CDC45 is a nuclear replication factor that forms the CMG helicase with the MCM2–7 motor and the GINS complex. It contributes the architecture needed for productive DNA unwinding and remains associated with the replication machinery during DNA synthesis. Purified human CDC45 also binds single-stranded and branched DNA. Its RecJ-related fold has lost the conserved nuclease active site, and ATP-driven unwinding is a property of the assembled CMG complex. Biallelic hypomorphic CDC45 variants cause Meier-Gorlin syndrome and craniosynostosis, linking impaired replication capacity to developmental growth defects.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000076 DNA replication checkpoint signaling | TAS PMID:9660782 The human homolog of Saccharomyces cerevisiae CDC45. | UNDECIDED | Summary: The precise checkpoint-signaling role remains unresolved. Reason: GO:0000076 requires participation in checkpoint signal transduction, not simply being a replication factor or a checkpoint-regulated target. The accessible PMID:9660782 abstract establishes human CDC45 cloning, cell-cycle expression, ORC2 association and nuclear fractionation; the full paper was not recovered. PMID:23910567 establishes cell-cycle-dependent CLSPN association and its response to UV, but this alone does not resolve a direct signaling role. Preserve the original TAS assertion without inferring that it is false. |
| GO:0000727 double-strand break repair via break-induced replication | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain the inherited break-induced replication role as a repair context of the replication machinery. Reason: The PAINT assertion is attached to PANTHER:PTN000053416. CDC45 is a conserved CMG component, and the experimental BIR study PMID:20516198 supports use of the replicative helicase in this origin-independent repair pathway. That study provides homolog context rather than a direct human CDC45 repair assay. No target-specific loss of the inherited function was established. Retain the curated inference outside the principal genome-duplication core; the donor count is not used to judge it. |
| GO:0003682 chromatin binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Chromatin association is consistent with the conserved CDC45 replication machinery. Reason: Human CMG is recovered from chromatin, and human CDC45 participates in nuclear replication complexes. This is consistent with the PAINT node PANTHER:PTN000053416 and provides no evidence of human loss. The term is retained as contextual binding; complex association is not treated as an independent purified chromatin-binding assay or a separate core activity. |
| GO:0003688 DNA replication origin binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain the curated origin-binding inference with its phylogenetic scope. Reason: PANTHER:PTN000053416 asserts an inherited origin-associated DNA-binding function. CDC45 is recruited into origin preinitiation complexes and has experimentally demonstrated DNA-binding capacity. These findings are compatible with the inference, but the purified human assays in PMID:24293646 test ssDNA and branched substrates rather than sequence-selective origin recognition. No target-specific loss is demonstrated, and the inference is not rejected because of a short donor list. Origin specificity is not promoted to the human molecular-function core. |
| GO:0003697 single-stranded DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: Human CDC45 directly binds single-stranded DNA. Reason: The inherited PAINT function is independently corroborated by EMSA with purified, full-length, C-terminally His6-tagged human CDC45 expressed in bacteria. Longer ssDNA substrates bound more strongly than shorter substrates. Branched-DNA preference and passive strand destabilization do not establish ATP-driven helicase activity of CDC45 alone. Supporting Evidence: GO_REF:0000033 PMID:24293646 hCdc45 bound long (113-mer or 80-mer) single-stranded DNA fragments |
| GO:0005515 protein binding | IPI PMID:10518787 Human CDC45 protein binds to minichromosome maintenance 7 pr... | UNDECIDED | Summary: The exact CDC45–POLA1 pair is not resolved from accessible evidence. Reason: The source partner P09884 is preserved. The verified abstract of PMID:10518787 explicitly reports binding to the p70 subunit of DNA polymerase alpha and to MCM7; the full paper was not recovered to determine whether it also tested POLA1/P09884. No exact target-pair record was recovered in the inspected IntAct query. This is an access and pair-specific uncertainty, not evidence that the original IPI annotation is misattributed or that CDC45 cannot associate with polymerase alpha. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15232106 Self-assembling protein microarrays. | KEEP AS NON CORE | Summary: The protein-array CDC45–CDKN1A interaction is supported. Reason: The exact O75419–P38936 pair is present in the IntAct record for PMID:15232106 (EBI-375344), using an in vitro protein-array assay. The paper cache is abstract-only; the target-specific curation record, rather than its general abstract, resolves this interaction. Retain generic binding as non-core under the ClinGen project instruction; this does not assign CDKN1A inhibitory activity to CDC45. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17887956 Characterization of the interaction between the human DNA to... | KEEP AS NON CORE | Summary: CDC45 associates with human TOPBP1. Reason: The source abstract directly describes GST pull-down and co-immunoprecipitation evidence, including synchronized HeLa-S3 cells; matching IntAct target records corroborate the pair. TOPBP1 BRCT-region interaction and altered CDC45 chromatin loading establish association, not a new molecular activity for CDC45. Retain generic binding outside the core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19805216 Assembly of the Cdc45-Mcm2-7-GINS complex in human cells req... | KEEP AS NON CORE | Summary: CDC45 association with MCM2/P49736 is consistent with human CMG assembly. Reason: PMID:19805216 reports CMG-component interactions by bimolecular fluorescence complementation in HeLa cells. Its accessible abstract does not resolve every construct pair, and the full paper could not be recovered. The preserved curator-defined pair is independently supported at the physical-complex level by purified human CMG and the human CMG structure. Retain the association without claiming a direct isolated binary-binding assay or transferring helicase catalysis to CDC45. |
| GO:0005515 protein binding | IPI PMID:19805216 Assembly of the Cdc45-Mcm2-7-GINS complex in human cells req... | KEEP AS NON CORE | Summary: CDC45 association with GINS4/Q9BRT9 is consistent with human CMG assembly. Reason: PMID:19805216 reports CMG-component interactions by bimolecular fluorescence complementation in HeLa cells. Its accessible abstract does not resolve every construct pair, and the full paper could not be recovered. The preserved curator-defined pair is independently supported at the physical-complex level by purified human CMG and the human CMG structure. Retain the association without claiming a direct isolated binary-binding assay or transferring helicase catalysis to CDC45. |
| GO:0005515 protein binding | IPI PMID:23910567 Cell cycle-dependent formation of Cdc45-Claspin complexes in... | KEEP AS NON CORE | Summary: The CDC45–RPA association is supported in the replication context. Reason: PMID:23910567 explicitly reports human CDC45 interaction with RPA and its persistence following UV treatment. Retain the original P15927 partner assertion, while recognizing that the accessible abstract describes RPA at complex level and does not independently establish an isolated RPA2 binary assay. This is a supported replication-protein association, not evidence for a separate CDC45 RPA-like activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23910567 Cell cycle-dependent formation of Cdc45-Claspin complexes in... | KEEP AS NON CORE | Summary: CDC45–CLSPN association varies with the cell cycle and DNA damage. Reason: The source abstract explicitly reports CDC45–CLSPN complex formation in human cells and reduced association after UV treatment. This supports the preserved Q9HAW4 interaction. Association and inhibitor experiments do not by themselves establish that CDC45 catalyzes or directly transmits a checkpoint signal. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | KEEP AS NON CORE | Summary: Endogenous CDC45–CDKN1A proximity is supported. Reason: The exact O75419–P38936 pair is present in IntAct EBI-6589845/IM-18707-19 for PMID:25241761, with a proximity-ligation assay in HeLa cells. This supports association/proximity in the tested cells, without establishing purified direct binding or a distinct CDC45 inhibitory activity. The abstract alone was not used as target-specific evidence. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: The CDC45–TTLL5 screening interaction is supported. Reason: Three exact O75419–Q53EZ4 IntAct records for PMID:25416956 include two-hybrid screening and validation (EBI-10188186, EBI-10345943, EBI-10506346), with human proteins tested in yeast. Retain generic binding as non-core. The evidence does not confer tubulin-modifying activity or a ciliary process on CDC45. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26167883 A unique binding mode enables MCM2 to chaperone histones H3-... | KEEP AS NON CORE | Summary: CDC45 associates with MCM2 in human replication complexes. Reason: The inspected Results and Figure 4 of PMID:26167883 describe CDC45 co-purification with MCM2 and reduced recovery with MCM2 histone-binding-domain mutants. This supports the physical association while preserving the distinction between MCM2 histone chaperoning and CDC45 function. No histone-chaperone activity is transferred to CDC45. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Summary: The CDC45–TTLL5 interaction is supported in the variant-screen assay. Reason: The exact pair is recorded in IntAct EBI-22145270/IM-27438-4264 for PMID:31515488, using a human-protein two-hybrid array in yeast. The TTLL5 features record variants with no interaction effect; they are not CDC45 mutations. This is target-specific interaction evidence, not a physiological tubulin-modification role for CDC45. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The HuRI CDC45–P61018 interaction is supported in the screened context. Reason: Exact accession and PMID joins identify three IntAct records for this human-protein pair, including validated two-hybrid record EBI-24686581; the assay host is yeast. These inspected curated target records substantiate the positive pair, without implying that the complete author network or every supplement was independently inspected. Retain generic binding as non-core and do not assign the partner's activity to CDC45. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The HuRI CDC45–Q53EZ4 interaction is supported in the screened context. Reason: Exact accession and PMID joins identify three IntAct records for this human-protein pair, including validated two-hybrid record EBI-24437429; the assay host is yeast. These inspected curated target records substantiate the positive pair, without implying that the complete author network or every supplement was independently inspected. Retain generic binding as non-core and do not assign the partner's activity to CDC45. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The HuRI CDC45–Q96D03 interaction is supported in the screened context. Reason: Exact accession and PMID joins identify three IntAct records for this human-protein pair, including validated two-hybrid record EBI-24272955; the assay host is yeast. These inspected curated target records substantiate the positive pair, without implying that the complete author network or every supplement was independently inspected. Retain generic binding as non-core and do not assign the partner's activity to CDC45. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The HuRI CDC45–Q9UGI0 interaction is supported in the screened context. Reason: Exact accession and PMID joins identify three IntAct records for this human-protein pair, including validated two-hybrid record EBI-24320690; the assay host is yeast. These inspected curated target records substantiate the positive pair, without implying that the complete author network or every supplement was independently inspected. Retain generic binding as non-core and do not assign the partner's activity to CDC45. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BioPlex recovers CDC45 association with GINS4. Reason: Exact O75419–Q9BRT9 records map to CDC45-bait affinity purification in HEK293T and HCT116 cells (EBI-54669885 and EBI-54923773). The records are spoke-expanded complex associations, not purified binary binding. They corroborate the replication complex while leaving generic protein binding non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BioPlex recovers CDC45 association with CLSPN. Reason: The exact O75419–Q9HAW4 pair is a spoke-expanded association from CDC45-bait affinity purification in HEK293T cells (EBI-54669885). Together with the independent CDC45–CLSPN study, it supports association without defining a new CDC45 molecular activity. |
| GO:0005515 protein binding | IPI PMID:39009827 Proteome-scale characterisation of motif-based interactome r... | KEEP AS NON CORE | Summary: CDC45 nuclear-localization peptides bind the importin KPNA4. Reason: The inspected Table 1 and related assay text of PMID:39009827 compare wild-type and R157C CDC45 residues 152–166 with engineered KPNA4 ARM-domain binding pockets using fluorescence polarization. Wild-type peptide binding and reduced mutant affinity support the pair; IntAct EBI-54804533 and EBI-55021140 preserve the mutation-effect features. The full-length co-immunoprecipitation example concerns KPNA7 and is not relabeled as KPNA4. CDC45 is the import cargo here, so this does not establish nuclear-import receptor activity. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:21383955 Interactions of MCP1 with components of the replication mach... | KEEP AS NON CORE | Summary: Nuclear CDC45 localization is directly supported. Reason: PMID:21383955 includes CDC45 in nuclear-fraction and immunoprecipitation experiments using human HeLa and K562 cells. This supports the source located_in assertion. The more informative functional setting is the nucleoplasmic chromatin-associated replication machinery. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:22474384 Properties of the human Cdc45/Mcm2-7/GINS helicase complex a... | KEEP AS NON CORE | Summary: Human nuclear/chromatin CMG supports CDC45 nuclear localization. Reason: PMID:22474384 reports CMG recovered from human chromatin and HeLa-cell experiments. The nuclear location is correct; CMG membership and nucleoplasmic replication supply the more informative core context. The isolated-complex biochemical experiments are kept distinct from cell localization. Supporting Evidence: |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The UniProt nuclear-location mapping is supported. Reason: The reviewed UniProt nuclear location is corroborated by human-cell fractionation and CMG chromatin recovery. Retain this correct broader location rather than treating an electronic location mapping as a distinct molecular function. |
| GO:0005634 nucleus | TAS PMID:9660782 The human homolog of Saccharomyces cerevisiae CDC45. | KEEP AS NON CORE | Summary: The early human CDC45 study supports nuclear association. Reason: The accessible PMID:9660782 abstract explicitly describes nuclear fractionation and changing association during S phase. This supports the broad located_in assertion without requiring that the source independently establish a nuclear biochemical activity. Supporting Evidence: |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Nucleoplasm is a supported CDC45 location relevant to genome replication. Reason: The target-specific Human Protein Atlas page for ENSG00000093009 reports nucleoplasm as its supported main location. HPA000614 and CAB009459 staining in human A-431, U-251MG and U2OS cells corroborates the original immunofluorescence-derived assertion. Human nuclear/chromatin replication experiments provide functional context, rather than inferring activity solely from staining. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-176298 | ACCEPT | Summary: The core nucleoplasmic location is supported independently of this pathway event. Reason: The cited Reactome event concerns ATR-dependent claspin activation. The cached event summary is pathway context rather than an independent CDC45 localization assay. Nucleoplasmic localization is nevertheless supported by the target HPA record and human nuclear/chromatin experiments. Retain the source assertion as a core location, without transferring the event catalyst's activity to CDC45. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-176318 | ACCEPT | Summary: The core nucleoplasmic location is supported independently of this pathway event. Reason: The cited Reactome event concerns claspin loading at replication initiation. The cached event summary is pathway context rather than an independent CDC45 localization assay. Nucleoplasmic localization is nevertheless supported by the target HPA record and human nuclear/chromatin experiments. Retain the source assertion as a core location, without transferring the event catalyst's activity to CDC45. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-68916 | ACCEPT | Summary: The core nucleoplasmic location is supported independently of this pathway event. Reason: The cited Reactome event concerns RPA association with the origin complex. The cached event summary is pathway context rather than an independent CDC45 localization assay. Nucleoplasmic localization is nevertheless supported by the target HPA record and human nuclear/chromatin experiments. Retain the source assertion as a core location, without transferring the event catalyst's activity to CDC45. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-68917 | ACCEPT | Summary: The core nucleoplasmic location is supported independently of this pathway event. Reason: The cited Reactome event concerns CDC45 recruitment to the preinitiation complex. The cached event summary is pathway context rather than an independent CDC45 localization assay. Nucleoplasmic localization is nevertheless supported by the target HPA record and human nuclear/chromatin experiments. Retain the source assertion as a core location, without transferring the event catalyst's activity to CDC45. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8961915 | ACCEPT | Summary: The core nucleoplasmic location is supported independently of this pathway event. Reason: The cited Reactome event concerns E2F1-dependent CDC45 gene expression. The cached event summary is pathway context rather than an independent CDC45 localization assay. Nucleoplasmic localization is nevertheless supported by the target HPA record and human nuclear/chromatin experiments. Retain the source assertion as a core location, without transferring the event catalyst's activity to CDC45. In particular, a gene-expression event does not make the resulting CDC45 protein a transcriptional activator. |
| GO:0005694 chromosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: CDC45 associates with replicating chromosomal chromatin. Reason: Human CMG is recovered from chromatin and operates in chromosome replication. This supports the UniProt chromosome-location mapping; it does not imply permanent residence throughout the cell cycle or an independent chromosome-structural function. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: A cytosolic CDC45 pool is supported by immunofluorescence. Reason: The current target-specific HPA record reports cytosol as a supported additional location, including CAB009459 staining in A-431 and U2OS cells. Retain the observed location outside the nucleoplasmic replication core; no cytosolic molecular role is inferred. Supporting Evidence: GO_REF:0000052 |
| GO:0006260 DNA replication | IDA PMID:22474384 Properties of the human Cdc45/Mcm2-7/GINS helicase complex a... | ACCEPT | Summary: CDC45 contributes directly to DNA replication as part of CMG. Reason: The human CMG complex was purified and assayed with human DNA polymerase epsilon in rolling-circle replication; later reconstitution with purified human replication proteins corroborates the role. This is structural participation in the replication apparatus, rather than a phenotype-only association. The catalytic ATPase/helicase motor resides in MCM2–7. Supporting Evidence: PMID:22474384 the coordinated action of these replication complexes supports leading strand synthesis |
| GO:0006270 DNA replication initiation | IBA GO_REF:0000033 | ACCEPT | Summary: The inherited replication-initiation role is a core CDC45 function. Reason: The conserved PAINT node PANTHER:PTN000053416 is consistent with recruitment of CDC45 into preinitiation complexes and assembly of active CMG. Human cell-cycle assembly and structural/biochemical evidence corroborate its participation. Differences in upstream loading factors across species do not demonstrate loss of CDC45 participation itself. Supporting Evidence: GO_REF:0000033 PMID:27374770 required for initiation of DNA replication origin firing |
| GO:0006270 DNA replication initiation | IEA GO_REF:0000002 | ACCEPT | Summary: The CDC45 family mapping to replication initiation is supported. Reason: The InterPro IPR003874 mapping is consistent with the conserved CDC45 family, human CMG assembly and experimentally established replication function. This is the correct biological process for the structural replication factor; it does not assign catalytic activity from a domain name. |
| GO:0006270 DNA replication initiation | TAS PMID:9660782 The human homolog of Saccharomyces cerevisiae CDC45. | ACCEPT | Summary: The early replication-initiation assignment remains biologically sound. Reason: The original abstract reports human CDC45 association with ORC2 and cell-cycle-dependent nuclear behavior. These early findings are corroborated by later human CMG assembly and functional reconstitution, so the original TAS assertion is retained as core even though the original full paper was not recovered. Supporting Evidence: PMID:9660782 Consistent with a role of CDC45L protein in the initiation of DNA replication |
| GO:0031261 DNA replication preinitiation complex | IBA GO_REF:0000033 | ACCEPT | Summary: CDC45 is a conserved component of the replication preinitiation machinery. Reason: The PAINT node PANTHER:PTN000053416 is consistent with human CDC45 participation in the preinitiation/CMG machinery. The source target O75419 appearing among descendant evidence is expected and is not circular. The more specific CMG complex is used in the core synthesis; the existing broader source annotation is preserved. Supporting Evidence: GO_REF:0000033 PMID:27374770 CDC45 encodes a component of both the pre-initiation (preIC) and CMG helicase complexes |
| GO:0036064 ciliary basal body | IDA PMID:29257953 Evolutionary Proteomics Uncovers Ancient Associations of Cil... | UNDECIDED | Summary: The source-specific basal-body localization remains unadjudicated. Reason: The full cached paper describes evolutionary ciliome proteomics and GFP-fusion localization screening in mammalian cells, including Table S5/Figure S1. The exact CDC45 construct and localization result were not recovered from those target-level supplementary data. The absence of the name in accessible main text does not invalidate the curator's IDA assertion. HPA centrosome localization is compatible background but is not a substitute for the specific ciliary basal-body assay. Preserve the annotation pending target evidence. Supporting Evidence: |
| GO:0071162 CMG complex | IPI PMID:22474384 Properties of the human Cdc45/Mcm2-7/GINS helicase complex a... | ACCEPT | Summary: CDC45 is a structural subunit of the human CMG helicase. Reason: Purified human CMG contains CDC45, the six MCM subunits and four GINS subunits. Human CMG structures and functional replication assays establish this membership and its central role. Complex-level ATP-dependent unwinding is represented as contributes_to molecular function, not autonomous CDC45 catalysis. Supporting Evidence: PMID:22474384 its association with Cdc45 and GINS (the CMG complex) |
| GO:1902977 mitotic DNA replication preinitiation complex assembly | IBA GO_REF:0000033 | ACCEPT | Summary: CDC45 contributes structurally to mitotic replication preinitiation-complex assembly. Reason: The inherited PAINT function is consistent with the conserved CDC45 interfaces that assemble the MCM/GINS architecture and human cell-cycle CMG formation. The human CDC45 crystal construct lacks residues 154–164; docking in that study used fly CMG and functional interface-mutant tests used Xenopus proteins/egg extracts. Those experiments support conserved assembly mechanics without being mislabeled as human mutant assays. Supporting Evidence: GO_REF:0000033 PMID:27189187 Cdc45 association with the MCM ring and GINS co-activator, critical for CMG assembly |
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Download this section (compressed HTML)Q: What target-specific experiments establish CDC45 participation in DNA replication checkpoint signal transduction, beyond replication activity, CLSPN association and being regulated during stress?
Q: Which CDC45 construct and localization image underlie the ciliary basal-body annotation in PMID:29257953, and does the result apply to endogenous human CDC45?
Q: How does CDC45 contact origin DNA within the human preinitiation complex, and does it possess origin-selective binding independently of its recruitment partners?
Q: Does the full text of PMID:10518787 assay the preserved POLA1/P09884 pair as well as the polymerase-alpha p70 subunit explicitly identified in the abstract?
Q: How do the preserved alternative products differ in DNA binding, CMG incorporation and nuclear transport? Existing source annotations do not resolve their functional equivalence.
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