ZNF555
Zinc finger protein 555 protein encoded by the ZNF555 gene. It is located on the short arm of the human chromosome 19 at position chr19:2,841,573-2,853,952, spanning 12,380 base pairs. It contains four coding exons.
It belongs to the Krüppel associated box C2H2 zinc-finger family and is predicted to act as a sequence-specific transcriptional regulator. Experimental work in human myoblasts suggests that ZNF555 can bind a 4qA-subtelomeric enhancer and modulate expression of the mitochondrial ADP/ATP translocase gene SLC25A4, implicating it in mechanisms proposed for facioscapulohumeral muscular dystrophy.
Nomenclature
ZNF555 is also known by the synonym DiPRO1, which was recently assigned based on newly discovered functions.
Structure
The ZNF555 protein is composed of 628 amino acids with a molecular weight of approximately 73.1 kDa. The protein contains one KRAB A-box domain and fifteen C2H2-type zinc finger domain.
Two additional isoforms are predicted:
- Q8NEP9-2, which consists of 543 amino acids and differs from the full-length isoform by lacking three zinc finger domains
- Q8NEP9-4, which has 627 amino acids and differs from the full-length isoform by a single amino acid.
Phylogenetic analysis suggests that the ZNF555 gene is conserved within placental mammals and may represent a relatively recent evolutionary development. Comparative genomic studies indicate a statistically significant expansion of the gene in pigs, American black bears, and ferrets, with these species possessing two copies of ZNF555. The gene is absent from most rodents, rabbits, and elephants, with the naked mole rat as an exception. This absence suggests that these common laboratory animal models may be unsuitable for research on ZNF555.
Function
ZNF555 belongs to the KRAB zinc finger protein family, which is involved in DNA and protein binding as well as transcriptional regulation. Although its precise biological function remains incompletely characterized, ZNF555 has been implicated in the epigenetic silencing of retrotransposable elements, as well as in muscle cell differentiation and proliferation. Depending on its interacting protein partners, ZNF555 may act either as a transcriptional activator or repressor. Additionally, it may play a role in the regulation of CpG island methylation.
Interactions
ZNF555/DiPRO1has been shown to interact with TIF1B/KAP1, UHRF1 and MCM protein complex. ZNF555 protein shares certain DNA-binding regions with SIX1, a transcription factor regulating myogenesis, and ZSCAN4, a zinc finger protein implicated in genomic stability.
Clinical significance
ZNF555 has been associated with Facioscapulohumeral Muscular Dystrophy. Additionally, ZNF555 has been linked to mesenchymal cancers, including rhabdomyosarcoma and Ewing sarcoma, where it is suggested to function as an inhibitor of cancer cell death.