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

    Gene ID: 10926, updated on 3-Nov-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, Nov 2024]
    Expression
    Biased expression in testis (RPKM 30.3), bone marrow (RPKM 10.3) and 9 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See DBF4 in Genome Data Viewer
    Location:
    7q21.12
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (87876493..87909553)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (89126406..89159470)
    RS_2024_09 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 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. The prognostic significance and potential mechanism of DBF4 zinc finger in hepatocellular carcinoma. Wu Z, et al. Sci Rep, 2024 May 9. PMID 38724606, Free PMC Article
    2. A 63-base pair DNA segment containing an Sp1 site but not a canonical E2F site can confer growth-dependent and E2F-mediated transcriptional stimulation of the human ASK gene encoding the regulatory subunit for human Cdc7-related kinase. Yamada M, et al. J Biol Chem, 2002 Aug 2. PMID 12015319
    3. 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
    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. 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

    See all (65) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. DBF4, not DRF1, is the crucial regulator of CDC7 kinase at replication forks.
      Title: DBF4, not DRF1, is the crucial regulator of CDC7 kinase at replication forks.
    2. The prognostic significance and potential mechanism of DBF4 zinc finger in hepatocellular carcinoma.
      Title: The prognostic significance and potential mechanism of DBF4 zinc finger in hepatocellular carcinoma.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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.
    Submit: New GeneRIF Correction See all GeneRIFs (28)

    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_2024_08

    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

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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