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

Summary

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, Dec 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

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_000007.14 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:1318404 (e-PCR)
- UniSTS:49709

SHGC-53468 (e-PCR)
- UniSTS:12592

ASK_7983 (e-PCR)
- UniSTS:468022

SHGC-144089 (e-PCR)
- UniSTS:172170

SHGC-64833 (e-PCR)
- UniSTS:22970

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)

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
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
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
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