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    ORC1 origin recognition complex subunit 1 [ Homo sapiens (human) ]

    Gene ID: 4998, updated on 12-Mar-2017
    Official Symbol
    ORC1provided by HGNC
    Official Full Name
    origin recognition complex subunit 1provided by HGNC
    Primary source
    HGNC:HGNC:8487
    See related
    Ensembl:ENSG00000085840 MIM:601902; Vega:OTTHUMG00000008104
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    ORC1L; PARC1; HSORC1
    Summary
    The origin recognition complex (ORC) is a highly conserved six subunits protein complex essential for the initiation of the DNA replication in eukaryotic cells. Studies in yeast demonstrated that ORC binds specifically to origins of replication and serves as a platform for the assembly of additional initiation factors such as Cdc6 and Mcm proteins. The protein encoded by this gene is the largest subunit of the ORC complex. While other ORC subunits are stable throughout the cell cycle, the levels of this protein vary during the cell cycle, which has been shown to be controlled by ubiquitin-mediated proteolysis after initiation of DNA replication. This protein is found to be selectively phosphorylated during mitosis. It is also reported to interact with MYST histone acetyltransferase 2 (MyST2/HBO1), a protein involved in control of transcription silencing. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]
    Orthologs
    Location:
    1p32.3
    Exon count:
    18
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 1 NC_000001.11 (52371408..52404471, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (52838501..52870143, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene zinc finger FYVE-type containing 9 Neighboring gene phospholipase A2 group XIIA pseudogene 1 Neighboring gene coiled-coil and C2 domain containing 1B Neighboring gene pre-mRNA processing factor 38A Neighboring gene zinc finger CCHC-type containing 11 Neighboring gene uncharacterized LOC105378723

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    • Activation of ATR in response to replication stress, organism-specific biosystem (from REACTOME)
      Activation of ATR in response to replication stress, organism-specific biosystemGenotoxic stress caused by DNA damage or stalled replication forks can lead to genomic instability. To guard against such instability, genotoxically-stressed cells activate checkpoint factors that ha...
    • Activation of the pre-replicative complex, organism-specific biosystem (from REACTOME)
      Activation of the pre-replicative complex, organism-specific biosystemIn S. cerevisiae, two ORC subunits, Orc1 and Orc5, both bind ATP, and Orc1 in addition has ATPase activity. Both ATP binding and ATP hydrolysis appear to be essential functions in vivo. ATP binding b...
    • Assembly of the ORC complex at the origin of replication, organism-specific biosystem (from REACTOME)
      Assembly of the ORC complex at the origin of replication, organism-specific biosystemIn Saccharomyces cerevisiae, the entire ORC complex is constitutively bound to the origin of replication. However, in mammalian cells, Orc1, and possibly other Orc subunits, dissociate from origins o...
    • Assembly of the pre-replicative complex, organism-specific biosystem (from REACTOME)
      Assembly of the pre-replicative complex, organism-specific biosystemDNA replication pre-initiation in eukaryotic cells begins with the formation of the pre-replicative complex (pre-RC) during the late M phase and continues in the G1 phase of the mitotic cell cycle, a...
    • Association of licensing factors with the pre-replicative complex, organism-specific biosystem (from REACTOME)
      Association of licensing factors with the pre-replicative complex, organism-specific biosystemThe eukaryotic six-subunit origin recognition complex (ORC) governs the initiation site of DNA replication and formation of the prereplication complex.
    • CDC6 association with the ORC:origin complex, organism-specific biosystem (from REACTOME)
      CDC6 association with the ORC:origin complex, organism-specific biosystemCdc6 is a regulator of DNA replication initiation in both yeasts and human cells, but its mechanism of action differs between the two systems. Genetic studies in budding yeast (S. cerevisiae) and fis...
    • CDT1 association with the CDC6:ORC:origin complex, organism-specific biosystem (from REACTOME)
      CDT1 association with the CDC6:ORC:origin complex, organism-specific biosystemInitiation protein Cdt1 was first identified in X. laevis, where it has been shown to be the second component of licensing factor (RLF-B) and in S. pombe. Cdt1 homologs have been identified in D. mel...
    • Cell Cycle, organism-specific biosystem (from WikiPathways)
      Cell Cycle, organism-specific biosystemThe cell cycle is the series of events that takes place in a cell leading to its division and duplication (replication). Regulation of the cell cycle involves processes crucial to the survival of a c...
    • Cell Cycle, organism-specific biosystem (from REACTOME)
      Cell Cycle, organism-specific biosystem
      Cell Cycle
    • Cell Cycle Checkpoints, organism-specific biosystem (from REACTOME)
      Cell Cycle Checkpoints, organism-specific biosystemA hallmark of the human cell cycle in normal somatic cells is its precision. This remarkable fidelity is achieved by a number of signal transduction pathways, known as checkpoints, which monitor cell...
    • Cell Cycle, Mitotic, organism-specific biosystem (from REACTOME)
      Cell Cycle, Mitotic, organism-specific biosystemThe replication of the genome and the subsequent segregation of chromosomes into daughter cells are controlled by a series of events collectively known as the cell cycle. DNA replication is carried o...
    • Cell cycle, organism-specific biosystem (from KEGG)
      Cell cycle, organism-specific biosystemMitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cycli...
    • Cell cycle, conserved biosystem (from KEGG)
      Cell cycle, conserved biosystemMitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cycli...
    • DNA Replication, organism-specific biosystem (from REACTOME)
      DNA Replication, organism-specific biosystemStudies in the past decade have suggested that the basic mechanism of DNA replication initiation is conserved in all kingdoms of life. Initiation in unicellular eukaryotes, in particular Saccharomyce...
    • DNA Replication, organism-specific biosystem (from WikiPathways)
      DNA Replication, organism-specific biosystemStudies in the past decade have suggested that the basic mechanism of DNA replication initiation is conserved in all kingdoms of life. Initiation in unicellular eukaryotes, in particular Saccharomyce...
    • DNA Replication Pre-Initiation, organism-specific biosystem (from REACTOME)
      DNA Replication Pre-Initiation, organism-specific biosystemAlthough, DNA replication occurs in the S phase of the cell cycle, the formation of the DNA replication pre-initiation complex begins during G1 phase.
    • E2F mediated regulation of DNA replication, organism-specific biosystem (from REACTOME)
      E2F mediated regulation of DNA replication, organism-specific biosystemProgression through G1 and G1 to S-phase transition that initiates DNA synthesis involve many complexes that are regulated by RB1:E2F pathway. RB1:E2F pathway plays a key role in gene expression regu...
    • E2F transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
      E2F transcription factor network, organism-specific biosystem
      E2F transcription factor network
    • E2F-enabled inhibition of pre-replication complex formation, organism-specific biosystem (from REACTOME)
      E2F-enabled inhibition of pre-replication complex formation, organism-specific biosystemUnder specific conditions, Cyclin B, a mitotic cyclin, can inhibit the functions of pre-replicative complex. E2F1 activates Cdc25A protein which regulates Cyclin B in a positive manner. Cyclin B/Cdk...
    • G1 to S cell cycle control, organism-specific biosystem (from WikiPathways)
      G1 to S cell cycle control, organism-specific biosystemIn the G1 phase there are two types of DNA damage responses, the p53-dependent and the p53-independent pathways. The p53-dependent responses inhibit CDKs through the up-regulation of genes encoding C...
    • G1/S Transition, organism-specific biosystem (from REACTOME)
      G1/S Transition, organism-specific biosystemCyclin E - Cdk2 complexes control the transition from G1 into S-phase. In this case, the binding of p21Cip1/Waf1 or p27kip1 is inhibitory. Important substrates for Cyclin E - Cdk2 complexes include p...
    • G1/S-Specific Transcription, organism-specific biosystem (from REACTOME)
      G1/S-Specific Transcription, organism-specific biosystemThe E2F family of transcription factors regulate the transition from the G1 to the S phase in the cell cycle. E2F activity is regulated by members of the retinoblastoma protein (pRb) family, resultin...
    • G2/M Checkpoints, organism-specific biosystem (from REACTOME)
      G2/M Checkpoints, organism-specific biosystemG2/M checkpoints include the checks for damaged DNA, unreplicated DNA, and checks that ensure that the genome is replicated once and only once per cell cycle. If cells pass these checkpoints, they f...
    • M/G1 Transition, organism-specific biosystem (from REACTOME)
      M/G1 Transition, organism-specific biosystemFinally, progression out of mitosis and division of the cell into two daughters (cytokinesis) requires the inactivation of Cyclin B - Cdc2 by ubiquitin-dependent proteolysis of Cyclin A and B, which ...
    • Mitotic G1-G1/S phases, organism-specific biosystem (from REACTOME)
      Mitotic G1-G1/S phases, organism-specific biosystem
      Mitotic G1-G1/S phases
    • Orc1 removal from chromatin, organism-specific biosystem (from REACTOME)
      Orc1 removal from chromatin, organism-specific biosystem
      Orc1 removal from chromatin
    • Origin recognition complex, organism-specific biosystem (from KEGG)
      Origin recognition complex, organism-specific biosystemStructural complex; Genetic information processing; Replication system
    • Origin recognition complex, conserved biosystem (from KEGG)
      Origin recognition complex, conserved biosystemStructural complex; Genetic information processing; Replication system
    • Regulation of DNA replication, organism-specific biosystem (from REACTOME)
      Regulation of DNA replication, organism-specific biosystemDNA replication is regulated at various levels via ORC proteins. This pathway includes annotation of individual events that lead to the regulation of replication.
    • Removal of licensing factors from origins, organism-specific biosystem (from REACTOME)
      Removal of licensing factors from origins, organism-specific biosystemLicensing factors are removed from the origin by various means like biochemical modification (phosphorylation) or by physical association with other proteins. This pathway includes the annotations of...
    • Retinoblastoma (RB) in Cancer, organism-specific biosystem (from WikiPathways)
      Retinoblastoma (RB) in Cancer, organism-specific biosystemDescribes the role of retinoblastoma (RB) gene in cancer.
    • S Phase, organism-specific biosystem (from REACTOME)
      S Phase, organism-specific biosystemDNA synthesis occurs in the S phase, or the synthesis phase, of the cell cycle. The cell duplicates its hereditary material, and two copies of the chromosome are formed. As DNA replication continues,...
    • Switching of origins to a post-replicative state, organism-specific biosystem (from REACTOME)
      Switching of origins to a post-replicative state, organism-specific biosystem
      Switching of origins to a post-replicative state
    • Synthesis of DNA, organism-specific biosystem (from REACTOME)
      Synthesis of DNA, organism-specific biosystemThe actual synthesis of DNA occurs in the S phase of the cell cycle. This includes the initiation of DNA replication, when the first nucleotide of the new strand is laid down during the synthesis of ...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding IEA
    Inferred from Electronic Annotation
    more info
     
    DNA binding IEA
    Inferred from Electronic Annotation
    more info
     
    chromatin binding IEA
    Inferred from Electronic Annotation
    more info
     
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    DNA replication TAS
    Traceable Author Statement
    more info
     
    DNA replication initiation TAS
    Traceable Author Statement
    more info
    PubMed 
    G1/S transition of mitotic cell cycle TAS
    Traceable Author Statement
    more info
     
    regulation of transcription involved in G1/S transition of mitotic cell cycle TAS
    Traceable Author Statement
    more info
     
    Component Evidence Code Pubs
    cytosol IDA
    Inferred from Direct Assay
    more info
     
    cytosol TAS
    Traceable Author Statement
    more info
     
    colocalizes_with nuclear chromosome, telomeric region IDA
    Inferred from Direct Assay
    more info
    PubMed 
    nuclear origin of replication recognition complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    nucleolus IDA
    Inferred from Direct Assay
    more info
     
    nucleoplasm TAS
    Traceable Author Statement
    more info
     
    nucleus IDA
    Inferred from Direct Assay
    more info
     
    origin recognition complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    plasma membrane IDA
    Inferred from Direct Assay
    more info
     
    Preferred Names
    origin recognition complex subunit 1
    Names
    origin recognition complex, subunit 1 homolog
    replication control protein 1

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_028251.1 RefSeqGene

      Range
      5001..36643
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001190818.1NP_001177747.1  origin recognition complex subunit 1 isoform 1

      See identical proteins and their annotated locations for NP_001177747.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) has an alternate splice site in the 5' UTR, resulting in 3 nt fewer than variant 1. Variants 1 and 2 encode the same isoform 1.
      Source sequence(s)
      BC011539, BP280383, U43416
      Consensus CDS
      CCDS566.1
      UniProtKB/Swiss-Prot
      Q13415
      UniProtKB/TrEMBL
      Q96F82
      Related
      ENSP00000360621, OTTHUMP00000009798, ENST00000371566, OTTHUMT00000022203
      Conserved Domains (5) summary
      cd04719
      Location:44170
      BAH_Orc1p_animal; BAH, or Bromo Adjacent Homology domain, as present in animal homologs of Saccharomyces cerevisiae Orc1p. Orc1 is part of the Yeast Sir1-origin recognition complex. The Orc1p BAH doman functions in epigenetic silencing. In vertebrates, a similar ORC ...
      pfam09079
      Location:778851
      Cdc6_C; CDC6, C terminal
      pfam13191
      Location:504554
      AAA_16; AAA ATPase domain
      pfam15091
      Location:394519
      DUF4554; Domain of unknown function (DUF4554)
      cl21455
      Location:530675
      P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases
    2. NM_001190819.1NP_001177748.1  origin recognition complex subunit 1 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) has an alternate splice site in the CDS, resulting in 15 nt fewer than variant 1. The resulting isoform (2) lacks internal 5 aa, as compared to isoform 1.
      Source sequence(s)
      AK303420, DB156841, U43416
      UniProtKB/Swiss-Prot
      Q13415
      UniProtKB/TrEMBL
      B7Z8H0
      Conserved Domains (4) summary
      cd04719
      Location:44170
      BAH_Orc1p_animal; BAH, or Bromo Adjacent Homology domain, as present in animal homologs of Saccharomyces cerevisiae Orc1p. Orc1 is part of the Yeast Sir1-origin recognition complex. The Orc1p BAH doman functions in epigenetic silencing. In vertebrates, a similar ORC ...
      pfam09079
      Location:773846
      Cdc6_C; CDC6, C terminal
      pfam13191
      Location:499549
      AAA_16; AAA ATPase domain
      cl21455
      Location:525670
      P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases
    3. NM_004153.3NP_004144.2  origin recognition complex subunit 1 isoform 1

      See identical proteins and their annotated locations for NP_004144.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) is the longest transcript and encodes the longer isoform (1).
      Source sequence(s)
      DB156841, U40152, U43416
      Consensus CDS
      CCDS566.1
      UniProtKB/Swiss-Prot
      Q13415
      Related
      ENSP00000360623, OTTHUMP00000009797, ENST00000371568, OTTHUMT00000022202
      Conserved Domains (5) summary
      cd04719
      Location:44170
      BAH_Orc1p_animal; BAH, or Bromo Adjacent Homology domain, as present in animal homologs of Saccharomyces cerevisiae Orc1p. Orc1 is part of the Yeast Sir1-origin recognition complex. The Orc1p BAH doman functions in epigenetic silencing. In vertebrates, a similar ORC ...
      pfam09079
      Location:778851
      Cdc6_C; CDC6, C terminal
      pfam13191
      Location:504554
      AAA_16; AAA ATPase domain
      pfam15091
      Location:394519
      DUF4554; Domain of unknown function (DUF4554)
      cl21455
      Location:530675
      P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...Open this link in a new tab

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p7 Primary Assembly

      Range
      52371408..52404471 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017001388.1XP_016856877.1  origin recognition complex subunit 1 isoform X1

    2. XM_017001389.1XP_016856878.1  origin recognition complex subunit 1 isoform X2

    3. XM_011541527.2XP_011539829.1  origin recognition complex subunit 1 isoform X3

      Conserved Domains (4) summary
      pfam09079
      Location:418491
      Cdc6_C; CDC6, C terminal
      pfam13191
      Location:144194
      AAA_16; AAA ATPase domain
      pfam15091
      Location:34159
      DUF4554; Domain of unknown function (DUF4554)
      cl21455
      Location:170315
      P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

    Alternate CHM1_1.1

    Genomic

    1. NC_018912.2 Alternate CHM1_1.1

      Range
      52955878..52987524 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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