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DBF4 DBF4-CDC7 kinase regulatory subunit [ Homo sapiens (human) ]

Gene ID: 10926, updated on 7-Apr-2024

Summary

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Official Symbol
DBF4provided by HGNC
Official Full Name
DBF4-CDC7 kinase regulatory subunitprovided by HGNC
Primary source
HGNC:HGNC:17364
See related
Ensembl:ENSG00000006634 MIM:604281; AllianceGenome:HGNC:17364
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
ASK; CHIF; DBF4A; ZDBF1
Summary
Predicted to enable protein serine/threonine kinase activator activity. Predicted to be involved in positive regulation of nuclear cell cycle DNA replication and regulation of cell cycle phase transition. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]
Expression
Biased expression in testis (RPKM 30.3), bone marrow (RPKM 10.3) and 9 other tissues See more
Orthologs
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Genomic context

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Location:
7q21.12
Exon count:
12
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (87876493..87909553)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (89126406..89159470)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (87505808..87538868)

Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene ATP binding cassette subfamily B member 1 Neighboring gene Sharpr-MPRA regulatory region 13989 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18351 Neighboring gene RUN domain containing 3B Neighboring gene ReSE screen-validated silencer GRCh37_chr7:87363145-87363320 Neighboring gene NANOG hESC enhancer GRCh37_chr7:87368534-87369080 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:87376668-87377257 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:87377258-87377846 Neighboring gene NANOG hESC enhancer GRCh37_chr7:87448246-87448747 Neighboring gene solute carrier family 25 member 40 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:87505271-87505780 Neighboring gene origin of replication in promoter of DBF4 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26234 Neighboring gene uncharacterized LOC124901690 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:87556085-87556653 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18354 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:87563985-87564562 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:87564563-87565140 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:87584727-87585228 Neighboring gene ADAM metallopeptidase domain 22 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:87663457-87663957 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26238 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26239 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26240 Neighboring gene uncharacterized LOC105375386 Neighboring gene MPRA-validated peak6626 silencer

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. Molecular functions of ASK family in diseases caused by stress-induced inflammation and apoptosis. Kojima K, et al. J Biochem, 2021 Apr 29. PMID 33377973
  2. The cell cycle arrest and the anti-invasive effects of nitrogen-containing bisphosphonates are not mediated by DBF4 in breast cancer cells. Mansouri M, et al. Biochimie, 2014 Apr. PMID 24287290
  3. Identification and functional characterization of ASK/Dbf4, a novel cell survival gene in cutaneous melanoma with prognostic relevance. Nambiar S, et al. Carcinogenesis, 2007 Dec. PMID 17768177
  4. An ATR- and Cdc7-dependent DNA damage checkpoint that inhibits initiation of DNA replication. Costanzo V, et al. Mol Cell, 2003 Jan. PMID 12535533
  5. Human Dbf4/ASK promoter is activated through the Sp1 and MluI cell-cycle box (MCB) transcription elements. Wu X, et al. Oncogene, 2002 Nov 7. PMID 12420215

See all (59) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. DBF4 Dependent Kinase Inhibition Suppresses Hepatocellular Carcinoma Progression and Potentiates Anti-Programmed Cell Death-1 Therapy.
    Title: DBF4 Dependent Kinase Inhibition Suppresses Hepatocellular Carcinoma Progression and Potentiates Anti-Programmed Cell Death-1 Therapy.
  2. Identification and Validation of a Prognostic Model Based on Three MVI-Related Genes in Hepatocellular Carcinoma.
    Title: Identification and Validation of a Prognostic Model Based on Three MVI-Related Genes in Hepatocellular Carcinoma.
  3. Molecular functions of ASK family in diseases caused by stress-induced inflammation and apoptosis.
    Title: Molecular functions of ASK family in diseases caused by stress-induced inflammation and apoptosis.
  4. High DBF4 expression is associated with oral cancer.
    Title: Cdc7-Dbf4-mediated phosphorylation of HSP90-S164 stabilizes HSP90-HCLK2-MRN complex to enhance ATR/ATM signaling that overcomes replication stress in cancer.
  5. CDC7-DBF4 kinase (DDK) has a primary role in the replication checkpoint to promote single-stranded DNA accumulation at stalled forks, which is required to initiate a robust checkpoint response and cell cycle arrest to maintain genome integrity.
    Title: DDK Has a Primary Role in Processing Stalled Replication Forks to Initiate Downstream Checkpoint Signaling.
  6. Both CDC7 and DBF4 promoters bind E2F, suggesting that increased E2F activity in RB1 mutant cancers promotes increased DDK expression. Surprisingly, increased DDK expression levels are also correlated with both increased chemoresistance and genome-wide mutation frequencies.
    Title: DDK Promotes Tumor Chemoresistance and Survival via Multiple Pathways.
  7. Histone H3 lysine 9 (H3K9) acetylation was most prevalent when the Dbf4 transcription level was highest whereas the H3K9me3 level was greatest during and just after replication.
    Title: Dynamic regulation of histone H3K9 is linked to the switch between replication and transcription at the Dbf4 origin-promoter locus.
  8. we propose that phosphorylation of TOP2A by CDC7/DBF4 in early S-phase prevents its localization and/or activity at centromeres, and inhibition of TOP2A function could be relevant to prevent premature separation of centromeric DNA.
    Title: DDK dependent regulation of TOP2A at centromeres revealed by a chemical genetics approach.
  9. The anti-invasive and cell cycle arrest-inducing effects of nitrogen-containing bisphosphonates are not DBF4 mediated in human breast cancer cells.
    Title: The cell cycle arrest and the anti-invasive effects of nitrogen-containing bisphosphonates are not mediated by DBF4 in breast cancer cells.
  10. Dbf4 is direct downstream target of ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR) protein to regulate intra-S-phase checkpoint.
    Title: Dbf4 is direct downstream target of ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR) protein to regulate intra-S-phase checkpoint.
Submit: New GeneRIF Correction See all GeneRIFs (26)

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

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 enzyme activator activity TAS
Traceable Author Statement
more info
 PubMed 
enables nucleic acid binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein serine/threonine kinase activator activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables zinc ion binding IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in DNA replication IEA
Inferred from Electronic Annotation
more info
  
involved_in G1/S transition of mitotic cell cycle TAS
Traceable Author Statement
more info
 PubMed 
involved_in positive regulation of nuclear cell cycle DNA replication IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of cell cycle phase transition IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
part_of Dbf4-dependent protein kinase complex IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nuclear body 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
  

General protein information

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Preferred Names
protein DBF4 homolog A
Names
DBF4 homolog
DBF4 zinc finger A
DBF4-type zinc finger-containing protein 1
activator of S phase kinase
chiffon homolog A
regulatory subunit of DDK
zinc finger, DBF-type containing 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.

mRNA and Protein(s)

  1. NM_001318060.2 → NP_001304989.1  protein DBF4 homolog A isoform 2

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) has multiple differences in the coding region, one of which results in a translational frameshift, compared to variant 1. The encoded isoform (2) has a shorter and distinct N-terminus compared to isoform 1.
    Source sequence(s)
    AB028069, AC005164, AK302010, BC014909, BC036045
    UniProtKB/Swiss-Prot
    Q9UBU7
    UniProtKB/TrEMBL
    B4DXK0
    Conserved Domains (1) summary
    pfam07535
    Location:61 → 101
    zf-DBF; DBF zinc finger

  2. NM_001318061.2 → NP_001304990.1  protein DBF4 homolog A isoform 3

    Status: VALIDATED

    Description
    Transcript Variant: This variant (3) has multiple differences, one of which results in a translational frameshift, compared to variant 1. The encoded isoform (3) has a shorter and distinct N-terminus compared to isoform 1.
    Source sequence(s)
    AB028069, AC005164, BC035632, BC036045
    UniProtKB/TrEMBL
    B7Z8C6
    Conserved Domains (1) summary
    cl02684
    Location:70 → 112
    zf-DBF; DBF zinc finger

  3. NM_001318062.2 → NP_001304991.1  protein DBF4 homolog A isoform 4

    Status: VALIDATED

    Description
    Transcript Variant: This variant (4) has multiple differences, one of which results in a translational frameshift, compared to variant 1. The encoded isoform (4) has a shorter and distinct N-terminus compared to isoform 1.
    Source sequence(s)
    AB028070, AC005164, BC036045
    UniProtKB/Swiss-Prot
    Q9UBU7
    Conserved Domains (1) summary
    pfam07535
    Location:34 → 74
    zf-DBF; DBF zinc finger

  4. NM_006716.4 → NP_006707.1  protein DBF4 homolog A isoform 1

    See identical proteins and their annotated locations for NP_006707.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AB028069, AC005164, BC036045
    Consensus CDS
    CCDS5611.1
    UniProtKB/Swiss-Prot
    A4D1D8, A8K954, O75226, Q75MS6, Q75N01, Q9UBU7, Q9Y2M6
    Related
    ENSP00000265728.1, ENST00000265728.6
    Conserved Domains (1) summary
    cl02684
    Location:294 → 336
    zf-DBF; DBF zinc finger

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_000007.14 Reference GRCh38.p14 Primary Assembly

    Range
    87876493..87909553
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060931.1 Alternate T2T-CHM13v2.0

    Range
    89126406..89159470
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9UBU7.1 GenPept UniProtKB/Swiss-Prot:Q9UBU7

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