ORC1

UniProt ID: P54784
Organism: Saccharomyces cerevisiae
Review Status: INITIALIZED
Aliases:
YML065W
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Gene Description

Origin recognition complex subunit 1 (ORC1) is the 120 kDa catalytic 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 chromatin remodeling.

Existing Annotations Review

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.
Supporting Evidence:
PMID:16824194
Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro
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).
Supporting Evidence:
PMID:16824194
Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro
GO:0033314 mitotic DNA replication checkpoint signaling
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: IBA annotation inferred from phylogenetic orthology. ORC1 is involved in checkpoint responses to aberrant replication.
Reason: While ORC1 is involved in replication checkpoint signaling, this is peripheral to its primary role in replication initiation. The checkpoint function is largely indirect through replication failure surveillance. IBA annotations are conservative and this may represent a non-essential secondary function.
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: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).
Supporting Evidence:
PMID:9372948
Architecture of the yeast origin recognition complex bound to origins of DNA replication
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.
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
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
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.
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
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.
Supporting Evidence:
PMID:9038340
Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex
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... 		KEEP AS NON CORE
Summary: IPI annotation from proteome survey identifies ORC1 interactions with ORC complex members and other proteins.
Reason: Generic protein binding annotation. While experimentally supported (IPI), this term lacks specificity. ORC1 has well-characterized interactions with ORC2, ORC3, ORC4, ORC5, ORC6, MCM10, TAH11, and SIR1, but the generic binding term obscures these specific interactions.
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... 		KEEP AS NON CORE
Summary: IPI annotation from global protein complex map confirms ORC1 protein-protein interactions.
Reason: Duplicate IPI annotation for generic protein binding. While experimentally valid, this is non-specific. ORC1s binding partners are well-characterized at molecular level but the broad protein binding term is uninformative.
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 ... 		KEEP AS NON CORE
Summary: IPI annotation from yeast two-hybrid screen documents protein-protein interactions.
Reason: Generic protein binding annotation supported by yeast two-hybrid data. While valid, the term lacks specificity regarding which proteins interact with ORC1.
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... 		KEEP AS NON CORE
Summary: IPI annotation from structural studies of ORC complex architecture documents protein interactions.
Reason: Generic protein binding term. While the cryo-EM structure reveals ORC1 interactions with other ORC subunits, the broad binding term lacks mechanistic specificity.
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. 		KEEP AS NON CORE
Summary: IPI annotation from chromatin-associated interactome defines ORC1 protein associations.
Reason: Generic protein binding. Experimentally supported but non-specific for ORC1s characterized interactions.
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... 		KEEP AS NON CORE
Summary: IPI annotation from cryo-EM structural analysis documents ORC1 protein-protein contacts.
Reason: Generic protein binding. Cryo-EM structure reveals detailed ORC subunit interactions, but broad binding term fails to capture this 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 ... 		KEEP AS NON CORE
Summary: IPI annotation from inter-species protein interaction network identifies ORC1 protein interactions.
Reason: Generic protein binding annotation. While documenting evolutionary conservation of protein interactions, the broad term lacks specificity.
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 ... 		KEEP AS NON CORE
Summary: IPI annotation from social and structural architecture study confirms ORC1 protein associations.
Reason: Generic protein binding. Recent interactome study confirms ORC1 interactions but the broad term is non-informative.
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 ... 		KEEP AS NON CORE
Summary: IPI annotation documents ORC1-SIR1 interaction critical for transcriptional silencing function.
Reason: Generic protein binding annotation. While the ORC1-SIR1 interaction is critical for silent locus silencing (and documented in UniProt interactions), the broad binding term obscures this mechanistically important interaction.
Supporting Evidence:
PMID:8622770
Role of interactions between the origin recognition complex and SIR1 in transcriptional silencing
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
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
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.
Supporting Evidence:
PMID:31263106
Structure and function of the Orc1 BAH-nucleosome complex
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
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.
Supporting Evidence:
PMID:12897051
Differential DNA affinity specifies roles for the origin recognition complex in budding yeast heterochromatin
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

Core Functions

ORC1 specifically recognizes and binds ARS consensus sequences (ACS) at chromosomal replication origins through its DBD domain. This is the initiating event for all replication origin function.

Molecular Function:
DNA replication origin binding
Directly Involved In:
DNA replication initiation
Supporting Evidence:
  • PMID:16824194
    Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro

ORC1 catalyzes ATP hydrolysis, which provides the energy for conformational changes required for origin binding, MCM loading, and complex assembly during pre-RC formation at G1.

Molecular Function:
ATP hydrolysis activity
Directly Involved In:
pre-replicative complex assembly involved in nuclear cell cycle DNA replication
In Complex:
nuclear origin of replication recognition complex

ORC1s BAH domain mediates specific nucleosome binding, which facilitates proper nucleosome positioning at replication origins and coordinates chromatin organization with replication initiation.

Molecular Function:
nucleosome binding
Directly Involved In:
nucleosome organization
Supporting Evidence:

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000043
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
GO_REF:0000117
Electronic Gene Ontology annotations created by ARBA machine learning models
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:8622770
Role of interactions between the origin recognition complex and SIR1 in transcriptional silencing.
PMID:9038340
Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex.
PMID:9335335
Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase.
PMID:9372948
Architecture of the yeast origin recognition complex bound to origins of DNA replication.
PMID:9554851
Formation of a preinitiation complex by S-phase cyclin CDK-dependent loading of Cdc45p onto chromatin.
PMID:11168584
Interactions between Mcm10p and other replication factors are required for proper initiation and elongation of chromosomal DNA replication in Saccharomyces cerevisiae.
PMID:12897051
Differential DNA affinity specifies roles for the origin recognition complex in budding yeast heterochromatin.
PMID:16429126
Proteome survey reveals modularity of the yeast cell machinery.
PMID:16554755
Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.
PMID:16581798
Structure and function of the Saccharomyces cerevisiae Sir3 BAH domain.
PMID:16716188
Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiae.
PMID:16824194
Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro.
PMID:17825064
Interaction between ORC and Cdt1p of Saccharomyces cerevisiae.
PMID:17825065
Yeast two-hybrid analysis of the origin recognition complex of Saccharomyces cerevisiae: interaction between subunits and identification of binding proteins.
PMID:18647841
The architecture of the DNA replication origin recognition complex in Saccharomyces cerevisiae.
PMID:21179020
Defining the budding yeast chromatin-associated interactome.
PMID:22405012
Cdc6-induced conformational changes in ORC bound to origin DNA revealed by cryo-electron microscopy.
PMID:27107014
An inter-species protein-protein interaction network across vast evolutionary distance.
PMID:31263106
Structure and function of the Orc1 BAH-nucleosome complex.
PMID:37020028
Establishment and function of chromatin organization at replication origins.
PMID:37968396
The social and structural architecture of the yeast protein interactome.
Reactome:R-SCE-9749345
CDT1-mediated loading of MCM2-7 to replication origin in budding yeast
Reactome:R-SCE-9749381
ATP-dependent release of CDT1 from the OCCM complex in budding yeast
Reactome:R-SCE-9749401
CTD1-mediated formation of MCM2-7 double hexamers at the replication origins in budding yeast

Suggested Questions for Experts

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?

Suggested Experiments

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

📄 View Raw YAML

 
id: P54784
gene_symbol: ORC1
aliases:
  - YML065W
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:559292
  label: Saccharomyces cerevisiae
description: 'Origin recognition complex subunit 1 (ORC1) is the 120 kDa catalytic 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 chromatin remodeling.'
existing_annotations:
- term:
    id: GO:0006270
    label: DNA replication initiation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.'
    action: ACCEPT
    reason: 'Core function. Multiple experimental studies (IDA, IMP, NAS) confirm ORC1s role in DNA replication initiation through pre-replicative complex assembly and MCM loading.'
    supported_by:
      - reference_id: PMID:16824194
        supporting_text: 'Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro'
- term:
    id: GO:0003688
    label: DNA replication origin binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'IBA annotation reflects the fundamental mechanism by which ORC1 initiates DNA replication through recognition of ARS consensus sequences.'
    action: ACCEPT
    reason: 'Core molecular function. ORC1 specifically binds ARS consensus sequences (ACS) at replication origins. This is well-established experimentally (IDA evidence PMID:16824194).'
    supported_by:
      - reference_id: PMID:16824194
        supporting_text: 'Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro'
- term:
    id: GO:0033314
    label: mitotic DNA replication checkpoint signaling
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'IBA annotation inferred from phylogenetic orthology. ORC1 is involved in checkpoint responses to aberrant replication.'
    action: KEEP_AS_NON_CORE
    reason: 'While ORC1 is involved in replication checkpoint signaling, this is peripheral to its primary role in replication initiation. The checkpoint function is largely indirect through replication failure surveillance. IBA annotations are conservative and this may represent a non-essential secondary function.'
    supported_by:
      - reference_id: PMID:16716188
        supporting_text: 'Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiae'
- term:
    id: GO:0005664
    label: nuclear origin of replication recognition complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'IBA annotation correctly identifies ORC1 as part of the ORC complex, a multi-subunit assembly.'
    action: ACCEPT
    reason: 'Accurate. ORC1 is a core structural component of the ORC complex. Experimentally validated (IDA, IMP evidence).'
    supported_by:
      - reference_id: PMID:9372948
        supporting_text: 'Architecture of the yeast origin recognition complex bound to origins of DNA replication'
- term:
    id: GO:0000166
    label: nucleotide binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: 'IEA annotation based on UniProtKB keyword mapping. ORC1 contains AAA+ ATPase domain with ATP binding capability.'
    action: KEEP_AS_NON_CORE
    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.'
    supported_by: []
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: 'IEA annotation based on UniProtKB keyword mapping reflects ORC1s well-documented ARS-binding capability.'
    action: KEEP_AS_NON_CORE
    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.'
    supported_by:
      - reference_id: PMID:16824194
        supporting_text: 'Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro'
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: 'IEA annotation inferred from InterPro BAH domain (IPR001025). ORC1 contains a BAH domain for nucleosome interaction.'
    action: ACCEPT
    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.'
    supported_by:
      - reference_id: PMID:31263106
        supporting_text: 'Structure and function of the Orc1 BAH-nucleosome complex'
- term:
    id: GO:0003688
    label: DNA replication origin binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'IEA annotation from ARBA machine learning model correctly identifies ORC1s origin binding function.'
    action: ACCEPT
    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).'
    supported_by:
      - reference_id: PMID:16824194
        supporting_text: 'Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro'
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'IEA annotation from combined automated methods identifies ATP binding in AAA+ domain.'
    action: ACCEPT
    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.'
    supported_by: []
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: 'IEA annotation from UniProtKB subcellular location vocabulary correctly identifies nuclear localization.'
    action: KEEP_AS_NON_CORE
    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.'
    supported_by:
      - reference_id: PMID:11168584
        supporting_text: 'Interactions between Mcm10p and other replication factors are required for proper initiation and elongation of chromosomal DNA replication in Saccharomyces cerevisiae'
- term:
    id: GO:0005694
    label: chromosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'IEA annotation from ARBA model identifies ORC1s chromosomal localization during S phase.'
    action: KEEP_AS_NON_CORE
    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.'
    supported_by: []
- term:
    id: GO:0006260
    label: DNA replication
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: 'IEA annotation based on UniProtKB keyword mapping reflects ORC1s essential role in DNA replication process.'
    action: ACCEPT
    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.'
    supported_by:
      - reference_id: PMID:16824194
        supporting_text: 'Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro'
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: 'IEA annotation inferred from InterPro AAA+ ATPase domain (IPR003959). ORC1 catalyzes ATP hydrolysis for nucleotide-dependent conformational changes.'
    action: ACCEPT
    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.'
    supported_by:
      - reference_id: PMID:9038340
        supporting_text: 'Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex'
- term:
    id: GO:0046872
    label: metal ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: 'IEA annotation from UniProtKB keyword reflects metal coordination in ORC1s ATP binding sites.'
    action: KEEP_AS_NON_CORE
    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.'
    supported_by: []
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16429126
  review:
    summary: 'IPI annotation from proteome survey identifies ORC1 interactions with ORC complex members and other proteins.'
    action: KEEP_AS_NON_CORE
    reason: 'Generic protein binding annotation. While experimentally supported (IPI), this term lacks specificity. ORC1 has well-characterized interactions with ORC2, ORC3, ORC4, ORC5, ORC6, MCM10, TAH11, and SIR1, but the generic binding term obscures these specific interactions.'
    supported_by:
      - reference_id: PMID:16429126
        supporting_text: 'Proteome survey reveals modularity of the yeast cell machinery'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16554755
  review:
    summary: 'IPI annotation from global protein complex map confirms ORC1 protein-protein interactions.'
    action: KEEP_AS_NON_CORE
    reason: 'Duplicate IPI annotation for generic protein binding. While experimentally valid, this is non-specific. ORC1s binding partners are well-characterized at molecular level but the broad protein binding term is uninformative.'
    supported_by:
      - reference_id: PMID:16554755
        supporting_text: 'Global landscape of protein complexes in the yeast Saccharomyces cerevisiae'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17825065
  review:
    summary: 'IPI annotation from yeast two-hybrid screen documents protein-protein interactions.'
    action: KEEP_AS_NON_CORE
    reason: 'Generic protein binding annotation supported by yeast two-hybrid data. While valid, the term lacks specificity regarding which proteins interact with ORC1.'
    supported_by:
      - reference_id: PMID:17825065
        supporting_text: 'Yeast two-hybrid analysis of the origin recognition complex of Saccharomyces cerevisiae: interaction between subunits and identification of binding proteins'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18647841
  review:
    summary: 'IPI annotation from structural studies of ORC complex architecture documents protein interactions.'
    action: KEEP_AS_NON_CORE
    reason: 'Generic protein binding term. While the cryo-EM structure reveals ORC1 interactions with other ORC subunits, the broad binding term lacks mechanistic specificity.'
    supported_by:
      - reference_id: PMID:18647841
        supporting_text: 'The architecture of the DNA replication origin recognition complex in Saccharomyces cerevisiae'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21179020
  review:
    summary: 'IPI annotation from chromatin-associated interactome defines ORC1 protein associations.'
    action: KEEP_AS_NON_CORE
    reason: 'Generic protein binding. Experimentally supported but non-specific for ORC1s characterized interactions.'
    supported_by:
      - reference_id: PMID:21179020
        supporting_text: 'Defining the budding yeast chromatin-associated interactome'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22405012
  review:
    summary: 'IPI annotation from cryo-EM structural analysis documents ORC1 protein-protein contacts.'
    action: KEEP_AS_NON_CORE
    reason: 'Generic protein binding. Cryo-EM structure reveals detailed ORC subunit interactions, but broad binding term fails to capture this specificity.'
    supported_by:
      - reference_id: PMID:22405012
        supporting_text: 'Cdc6-induced conformational changes in ORC bound to origin DNA revealed by cryo-electron microscopy'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27107014
  review:
    summary: 'IPI annotation from inter-species protein interaction network identifies ORC1 protein interactions.'
    action: KEEP_AS_NON_CORE
    reason: 'Generic protein binding annotation. While documenting evolutionary conservation of protein interactions, the broad term lacks specificity.'
    supported_by:
      - reference_id: PMID:27107014
        supporting_text: 'An inter-species protein-protein interaction network across vast evolutionary distance'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37968396
  review:
    summary: 'IPI annotation from social and structural architecture study confirms ORC1 protein associations.'
    action: KEEP_AS_NON_CORE
    reason: 'Generic protein binding. Recent interactome study confirms ORC1 interactions but the broad term is non-informative.'
    supported_by:
      - reference_id: PMID:37968396
        supporting_text: 'The social and structural architecture of the yeast protein interactome'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:8622770
  review:
    summary: 'IPI annotation documents ORC1-SIR1 interaction critical for transcriptional silencing function.'
    action: KEEP_AS_NON_CORE
    reason: 'Generic protein binding annotation. While the ORC1-SIR1 interaction is critical for silent locus silencing (and documented in UniProt interactions), the broad binding term obscures this mechanistically important interaction.'
    supported_by:
      - reference_id: PMID:8622770
        supporting_text: 'Role of interactions between the origin recognition complex and SIR1 in transcriptional silencing'
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: EXP
  original_reference_id: PMID:16824194
  review:
    summary: 'EXP annotation documents nuclear localization of ORC1 from in vitro reconstitution studies.'
    action: KEEP_AS_NON_CORE
    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.'
    supported_by:
      - reference_id: PMID:16824194
        supporting_text: 'Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro'
- term:
    id: GO:0006270
    label: DNA replication initiation
  evidence_type: NAS
  original_reference_id: PMID:16824194
  review:
    summary: 'NAS (Not Annotated Source) evidence from reconstitution studies documents ORC1s essential role in initiation.'
    action: ACCEPT
    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.'
    supported_by:
      - reference_id: PMID:16824194
        supporting_text: 'Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro'
- term:
    id: GO:0034728
    label: nucleosome organization
  evidence_type: IMP
  original_reference_id: PMID:37020028
  review:
    summary: 'IMP annotation from recent study characterizes ORC1s role in chromatin organization at replication origins.'
    action: ACCEPT
    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.'
    supported_by:
      - reference_id: PMID:37020028
        supporting_text: 'Establishment and function of chromatin organization at replication origins'
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-SCE-9749345
  review:
    summary: 'TAS annotation from Reactome identifies nucleoplasm as the functional compartment for MCM loading.'
    action: KEEP_AS_NON_CORE
    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.'
    supported_by: []
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-SCE-9749381
  review:
    summary: 'TAS annotation from Reactome pathway identifies nucleoplasm localization during CDT1 release.'
    action: KEEP_AS_NON_CORE
    reason: 'Correct but redundant subcellular localization. Multiple pathway annotations for nucleoplasm are unnecessary.'
    supported_by: []
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-SCE-9749401
  review:
    summary: 'TAS annotation from Reactome identifies nucleoplasm during MCM double hexamer formation.'
    action: KEEP_AS_NON_CORE
    reason: 'Correct but redundant subcellular localization. This duplicates the nucleoplasm annotation from other Reactome pathways.'
    supported_by: []
- term:
    id: GO:0031491
    label: nucleosome binding
  evidence_type: IDA
  original_reference_id: PMID:31263106
  review:
    summary: 'IDA annotation directly demonstrates ORC1s BAH domain interaction with nucleosomes.'
    action: ACCEPT
    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.'
    supported_by:
      - reference_id: PMID:31263106
        supporting_text: 'Structure and function of the Orc1 BAH-nucleosome complex'
- term:
    id: GO:0043007
    label: maintenance of rDNA
  evidence_type: IDA
  original_reference_id: PMID:31263106
  review:
    summary: 'IDA annotation documents ORC1s role in ribosomal DNA maintenance and nucleosome organization at rDNA loci.'
    action: ACCEPT
    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.'
    supported_by:
      - reference_id: PMID:31263106
        supporting_text: 'Structure and function of the Orc1 BAH-nucleosome complex'
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IDA
  original_reference_id: PMID:11168584
  review:
    summary: 'IDA annotation directly demonstrates ORC1s chromatin binding through interactions with MCM10 and other chromatin factors.'
    action: ACCEPT
    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.'
    supported_by:
      - reference_id: PMID:11168584
        supporting_text: 'Interactions between Mcm10p and other replication factors are required for proper initiation and elongation of chromosomal DNA replication in Saccharomyces cerevisiae'
- term:
    id: GO:0003688
    label: DNA replication origin binding
  evidence_type: IDA
  original_reference_id: PMID:16824194
  review:
    summary: 'IDA annotation provides direct experimental evidence for ORC1s origin binding function.'
    action: ACCEPT
    reason: 'Core molecular function. Direct assay evidence (IDA) from in vitro reconstitution unequivocally demonstrates ORC1s specific binding to origin DNA at ARS consensus sequences.'
    supported_by:
      - reference_id: PMID:16824194
        supporting_text: 'Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro'
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IDA
  original_reference_id: PMID:17825064
  review:
    summary: 'IDA annotation directly assays ATP binding in ORC1 and Cdt1 interaction studies.'
    action: ACCEPT
    reason: 'Core molecular function. Direct experimental evidence (IDA) confirms ATP binding. This is mechanistically essential for ORC1s regulatory ATPase activity.'
    supported_by:
      - reference_id: PMID:17825064
        supporting_text: 'Interaction between ORC and Cdt1p of Saccharomyces cerevisiae'
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IMP
  original_reference_id: PMID:9038340
  review:
    summary: 'IMP annotation documents ATP binding as essential for ORC complex ATPase activity regulation.'
    action: ACCEPT
    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.'
    supported_by:
      - reference_id: PMID:9038340
        supporting_text: 'Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex'
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:11168584
  review:
    summary: 'IDA annotation directly demonstrates nuclear localization of ORC1.'
    action: KEEP_AS_NON_CORE
    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.'
    supported_by:
      - reference_id: PMID:11168584
        supporting_text: 'Interactions between Mcm10p and other replication factors are required for proper initiation and elongation of chromosomal DNA replication in Saccharomyces cerevisiae'
- term:
    id: GO:0005656
    label: nuclear pre-replicative complex
  evidence_type: IDA
  original_reference_id: PMID:16824194
  review:
    summary: 'IDA annotation directly identifies ORC1 as a structural component of the pre-replicative complex.'
    action: ACCEPT
    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.'
    supported_by:
      - reference_id: PMID:16824194
        supporting_text: 'Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro'
- term:
    id: GO:0005656
    label: nuclear pre-replicative complex
  evidence_type: IDA
  original_reference_id: PMID:9335335
  review:
    summary: 'IDA annotation from cell cycle studies documents ORC1 as core component of pre-RC during S phase.'
    action: ACCEPT
    reason: 'Duplicate annotation for core component. Experimental evidence (IDA) from MCM protein redistribution studies confirms ORC1s role in pre-RC assembly and dynamics.'
    supported_by:
      - reference_id: PMID:9335335
        supporting_text: 'Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase'
- term:
    id: GO:0005664
    label: nuclear origin of replication recognition complex
  evidence_type: IDA
  original_reference_id: PMID:9372948
  review:
    summary: 'IDA annotation directly identifies ORC1 as integral component of the ORC complex through structural analysis.'
    action: ACCEPT
    reason: 'Core cellular component. ORC1 is essential to ORC complex assembly. Experimental evidence (IDA) from origin-bound ORC architecture studies provides direct confirmation.'
    supported_by:
      - reference_id: PMID:9372948
        supporting_text: 'Architecture of the yeast origin recognition complex bound to origins of DNA replication'
- term:
    id: GO:0005664
    label: nuclear origin of replication recognition complex
  evidence_type: IMP
  original_reference_id: PMID:9372948
  review:
    summary: 'IMP annotation documents ORC1s functional role in ORC complex assembly through mutational analysis.'
    action: ACCEPT
    reason: 'Core component. Duplicate annotation with different evidence type (IMP). Functional mutations demonstrate ORC1s essential role in complex formation and origin recognition.'
    supported_by:
      - reference_id: PMID:9372948
        supporting_text: 'Architecture of the yeast origin recognition complex bound to origins of DNA replication'
- term:
    id: GO:0006267
    label: pre-replicative complex assembly involved in nuclear cell cycle DNA replication
  evidence_type: IDA
  original_reference_id: PMID:16824194
  review:
    summary: 'IDA annotation directly demonstrates ORC1s active role in pre-replicative complex assembly through in vitro reconstitution.'
    action: ACCEPT
    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.'
    supported_by:
      - reference_id: PMID:16824194
        supporting_text: 'Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro'
- term:
    id: GO:0006267
    label: pre-replicative complex assembly involved in nuclear cell cycle DNA replication
  evidence_type: IMP
  original_reference_id: PMID:9335335
  review:
    summary: 'IMP annotation from cell cycle studies documents ORC1s essential role in pre-RC assembly.'
    action: ACCEPT
    reason: 'Duplicate annotation for core process. Experimental evidence (IMP) from MCM redistribution and functional studies confirms ORC1s requirement for pre-RC assembly.'
    supported_by:
      - reference_id: PMID:9335335
        supporting_text: 'Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase'
- term:
    id: GO:0006270
    label: DNA replication initiation
  evidence_type: IMP
  original_reference_id: PMID:16716188
  review:
    summary: 'IMP annotation documents ORC1s essential role in DNA replication initiation through checkpoint and cell cycle execution point analysis.'
    action: ACCEPT
    reason: 'Core biological process. Conditional inactivation of ORC (including ORC1) results in failure of replication initiation, confirming essential role.'
    supported_by:
      - reference_id: PMID:16716188
        supporting_text: 'Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiae'
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IMP
  original_reference_id: PMID:9038340
  review:
    summary: 'IMP annotation demonstrates ATP hydrolysis activity is functionally essential for ORC1s regulatory mechanism.'
    action: ACCEPT
    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.'
    supported_by:
      - reference_id: PMID:9038340
        supporting_text: 'Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex'
- term:
    id: GO:0030466
    label: silent mating-type cassette heterochromatin formation
  evidence_type: IDA
  original_reference_id: PMID:12897051
  review:
    summary: 'IDA annotation directly demonstrates ORC1s role in transcriptional silencing at HMR/HML loci.'
    action: ACCEPT
    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.'
    supported_by:
      - reference_id: PMID:12897051
        supporting_text: 'Differential DNA affinity specifies roles for the origin recognition complex in budding yeast heterochromatin'
- term:
    id: GO:0030466
    label: silent mating-type cassette heterochromatin formation
  evidence_type: IDA
  original_reference_id: PMID:16581798
  review:
    summary: 'IDA annotation directly confirms ORC1-SIR3 interaction in heterochromatin establishment.'
    action: ACCEPT
    reason: 'Duplicate annotation for core silencing function. Experimental evidence (IDA) from Sir3 BAH domain structure studies demonstrates ORC1s functional role in recruiting silencing machinery.'
    supported_by:
      - reference_id: PMID:16581798
        supporting_text: 'Structure and function of the Saccharomyces cerevisiae Sir3 BAH domain'
- term:
    id: GO:0030466
    label: silent mating-type cassette heterochromatin formation
  evidence_type: IGI
  original_reference_id: PMID:16581798
  review:
    summary: 'IGI annotation documents genetic interaction between ORC1 and SIR3 in heterochromatin formation.'
    action: ACCEPT
    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.'
    supported_by:
      - reference_id: PMID:16581798
        supporting_text: 'Structure and function of the Saccharomyces cerevisiae Sir3 BAH domain'
- term:
    id: GO:0031261
    label: DNA replication preinitiation complex
  evidence_type: IDA
  original_reference_id: PMID:9554851
  review:
    summary: 'IDA annotation directly identifies ORC1 as component of preinitiation complex formed during S phase.'
    action: ACCEPT
    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.'
    supported_by:
      - reference_id: PMID:9554851
        supporting_text: 'Formation of a preinitiation complex by S-phase cyclin CDK-dependent loading of Cdc45p onto chromatin'
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:8622770
  title: Role of interactions between the origin recognition complex and SIR1 in transcriptional
    silencing.
  findings: []
- id: PMID:9038340
  title: Coordinate binding of ATP and origin DNA regulates the ATPase activity of
    the origin recognition complex.
  findings: []
- id: PMID:9335335
  title: 'Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution
    of MCM proteins and Cdc45p during S phase.'
  findings: []
- id: PMID:9372948
  title: Architecture of the yeast origin recognition complex bound to origins of
    DNA replication.
  findings: []
- id: PMID:9554851
  title: Formation of a preinitiation complex by S-phase cyclin CDK-dependent loading
    of Cdc45p onto chromatin.
  findings: []
- id: PMID:11168584
  title: Interactions between Mcm10p and other replication factors are required for
    proper initiation and elongation of chromosomal DNA replication in Saccharomyces
    cerevisiae.
  findings: []
- id: PMID:12897051
  title: Differential DNA affinity specifies roles for the origin recognition complex
    in budding yeast heterochromatin.
  findings: []
- id: PMID:16429126
  title: Proteome survey reveals modularity of the yeast cell machinery.
  findings: []
- id: PMID:16554755
  title: Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.
  findings: []
- id: PMID:16581798
  title: Structure and function of the Saccharomyces cerevisiae Sir3 BAH domain.
  findings: []
- id: PMID:16716188
  title: Cell cycle execution point analysis of ORC function and characterization
    of the checkpoint response to ORC inactivation in Saccharomyces cerevisiae.
  findings: []
- id: PMID:16824194
  title: Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly
    in vitro.
  findings: []
- id: PMID:17825064
  title: Interaction between ORC and Cdt1p of Saccharomyces cerevisiae.
  findings: []
- id: PMID:17825065
  title: 'Yeast two-hybrid analysis of the origin recognition complex of Saccharomyces
    cerevisiae: interaction between subunits and identification of binding proteins.'
  findings: []
- id: PMID:18647841
  title: The architecture of the DNA replication origin recognition complex in Saccharomyces
    cerevisiae.
  findings: []
- id: PMID:21179020
  title: Defining the budding yeast chromatin-associated interactome.
  findings: []
- id: PMID:22405012
  title: Cdc6-induced conformational changes in ORC bound to origin DNA revealed by
    cryo-electron microscopy.
  findings: []
- id: PMID:27107014
  title: An inter-species protein-protein interaction network across vast evolutionary
    distance.
  findings: []
- id: PMID:31263106
  title: Structure and function of the Orc1 BAH-nucleosome complex.
  findings: []
- id: PMID:37020028
  title: Establishment and function of chromatin organization at replication origins.
  findings: []
- id: PMID:37968396
  title: The social and structural architecture of the yeast protein interactome.
  findings: []
- id: Reactome:R-SCE-9749345
  title: CDT1-mediated loading of MCM2-7 to replication origin in budding yeast
  findings: []
- id: Reactome:R-SCE-9749381
  title: ATP-dependent release of CDT1 from the OCCM complex in budding yeast
  findings: []
- id: Reactome:R-SCE-9749401
  title: CTD1-mediated formation of MCM2-7 double hexamers at the replication origins
    in budding yeast
  findings: []
core_functions:
- molecular_function:
    id: GO:0003688
    label: DNA replication origin binding
  description: 'ORC1 specifically recognizes and binds ARS consensus sequences (ACS) at chromosomal replication origins through its DBD domain. This is the initiating event for all replication origin function.'
  directly_involved_in:
    - id: GO:0006270
      label: DNA replication initiation
  supported_by:
    - reference_id: PMID:16824194
      supporting_text: 'Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro'
- molecular_function:
    id: GO:0016887
    label: ATP hydrolysis activity
  description: 'ORC1 catalyzes ATP hydrolysis, which provides the energy for conformational changes required for origin binding, MCM loading, and complex assembly during pre-RC formation at G1.'
  directly_involved_in:
    - id: GO:0006267
      label: pre-replicative complex assembly involved in nuclear cell cycle DNA replication
  in_complex:
    id: GO:0005664
    label: nuclear origin of replication recognition complex
- molecular_function:
    id: GO:0031491
    label: nucleosome binding
  description: 'ORC1s BAH domain mediates specific nucleosome binding, which facilitates proper nucleosome positioning at replication origins and coordinates chromatin organization with replication initiation.'
  directly_involved_in:
    - id: GO:0034728
      label: nucleosome organization
  supported_by:
    - reference_id: PMID:31263106
      supporting_text: 'Structure and function of the Orc1 BAH-nucleosome complex'
proposed_new_terms: []
suggested_questions:
- question: 'What is the functional role of ORC1s N-terminal domain versus C-terminal ATPase domain in origin recognition versus silencing?'
- question: 'How does ORC1s BAH domain nucleosome binding affect MCM loading efficiency and origin firing timing?'
- question: 'Why does ORC1 have dual roles in both replication initiation and transcriptional silencing - are these mechanistically linked?'
suggested_experiments:
- description: 'Structural analysis of ORC1 bound to both origin DNA and nucleosomes simultaneously to understand coordination'
  experiment_type: 'Structural biology (Cryo-EM, X-ray crystallography)'
- description: 'Single-molecule studies of MCM loading kinetics with wild-type versus nucleosome-binding deficient ORC1'
  experiment_type: 'Biophysics'
- description: 'Quantitative analysis of SIR protein recruitment and heterochromatin spreading at silent loci versus origin binding sites'
  experiment_type: 'Quantitative cell biology'