 protein binding | IPI PMID:20850016 Quantitative interaction proteomics and genome-wide profilin... | KEEP AS NON CORE | Summary: Quantitative interaction proteomics showing CHAMP1 binds POGZ, CBX1, CBX3, and CBX5 (HP1 proteins). These interactions are part of a heterochromatin complex that regulates H3K9me3-marked chromatin. Supporting Evidence: PMID:20850016 Quantitative interaction proteomics and genome-wide profiling of epigenetic histone marks and their readers. |
| GO:0043515 kinetochore binding | IDA PMID:21063390 CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-m... | NEW | Summary: CHAMP1 binds to kinetochores via its FPE region. This binding is essential for maintaining kinetochore-microtubule attachment and is a core molecular function. Supporting Evidence: PMID:21063390 CAMP localizes to chromosomes and the spindle including kinetochores |
| GO:0000725 recombinational repair | IMP PMID:36044844 CHAMP1 binds to REV7/FANCV and promotes homologous recombina... | NEW | Summary: Core function. CHAMP1 promotes homologous recombination DNA repair by binding REV7/MAD2L2 via its WK motif (WKPAKPAPS at positions 334-335). This competes with SHLD3 for REV7 binding, reducing Shieldin-mediated NHEJ and favoring HR. CHAMP1 knockout reduces HR activity by ~60% and sensitizes cells to PARP inhibitors. Supporting Evidence: file:human/CHAMP1/CHAMP1-deep-research-cyberian.md CHAMP1 is a third REV7 seatbelt-binding partner, and that CHAMP1 binding activates HR repair... Site-directed mutagenesis creating a CHAMP1-W334A/K335A double mutant (designated CHAMP1-2A) abolished REV7 binding PMID:36044844 CHAMP1 binds to REV7/FANCV and promotes homologous recombination repair. |
| GO:0031134 sister chromatid biorientation | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference consistent with experimental evidence |
| GO:0031134 sister chromatid biorientation | IMP PMID:21063390 CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-m... | ACCEPT | Summary: Core function. CHAMP1 depletion causes severe chromosome misalignment associated with poor K-fiber resistance to tension during bi-orientation. Reduced inter-kinetochore distances indicate failure to achieve proper bi-orientation. Supporting Evidence: PMID:21063390 CAMP-depleted cells showed severe chromosome misalignment, which was associated with the poor resistance of K-fibres to the tension exerted upon establishment of sister kinetochore bi-orientation |
| GO:0034501 protein localization to kinetochore | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference consistent with experimental evidence |
| GO:0034501 protein localization to kinetochore | IMP PMID:21063390 CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-m... | ACCEPT | Summary: Core function. CHAMP1 is required for proper kinetochore localization of CENP-E and CENP-F, which function as downstream effectors for chromosome alignment. Supporting Evidence: PMID:21063390 Kinetochore localization of CENP-E and CENP-F was affected by CAMP depletion, and by expressing CAMP mutants that cannot functionally rescue CAMP depletion, placing CENP-E and CENP-F as downstream effectors of CAMP |
| GO:0035372 protein localization to microtubule | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference consistent with experimental evidence |
| GO:0035372 protein localization to microtubule | IMP PMID:21063390 CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-m... | ACCEPT | Summary: CHAMP1 promotes localization of proteins including CENP-E and CENP-F to spindle microtubules. Supporting Evidence: PMID:21063390 CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-microtubule attachment. |
| GO:0051315 attachment of mitotic spindle microtubules to kinetochore | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference consistent with experimental evidence |
| GO:0051315 attachment of mitotic spindle microtubules to kinetochore | IEA GO_REF:0000002 | ACCEPT | Summary: Electronic annotation from InterPro domain (CAMP domain IPR039330). This is the defining function of the CAMP domain family. |
| GO:0051315 attachment of mitotic spindle microtubules to kinetochore | IMP PMID:21063390 CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-m... | ACCEPT | Summary: Core function of CHAMP1. Experimental evidence shows CHAMP1 is required for maintaining kinetochore-microtubule attachment. Cold-stability assays demonstrated reduced microtubule attachments at kinetochores in CHAMP1-depleted cells. The FPE region is essential for this function. Supporting Evidence: PMID:21063390 CAMP is required for maintaining kinetochore-microtubule attachment during bi-orientation |
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Download this section (compressed HTML)Q: What is the mechanism by which CHAMP1 regulates CENP-E and CENP-F localization to kinetochores? No direct physical interaction has been detected.
Suggested experts: Mitosis/kinetochore biology
Experiment: Determine whether CHAMP1's DNA repair and mitotic functions are independently regulated or coordinated through REV7 binding.
Hypothesis: CHAMP1-REV7 interaction may be differentially regulated in mitosis vs DNA damage response contexts.
Type: Functional assay
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