MCM4 (CDC54) encodes one of the six related AAA+ ATPase subunits of the heterohexameric Mcm2-7 complex, the motor of the eukaryotic replicative DNA helicase. In G1, ORC, Cdc6 and Cdt1 load Mcm2-7 onto origin DNA as an inactive head-to-head double hexamer that encircles and can slide on dsDNA (origin licensing, pre-RC formation). At origin firing in S phase, Dbf4-dependent kinase phosphorylates Mcm4 (its principal MCM target) to recruit Cdc45, and with GINS the Cdc45-Mcm2-7-GINS (CMG) helicase forms, encircles the leading-strand template and translocates 3'->5' to unwind DNA ahead of the replisome. Mcm2-7 function is needed continuously for fork progression, and the CMG is also required for break-induced replication. Mcm4 contributes Walker A/B motifs and an arginine finger to inter-subunit ATPase sites, an N-terminal zinc-binding and OB-fold domain with DNA-binding residues, and with Mcm6 and Mcm7 forms an Mcm467 subcomplex with in vitro 3'->5' helicase activity. CDK activity drives net nuclear export of Mcm2-7 after S phase, helping restrict replication to once per cell cycle.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000727 double-strand break repair via break-induced replication | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Break-induced replication (BIR) uses the replicative CMG helicase to copy the donor template after strand invasion; Lydeard et al. showed in S. cerevisiae that BIR requires Mcm2-7, Cdc45 and GINS (but not the ORC/Cdc6 loading step). Mcm4, as a motor subunit of the helicase, does part of the work (DNA unwinding) of this repair-coupled replication, so participation is satisfied, but it is a specialised use of the replicative helicase rather than a core, dedicated role. Reason: The PAINT IBD at the Mcm4 subfamily node PTN000179968 is seeded by this gene's own IMP annotation (SGD:S000006223), which is the expected pattern, not circularity. Kept, but as non-core: BIR is a repair context for the same helicase activity. Supporting Evidence: PMID:20516198 Here we show that BIR requires the replicative DNA helicase (Cdc45, the GINS, and Mcm2-7 proteins) as well as Cdt1 |
| GO:0000727 double-strand break repair via break-induced replication | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Break-induced replication (BIR) uses the replicative CMG helicase to copy the donor template after strand invasion; Lydeard et al. showed in S. cerevisiae that BIR requires Mcm2-7, Cdc45 and GINS (but not the ORC/Cdc6 loading step). Mcm4, as a motor subunit of the helicase, does part of the work (DNA unwinding) of this repair-coupled replication, so participation is satisfied, but it is a specialised use of the replicative helicase rather than a core, dedicated role. Reason: ARBA electronic mapping consistent with the IMP and IBA annotations; kept as non-core. Supporting Evidence: PMID:20516198 Here we show that BIR requires the replicative DNA helicase (Cdc45, the GINS, and Mcm2-7 proteins) as well as Cdt1 |
| GO:0000727 double-strand break repair via break-induced replication | IMP PMID:20516198 Break-induced replication requires all essential DNA replica... | KEEP AS NON CORE | Summary: Break-induced replication (BIR) uses the replicative CMG helicase to copy the donor template after strand invasion; Lydeard et al. showed in S. cerevisiae that BIR requires Mcm2-7, Cdc45 and GINS (but not the ORC/Cdc6 loading step). Mcm4, as a motor subunit of the helicase, does part of the work (DNA unwinding) of this repair-coupled replication, so participation is satisfied, but it is a specialised use of the replicative helicase rather than a core, dedicated role. Reason: Direct genetic evidence in S. cerevisiae (degron/ts inactivation of Mcm2-7 subunits blocks BIR). Non-core because it is a specialised repair use of the replicative helicase. Supporting Evidence: PMID:20516198 Here we show that BIR requires the replicative DNA helicase (Cdc45, the GINS, and Mcm2-7 proteins) as well as Cdt1 |
| GO:0003677 DNA binding | IEA GO_REF:0000002 | MODIFY | Summary: Generic DNA binding from InterPro MCM domain signatures. Reason: Correct but too general. Mcm4-containing complexes have characterised ATP-dependent ssDNA binding (Bochman & Schwacha 2007), and loaded Mcm2-7 double hexamers encircle and slide on dsDNA (Remus et al. 2009). Replace with the two specific terms; ssDNA binding is already carried by this gene (IBA, IMP). Proposed replacements: single-stranded DNA binding double-stranded DNA binding Supporting Evidence: PMID:17895243 We demonstrate that both complexes are toroidal and possess a similar ATP-dependent single-stranded DNA (ssDNA) binding activity PMID:19896182 DNA runs through a central channel in the double hexamer, and, once loaded, Mcm2-7 can slide passively along double-stranded DNA |
| GO:0003678 DNA helicase activity | IDA PMID:15723534 The Mcm467 complex of Saccharomyces cerevisiae is preferenti... | MODIFY | Summary: DNA helicase activity for Mcm4. In S. cerevisiae Mcm4 is a motor subunit of the Mcm2-7 ring; helicase activity has been measured for the Mcm467 subcomplex (Kaplan et al. 2003; Biswas-Fiss et al. 2005), for reconstituted Mcm2-7 under gate-closing conditions (Bochman & Schwacha 2008, where Mcm4 K574A abolishes activity), and physiologically for the CMG holoenzyme. The activity is a property of the assembled ring (ATPase sites form in trans between neighbouring subunits), so Mcm4 contributes to it rather than enabling it alone. Reason: Correct but less specific than the evidence supports. Mcm4,6,7 and CMG translocate on the leading strand with 3'->5' polarity (opposite to DnaB), so the supported, more specific term is GO:0043138 3'-5' DNA helicase activity (already annotated to this gene by IDA, contributes_to), together with GO:0017116 single-stranded DNA helicase activity (IBA/IDA, contributes_to). Any retained annotation should carry contributes_to. Proposed replacements: 3'-5' DNA helicase activity single-stranded DNA helicase activity Supporting Evidence: PMID:15723534 The DNA helicase activity of Mcm467 complex is also significantly stimulated by the ARS1-derived sequences PMID:13679365 The Mcm4,6,7 mechanism is very similar to DnaB, except the proteins translocate with opposite polarity along DNA |
| GO:0003678 DNA helicase activity | IEA GO_REF:0000120 | MODIFY | Summary: DNA helicase activity for Mcm4. In S. cerevisiae Mcm4 is a motor subunit of the Mcm2-7 ring; helicase activity has been measured for the Mcm467 subcomplex (Kaplan et al. 2003; Biswas-Fiss et al. 2005), for reconstituted Mcm2-7 under gate-closing conditions (Bochman & Schwacha 2008, where Mcm4 K574A abolishes activity), and physiologically for the CMG holoenzyme. The activity is a property of the assembled ring (ATPase sites form in trans between neighbouring subunits), so Mcm4 contributes to it rather than enabling it alone. Reason: Correct but less specific than the evidence supports. Mcm4,6,7 and CMG translocate on the leading strand with 3'->5' polarity (opposite to DnaB), so the supported, more specific term is GO:0043138 3'-5' DNA helicase activity (already annotated to this gene by IDA, contributes_to), together with GO:0017116 single-stranded DNA helicase activity (IBA/IDA, contributes_to). Any retained annotation should carry contributes_to. This row is asserted with 'enables', which overstates an isolated subunit's capacity; the replacement should be qualified contributes_to. Proposed replacements: 3'-5' DNA helicase activity single-stranded DNA helicase activity Supporting Evidence: PMID:13679365 Mcm4,6,7 binds to only one strand of a duplex during unwinding, corresponding to the leading strand of a replication fork PMID:13679365 The Mcm4,6,7 mechanism is very similar to DnaB, except the proteins translocate with opposite polarity along DNA PMID:18657510 Our results show that purified Mcm2-7 acts as a helicase file:yeast/MCM4/MCM4-uniprot.txt K->A: Loss of MCM2-7 complex helicase activity. |
| GO:0003688 DNA replication origin binding | IDA PMID:11756674 The B2 element of the Saccharomyces cerevisiae ARS1 origin o... | KEEP AS NON CORE | Summary: DNA replication origin binding. Mcm2-7 is recruited to origins by ORC-Cdc6-Cdt1 and is loaded around origin dsDNA as a head-to-head double hexamer; origin association of Mcm2-7 depends on ORC binding elements and the B2 element of ARS1. Wilmes & Bell measured Mcm2-7 origin association by ChIP at ARS1 B2 mutants. Reason: Mcm2-7 associates with origin DNA, but sequence recognition is done by ORC and the loaded double hexamer topologically encircles and slides on dsDNA without sequence specificity. The term is defensible as a description of where the loaded complex sits, but it is not the intrinsic activity of Mcm4; kept as non-core. The intrinsic activities are captured by ssDNA binding and helicase terms. Supporting Evidence: PMID:11756674 Nonfunctional B2 sequences show a corresponding loss in Mcm2-7p origin association PMID:19896182 DNA runs through a central channel in the double hexamer, and, once loaded, Mcm2-7 can slide passively along double-stranded DNA |
| GO:0003688 DNA replication origin binding | IDA PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative co... | KEEP AS NON CORE | Summary: DNA replication origin binding. Mcm2-7 is recruited to origins by ORC-Cdc6-Cdt1 and is loaded around origin dsDNA as a head-to-head double hexamer; origin association of Mcm2-7 depends on ORC binding elements and the B2 element of ARS1. Kawasaki et al. reconstituted pre-RC assembly on ARS1 DNA and observed structure-specific (bubble/Y) DNA binding by Cdt1-Mcm2-7. Reason: Mcm2-7 associates with origin DNA, but sequence recognition is done by ORC and the loaded double hexamer topologically encircles and slides on dsDNA without sequence specificity. The term is defensible as a description of where the loaded complex sits, but it is not the intrinsic activity of Mcm4; kept as non-core. The intrinsic activities are captured by ssDNA binding and helicase terms. Supporting Evidence: PMID:16824194 The results reveal sequential recruitment of ORC, Cdc6p, Cdt1p and Mcm2-7p on to ARS1 DNA PMID:16824194 exhibits structure-specific DNA binding, interacting only with bubble- or Y-shape-DNA |
| GO:0003688 DNA replication origin binding | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: DNA replication origin binding. Mcm2-7 is recruited to origins by ORC-Cdc6-Cdt1 and is loaded around origin dsDNA as a head-to-head double hexamer; origin association of Mcm2-7 depends on ORC binding elements and the B2 element of ARS1. Reason: Mcm2-7 associates with origin DNA, but sequence recognition is done by ORC and the loaded double hexamer topologically encircles and slides on dsDNA without sequence specificity. The term is defensible as a description of where the loaded complex sits, but it is not the intrinsic activity of Mcm4; kept as non-core. The intrinsic activities are captured by ssDNA binding and helicase terms. ARBA mapping, consistent with the IDA rows. Supporting Evidence: PMID:19910535 MCM2-7 loading was found to be dependent on the presence of all pre-RC proteins, origin DNA, and ATP hydrolysis PMID:19910535 Using electron microscopy (EM), we observed that loaded MCM2-7 encircles DNA |
| GO:0003697 single-stranded DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: Single-stranded DNA binding. Both MCM2-7 and MCM467 from S. cerevisiae show ATP-dependent ssDNA binding; the Mcm4 OB-fold carries conserved DNA-binding arginines essential for function, and in CMG the leading-strand ssDNA passes through the Mcm ring. Reason: PAINT IBD at the MCM2-7 family node PTN000179711, seeded by this gene (SGD:S000006223). ssDNA binding is the substrate-engaging activity of the translocating helicase and is experimentally supported in yeast. Supporting Evidence: PMID:17895243 We demonstrate that both complexes are toroidal and possess a similar ATP-dependent single-stranded DNA (ssDNA) binding activity PMID:26854665 two conserved DNA binding arginine residues in the yeast Mcm4 and Mcm7 OB domains are essential for function |
| GO:0003697 single-stranded DNA binding | IMP PMID:17895243 Differences in the single-stranded DNA binding activities of... | ACCEPT | Summary: Single-stranded DNA binding. Both MCM2-7 and MCM467 from S. cerevisiae show ATP-dependent ssDNA binding; the Mcm4 OB-fold carries conserved DNA-binding arginines essential for function, and in CMG the leading-strand ssDNA passes through the Mcm ring. Reason: Direct biochemical evidence (Bochman & Schwacha 2007) with yeast complexes containing Mcm4. Supporting Evidence: PMID:17895243 We demonstrate that both complexes are toroidal and possess a similar ATP-dependent single-stranded DNA (ssDNA) binding activity |
| GO:0004386 helicase activity | EXP PMID:13679365 Mcm4,6,7 uses a "pump in ring" mechanism to unwind DNA by st... | MODIFY | Summary: helicase activity for Mcm4. In S. cerevisiae Mcm4 is a motor subunit of the Mcm2-7 ring; helicase activity has been measured for the Mcm467 subcomplex (Kaplan et al. 2003; Biswas-Fiss et al. 2005), for reconstituted Mcm2-7 under gate-closing conditions (Bochman & Schwacha 2008, where Mcm4 K574A abolishes activity), and physiologically for the CMG holoenzyme. The activity is a property of the assembled ring (ATPase sites form in trans between neighbouring subunits), so Mcm4 contributes to it rather than enabling it alone. Reason: Correct but less specific than the evidence supports. Mcm4,6,7 and CMG translocate on the leading strand with 3'->5' polarity (opposite to DnaB), so the supported, more specific term is GO:0043138 3'-5' DNA helicase activity (already annotated to this gene by IDA, contributes_to), together with GO:0017116 single-stranded DNA helicase activity (IBA/IDA, contributes_to). Any retained annotation should carry contributes_to. This row is asserted with 'enables', which overstates an isolated subunit's capacity; the replacement should be qualified contributes_to. Proposed replacements: 3'-5' DNA helicase activity single-stranded DNA helicase activity Supporting Evidence: PMID:13679365 Mcm4,6,7 binds to only one strand of a duplex during unwinding, corresponding to the leading strand of a replication fork PMID:13679365 The Mcm4,6,7 mechanism is very similar to DnaB, except the proteins translocate with opposite polarity along DNA PMID:18657510 Our results show that purified Mcm2-7 acts as a helicase file:yeast/MCM4/MCM4-uniprot.txt K->A: Loss of MCM2-7 complex helicase activity. |
| GO:0004386 helicase activity | IEA GO_REF:0000117 | MODIFY | Summary: helicase activity for Mcm4. In S. cerevisiae Mcm4 is a motor subunit of the Mcm2-7 ring; helicase activity has been measured for the Mcm467 subcomplex (Kaplan et al. 2003; Biswas-Fiss et al. 2005), for reconstituted Mcm2-7 under gate-closing conditions (Bochman & Schwacha 2008, where Mcm4 K574A abolishes activity), and physiologically for the CMG holoenzyme. The activity is a property of the assembled ring (ATPase sites form in trans between neighbouring subunits), so Mcm4 contributes to it rather than enabling it alone. Reason: Correct but less specific than the evidence supports. Mcm4,6,7 and CMG translocate on the leading strand with 3'->5' polarity (opposite to DnaB), so the supported, more specific term is GO:0043138 3'-5' DNA helicase activity (already annotated to this gene by IDA, contributes_to), together with GO:0017116 single-stranded DNA helicase activity (IBA/IDA, contributes_to). Any retained annotation should carry contributes_to. This row is asserted with 'enables', which overstates an isolated subunit's capacity; the replacement should be qualified contributes_to. Proposed replacements: 3'-5' DNA helicase activity single-stranded DNA helicase activity Supporting Evidence: PMID:13679365 Mcm4,6,7 binds to only one strand of a duplex during unwinding, corresponding to the leading strand of a replication fork PMID:13679365 The Mcm4,6,7 mechanism is very similar to DnaB, except the proteins translocate with opposite polarity along DNA PMID:18657510 Our results show that purified Mcm2-7 acts as a helicase file:yeast/MCM4/MCM4-uniprot.txt K->A: Loss of MCM2-7 complex helicase activity. |
| GO:0005515 protein binding | IPI PMID:12480933 Reconstitution of the Mcm2-7p heterohexamer, subunit arrange... | REMOVE | Summary: IPI interaction of Mcm4 with Mcm2, reported in pairwise interaction mapping of recombinant MCM subunits during reconstitution of Mcm2-7. Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005515 protein binding | IPI PMID:12480933 Reconstitution of the Mcm2-7p heterohexamer, subunit arrange... | REMOVE | Summary: IPI interaction of Mcm4 with Mcm7, reported in pairwise interaction mapping of recombinant MCM subunits during reconstitution of Mcm2-7. Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005515 protein binding | IPI PMID:12480933 Reconstitution of the Mcm2-7p heterohexamer, subunit arrange... | REMOVE | Summary: IPI interaction of Mcm4 with Mcm6, reported in pairwise interaction mapping of recombinant MCM subunits during reconstitution of Mcm2-7. Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005515 protein binding | IPI PMID:18719252 High-quality binary protein interaction map of the yeast int... | REMOVE | Summary: IPI interaction of Mcm4 with Mcm2, reported in a high-throughput yeast two-hybrid binary interactome map. Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005515 protein binding | IPI PMID:19896182 Concerted loading of Mcm2-7 double hexamers around DNA durin... | REMOVE | Summary: IPI interaction of Mcm4 with Mcm2, reported in purification of Mcm2-7 via FLAG-tagged Mcm4 and reconstitution of double-hexamer loading. Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005515 protein binding | IPI PMID:19896182 Concerted loading of Mcm2-7 double hexamers around DNA durin... | REMOVE | Summary: IPI interaction of Mcm4 with Mcm7, reported in purification of Mcm2-7 via FLAG-tagged Mcm4 and reconstitution of double-hexamer loading. Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005515 protein binding | IPI PMID:19896182 Concerted loading of Mcm2-7 double hexamers around DNA durin... | REMOVE | Summary: IPI interaction of Mcm4 with Mcm6, reported in purification of Mcm2-7 via FLAG-tagged Mcm4 and reconstitution of double-hexamer loading. Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005515 protein binding | IPI PMID:19910535 A double-hexameric MCM2-7 complex is loaded onto origin DNA ... | REMOVE | Summary: IPI interaction of Mcm4 with Mcm2, reported in reconstitution of MCM2-7 double-hexamer loading. Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005515 protein binding | IPI PMID:19910927 SCF(Dia2) regulates DNA replication forks during S-phase in ... | REMOVE | Summary: IPI interaction of Mcm4 with Mcm2, reported in a two-hybrid/co-IP study of SCF(Dia2) replisome partners. Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005515 protein binding | IPI PMID:22433841 Mcm10 associates with the loaded DNA helicase at replication... | REMOVE | Summary: IPI interaction of Mcm4 with Mcm2, reported in co-immunoprecipitation of Mcm4 with Mcm2-7, Mcm10 and CMG/replisome components. Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005515 protein binding | IPI PMID:22433841 Mcm10 associates with the loaded DNA helicase at replication... | REMOVE | Summary: IPI interaction of Mcm4 with Mcm10, reported in co-immunoprecipitation of Mcm4 with Mcm2-7, Mcm10 and CMG/replisome components. Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005515 protein binding | IPI PMID:22433841 Mcm10 associates with the loaded DNA helicase at replication... | REMOVE | Summary: IPI interaction of Mcm4 with Mcm7, reported in co-immunoprecipitation of Mcm4 with Mcm2-7, Mcm10 and CMG/replisome components. Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005515 protein binding | IPI PMID:22433841 Mcm10 associates with the loaded DNA helicase at replication... | REMOVE | Summary: IPI interaction of Mcm4 with Mcm6, reported in co-immunoprecipitation of Mcm4 with Mcm2-7, Mcm10 and CMG/replisome components. Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005515 protein binding | IPI PMID:22433841 Mcm10 associates with the loaded DNA helicase at replication... | REMOVE | Summary: IPI interaction of Mcm4 with Psf1 (GINS), reported in co-immunoprecipitation of Mcm4 with Mcm2-7, Mcm10 and CMG/replisome components. Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005515 protein binding | IPI PMID:23851460 Cryo-EM structure of a helicase loading intermediate contain... | REMOVE | Summary: IPI interaction of Mcm4 with Mcm2, reported in cryo-EM and pull-downs of the ORC-Cdc6-Cdt1-MCM2-7 (OCCM) loading intermediate. Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005515 protein binding | IPI PMID:24805245 A Ctf4 trimer couples the CMG helicase to DNA polymerase Ξ± i... | REMOVE | Summary: IPI interaction of Mcm4 with Mcm2, reported in co-immunoprecipitation of Mcm4-5FLAG with CMG and Ctf4 in a study of Ctf4-GINS coupling. Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005515 protein binding | IPI PMID:24805245 A Ctf4 trimer couples the CMG helicase to DNA polymerase Ξ± i... | REMOVE | Summary: IPI interaction of Mcm4 with Mcm6, reported in co-immunoprecipitation of Mcm4-5FLAG with CMG and Ctf4 in a study of Ctf4-GINS coupling. Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005515 protein binding | IPI PMID:24805245 A Ctf4 trimer couples the CMG helicase to DNA polymerase Ξ± i... | REMOVE | Summary: IPI interaction of Mcm4 with Psf1 (GINS), reported in co-immunoprecipitation of Mcm4-5FLAG with CMG and Ctf4 in a study of Ctf4-GINS coupling. Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005515 protein binding | IPI PMID:26222030 Structure of the eukaryotic MCM complex at 3.8 Γ . | REMOVE | Summary: IPI interaction of Mcm4 with Mcm2, reported in the cryo-EM structure of the MCM2-7 double hexamer. Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005515 protein binding | IPI PMID:26854664 A new MCM modification cycle regulates DNA replication initi... | REMOVE | Summary: IPI interaction of Mcm4 with Smt3 (SUMO), reported in analysis of MCM SUMOylation and its effect on CMG assembly. Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005515 protein binding | IPI PMID:26854664 A new MCM modification cycle regulates DNA replication initi... | REMOVE | Summary: IPI interaction of Mcm4 with Psf1 (GINS), reported in analysis of MCM SUMOylation and its effect on CMG assembly. Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: IPI interaction of Mcm4 with Mcm2, reported in a proteome-scale yeast interactome (co-fractionation/AP-MS with structural modelling). Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: IPI interaction of Mcm4 with Mcm10, reported in a proteome-scale yeast interactome (co-fractionation/AP-MS with structural modelling). Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: IPI interaction of Mcm4 with Mcm7, reported in a proteome-scale yeast interactome (co-fractionation/AP-MS with structural modelling). Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: IPI interaction of Mcm4 with Mcm6, reported in a proteome-scale yeast interactome (co-fractionation/AP-MS with structural modelling). Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: IPI interaction of Mcm4 with Psf1 (GINS), reported in a proteome-scale yeast interactome (co-fractionation/AP-MS with structural modelling). Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005515 protein binding | IPI PMID:9154825 A lesion in the DNA replication initiation factor Mcm10 indu... | REMOVE | Summary: IPI interaction of Mcm4 with Mcm10, reported in identification of Mcm10 as an interactor of MCM2-7 subunits. Reason: Bare GO:0005515 protein binding is uninformative and is removed under the repository protein-binding policy. The interaction itself is not in doubt: Mcm4 is a stoichiometric subunit of the Mcm2-7 hexamer and of the CMG helicase, and the functionally meaningful content of these interactions is already captured by the MCM complex (GO:0042555), CMG complex (GO:0071162), pre-RC (GO:0005656) and helicase-activity annotations. No more specific molecular-function term (e.g. an adaptor or regulator activity) is supported for Mcm4 by these binary interaction data. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: ATP binding, from InterPro MCM domain signatures. Mcm4 has a Walker A motif (568-575) in its AAA+ domain, and K574A abolishes Mcm2-7 helicase activity. Reason: Correct; the Walker A lysine is required for helicase function. Non-core because the informative function is the ATP-driven helicase activity. Supporting Evidence: file:yeast/MCM4/MCM4-uniprot.txt /note="Walker A" file:yeast/MCM4/MCM4-uniprot.txt K->A: Loss of MCM2-7 complex helicase activity. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Nuclear localization of Mcm4. PAINT IBD at PTN000179712 for the MCM family. Reason: Mcm2-7 acts on nuclear chromosomes; nucleus is supported experimentally in yeast. Supporting Evidence: PMID:10704410 Mcm2-4, 6 and 7 were concentrated in the nucleus in G1 phase, gradually exported to the cytoplasm during S phase, and excluded from the nucleus by G2 and M phase |
| GO:0005634 nucleus | IDA PMID:10559985 G1-phase and B-type cyclins exclude the DNA-replication fact... | ACCEPT | Summary: Nuclear localization of Mcm4. Labib et al. showed Mcm4 is nuclear in G1 and excluded from the nucleus by CDKs. Reason: Direct localization evidence in S. cerevisiae. Supporting Evidence: PMID:10559985 We show here that, in budding yeast, CDKs exclude the essential prereplicative-complex component Mcm4 from the nucleus |
| GO:0005634 nucleus | IDA PMID:10704410 Clb/Cdc28 kinases promote nuclear export of the replication ... | ACCEPT | Summary: Nuclear localization of Mcm4. Nguyen et al. showed cell-cycle-regulated nuclear accumulation of Mcm2-7 in G1. Reason: Direct localization evidence in S. cerevisiae. Supporting Evidence: PMID:10704410 Mcm2-4, 6 and 7 were concentrated in the nucleus in G1 phase, gradually exported to the cytoplasm during S phase, and excluded from the nucleus by G2 and M phase |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Nuclear localization of Mcm4. UniProt subcellular-location mapping. Reason: Consistent with experimental localization. Supporting Evidence: PMID:10704410 Mcm2-4, 6 and 7 were concentrated in the nucleus in G1 phase, gradually exported to the cytoplasm during S phase, and excluded from the nucleus by G2 and M phase |
| GO:0005634 nucleus | NAS PMID:25313033 CMG helicase and DNA polymerase Ξ΅ form a functional 15-subun... | ACCEPT | Summary: Nuclear localization of Mcm4. NAS from the CMG-Pol epsilon reconstitution paper. Reason: Correct; experimentally supported by other rows. Supporting Evidence: PMID:10704410 Mcm2-4, 6 and 7 were concentrated in the nucleus in G1 phase, gradually exported to the cytoplasm during S phase, and excluded from the nucleus by G2 and M phase |
| GO:0005654 nucleoplasm | TAS Reactome:R-SCE-169439 | ACCEPT | Summary: Nucleoplasm, from Reactome yeast replication reactions (MCM loading and Mcm2-7 fork unwinding). Reason: Correct location for a chromatin-acting replication factor; Reactome reactions place the MCM2-7 events in the nucleoplasm. Supporting Evidence: Reactome:R-SCE-169439 The MCM2-7 complex is the putative replicative helicase that unwinds replication forks |
| GO:0005654 nucleoplasm | TAS Reactome:R-SCE-9749300 | ACCEPT | Summary: Nucleoplasm, from Reactome yeast replication reactions (MCM loading and Mcm2-7 fork unwinding). Reason: Correct location for a chromatin-acting replication factor; Reactome reactions place the MCM2-7 events in the nucleoplasm. Supporting Evidence: PMID:10704410 Mcm2-4, 6 and 7 were concentrated in the nucleus in G1 phase, gradually exported to the cytoplasm during S phase, and excluded from the nucleus by G2 and M phase |
| GO:0005654 nucleoplasm | TAS Reactome:R-SCE-9749345 | ACCEPT | Summary: Nucleoplasm, from Reactome yeast replication reactions (MCM loading and Mcm2-7 fork unwinding). Reason: Correct location for a chromatin-acting replication factor; Reactome reactions place the MCM2-7 events in the nucleoplasm. Supporting Evidence: PMID:10704410 Mcm2-4, 6 and 7 were concentrated in the nucleus in G1 phase, gradually exported to the cytoplasm during S phase, and excluded from the nucleus by G2 and M phase |
| GO:0005654 nucleoplasm | TAS Reactome:R-SCE-9749381 | ACCEPT | Summary: Nucleoplasm, from Reactome yeast replication reactions (MCM loading and Mcm2-7 fork unwinding). Reason: Correct location for a chromatin-acting replication factor; Reactome reactions place the MCM2-7 events in the nucleoplasm. Supporting Evidence: PMID:10704410 Mcm2-4, 6 and 7 were concentrated in the nucleus in G1 phase, gradually exported to the cytoplasm during S phase, and excluded from the nucleus by G2 and M phase |
| GO:0005654 nucleoplasm | TAS Reactome:R-SCE-9749401 | ACCEPT | Summary: Nucleoplasm, from Reactome yeast replication reactions (MCM loading and Mcm2-7 fork unwinding). Reason: Correct location for a chromatin-acting replication factor; Reactome reactions place the MCM2-7 events in the nucleoplasm. Supporting Evidence: Reactome:R-SCE-9749401 MCM2-7 double hexamers are connected head-to-head via their N-terminal rings |
| GO:0005656 nuclear pre-replicative complex | IDA PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative co... | ACCEPT | Summary: Mcm4 is part of the nuclear pre-replicative complex as a subunit of the loaded Mcm2-7 double hexamer. Reason: In vitro reconstitution of pre-RC assembly with Mcm2-7. Supporting Evidence: PMID:16824194 The results reveal sequential recruitment of ORC, Cdc6p, Cdt1p and Mcm2-7p on to ARS1 DNA |
| GO:0005656 nuclear pre-replicative complex | IDA PMID:9335335 Components and dynamics of DNA replication complexes in S. c... | ACCEPT | Summary: Mcm4 is part of the nuclear pre-replicative complex as a subunit of the loaded Mcm2-7 double hexamer. Reason: Aparicio et al. identified MCM proteins as pre-RC components by ChIP. Supporting Evidence: PMID:9335335 We demonstrate that ORC, Cdc45p, and MCM proteins are components of prereplication complexes (pre-RC) |
| GO:0005656 nuclear pre-replicative complex | IEA GO_REF:0000117 | ACCEPT | Summary: Mcm4 is part of the nuclear pre-replicative complex as a subunit of the loaded Mcm2-7 double hexamer. Reason: ARBA mapping consistent with experimental rows. Supporting Evidence: PMID:19896182 single heptamers of Cdt1*Mcm2-7 are loaded cooperatively and result in association of stable, head-to-head Mcm2-7 double hexamers connected via their N-terminal rings |
| GO:0005737 cytoplasm | IDA PMID:10559985 G1-phase and B-type cyclins exclude the DNA-replication fact... | KEEP AS NON CORE | Summary: Cytoplasm. In S. cerevisiae, Mcm2-7 subunits (including Mcm4) are exported to the cytoplasm during S phase and excluded from the nucleus in G2/M under CDK control. Reason: Genuine, regulated localization that restricts re-licensing, but the protein acts in the nucleus; cytoplasmic residence is a regulatory state, not a site of function. Supporting Evidence: PMID:10559985 We show here that, in budding yeast, CDKs exclude the essential prereplicative-complex component Mcm4 from the nucleus |
| GO:0005737 cytoplasm | IDA PMID:10704410 Clb/Cdc28 kinases promote nuclear export of the replication ... | KEEP AS NON CORE | Summary: Cytoplasm. In S. cerevisiae, Mcm2-7 subunits (including Mcm4) are exported to the cytoplasm during S phase and excluded from the nucleus in G2/M under CDK control. Reason: Genuine, regulated localization that restricts re-licensing, but the protein acts in the nucleus; cytoplasmic residence is a regulatory state, not a site of function. Supporting Evidence: PMID:10704410 Mcm2-4, 6 and 7 were concentrated in the nucleus in G1 phase, gradually exported to the cytoplasm during S phase, and excluded from the nucleus by G2 and M phase |
| GO:0006260 DNA replication | IDA PMID:13679365 Mcm4,6,7 uses a "pump in ring" mechanism to unwind DNA by st... | MODIFY | Summary: DNA replication. Reason: DNA replication is correct but general. Mcm4 participates in two specific, experimentally supported steps: replication initiation (as the helicase loaded at origins and activated by DDK/CDK) and replication fork progression/strand elongation (degron depletion after initiation blocks fork progression). Replace with GO:0006271 and GO:1902975, both already carried by this gene. Proposed replacements: DNA strand elongation involved in DNA replication mitotic DNA replication initiation Supporting Evidence: PMID:13679365 Mcm4,6,7 is a ring-shaped heterohexamer and the putative eukaryotic replication fork helicase PMID:10834843 depletion of MCMs after initiation irreversibly blocks the progression of replication forks in Saccharomyces cerevisiae |
| GO:0006260 DNA replication | IDA PMID:15723534 The Mcm467 complex of Saccharomyces cerevisiae is preferenti... | MODIFY | Summary: DNA replication. Reason: DNA replication is correct but general. Mcm4 participates in two specific, experimentally supported steps: replication initiation (as the helicase loaded at origins and activated by DDK/CDK) and replication fork progression/strand elongation (degron depletion after initiation blocks fork progression). Replace with GO:0006271 and GO:1902975, both already carried by this gene. Proposed replacements: DNA strand elongation involved in DNA replication mitotic DNA replication initiation Supporting Evidence: PMID:15723534 The DNA helicase activity of Mcm467 complex is also significantly stimulated by the ARS1-derived sequences PMID:10834843 depletion of MCMs after initiation irreversibly blocks the progression of replication forks in Saccharomyces cerevisiae |
| GO:0006260 DNA replication | IDA PMID:25313033 CMG helicase and DNA polymerase Ξ΅ form a functional 15-subun... | MODIFY | Summary: DNA replication. Reason: DNA replication is correct but general. Mcm4 participates in two specific, experimentally supported steps: replication initiation (as the helicase loaded at origins and activated by DDK/CDK) and replication fork progression/strand elongation (degron depletion after initiation blocks fork progression). Replace with GO:0006271 and GO:1902975, both already carried by this gene. Proposed replacements: DNA strand elongation involved in DNA replication mitotic DNA replication initiation Supporting Evidence: PMID:25313033 The CMG (Cdc45-MCM-GINS) helicase surrounds the leading strand PMID:10834843 depletion of MCMs after initiation irreversibly blocks the progression of replication forks in Saccharomyces cerevisiae |
| GO:0006260 DNA replication | IEA GO_REF:0000002 | MODIFY | Summary: DNA replication. Reason: DNA replication is correct but general. Mcm4 participates in two specific, experimentally supported steps: replication initiation (as the helicase loaded at origins and activated by DDK/CDK) and replication fork progression/strand elongation (degron depletion after initiation blocks fork progression). Replace with GO:0006271 and GO:1902975, both already carried by this gene. Proposed replacements: DNA strand elongation involved in DNA replication mitotic DNA replication initiation Supporting Evidence: PMID:10834843 depletion of MCMs after initiation irreversibly blocks the progression of replication forks in Saccharomyces cerevisiae PMID:2044962 Here, we show that the other genes, like CDC46, are all involved in an early step of DNA replication, possibly initiation of DNA synthesis |
| GO:0006267 pre-replicative complex assembly involved in nuclear cell cycle DNA replication | IDA PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative co... | ACCEPT | Summary: Pre-RC assembly (origin licensing). Mcm4 is part of the Mcm2-7 hexamer that is loaded by ORC-Cdc6-Cdt1 onto origin DNA as a double hexamer; loading requires ATP hydrolysis and the MCM complex itself is the loaded entity whose ATPase sites participate in the reaction. Reason: Experimentally reconstituted in S. cerevisiae (Kawasaki et al. 2006; Remus et al. 2009; Evrin et al. 2009). Mcm2-7 is not merely a substrate here: it is the complex being assembled, and the pre-RC is defined by its presence. Licensing is a core function. Note that PAINT did not propagate this term at the Mcm4 node; for transfer to other species rely on the complex-membership terms. Supporting Evidence: PMID:16824194 The results reveal sequential recruitment of ORC, Cdc6p, Cdt1p and Mcm2-7p on to ARS1 DNA PMID:19896182 single heptamers of Cdt1*Mcm2-7 are loaded cooperatively and result in association of stable, head-to-head Mcm2-7 double hexamers connected via their N-terminal rings |
| GO:0006267 pre-replicative complex assembly involved in nuclear cell cycle DNA replication | IEA GO_REF:0000117 | ACCEPT | Summary: Pre-RC assembly (origin licensing). Mcm4 is part of the Mcm2-7 hexamer that is loaded by ORC-Cdc6-Cdt1 onto origin DNA as a double hexamer; loading requires ATP hydrolysis and the MCM complex itself is the loaded entity whose ATPase sites participate in the reaction. Reason: Experimentally reconstituted in S. cerevisiae (Kawasaki et al. 2006; Remus et al. 2009; Evrin et al. 2009). Mcm2-7 is not merely a substrate here: it is the complex being assembled, and the pre-RC is defined by its presence. Licensing is a core function. Note that PAINT did not propagate this term at the Mcm4 node; for transfer to other species rely on the complex-membership terms. Supporting Evidence: PMID:19910535 MCM2-7 loading was found to be dependent on the presence of all pre-RC proteins, origin DNA, and ATP hydrolysis |
| GO:0006270 DNA replication initiation | IEA GO_REF:0000120 | ACCEPT | Summary: DNA replication initiation (IEA). Reason: Consistent with genetic and biochemical evidence in yeast. Supporting Evidence: PMID:2044962 Here, we show that the other genes, like CDC46, are all involved in an early step of DNA replication, possibly initiation of DNA synthesis PMID:26854664 Dbf4-dependent kinase (DDK, composed of Cdc7 and Dbf4) phosphorylation of primarily Mcm4 recruits Cdc45 |
| GO:0006270 DNA replication initiation | IGI PMID:2044962 A group of interacting yeast DNA replication genes. | ACCEPT | Summary: DNA replication initiation, from genetic interactions among CDC54 (MCM4), CDC45, CDC46 (MCM5) and CDC47 (MCM7) (Hennessy et al. 1991). Reason: Conditional cdc54 mutants arrest at the onset of DNA synthesis and interact genetically with other initiation genes. Mcm4 is also the principal DDK target whose phosphorylation recruits Cdc45 at origin firing. Core function. Supporting Evidence: PMID:2044962 Here, we show that the other genes, like CDC46, are all involved in an early step of DNA replication, possibly initiation of DNA synthesis PMID:2044962 Conditional mutants in this group, under fully nonpermissive conditions, show cell-cycle arrest at the beginning of DNA synthesis PMID:26854664 Dbf4-dependent kinase (DDK, composed of Cdc7 and Dbf4) phosphorylation of primarily Mcm4 recruits Cdc45 |
| GO:0006271 DNA strand elongation involved in DNA replication | IBA GO_REF:0000033 | ACCEPT | Summary: DNA strand elongation, PAINT IBD at the Mcm4 subfamily node PTN000179968 seeded by this gene's IMP annotation. Reason: Correct; the self-seed is expected and shows experimental grounding on the target. Supporting Evidence: PMID:10834843 depletion of MCMs after initiation irreversibly blocks the progression of replication forks in Saccharomyces cerevisiae PMID:26524492 The eukaryotic helicase is an 11-subunit CMG complex that encircles the leading strand during unwinding and consists of the Mcm2-7 motor subunits, the GINS heterotetramer and the Cdc45 subunit |
| GO:0006271 DNA strand elongation involved in DNA replication | IEA GO_REF:0000117 | ACCEPT | Summary: DNA strand elongation (ARBA). Reason: Consistent with IMP and IBA. Supporting Evidence: PMID:10834843 depletion of MCMs after initiation irreversibly blocks the progression of replication forks in Saccharomyces cerevisiae |
| GO:0006271 DNA strand elongation involved in DNA replication | IMP PMID:10834843 Uninterrupted MCM2-7 function required for DNA replication f... | ACCEPT | Summary: DNA strand elongation. Labib et al. depleted Mcm2-7 subunits with degron alleles after initiation and showed replication forks stop irreversibly. Reason: Direct in vivo evidence that the MCM helicase is required continuously at the fork, where it unwinds the template. Core function. Supporting Evidence: PMID:10834843 depletion of MCMs after initiation irreversibly blocks the progression of replication forks in Saccharomyces cerevisiae PMID:10834843 the MCM complex is loaded at origins before initiation and is essential for elongation |
| GO:0006279 premeiotic DNA replication | IDA PMID:20484375 The Saccharomyces cerevisiae Mcm6/2 and Mcm5/3 ATPase active... | UNDECIDED | Summary: Premeiotic DNA replication. The cited paper (Bochman & Schwacha 2010) is a biochemical study of Mcm2-7 ATPase active sites; its cached full text contains no meiotic or sporulation experiments. Reason: Biologically plausible (the MCM helicase is expected to drive all nuclear chromosomal replication, including premeiotic S phase), but the cited reference does not appear to contain data supporting a meiosis-specific role, so the evidence for this specific annotation cannot be verified. Possibly a mis-keyed reference at the source. |
| GO:0006279 premeiotic DNA replication | IEA GO_REF:0000117 | UNDECIDED | Summary: Premeiotic DNA replication. ARBA electronic annotation. Reason: No yeast premeiotic-replication data for Mcm4 located in the cached literature; the only experimental row cites a paper without meiotic data. Plausible but unverified. |
| GO:0008270 zinc ion binding | RCA PMID:30358795 The cellular economy of the Saccharomyces cerevisiae zinc pr... | KEEP AS NON CORE | Summary: Zinc ion binding, from a bioinformatic survey of the yeast zinc proteome (RCA). Mcm N-terminal domains contain a zinc-binding motif; yeast Mcm4 has a C4 cluster (Cys349, Cys352, Cys371, Cys376) consistent with the MCM zinc-finger subdomain. Reason: Structural zinc in the N-terminal domain is well established for MCM subunits; it is a structural cofactor rather than the informative function. Supporting Evidence: PMID:30358795 The yeast zinc proteome of 582 known or potential zinc-binding proteins was identified using a bioinformatics analysis that combined global domain searches with local motif searches PMID:23851460 Each Mcm protein is composed of an N-terminal domain (NTD) that complexes zinc and an ATP-binding C-terminal AAA+ domain (CTD) |
| GO:0009378 four-way junction helicase activity | IDA PMID:13679365 Mcm4,6,7 uses a "pump in ring" mechanism to unwind DNA by st... | KEEP AS NON CORE | Summary: Four-way junction helicase activity: the Mcm4,6,7 ring translocates on duplex DNA and can drive Holliday junction branch migration in vitro. Reason: Real in vitro activity of the Mcm467 subcomplex (contributes_to is correctly applied), but there is no evidence that Mcm2-7 or CMG processes Holliday junctions in vivo; it is a mechanistic by-product of duplex translocation, not a physiological role. Supporting Evidence: PMID:13679365 The Mcm4,6,7 ring also actively translocates along duplex DNA, enabling the protein to drive branch migration of Holliday junctions |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000116 | KEEP AS NON CORE | Summary: ATP hydrolysis activity (Rhea mapping from EC 3.6.4.12). MCM ATPase sites form at subunit interfaces; Mcm4 contributes the Walker A/B motifs or arginine finger to the 7/4 and 4/6 sites. Reason: Correct for the complex, but no individual MCM subunit hydrolyses ATP efficiently on its own, so this should be read as contributes_to; the informative activity is the helicase. Supporting Evidence: PMID:12480933 no MCM protein hydrolyzes ATP efficiently. ATP hydrolysis requires a combination of two MCM proteins PMID:20484375 Five of the six ATPase active sites (Mcm5/3, 3/7, 7/4, 4/6 and 6/2) have been directly demonstrated by subunit association experiments |
| GO:0017116 single-stranded DNA helicase activity | IBA GO_REF:0000033 | ACCEPT | Summary: ssDNA helicase activity, contributes_to, PAINT IBD at MCM2-7 node PTN000179711 seeded by yeast MCM2-7 subunits and fission yeast orthologs. Reason: Correct and correctly qualified contributes_to; core function. Supporting Evidence: PMID:18657510 Our results show that purified Mcm2-7 acts as a helicase PMID:26524492 The eukaryotic helicase is an 11-subunit CMG complex that encircles the leading strand during unwinding and consists of the Mcm2-7 motor subunits, the GINS heterotetramer and the Cdc45 subunit |
| GO:0017116 single-stranded DNA helicase activity | IDA PMID:15723534 The Mcm467 complex of Saccharomyces cerevisiae is preferenti... | ACCEPT | Summary: ssDNA-dependent helicase activity of the Mcm467 complex stimulated by ARS1 ssDNA. Reason: Direct biochemical evidence; contributes_to correctly applied. Supporting Evidence: PMID:15723534 The DNA helicase activity of Mcm467 complex is also significantly stimulated by the ARS1-derived sequences PMID:15723534 the ssDNA sequences containing A and B1 motifs of ARS1, activate the Mcm467 complex and stimulate its ATPase and DNA helicase activities |
| GO:0017116 single-stranded DNA helicase activity | IDA PMID:18657510 The Mcm2-7 complex has in vitro helicase activity. | ACCEPT | Summary: Helicase activity of reconstituted Mcm2-7 (Bochman & Schwacha 2008). Reason: Direct biochemical evidence; Mcm4 Walker A K574A abolishes activity. Supporting Evidence: PMID:18657510 Our results show that purified Mcm2-7 acts as a helicase file:yeast/MCM4/MCM4-uniprot.txt K->A: Loss of MCM2-7 complex helicase activity. |
| GO:0031261 DNA replication preinitiation complex | IDA PMID:9554851 Formation of a preinitiation complex by S-phase cyclin CDK-d... | ACCEPT | Summary: DNA replication preinitiation complex: Cdc45 associates with MCM proteins on chromatin in late G1/S in a CDK-dependent manner. Reason: Mcm2-7 is the core of the pre-IC onto which Cdc45 and GINS assemble. Supporting Evidence: PMID:9554851 During S phase, Cdc45p physically interacts with minichromosome maintenance (MCM) proteins on chromatin |
| GO:0033260 nuclear DNA replication | IMP PMID:2044962 A group of interacting yeast DNA replication genes. | MODIFY | Summary: Nuclear DNA replication, from cdc54 mutant phenotypes (Hennessy et al. 1991). Reason: Correct but general. The phenotype (arrest at the onset of DNA synthesis) and the authors' conclusion point to an early, initiation step; replace with GO:1902975 mitotic DNA replication initiation, which this gene already carries. Proposed replacements: mitotic DNA replication initiation Supporting Evidence: PMID:2044962 Here, we show that the other genes, like CDC46, are all involved in an early step of DNA replication, possibly initiation of DNA synthesis PMID:2044962 Conditional mutants in this group, under fully nonpermissive conditions, show cell-cycle arrest at the beginning of DNA synthesis |
| GO:0042555 MCM complex | IBA GO_REF:0000033 | ACCEPT | Summary: Mcm4 is a stoichiometric subunit of the heterohexameric Mcm2-7 complex. Reason: Extensively supported by reconstitution and structure in S. cerevisiae. Supporting Evidence: PMID:12480933 have reconstituted the Mcm2-7p complex from individual subunits |
| GO:0042555 MCM complex | IDA PMID:12480933 Reconstitution of the Mcm2-7p heterohexamer, subunit arrange... | ACCEPT | Summary: Mcm4 is a stoichiometric subunit of the heterohexameric Mcm2-7 complex. Reason: Extensively supported by reconstitution and structure in S. cerevisiae. Supporting Evidence: PMID:12480933 have reconstituted the Mcm2-7p complex from individual subunits |
| GO:0042555 MCM complex | IEA GO_REF:0000120 | ACCEPT | Summary: Mcm4 is a stoichiometric subunit of the heterohexameric Mcm2-7 complex. Reason: Extensively supported by reconstitution and structure in S. cerevisiae. Supporting Evidence: file:yeast/MCM4/MCM4-uniprot.txt Component of the MCM2-7 complex. The complex forms a toroidal |
| GO:0042555 MCM complex | IPI PMID:26222030 Structure of the eukaryotic MCM complex at 3.8 Γ . | ACCEPT | Summary: Mcm4 is a stoichiometric subunit of the heterohexameric Mcm2-7 complex. Reason: Extensively supported by reconstitution and structure in S. cerevisiae. Supporting Evidence: PMID:26222030 we report a near-atomic structure of the MCM2-7 double hexamer purified from yeast G1 chromatin |
| GO:0043138 3'-5' DNA helicase activity | IDA PMID:13679365 Mcm4,6,7 uses a "pump in ring" mechanism to unwind DNA by st... | ACCEPT | Summary: 3'-5' DNA helicase activity of Mcm4,6,7 (contributes_to). Reason: Kaplan et al. showed Mcm4,6,7 tracks on the leading strand with polarity opposite to DnaB (i.e. 3'->5'), matching the 3'->5' translocation of CMG. Core function; contributes_to correctly reflects that activity belongs to the assembled ring. Supporting Evidence: PMID:13679365 Mcm4,6,7 binds to only one strand of a duplex during unwinding, corresponding to the leading strand of a replication fork PMID:13679365 The Mcm4,6,7 mechanism is very similar to DnaB, except the proteins translocate with opposite polarity along DNA PMID:26854665 DNA in the 3β to 5β direction for bidirectional replication |
| GO:0043596 nuclear replication fork | IDA PMID:16103218 Molecular anatomy and regulation of a stable replisome at a ... | ACCEPT | Summary: Nuclear replication fork: MCM-Cdc45-GINS remains in paused replisomes at fork barriers. Reason: Direct ChIP evidence in yeast. Supporting Evidence: PMID:16103218 We show that paused forks maintain an intact replisome that contains Mrc1, Tof1, MCM-Cdc45, GINS, and DNA polymerases alpha and epsilon |
| GO:0043596 nuclear replication fork | IDA PMID:25313033 CMG helicase and DNA polymerase Ξ΅ form a functional 15-subun... | ACCEPT | Summary: Nuclear replication fork: CMG with Pol epsilon forms a leading-strand holoenzyme on model forks. Reason: Consistent with fork location. Supporting Evidence: PMID:25313033 reconstituted a stable 15-subunit CMG-Pol PMID:9335335 suggest that after initiation MCM proteins and Cdc45p move with eukaryotic replication forks |
| GO:0043596 nuclear replication fork | IEA GO_REF:0000117 | ACCEPT | Summary: Nuclear replication fork (ARBA). Reason: Consistent with experimental rows. Supporting Evidence: PMID:9335335 suggest that after initiation MCM proteins and Cdc45p move with eukaryotic replication forks |
| GO:0071162 CMG complex | IDA PMID:26524492 The architecture of a eukaryotic replisome. | ACCEPT | Summary: Mcm4 is a subunit of the CMG (Cdc45-Mcm2-7-GINS) helicase. Reason: Structural and biochemical evidence in S. cerevisiae; the CMG is the active replicative helicase. Supporting Evidence: PMID:26524492 The eukaryotic helicase is an 11-subunit CMG complex that encircles the leading strand during unwinding and consists of the Mcm2-7 motor subunits, the GINS heterotetramer and the Cdc45 subunit |
| GO:0071162 CMG complex | IEA GO_REF:0000117 | ACCEPT | Summary: Mcm4 is a subunit of the CMG (Cdc45-Mcm2-7-GINS) helicase. Reason: Structural and biochemical evidence in S. cerevisiae; the CMG is the active replicative helicase. Supporting Evidence: PMID:26524492 The eukaryotic helicase is an 11-subunit CMG complex that encircles the leading strand during unwinding and consists of the Mcm2-7 motor subunits, the GINS heterotetramer and the Cdc45 subunit |
| GO:0071162 CMG complex | IPI PMID:26854665 Structure of the eukaryotic replicative CMG helicase suggest... | ACCEPT | Summary: Mcm4 is a subunit of the CMG (Cdc45-Mcm2-7-GINS) helicase. Reason: Structural and biochemical evidence in S. cerevisiae; the CMG is the active replicative helicase. Supporting Evidence: PMID:26854665 The CMG helicase is composed of Cdc45, Mcm2-7 and GINS. Here we report the structure of the Saccharomyces cerevisiae CMG |
| GO:0097373 MCM core complex | IDA PMID:13679365 Mcm4,6,7 uses a "pump in ring" mechanism to unwind DNA by st... | KEEP AS NON CORE | Summary: MCM core complex (Mcm4/6/7): the Mcm467 subcomplex has in vitro helicase activity. Reason: The Mcm467 complex is a real biochemical entity used to study helicase mechanism, but its physiological significance is unclear; in vivo all six subunits act together. Non-core. Supporting Evidence: PMID:13679365 Mcm4,6,7 is a ring-shaped heterohexamer and the putative eukaryotic replication fork helicase file:yeast/MCM4/MCM4-uniprot.txt have in vitro helicase activity which is inhibited by the MCM2 subunit. |
| GO:0097373 MCM core complex | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: MCM core complex (Mcm4/6/7): the Mcm467 subcomplex has in vitro helicase activity. Reason: The Mcm467 complex is a real biochemical entity used to study helicase mechanism, but its physiological significance is unclear; in vivo all six subunits act together. Non-core. Supporting Evidence: PMID:13679365 Mcm4,6,7 is a ring-shaped heterohexamer and the putative eukaryotic replication fork helicase file:yeast/MCM4/MCM4-uniprot.txt have in vitro helicase activity which is inhibited by the MCM2 subunit. |
| GO:1902975 mitotic DNA replication initiation | IBA GO_REF:0000033 | ACCEPT | Summary: Mitotic DNA replication initiation, PAINT IBD at the Mcm4 subfamily node PTN000179968 seeded by S. pombe Cdc21 (Mcm4 ortholog). Reason: Correct for S. cerevisiae Mcm4 as well: cdc54 mutants arrest at the onset of S phase and Mcm4 is the key DDK substrate that triggers Cdc45 recruitment at origin firing. Core. Supporting Evidence: PMID:2044962 Conditional mutants in this group, under fully nonpermissive conditions, show cell-cycle arrest at the beginning of DNA synthesis PMID:26854664 Dbf4-dependent kinase (DDK, composed of Cdc7 and Dbf4) phosphorylation of primarily Mcm4 recruits Cdc45 |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: Is the GO:0006279 premeiotic DNA replication IDA annotation (PMID:20484375) keyed to the intended paper? The cited study analyses Mcm2-7 ATPase active-site mutants biochemically and has no meiotic experiments; is there direct S. cerevisiae evidence for MCM4 in premeiotic S phase?
Q: Should the Mcm4-specific regulatory role as the principal DDK substrate (its N-terminal serine/threonine-rich region gating Cdc45 recruitment) be captured as a GO-CAM has_input relation on Cdc7-Dbf4 kinase activity rather than as any Mcm4 annotation?
Q: Which annotations are safe to transfer to orthologs in PTHR11630:SF66? PAINT propagated BIR, strand elongation and mitotic initiation at node PTN000179968 but not pre-RC assembly or origin binding; is that omission deliberate?
Experiment: Introduce cysteine-to-alanine substitutions at the chromosomal MCM4 locus (plasmid shuffle), test viability, and assay purified mutant Mcm2-7 in reconstituted loading and CMG helicase reactions.
Hypothesis: The Mcm4 N-terminal zinc-binding cysteine cluster (C349/C352/C371/C376) is required for double-hexamer formation or CMG stability rather than for ATPase activity.
Essential helicase component of heterohexameric MCM2-7 complexes; MCM2-7 complexes bind pre-replication complexes on DNA and melt DNA prior to replication; forms an Mcm4p-6p-7p subcomplex; shows nuclear accumulation in G1; homolog of S. pombe Cdc21p
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)