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Zinc finger protein 365 (ZNF365)
- Target
- ZNF365
- Molecular classification
- Transcription factor (contains a C2H2-type zinc finger motif), DNA damage response protein, Lipid antigen/LPS-binding protein (in zebrafish)
01
Overview
Zinc finger protein 365 (ZNF365) is a C2H2-type zinc finger DNA-binding protein central to the maintenance of genomic stability, DNA repair, and cell cycle regulation. ZNF365 forms complexes with proteins involved in DNA repair, such as PARP1 and MRE11, and is activated by DNA damage signals including telomere dysfunction and double-strand breaks. In addition to its role in genome maintenance and cellular senescence, ZNF365 promotes defense against Gram-negative pathogens by binding LPS (lipopolysaccharide) through its N-terminal domain (mainly studied in zebrafish). Loss of ZNF365 impairs proliferation of epithelial cells and defense against pathogens, elevates genomic instability, and is associated with susceptibility to breast cancer, uric acid nephrolithiasis, Crohn’s disease, and idiopathic pulmonary fibrosis. Despite multiple aliases, there is no evidence ZNF365 is a therapeutic target of drugs or a receptor/enzyme/transporter; its main role is in transcriptional regulation and cell protection.
- Other names
- TalaninKIAA0844Protein ZNF365DBZUANSu48ZNF365DDISC1-binding zinc-finger proteinprotein su48
02
Biological functions
DNA repair (restart of stalled DNA replication forks; homologous recombination)Maintenance of genome stability (suppresses common fragile sites, telomere protection, prevents aberrant recombination)Cell cycle regulation (loss causes mitotic delay, cytokinesis failure, aneuploidy)Cellular senescence regulationDefense response to pathogens (in zebrafish and epithelial cells, protects against Gram-negative bacteria via LPS binding)
03
Disease associations
Cancer (breast cancer susceptibility, especially in BRCA1/2 mutation carriers; genome instability-related cancers)Uric acid nephrolithiasis (kidney stones)Crohn’s disease (genetic association)Idiopathic pulmonary fibrosis (protective upregulation)
04
Safety considerations
no notable drug-related safety concerns identified, but genomic instability due to ZNF365 deficiency is linked to cancer risk
05
Biomarkers
SNPs rs10822013 and rs10995190 in ZNF365 have been studied as genetic risk factors for mammographic density and sporadic breast cancer riskLoss or mutation can be used as a biomarker for increased genomic instability or susceptibility to some cancers
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