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

Gene ID: 5000, updated on 9-Dec-2018

Summary

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
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

Genomic context

See ORC4 in Genome Data Viewer
Location:
2q23.1
Exon count:
18
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 2 NC_000002.12 (147930397..148021604, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (148687966..148779173, complement)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene ribosomal protein L26 pseudogene 14 Neighboring gene RNA, U6 small nuclear 1275, pseudogene Neighboring gene activin A receptor type 2A Neighboring gene uncharacterized LOC105373674 Neighboring gene uncharacterized LOC105373673 Neighboring gene methyl-CpG binding domain protein 5 Neighboring gene ubiquitin specific peptidase 12 pseudogene

Genomic regions, transcripts, and products

Expression

  • 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

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Meier-Gorlin syndrome 2
MedGen: C3151097 OMIM: 613800 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

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

Pathways from BioSystems

  • 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-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...
  • 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...
  • 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 ...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • FLJ46668

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
 
DNA replication origin binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
DNA replication origin binding IMP
Inferred from Mutant Phenotype
more info
PubMed 
nucleotide binding IDA
Inferred from Direct Assay
more info
PubMed 
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 IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
DNA replication initiation IMP
Inferred from Mutant Phenotype
more info
PubMed 
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
 
nuclear chromosome, telomeric region HDA PubMed 
colocalizes_with nuclear chromosome, telomeric region IDA
Inferred from Direct Assay
more info
PubMed 
nuclear origin of replication recognition complex IBA
Inferred from Biological aspect of Ancestor
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
PubMed 
origin recognition complex IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
origin recognition complex subunit 4
Names
origin recognition complex, subunit 4 homolog

NCBI Reference Sequences (RefSeq)

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
    5001..96208
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001190879.2NP_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
    O43929
    Related
    ENSP00000441953.1, ENST00000535373.5
    Conserved Domains (2) summary
    COG1474
    Location:43226
    CDC6; Cdc6-related protein, AAA superfamily ATPase [Replication, recombination and repair]
    pfam14629
    Location:228415
    ORC4_C; Origin recognition complex (ORC) subunit 4 C-terminus
  2. NM_001190881.2NP_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/Swiss-Prot
    O43929
    Related
    ENSP00000441502.1, ENST00000536575.5
    Conserved Domains (2) summary
    COG1474
    Location:2142
    CDC6; Cdc6-related protein, AAA superfamily ATPase [Replication, recombination and repair]
    pfam14629
    Location:144331
    ORC4_C; Origin recognition complex (ORC) subunit 4 C-terminus
  3. NM_001190882.2NP_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/Swiss-Prot
    O43929
    Related
    ENSP00000438326.1, ENST00000540442.5
    Conserved Domains (3) summary
    COG1474
    Location:4152
    CDC6; Cdc6-related protein, AAA superfamily ATPase [Replication, recombination and repair]
    pfam14629
    Location:154331
    ORC4_C; Origin recognition complex (ORC) subunit 4 C-terminus
    cl21455
    Location:50139
    P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases
  4. NM_002552.4NP_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
    O43929
    UniProtKB/TrEMBL
    A8K7H4
    Conserved Domains (2) summary
    COG1474
    Location:43226
    CDC6; Cdc6-related protein, AAA superfamily ATPase [Replication, recombination and repair]
    pfam14629
    Location:228415
    ORC4_C; Origin recognition complex (ORC) subunit 4 C-terminus
  5. NM_181741.3NP_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
    O43929
    Related
    ENSP00000376597.4, ENST00000392857.9
    Conserved Domains (2) summary
    COG1474
    Location:43226
    CDC6; Cdc6-related protein, AAA superfamily ATPase [Replication, recombination and repair]
    pfam14629
    Location:228415
    ORC4_C; Origin recognition complex (ORC) subunit 4 C-terminus
  6. NM_181742.3NP_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
    O43929
    UniProtKB/TrEMBL
    Q96B14
    Related
    ENSP00000264169.2, ENST00000264169.6
    Conserved Domains (2) summary
    COG1474
    Location:43226
    CDC6; Cdc6-related protein, AAA superfamily ATPase [Replication, recombination and repair]
    pfam14629
    Location:228415
    ORC4_C; Origin recognition complex (ORC) subunit 4 C-terminus

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p12 Primary Assembly

    Range
    147930397..148021604 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_024452929.1XP_024308697.1  origin recognition complex subunit 4 isoform X2

    Conserved Domains (2) summary
    COG1474
    Location:2142
    CDC6; Cdc6-related protein, AAA superfamily ATPase [Replication, recombination and repair]
    pfam14629
    Location:144331
    ORC4_C; Origin recognition complex (ORC) subunit 4 C-terminus
  2. XM_011511255.2XP_011509557.1  origin recognition complex subunit 4 isoform X1

    See identical proteins and their annotated locations for XP_011509557.1

    UniProtKB/Swiss-Prot
    O43929
    Conserved Domains (2) summary
    COG1474
    Location:43226
    CDC6; Cdc6-related protein, AAA superfamily ATPase [Replication, recombination and repair]
    pfam14629
    Location:228415
    ORC4_C; Origin recognition complex (ORC) subunit 4 C-terminus
  3. XM_017004226.2XP_016859715.1  origin recognition complex subunit 4 isoform X1

    UniProtKB/Swiss-Prot
    O43929
    Conserved Domains (2) summary
    COG1474
    Location:43226
    CDC6; Cdc6-related protein, AAA superfamily ATPase [Replication, recombination and repair]
    pfam14629
    Location:228415
    ORC4_C; Origin recognition complex (ORC) subunit 4 C-terminus
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