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    ORC4 origin recognition complex subunit 4 [ Homo sapiens (human) ]

    Gene ID: 5000, updated on 3-Apr-2024

    Summary

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    Official Symbol
    ORC4provided by HGNC
    Official Full Name
    origin recognition complex subunit 4provided by HGNC
    Primary source
    HGNC:HGNC:8490
    See related
    Ensembl:ENSG00000115947 MIM:603056; AllianceGenome:HGNC:8490
    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
    ORC4L; ORC4P
    Summary
    The origin recognition complex (ORC) is a highly conserved six subunit 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. This gene encodes a subunit of the ORC complex. Several alternatively spliced transcript variants, some of which encode the same protein, have been reported for this gene. [provided by RefSeq, Oct 2010]
    Expression
    Ubiquitous expression in brain (RPKM 7.5), skin (RPKM 6.5) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    2q23.1
    Exon count:
    18
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (147930396..148021551, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (148380848..148472005, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (148687965..148779120, complement)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene ribosomal protein L26 pseudogene 14 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:148600948-148601698 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11995 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11996 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11997 Neighboring gene RNA, U6 small nuclear 1275, pseudogene Neighboring gene activin A receptor type 2A Neighboring gene uncharacterized LOC105373674 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr2:148765513-148766712 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:148777951-148778548 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16614 Neighboring gene uncharacterized LOC105373673 Neighboring gene NANOG hESC enhancer GRCh37_chr2:148795224-148795725 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16615 Neighboring gene methyl-CpG binding domain protein 5 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:148946661-148947364 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr2:149016781-149017980 Neighboring gene small nucleolar RNA SNORA48

    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. HsOrc4-Dependent Dna Remodeling of the ori-β Dhfr Replicator. Tomic B, et al. Cell Mol Biol Lett, 2015 Dec. PMID 26124052
    2. Novel ORC4L gene mutation in B-cell lymphoproliferative disorders. Radojkovic M, et al. Am J Med Sci, 2009 Dec. PMID 20010161
    3. Stability, chromatin association and functional activity of mammalian pre-replication complex proteins during the cell cycle. Okuno Y, et al. EMBO J, 2001 Aug 1. PMID 11483529, Free PMC Article
    4. Assignment of the homologue of the yeast origin recognition complex subunit ORC4 (ORC4L) to human chromosome band 2q22-->q23 by in situ hybridization and somatic cell hybrid analysis. Eki T, et al. Cytogenet Cell Genet, 1998. PMID 9691185
    5. Human initiation protein Orc4 prefers triple stranded DNA. Kusic J, et al. Mol Biol Rep, 2010 Jun. PMID 19690980

    See all (85) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Since the site of one of the missense mutations in the human ORC4 alleles is conserved between humans and yeast, we sought to determine in what way this single amino acid change affects the process of chromosome replication, by introducing the comparable mutation into yeast (orc4Y232C).
      Title: Defective replication initiation results in locus specific chromosome breakage and a ribosomal RNA deficiency in yeast.
    2. HsOrc4 could have a fundamental function in the process of initiation of replication by remodeling the structure of origin of replication using the energy of supercoiled DNA.
      Title: HsOrc4-Dependent Dna Remodeling of the ori-β Dhfr Replicator.
    3. compared with homozygous missense mutations, compound heterozygous mutations appeared to have a more severe effect on phenotype, causing more severe growth retardation in ORC4
      Title: Meier-Gorlin syndrome genotype-phenotype studies: 35 individuals with pre-replication complex gene mutations and 10 without molecular diagnosis.
    4. identified three different mutations in the gene encoding ORC4, a component of the eukaryotic origin recognition complex, in five individuals with Meier-Gorlin syndrome
      Title: Mutations in origin recognition complex gene ORC4 cause Meier-Gorlin syndrome.
    5. DNA binding activity of HsOrc4 depends on length and structure of DNA with triplex being the protein's preferred binding target.
      Title: Human initiation protein Orc4 prefers triple stranded DNA.
    6. describe 3 patients with B-cell lymphoproliferative disorders (2 with non-Hodgkin lymphoma and 1 with nonsecretory multiple myeloma) carrying a novel A286V mutation within ORC4L gene
      Title: Novel ORC4L gene mutation in B-cell lymphoproliferative disorders.
    7. Observational study of gene-disease association. (HuGE Navigator)
      Title: Genetic variants in apoptosis and immunoregulation-related genes are associated with risk of chronic lymphocytic leukemia.
    8. Study using HCT116 haplo-insufficient cells and Orc2 hypomorphic cells demonstrates that the binding of human Ku to replication origins precedes that of Orc-3, -4, and -6 subunit binding.
      Title: Ku80 binds to human replication origins prior to the assembly of the ORC complex.
    9. Biochemical characterization of the mouse homolog
      Title: Identification and characterization of MmORC4 and MmORC5, two subunits of the mouse origin of replication recognition complex.
    Submit: New GeneRIF Correction

    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 2
    MedGen: C3151097 OMIM: 613800 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.
    EBI GWAS Catalog

    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

    Clone Names

    • FLJ46668

    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 replication origin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables DNA replication origin binding IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables nucleotide binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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 DNA replication initiation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in polar body extrusion after meiotic divisions IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein polymerization IEA
    Inferred from Electronic Annotation
    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 IDA
    Inferred from Direct Assay
    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 nucleolus IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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 4
    Names
    origin recognition complex, subunit 4 homolog

    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_028252.1 RefSeqGene

      Range
      5868..96209
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001190879.3 → NP_001177808.1  origin recognition complex subunit 4 isoform 1

      See identical proteins and their annotated locations for NP_001177808.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) represents the longest transcript. Variants 1 through 4 encode the same protein (isoform 1).
      Source sequence(s)
      AC009480, BC014847, BX423253, DC302315, DC399282
      Consensus CDS
      CCDS2187.1
      UniProtKB/Swiss-Prot
      B7Z3D0, B7Z5F1, D3DP86, F5H069, O43929, Q96C42
      UniProtKB/TrEMBL
      A8K7H4
      Related
      ENSP00000441953.1, ENST00000535373.5
      Conserved Domains (2) summary
      COG1474
      Location:43 → 226
      CDC6; Cdc6-related protein, AAA superfamily ATPase [Replication, recombination and repair]
      pfam14629
      Location:228 → 415
      ORC4_C; Origin recognition complex (ORC) subunit 4 C-terminus

    2. NM_001190881.3 → NP_001177810.1  origin recognition complex subunit 4 isoform 2

      See identical proteins and their annotated locations for NP_001177810.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) lacks several exons in the 5' region, which results in the use of a downstream start codon, compared to variant 4. The resulting protein (isoform 2) has a shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      AC009480, AK295721, BP277082
      Consensus CDS
      CCDS54404.1
      UniProtKB/TrEMBL
      Q96B14
      Related
      ENSP00000441502.1, ENST00000536575.5
      Conserved Domains (2) summary
      COG1474
      Location:2 → 142
      CDC6; Cdc6-related protein, AAA superfamily ATPase [Replication, recombination and repair]
      pfam14629
      Location:144 → 331
      ORC4_C; Origin recognition complex (ORC) subunit 4 C-terminus

    3. NM_001190882.3 → NP_001177811.1  origin recognition complex subunit 4 isoform 3

      See identical proteins and their annotated locations for NP_001177811.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) lacks two consecutive exons in the 5' region, which results in the use of a downstream start codon, compared to variant 4. The resulting protein (isoform 3) has a shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      AC009480, AK298862, BC005388
      Consensus CDS
      CCDS54405.1
      UniProtKB/TrEMBL
      Q96B14
      Related
      ENSP00000438326.1, ENST00000540442.5
      Conserved Domains (3) summary
      COG1474
      Location:4 → 152
      CDC6; Cdc6-related protein, AAA superfamily ATPase [Replication, recombination and repair]
      pfam14629
      Location:154 → 331
      ORC4_C; Origin recognition complex (ORC) subunit 4 C-terminus
      cl21455
      Location:50 → 139
      P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

    4. NM_001374270.1 → NP_001361199.1  origin recognition complex subunit 4 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC009480, AC019226
      Consensus CDS
      CCDS2187.1
      UniProtKB/Swiss-Prot
      B7Z3D0, B7Z5F1, D3DP86, F5H069, O43929, Q96C42
      UniProtKB/TrEMBL
      A8K7H4
      Conserved Domains (2) summary
      COG1474
      Location:43 → 226
      CDC6; Cdc6-related protein, AAA superfamily ATPase [Replication, recombination and repair]
      pfam14629
      Location:228 → 415
      ORC4_C; Origin recognition complex (ORC) subunit 4 C-terminus

    5. NM_001374272.1 → NP_001361201.1  origin recognition complex subunit 4 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC009480, AC019226
      Consensus CDS
      CCDS54404.1
      UniProtKB/TrEMBL
      Q96B14
      Conserved Domains (2) summary
      COG1474
      Location:2 → 142
      CDC6; Cdc6-related protein, AAA superfamily ATPase [Replication, recombination and repair]
      pfam14629
      Location:144 → 331
      ORC4_C; Origin recognition complex (ORC) subunit 4 C-terminus

    6. NM_002552.5 → NP_002543.2  origin recognition complex subunit 4 isoform 1

      See identical proteins and their annotated locations for NP_002543.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) has an alternate segment in the 5' UTR, compared to variant 4. Variants 1 through 4 encode the same protein (isoform 1).
      Source sequence(s)
      AC009480, AK291989, AK298862, DC317404
      Consensus CDS
      CCDS2187.1
      UniProtKB/Swiss-Prot
      B7Z3D0, B7Z5F1, D3DP86, F5H069, O43929, Q96C42
      UniProtKB/TrEMBL
      A8K7H4
      Conserved Domains (2) summary
      COG1474
      Location:43 → 226
      CDC6; Cdc6-related protein, AAA superfamily ATPase [Replication, recombination and repair]
      pfam14629
      Location:228 → 415
      ORC4_C; Origin recognition complex (ORC) subunit 4 C-terminus

    7. NM_181741.4 → NP_859525.1  origin recognition complex subunit 4 isoform 1

      See identical proteins and their annotated locations for NP_859525.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) lacks an exon in the 5' UTR, compared to variant 4. Variants 1 through 4 encode the same protein (isoform 1).
      Source sequence(s)
      AC009480, BC014847, DA227202
      Consensus CDS
      CCDS2187.1
      UniProtKB/Swiss-Prot
      B7Z3D0, B7Z5F1, D3DP86, F5H069, O43929, Q96C42
      UniProtKB/TrEMBL
      A8K7H4
      Related
      ENSP00000376597.5, ENST00000392857.10
      Conserved Domains (2) summary
      COG1474
      Location:43 → 226
      CDC6; Cdc6-related protein, AAA superfamily ATPase [Replication, recombination and repair]
      pfam14629
      Location:228 → 415
      ORC4_C; Origin recognition complex (ORC) subunit 4 C-terminus

    8. NM_181742.4 → NP_859526.1  origin recognition complex subunit 4 isoform 1

      See identical proteins and their annotated locations for NP_859526.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, as compared to variant 4. Variants 1 through 4 encode the same protein (isoform 1).
      Source sequence(s)
      AC009480, BC016177, DC365653
      Consensus CDS
      CCDS2187.1
      UniProtKB/Swiss-Prot
      B7Z3D0, B7Z5F1, D3DP86, F5H069, O43929, Q96C42
      UniProtKB/TrEMBL
      A8K7H4
      Related
      ENSP00000264169.2, ENST00000264169.6
      Conserved Domains (2) summary
      COG1474
      Location:43 → 226
      CDC6; Cdc6-related protein, AAA superfamily ATPase [Replication, recombination and repair]
      pfam14629
      Location:228 → 415
      ORC4_C; Origin recognition complex (ORC) subunit 4 C-terminus

    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_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      147930396..148021551 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011511255.3 → XP_011509557.1  origin recognition complex subunit 4 isoform X1

      See identical proteins and their annotated locations for XP_011509557.1

      UniProtKB/Swiss-Prot
      B7Z3D0, B7Z5F1, D3DP86, F5H069, O43929, Q96C42
      UniProtKB/TrEMBL
      A8K7H4
      Conserved Domains (2) summary
      COG1474
      Location:43 → 226
      CDC6; Cdc6-related protein, AAA superfamily ATPase [Replication, recombination and repair]
      pfam14629
      Location:228 → 415
      ORC4_C; Origin recognition complex (ORC) subunit 4 C-terminus

    2. XM_047444573.1 → XP_047300529.1  origin recognition complex subunit 4 isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      148380848..148472005 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054342311.1 → XP_054198286.1  origin recognition complex subunit 4 isoform X1

      UniProtKB/Swiss-Prot
      B7Z3D0, B7Z5F1, D3DP86, F5H069, O43929, Q96C42

    2. XM_054342312.1 → XP_054198287.1  origin recognition complex subunit 4 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O43929.2 GenPept UniProtKB/Swiss-Prot:O43929

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