Origin recognition complex subunit 1 (ORC1) is the largest catalytic AAA+ ATPase subunit of the ORC complex, essential for DNA replication initiation and mating-type transcriptional silencing. ORC1 recognizes and binds ARS consensus sequences at replication origins, recruits MCM2-7 loading factors during G1, and interacts with SIR proteins to establish heterochromatin at silent mating loci. The protein contains an N-terminal BAH (bromo-adjacent homology) domain for nucleosome binding and a C-terminal AAA+ ATPase domain for ATP-dependent origin licensing.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006270 DNA replication initiation | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation well-supported by experimental evidence and phylogenetic orthology. ORC1 is essential for G1/S loading of MCM complexes and formation of the pre-replicative complex. Reason: Core function. Multiple experimental studies (IDA, IMP, NAS) confirm ORC1s role in DNA replication initiation through pre-replicative complex assembly and MCM loading. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000080056 · PTN000080056 SUPPORTS TRANSFER This ancestral eukaryotic ORC1-family node correctly transfers the conserved role of Orc1 in origin-dependent pre-RC assembly to budding-yeast ORC1. Supporting Evidence: PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro file:yeast/ORC1/ORC1-deep-research-falcon.md In early G1, ORC (including Orc1) recruits **Cdc6**, then **Cdt1–MCM2–7**, loading MCM one hexamer at a time to form a head-to-head MCM double hexamer |
| GO:0003688 DNA replication origin binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation reflects the fundamental mechanism by which ORC1 initiates DNA replication through recognition of ARS consensus sequences. Reason: Core molecular function. ORC1 specifically binds ARS consensus sequences (ACS) at replication origins. This is well-established experimentally (IDA evidence PMID:16824194). Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000080056 · PTN000080056 SUPPORTS TRANSFER The PTN000080056 origin-recognition assertion matches the conserved ORC1 role and yeast ORC1-specific experimental evidence for origin DNA binding. Supporting Evidence: PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro file:yeast/ORC1/ORC1-deep-research-falcon.md recognizes a replication-origin DNA consensus (ARS consensus sequence, ACS) and acts as the platform that seeds helicase loading and replication initiation |
| GO:0033314 mitotic DNA replication checkpoint signaling | IBA GO_REF:0000033 | REMOVE | Summary: This IBA over-interprets the replication checkpoint phenotype of ORC inactivation. Yeast Orc1 is an origin-recognition and pre-RC assembly factor; conditional ORC1/ORC2/ORC5 defects cause incomplete replication and consequent checkpoint arrest, but that does not make Orc1 a direct participant in checkpoint signaling. Reason: The current ORC1 GOA refresh no longer carries this IBA, and the refreshed PTHR10763 PAINT cache has no GO:0033314 IBD assertion at PTN000080056. Biologically, PMID:16716188 describes DNA damage and spindle checkpoint arrest downstream of incomplete replication in ORC mutants, so the checkpoint term conflates a phenotype caused by ORC inactivation with the checkpoint-signaling machinery. Propagation Review Root cause: SOURCE STALE OR MISSING Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN000080056 · PTN000080056 SOURCE STALE OR MISSING The historical GOA row pointed this checkpoint IBA at PTN000080056, but the refreshed PTHR10763 PAINT table has no GO:0033314 IBD for that node and current GOA no longer emits the ORC1 row. The checkpoint term also describes perturbation-triggered arrest downstream of failed ORC initiation rather than Orc1's own molecular role. Supporting Evidence: PMID:16716188 Defective initiation in ORC mutant cells results in incomplete replication and mitotic arrest enforced by the DNA damage and spindle assembly checkpoint pathways. |
| GO:0005664 nuclear origin of replication recognition complex | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation correctly identifies ORC1 as part of the ORC complex, a multi-subunit assembly. Reason: Accurate. ORC1 is a core structural component of the ORC complex. Experimentally validated (IDA, IMP evidence). Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000080057 · PTN000080057 SUPPORTS TRANSFER PTN000080057 transfers eukaryotic ORC-complex membership to Orc1; budding-yeast Orc1 is experimentally established as a core subunit of the nuclear origin recognition complex. Supporting Evidence: PMID:9372948 Architecture of the yeast origin recognition complex bound to origins of DNA replication file:yeast/ORC1/ORC1-deep-research-falcon.md ORC is a large (~400 kDa) heterohexamer (Orc1–6) that recognizes a replication-origin DNA consensus |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: IEA annotation based on UniProtKB keyword mapping. ORC1 contains AAA+ ATPase domain with ATP binding capability. Reason: Mechanically correct but overly generic. ORC1 contains multiple ATP binding sites (documented in UniProt features), but the more specific ATP binding annotation (GO:0005524) is more informative. Nucleotide binding as a general term lacks specificity for ORC1s characterized ATP hydrolysis activity. Supporting Evidence: file:yeast/ORC1/ORC1-deep-research-falcon.md ATP binding by Orc1 is required for ORC DNA binding |
| GO:0003677 DNA binding | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: IEA annotation based on UniProtKB keyword mapping reflects ORC1s well-documented ARS-binding capability. Reason: Technically accurate but too generic. GO:0003688 (DNA replication origin binding) is more specific and informative. General DNA binding term obscures the specialized function of recognizing specific ARS sequences. Supporting Evidence: PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro file:yeast/ORC1/ORC1-deep-research-falcon.md Orc1 and Orc2 contribute **minor-groove interactions** (e.g., Orc1 basic patch) |
| GO:0003682 chromatin binding | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation inferred from InterPro BAH domain (IPR001025). ORC1 contains a BAH domain for nucleosome interaction. Reason: Mechanically correct - ORC1 has a BAH domain and binds chromatin/nucleosomes. The more specific nucleosome binding term (GO:0031491) is also annotated with IDA evidence, so this broader term is acceptable as a complementary annotation. Supporting Evidence: PMID:31263106 Structure and function of the Orc1 BAH-nucleosome complex file:yeast/ORC1/ORC1-deep-research-falcon.md The N-terminal BAH domain of Orc1 is a chromatin-binding module distinct from the AAA+ region |
| GO:0003688 DNA replication origin binding | IEA GO_REF:0000117 | ACCEPT | Summary: IEA annotation from ARBA machine learning model correctly identifies ORC1s origin binding function. Reason: Well-supported. This duplicates the IBA and IDA annotations for the same term but with different evidence code. Core molecular function. Experimental validation exists (IDA PMID:16824194). Supporting Evidence: PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation from combined automated methods identifies ATP binding in AAA+ domain. Reason: Mechanically correct - ORC1 has well-documented ATP binding sites (see UniProt features at positions 435, 479-487, 567, 600, 704, 726-733). While ATP hydrolysis activity is also annotated, ATP binding is a distinct and essential molecular function. Supporting Evidence: file:yeast/ORC1/ORC1-deep-research-falcon.md ATP binding by Orc1 is required for ORC DNA binding |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: IEA annotation from UniProtKB subcellular location vocabulary correctly identifies nuclear localization. Reason: Correct but non-specific cellular component term. ORC1 is nuclear, but this is required for all its functions. Experimental evidence (EXP, IDA) for nucleoplasm and nucleus localization available. Supporting Evidence: PMID:11168584 Interactions between Mcm10p and other replication factors are required for proper initiation and elongation of chromosomal DNA replication in Saccharomyces cerevisiae |
| GO:0005694 chromosome | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA annotation from ARBA model identifies ORC1s chromosomal localization during S phase. Reason: Correct but redundant with nucleus/nucleoplasm annotations. ORC1 binds chromosomal DNA at replication origins, but this is implicit in its origin binding function. Not a distinct function, rather a cellular location consequence. |
| GO:0006260 DNA replication | IEA GO_REF:0000043 | ACCEPT | Summary: IEA annotation based on UniProtKB keyword mapping reflects ORC1s essential role in DNA replication process. Reason: Core biological process. ORC1 is essential for DNA replication initiation phase. While GO:0006270 (DNA replication initiation) is more specific, this broader term is acceptable for capturing the overall replication process involvement. Supporting Evidence: PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro file:yeast/ORC1/ORC1-deep-research-falcon.md ORC binds sequence-defined ARS elements and, together with **Cdc6** and **Cdt1**, loads MCM2–7 to form the pre-RC |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation inferred from InterPro AAA+ ATPase domain (IPR003959). ORC1 catalyzes ATP hydrolysis for nucleotide-dependent conformational changes. Reason: Core molecular function. ORC1 is an AAA+ ATPase with documented ATP hydrolysis activity. This is essential for ORC complex assembly, DNA binding, and MCM loading. Experimental evidence (IMP PMID:9038340) supports this. Falcon deep research notes Orc1 is the only ORC subunit experimentally demonstrated to possess ATPase activity, reinforcing this as a core enzymatic function. Supporting Evidence: PMID:9038340 Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex file:yeast/ORC1/ORC1-deep-research-falcon.md Orc1 is the only ORC subunit experimentally demonstrated to have ATPase activity |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: IEA annotation from UniProtKB keyword reflects metal coordination in ORC1s ATP binding sites. Reason: Technically correct - ORC1 binds Mg(2+) ions at ATP binding sites (documented in UniProt). However, this is a mechanistic detail subordinate to ATP binding and hydrolysis. The more specific ATP-related terms are more informative. |
| GO:0005515 protein binding | IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine... | REMOVE | Summary: IPI annotation from proteome survey identifies ORC1 interactions with ORC complex members and other proteins. Reason: Bare protein binding carries no mechanistic meaning for ORC1 and should not be preserved as a non-core function. The ORC-subunit and Sir-protein associations remain captured more informatively by origin-recognition-complex membership and heterochromatin annotations. Supporting Evidence: PMID:16429126 Proteome survey reveals modularity of the yeast cell machinery |
| GO:0005515 protein binding | IPI PMID:16554755 Global landscape of protein complexes in the yeast Saccharom... | REMOVE | Summary: IPI annotation from global protein complex map confirms ORC1 protein-protein interactions. Reason: Bare protein binding is an uninformative readout of complex membership/interactome data and does not state a molecular function. Removing this row does not dispute the reported physical associations. Supporting Evidence: PMID:16554755 Global landscape of protein complexes in the yeast Saccharomyces cerevisiae |
| GO:0005515 protein binding | IPI PMID:17825065 Yeast two-hybrid analysis of the origin recognition complex ... | REMOVE | Summary: IPI annotation from yeast two-hybrid screen documents protein-protein interactions. Reason: GO:0005515 is too generic to preserve as an ORC1 function. The two-hybrid evidence documents specific ORC subunit interactions, but the annotation term loses that specificity. Supporting Evidence: PMID:17825065 Yeast two-hybrid analysis of the origin recognition complex of Saccharomyces cerevisiae: interaction between subunits and identification of binding proteins |
| GO:0005515 protein binding | IPI PMID:18647841 The architecture of the DNA replication origin recognition c... | REMOVE | Summary: IPI annotation from structural studies of ORC complex architecture documents protein interactions. Reason: The cryo-EM study supports ORC architecture, already represented by the ORC complex component annotation. A separate bare protein-binding assertion is redundant and non-informative. Supporting Evidence: PMID:18647841 The architecture of the DNA replication origin recognition complex in Saccharomyces cerevisiae |
| GO:0005515 protein binding | IPI PMID:21179020 Defining the budding yeast chromatin-associated interactome. | REMOVE | Summary: IPI annotation from chromatin-associated interactome defines ORC1 protein associations. Reason: A chromatin-associated interactome hit does not make GO:0005515 an informative ORC1 function. Curated ORC complex membership and chromatin/origin-binding terms capture the relevant biology more precisely. Supporting Evidence: PMID:21179020 Defining the budding yeast chromatin-associated interactome |
| GO:0005515 protein binding | IPI PMID:22405012 Cdc6-induced conformational changes in ORC bound to origin D... | REMOVE | Summary: IPI annotation from cryo-EM structural analysis documents ORC1 protein-protein contacts. Reason: The Cdc6-induced ORC structural result is better represented by pre-RC assembly and ORC complex annotations; a bare protein-binding row adds no functional specificity. Supporting Evidence: PMID:22405012 Cdc6-induced conformational changes in ORC bound to origin DNA revealed by cryo-electron microscopy |
| GO:0005515 protein binding | IPI PMID:27107014 An inter-species protein-protein interaction network across ... | REMOVE | Summary: IPI annotation from inter-species protein interaction network identifies ORC1 protein interactions. Reason: The inter-species interaction row is a generic protein-binding assertion with no specific ORC1 activity, complex, or pathway role. It should not be kept as a function annotation. Supporting Evidence: PMID:27107014 An inter-species protein-protein interaction network across vast evolutionary distance |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: IPI annotation from social and structural architecture study confirms ORC1 protein associations. Reason: The recent interactome study may confirm ORC1 associations, but GO:0005515 itself is uninformative and should not be retained when ORC1's complex and chromatin functions are already curated. Supporting Evidence: PMID:37968396 The social and structural architecture of the yeast protein interactome |
| GO:0005515 protein binding | IPI PMID:8622770 Role of interactions between the origin recognition complex ... | MODIFY | Summary: IPI annotation documents ORC1-SIR1 interaction critical for transcriptional silencing function. Reason: The Orc1-Sir1 interaction is a specific silencer-tethering activity. GO:0005515 obscures that mechanism and should be replaced by chromatin-protein adaptor activity, coupled to silent mating-type cassette heterochromatin formation. Proposed replacements: chromatin-protein adaptor activity Supporting Evidence: PMID:8622770 SIR1 can bind directly to ORC1, the largest of the ORC subunits, and that targeting of SIR1 to ORC1 at a silencer is sufficient to establish a silenced state |
| GO:0005634 nucleus | EXP PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative co... | KEEP AS NON CORE | Summary: EXP annotation documents nuclear localization of ORC1 from in vitro reconstitution studies. Reason: Experimentally validated localization. However, nucleus is a broad cellular compartment term. The more specific nucleoplasm annotations (GO:0005654 TAS) and nuclear pre-replicative complex (GO:0005656 IDA) better describe ORC1s functional location. Supporting Evidence: PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro |
| GO:0006270 DNA replication initiation | NAS PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative co... | ACCEPT | Summary: NAS (Not Annotated Source) evidence from reconstitution studies documents ORC1s essential role in initiation. Reason: Duplicate annotation for core function with different evidence type (NAS). The in vitro reconstitution studies provide mechanistic support for ORC1s role in pre-replicative complex assembly and DNA replication initiation. Supporting Evidence: PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro |
| GO:0034728 nucleosome organization | IMP PMID:37020028 Establishment and function of chromatin organization at repl... | ACCEPT | Summary: IMP annotation from recent study characterizes ORC1s role in chromatin organization at replication origins. Reason: ORC1s BAH domain mediates nucleosome binding and influences nucleosome positioning at replication origins. This facilitates origin activation and is a documented secondary function. Experimental (IMP) evidence provides functional validation. Supporting Evidence: PMID:37020028 Establishment and function of chromatin organization at replication origins file:yeast/ORC1/ORC1-deep-research-falcon.md Structural work shows Orc1 BAH binds the nucleosome core directly |
| GO:0005654 nucleoplasm | TAS Reactome:R-SCE-9749345 | KEEP AS NON CORE | Summary: TAS annotation from Reactome identifies nucleoplasm as the functional compartment for MCM loading. Reason: Correct subcellular localization but redundant with nucleus and nuclear pre-replicative complex annotations. Nucleoplasm is the appropriate compartment for ORC1 function but this is implicit in its replication initiation role. |
| GO:0005654 nucleoplasm | TAS Reactome:R-SCE-9749381 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway identifies nucleoplasm localization during CDT1 release. Reason: Correct but redundant subcellular localization. Multiple pathway annotations for nucleoplasm are unnecessary. |
| GO:0005654 nucleoplasm | TAS Reactome:R-SCE-9749401 | KEEP AS NON CORE | Summary: TAS annotation from Reactome identifies nucleoplasm during MCM double hexamer formation. Reason: Correct but redundant subcellular localization. This duplicates the nucleoplasm annotation from other Reactome pathways. |
| GO:0031491 nucleosome binding | IDA PMID:31263106 Structure and function of the Orc1 BAH-nucleosome complex. | ACCEPT | Summary: IDA annotation directly demonstrates ORC1s BAH domain interaction with nucleosomes. Reason: Experimental evidence (IDA) from structural and functional studies. ORC1s BAH domain specifically binds nucleosomes, facilitating nucleosome-mediated origin regulation. This is a characterized and important secondary function. Supporting Evidence: PMID:31263106 Structure and function of the Orc1 BAH-nucleosome complex PMID:38597680 At silencing-associated sites lacking the motif, ORC binding and activity were fully explained by a BAH domain. file:yeast/ORC1/ORC1-deep-research-falcon.md A structural study determined the Orc1 BAH–nucleosome complex at **3.3 Å** and reported that Orc1 BAH forms extensive contacts with core histones, **burying ~1590 Ų** of surface |
| GO:0043007 maintenance of rDNA | IDA PMID:31263106 Structure and function of the Orc1 BAH-nucleosome complex. | ACCEPT | Summary: IDA annotation documents ORC1s role in ribosomal DNA maintenance and nucleosome organization at rDNA loci. Reason: Experimental evidence (IDA) supports ORC1s function in rDNA maintenance through nucleosome-based regulation. rDNA regions contain active replication origins and require specialized chromatin organization. This is a characterized secondary function. Falcon deep research adds that Orc1 BAH-nucleosome binding protects rDNA border integrity during meiosis, with reduced BAH affinity increasing double-strand breaks. Supporting Evidence: PMID:31263106 Structure and function of the Orc1 BAH-nucleosome complex file:yeast/ORC1/ORC1-deep-research-falcon.md Orc1 BAH–nucleosome interactions contribute to genome stability at rDNA borders during meiosis; reduced Orc1-BAH affinity is associated with increased double-strand breaks |
| GO:0003682 chromatin binding | IDA PMID:11168584 Interactions between Mcm10p and other replication factors ar... | ACCEPT | Summary: IDA annotation directly demonstrates ORC1s chromatin binding through interactions with MCM10 and other chromatin factors. Reason: Experimental evidence (IDA) for chromatin binding. While not as specific as DNA replication origin binding or nucleosome binding, this annotation correctly captures ORC1s broader chromatin association function. Supporting Evidence: PMID:11168584 Interactions between Mcm10p and other replication factors are required for proper initiation and elongation of chromosomal DNA replication in Saccharomyces cerevisiae |
| GO:0003688 DNA replication origin binding | IDA PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative co... | ACCEPT | Summary: IDA annotation provides direct experimental evidence for ORC1s origin binding function. Reason: Core molecular function. Direct assay evidence (IDA) from in vitro reconstitution unequivocally demonstrates ORC1s specific binding to origin DNA at ARS consensus sequences. Supporting Evidence: PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro |
| GO:0005524 ATP binding | IDA PMID:17825064 Interaction between ORC and Cdt1p of Saccharomyces cerevisia... | ACCEPT | Summary: IDA annotation directly assays ATP binding in ORC1 and Cdt1 interaction studies. Reason: Core molecular function. Direct experimental evidence (IDA) confirms ATP binding. This is mechanistically essential for ORC1s regulatory ATPase activity. Supporting Evidence: PMID:17825064 Interaction between ORC and Cdt1p of Saccharomyces cerevisiae |
| GO:0005524 ATP binding | IMP PMID:9038340 Coordinate binding of ATP and origin DNA regulates the ATPas... | ACCEPT | Summary: IMP annotation documents ATP binding as essential for ORC complex ATPase activity regulation. Reason: Core function. Mutational/functional evidence (IMP) shows ATP binding is required for coordinate regulation of origin binding and ATPase activity. Duplicates the IDA annotation but different evidence code validates importance. Supporting Evidence: PMID:9038340 Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex |
| GO:0005634 nucleus | IDA PMID:11168584 Interactions between Mcm10p and other replication factors ar... | KEEP AS NON CORE | Summary: IDA annotation directly demonstrates nuclear localization of ORC1. Reason: Experimental validation of nuclear localization. However, this broad cellular component term is less informative than the nuclear pre-replicative complex and nucleoplasm annotations that specify ORC1s functional compartments. Supporting Evidence: PMID:11168584 Interactions between Mcm10p and other replication factors are required for proper initiation and elongation of chromosomal DNA replication in Saccharomyces cerevisiae |
| GO:0005656 nuclear pre-replicative complex | IDA PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative co... | ACCEPT | Summary: IDA annotation directly identifies ORC1 as a structural component of the pre-replicative complex. Reason: Core cellular component. ORC1 is a required component of the nuclear pre-replicative complex (pre-RC) that forms at G1. Experimental evidence (IDA) from in vitro reconstitution and cellular studies confirms this. Supporting Evidence: PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro |
| GO:0005656 nuclear pre-replicative complex | IDA PMID:9335335 Components and dynamics of DNA replication complexes in S. c... | ACCEPT | Summary: IDA annotation from cell cycle studies documents ORC1 as core component of pre-RC during S phase. Reason: Duplicate annotation for core component. Experimental evidence (IDA) from MCM protein redistribution studies confirms ORC1s role in pre-RC assembly and dynamics. Supporting Evidence: PMID:9335335 Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase |
| GO:0005664 nuclear origin of replication recognition complex | IDA PMID:9372948 Architecture of the yeast origin recognition complex bound t... | ACCEPT | Summary: IDA annotation directly identifies ORC1 as integral component of the ORC complex through structural analysis. Reason: Core cellular component. ORC1 is essential to ORC complex assembly. Experimental evidence (IDA) from origin-bound ORC architecture studies provides direct confirmation. Supporting Evidence: PMID:9372948 Architecture of the yeast origin recognition complex bound to origins of DNA replication |
| GO:0005664 nuclear origin of replication recognition complex | IMP PMID:9372948 Architecture of the yeast origin recognition complex bound t... | ACCEPT | Summary: IMP annotation documents ORC1s functional role in ORC complex assembly through mutational analysis. Reason: Core component. Duplicate annotation with different evidence type (IMP). Functional mutations demonstrate ORC1s essential role in complex formation and origin recognition. Supporting Evidence: PMID:9372948 Architecture of the yeast origin recognition complex bound to origins of DNA replication |
| GO:0006267 pre-replicative complex assembly involved in nuclear cell cycle DNA replication | IDA PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative co... | ACCEPT | Summary: IDA annotation directly demonstrates ORC1s active role in pre-replicative complex assembly through in vitro reconstitution. Reason: Core biological process. ORC1 is the rate-limiting or nucleation factor for pre-RC assembly. Experimental evidence (IDA, IMP) from multiple studies unambiguously supports this essential function. Supporting Evidence: PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro file:yeast/ORC1/ORC1-deep-research-falcon.md ORC bends DNA at origin elements in a manner that helps align and insert DNA into the MCM ring during formation of helicase-loading intermediates |
| GO:0006267 pre-replicative complex assembly involved in nuclear cell cycle DNA replication | IMP PMID:9335335 Components and dynamics of DNA replication complexes in S. c... | ACCEPT | Summary: IMP annotation from cell cycle studies documents ORC1s essential role in pre-RC assembly. Reason: Duplicate annotation for core process. Experimental evidence (IMP) from MCM redistribution and functional studies confirms ORC1s requirement for pre-RC assembly. Supporting Evidence: PMID:9335335 Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase |
| GO:0006270 DNA replication initiation | IMP PMID:16716188 Cell cycle execution point analysis of ORC function and char... | ACCEPT | Summary: IMP annotation documents ORC1s essential role in DNA replication initiation through checkpoint and cell cycle execution point analysis. Reason: Core biological process. Conditional inactivation of ORC (including ORC1) results in failure of replication initiation, confirming essential role. Supporting Evidence: PMID:16716188 Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiae |
| GO:0016887 ATP hydrolysis activity | IMP PMID:9038340 Coordinate binding of ATP and origin DNA regulates the ATPas... | ACCEPT | Summary: IMP annotation demonstrates ATP hydrolysis activity is functionally essential for ORC1s regulatory mechanism. Reason: Core molecular function. Experimental evidence (IMP) shows ORC1s ATP hydrolysis is required for complex assembly and origin regulation. Mutations affecting ATPase activity impair ORC function. Supporting Evidence: PMID:9038340 Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex |
| GO:0030466 silent mating-type cassette heterochromatin formation | IDA PMID:12897051 Differential DNA affinity specifies roles for the origin rec... | ACCEPT | Summary: IDA annotation directly demonstrates ORC1s role in transcriptional silencing at HMR/HML loci. Reason: Core function. ORC1s interaction with SIR1 and other SIR proteins is essential for establishing heterochromatin at silent mating-type loci. Experimental evidence (IDA) from differential DNA affinity studies confirms this role. Falcon deep research clarifies the mechanism: the Orc1 BAH domain binds silencer elements and recruits Sir1, which nucleates the Sir2/Sir3/Sir4 silencing machinery, and shows this silencing-locus binding is genetically separable from origin binding (BAH deletion abolishes silencing-site binding but not origin binding). Supporting Evidence: PMID:12897051 Differential DNA affinity specifies roles for the origin recognition complex in budding yeast heterochromatin PMID:38597680 At silencing-associated sites lacking the motif, ORC binding and activity were fully explained by a BAH domain. file:yeast/ORC1/ORC1-deep-research-falcon.md Orc1 BAH binds at DNA silencer elements and recruits **Sir1**, which then helps recruit the Sir2/Sir3/Sir4 silencing machinery file:yeast/ORC1/ORC1-deep-research-falcon.md Orc1 lacking the BAH domain is **lost from silencing-associated sites but remains bound to replication origins** |
| GO:0030466 silent mating-type cassette heterochromatin formation | IDA PMID:16581798 Structure and function of the Saccharomyces cerevisiae Sir3 ... | ACCEPT | Summary: IDA annotation directly confirms ORC1-SIR3 interaction in heterochromatin establishment. Reason: Duplicate annotation for core silencing function. Experimental evidence (IDA) from Sir3 BAH domain structure studies demonstrates ORC1s functional role in recruiting silencing machinery. Supporting Evidence: PMID:16581798 Structure and function of the Saccharomyces cerevisiae Sir3 BAH domain |
| GO:0030466 silent mating-type cassette heterochromatin formation | IGI PMID:16581798 Structure and function of the Saccharomyces cerevisiae Sir3 ... | ACCEPT | Summary: IGI annotation documents genetic interaction between ORC1 and SIR3 in heterochromatin formation. Reason: Genetic interaction evidence (IGI) supports ORC1s role in silencing. ORC1-SIR3 genetic interaction (with SGD:S000001809 = SIR3) demonstrates functional interdependence in establishing silent loci. Supporting Evidence: PMID:16581798 Structure and function of the Saccharomyces cerevisiae Sir3 BAH domain |
| GO:0031261 DNA replication preinitiation complex | IDA PMID:9554851 Formation of a preinitiation complex by S-phase cyclin CDK-d... | ACCEPT | Summary: IDA annotation directly identifies ORC1 as component of preinitiation complex formed during S phase. Reason: Related to core function. ORC1 is part of the pre-initiation complex (loaded Cdc45). Experimental evidence (IDA) confirms ORC1s presence in this complex. Closely related to pre-replicative complex annotations. Supporting Evidence: PMID:9554851 Formation of a preinitiation complex by S-phase cyclin CDK-dependent loading of Cdc45p onto chromatin |
| GO:0005515 protein binding | IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine... | REMOVE | Summary: IPI exact-source split from the Gavin et al. affinity-purification interactome reports ORC1 association with Orc4. Reason: The exact Orc4 source is consistent with the older PMID:16429126 IntAct row and with ORC complex membership, but GO:0005515 is a generic physical-binding assertion rather than an informative ORC1 activity. Removing the row does not dispute the interaction. Supporting Evidence: PMID:16429126 Proteome survey reveals modularity of the yeast cell machinery |
| GO:0005515 protein binding | IPI PMID:22405012 Cdc6-induced conformational changes in ORC bound to origin D... | REMOVE | Summary: IPI exact-source split from a cryo-EM study reports ORC1 association with Orc4. Reason: PMID:22405012 informs ORC/Cdc6/origin-DNA architecture, and the ORC subunit relationship is already captured by nuclear ORC complex membership and pre-RC assembly annotations. A separate GO:0005515 row adds no functional specificity. Supporting Evidence: PMID:22405012 Cdc6-induced conformational changes in ORC bound to origin DNA revealed by cryo-electron microscopy |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: IPI exact-source split from the Michaelis et al. yeast interactome reports ORC1 association with Orc4. Reason: The high-throughput affinity-enrichment/MS interaction is compatible with ORC complex membership, but GO:0005515 is still an uninformative generic interaction term and should not be retained as a standalone ORC1 molecular function. Supporting Evidence: PMID:37968396 The social and structural architecture of the yeast protein interactome |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO maps ORC1's conserved AAA+ ATPase core to ATP binding. Reason: The IPR003959 source is the same AAA+ ATPase core that supports the accepted InterPro2GO ATP hydrolysis row. ATP binding is a direct Orc1 molecular activity with independent IDA/IMP support and is required for ORC nucleotide-state control during origin licensing. Supporting Evidence: file:yeast/ORC1/ORC1-deep-research-falcon.md ATP binding by Orc1 is required for ORC DNA binding PMID:17825064 Cdt1p neither bound to origin DNA and ATP nor affected ORC-binding to origin DNA and ATP PMID:9038340 two subunits, Orc1p and Orc5p, bind ATP and that Orc1p also hydrolyzes ATP |
| GO:0005664 nuclear origin of replication recognition complex | IPI PMID:27148210 Rapid Purification and Characterization of Mutant Origin Rec... | ACCEPT | Summary: ComplexPortal IPI row identifies Orc1 as part of the six-subunit yeast ORC. Reason: The ComplexPortal row is directly consistent with ORC1 being an obligate subunit of the yeast ORC heterohexamer and duplicates existing accepted IBA, IDA, and IMP evidence for GO:0005664 rather than making a new claim. Supporting Evidence: PMID:27148210 Orc1-His and five major proteins corresponding to Orc2/3/4/5/6 were co-pulled down |
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Download this section (compressed HTML)Q: What is the functional role of ORC1s N-terminal domain versus C-terminal ATPase domain in origin recognition versus silencing?
Q: How does ORC1s BAH domain nucleosome binding affect MCM loading efficiency and origin firing timing?
Q: Why does ORC1 have dual roles in both replication initiation and transcriptional silencing - are these mechanistically linked?
Experiment: Structural analysis of ORC1 bound to both origin DNA and nucleosomes simultaneously to understand coordination
Type: Structural biology (Cryo-EM, X-ray crystallography)
Experiment: Single-molecule studies of MCM loading kinetics with wild-type versus nucleosome-binding deficient ORC1
Type: Biophysics
Experiment: Quantitative analysis of SIR protein recruitment and heterochromatin spreading at silent loci versus origin binding sites
Type: Quantitative cell biology
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Download this section (compressed HTML)Largest subunit of the origin recognition complex; involved in directing DNA replication by binding to replication origins; also involved in transcriptional silencing; exhibits ATPase activity; role in chromatin organization at replication origins, along with chromatin remodellers; ORC1 has a paralog, SIR3, that arose from the whole genome duplication
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