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

Gene ID: 4998, updated on 11-Apr-2024

Summary

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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; AllianceGenome:HGNC:8487
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]
Expression
Biased expression in bone marrow (RPKM 7.3), lymph node (RPKM 2.5) and 10 other tissues See more
Orthologs
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Genomic context

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Location:
1p32.3
Exon count:
18
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (52372829..52409503, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (52254294..52290972, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (52838501..52870095, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene NANOG-H3K27ac hESC enhancers GRCh37_chr1:52815874-52816848 and GRCh37_chr1:52816849-52817822 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:52822843-52823344 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 886 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 887 Neighboring gene coiled-coil and C2 domain containing 1B Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1031 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 888 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 889 Neighboring gene phospholipase A2 group XIIA pseudogene 1 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr1:52869594-52870793 Neighboring gene uncharacterized LOC124904850 Neighboring gene Sharpr-MPRA regulatory region 15542 Neighboring gene pre-mRNA processing factor 38A Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1032 Neighboring gene terminal uridylyl transferase 4 Neighboring gene MPRA-validated peak227 silencer Neighboring gene MPRA-validated peak228 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:52963547-52964066 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:52964067-52964586 Neighboring gene uncharacterized LOC105378723 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1033 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 890

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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 Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Origin recognition complex subunit 1 (ORC1) augments malignant behaviors of lung adenocarcinoma cells via targeting Wnt signaling. Han L, et al. Bioengineered, 2022 May. PMID 36700467, Free PMC Article
  2. Origin recognition complex subunit 1 regulates cell growth and metastasis in glioma by altering activation of ERK and JNK signaling pathway. Xiong W, et al. Mol Cell Probes, 2020 Feb. PMID 31866342
  3. Orc1 Binding to Mitotic Chromosomes Precedes Spatial Patterning during G1 Phase and Assembly of the Origin Recognition Complex in Human Cells. Kara N, et al. J Biol Chem, 2015 May 8. PMID 25784553, Free PMC Article
  4. Human origin recognition complex binds preferentially to G-quadruplex-preferable RNA and single-stranded DNA. Hoshina S, et al. J Biol Chem, 2013 Oct 18. PMID 24003239, Free PMC Article
  5. Meier-Gorlin syndrome mutations disrupt an Orc1 CDK inhibitory domain and cause centrosome reduplication. Hossain M, et al. Genes Dev, 2012 Aug 15. PMID 22855792, Free PMC Article

See all (88) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Direct regulation of FNIP1 and FNIP2 by MEF2 sustains MTORC1 activation and tumor progression in pancreatic cancer.
    Title: Direct regulation of FNIP1 and FNIP2 by MEF2 sustains MTORC1 activation and tumor progression in pancreatic cancer.
  2. Origin recognition complex subunit 1(ORC1) is a potential biomarker and therapeutic target in cancer.
    Title: Origin recognition complex subunit 1(ORC1) is a potential biomarker and therapeutic target in cancer.
  3. Origin recognition complex subunit 1 (ORC1) augments malignant behaviors of lung adenocarcinoma cells via targeting Wnt signaling.
    Title: Origin recognition complex subunit 1 (ORC1) augments malignant behaviors of lung adenocarcinoma cells via targeting Wnt signaling.
  4. Multiple, short protein binding motifs in ORC1 and CDC6 control the initiation of DNA replication.
    Title: Multiple, short protein binding motifs in ORC1 and CDC6 control the initiation of DNA replication.
  5. Origin recognition complex subunit 1 regulates cell growth and metastasis in glioma by altering activation of ERK and JNK signaling pathway.
    Title: Origin recognition complex subunit 1 regulates cell growth and metastasis in glioma by altering activation of ERK and JNK signaling pathway.
  6. Authors report the crystal structure of Cyclin A-CDK2 complex bound to a peptide derived from ORC1 at 2.54 a resolution; structure revealed that the ORC1 peptide interacts with a hydrophobic groove, termed cyclin binding groove, of Cyclin A via a KXL motif.
    Title: Structural basis for the ORC1-Cyclin A association.
  7. The opposing effects of ORC1 (represor) and CDC6 (gene activator) in controlling the level of Cyclin E ensures genome stability and a mechanism for linking directly DNA replication and cell division commitment.
    Title: Opposing roles for DNA replication initiator proteins ORC1 and CDC6 in control of Cyclin E gene transcription.
  8. The authors have discovered that human cell lines in culture proliferate with intact chromosomal origins of replication after disruption of both alleles of ORC2 or of the ATPase subunit, ORC1.
    Title: Two subunits of human ORC are dispensable for DNA replication and proliferation.
  9. Orc1 acts as a nucleating center for origin recognition complex assembly and then pre-replication complex assembly by binding to mitotic chromosomes, followed by gradual removal from chromatin during the G1 phase.
    Title: Orc1 Binding to Mitotic Chromosomes Precedes Spatial Patterning during G1 Phase and Assembly of the Origin Recognition Complex in Human Cells.
  10. ORC1 harbors a G-rich RNA/ssDNA-binding domain, which may be involved in the preferential binding to G-quadruplex-formable RNA/DNA by ORC. Structure modeling predicts the structural similarity between the G-rich RNA/ssDNA-binding domain of ORC1 and part of mammalian DNA methyltransferase 1.
    Title: Human origin recognition complex binds preferentially to G-quadruplex-preferable RNA and single-stranded DNA.
Submit: New GeneRIF Correction See all GeneRIFs (30)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Meier-Gorlin syndrome 1
MedGen: C4552001 OMIM: 224690 GeneReviews: Not available
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables ATP hydrolysis activity IEA
Inferred from Electronic Annotation
more info
  
enables DNA binding TAS
Traceable Author Statement
more info
 PubMed 
enables DNA replication origin binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables chromatin binding IEA
Inferred from Electronic Annotation
more info
  
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in DNA replication initiation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in DNA replication initiation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in mitotic DNA replication checkpoint signaling IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
located_in chromosome, telomeric region HDA PubMed 
colocalizes_with chromosome, telomeric region IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
part_of nuclear origin of replication recognition complex IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of nuclear origin of replication recognition complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of nuclear origin of replication recognition complex IPI
Inferred from Physical Interaction
more info
 PubMed 
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
located_in nucleus NAS
Non-traceable Author Statement
more info
 PubMed 
part_of origin recognition complex IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
origin recognition complex subunit 1
Names
origin recognition complex, subunit 1 homolog
replication control protein 1

NCBI Reference Sequences (RefSeq)

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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_028251.2 RefSeqGene

    Range
    10080..41674
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001190818.2 → NP_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
    D3DQ34, Q13415, Q13471, Q5T0F5
    UniProtKB/TrEMBL
    A8K794, Q96F82
    Related
    ENSP00000360621.1, ENST00000371566.1
    Conserved Domains (4) summary
    PRK10811
    Location:362 → 487
    rne; ribonuclease E; Reviewed
    cd04719
    Location:44 → 170
    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 ...
    PTZ00112
    Location:495 → 743
    PTZ00112; origin recognition complex 1 protein; Provisional
    pfam09079
    Location:778 → 857
    Cdc6_C; CDC6, C terminal winged helix domain

  2. NM_001190819.2 → NP_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/TrEMBL
    B7Z8H0
    Conserved Domains (4) summary
    cd04719
    Location:44 → 170
    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:773 → 846
    Cdc6_C; CDC6, C terminal
    pfam13191
    Location:499 → 549
    AAA_16; AAA ATPase domain
    cl21455
    Location:525 → 670
    P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

  3. NM_004153.4 → NP_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)
    U40152, U43416
    Consensus CDS
    CCDS566.1
    UniProtKB/Swiss-Prot
    D3DQ34, Q13415, Q13471, Q5T0F5
    UniProtKB/TrEMBL
    A8K794, Q96F82
    Related
    ENSP00000360623.3, ENST00000371568.8
    Conserved Domains (4) summary
    PRK10811
    Location:362 → 487
    rne; ribonuclease E; Reviewed
    cd04719
    Location:44 → 170
    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 ...
    PTZ00112
    Location:495 → 743
    PTZ00112; origin recognition complex 1 protein; Provisional
    pfam09079
    Location:778 → 857
    Cdc6_C; CDC6, C terminal winged helix domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    52372829..52409503 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047421674.1 → XP_047277630.1  origin recognition complex subunit 1 isoform X1

    UniProtKB/Swiss-Prot
    D3DQ34, Q13415, Q13471, Q5T0F5

  2. XM_047421680.1 → XP_047277636.1  origin recognition complex subunit 1 isoform X2

  3. XM_017001388.3 → XP_016856877.1  origin recognition complex subunit 1 isoform X2

    UniProtKB/TrEMBL
    A8K794, Q96F82

  4. XM_011541527.4 → XP_011539829.1  origin recognition complex subunit 1 isoform X3

    Conserved Domains (4) summary
    pfam09079
    Location:418 → 491
    Cdc6_C; CDC6, C terminal
    pfam13191
    Location:144 → 194
    AAA_16; AAA ATPase domain
    pfam15091
    Location:34 → 159
    DUF4554; Domain of unknown function (DUF4554)
    cl21455
    Location:170 → 315
    P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    52254294..52290972 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054336824.1 → XP_054192799.1  origin recognition complex subunit 1 isoform X1

    UniProtKB/Swiss-Prot
    D3DQ34, Q13415, Q13471, Q5T0F5

  2. XM_054336826.1 → XP_054192801.1  origin recognition complex subunit 1 isoform X2

  3. XM_054336825.1 → XP_054192800.1  origin recognition complex subunit 1 isoform X2

  4. XM_054336827.1 → XP_054192802.1  origin recognition complex subunit 1 isoform X3

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q13415.2 GenPept UniProtKB/Swiss-Prot:Q13415

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