ZNF555

Last updated

ZNF555
Identifiers
Aliases ZNF555 , zinc finger protein 555
External IDs HomoloGene: 65060; GeneCards: ZNF555; OMA:ZNF555 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

148254

n/a

Ensembl

ENSG00000186300

n/a

UniProt

Q8NEP9

n/a

RefSeq (mRNA)

NM_001172775
NM_152791

n/a

RefSeq (protein)

NP_001166246
NP_690004

n/a

Location (UCSC) Chr 19: 2.84 – 2.86 Mb n/a
PubMed search [2] n/a
Wikidata
View/Edit Human

Zinc finger protein 555 (ZNF555) protein encoded by the ZNF555 gene. [3] It is located on the short arm (19p13.3 ) [4] of the human chromosome 19 (hg38) at position chr19:2,841,573-2,853,952, spanning 12,380 base pairs. [5] It contains four coding exons.

Contents

It belongs to the Krüppel associated box (KRAB) 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 (ANT1) [6] , implicating it in mechanisms proposed for facioscapulohumeral muscular dystrophy (FSHD). [7]

Nomenclature

ZNF555 is also known by the synonym DiPRO1 (Death, Differentiation, and PROliferation-related PROtein 1), which was recently assigned based on newly discovered functions. [8]

Predicted three-dimensional structure model of the human protein ZNF555 (UniProt ID: Q8NEP9), generated by the AlphaFold Protein Structure Database (DeepMind / EMBL-EBI). AlphaFold ZNF555 Protein Structure.png
Predicted three-dimensional structure model of the human protein ZNF555 (UniProt ID: Q8NEP9), generated by the AlphaFold Protein Structure Database (DeepMind / EMBL-EBI).

[ZNF555 Protein Structure.png]

Structure

The ZNF555 protein (Q8NEP9 · ZN555_HUMAN) is composed of 628 amino acids with a molecular weight of approximately 73.1 kDa. [9] The protein contains one KRAB A-box domain and fifteen C2H2-type zinc finger domain.

Two additional isoforms are predicted:

Evolutionary history of gain/loss events of the DiPRO1/ZNF555 gene (chr19:2.841.435-2.860.471, GRCh38). Adapted from Rich et al., 2024, EMBO Molecular Medicine, doi:10.1038/s44321-024-00097-z, under CC BY 4.0 license. Phylogenetic tree of ZNF555 gene.png
Evolutionary history of gain/loss events of the DiPRO1/ZNF555 gene (chr19:2.841.435-2.860.471, GRCh38). Adapted from Rich et al., 2024, EMBO Molecular Medicine, doi:10.1038/s44321-024-00097-z, under CC BY 4.0 license.

Evolution and species distribution

Phylogenetic analysis suggests that the ZNF555 gene is conserved within placental mammals and may represent a relatively recent evolutionary development. [8] 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 (Kruppel-associated box) zinc finger protein (KRAB-ZFPs) family, [10] , 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 (REs), [10] as well as in muscle cell differentiation and proliferation [8] . 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. [8]

ZNF555 (DiPRO1) functions. ZNF555 Function.png
ZNF555 (DiPRO1) functions.

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Interactions

ZNF555/DiPRO1has been shown to interact with TIF1B/KAP1, UHRF1 and MCM protein complex. [8] ZNF555 protein shares certain DNA-binding regions with SIX1, a transcription factor regulating myogenesis [11] [12] , and ZSCAN4, a zinc finger protein implicated in genomic stability. [8]

Clinical significance

ZNF555 has been associated with Facioscapulohumeral Muscular Dystrophy (FSHD). [7] 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. [8]

See also

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000186300 – Ensembl, May 2017
  2. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ↑ "Homo sapiens zinc finger protein 555 (ZNF555), transcript variant 1, mRNA". NIH. 2025-04-27.
  4. ↑ "Gene symbol report | HUGO Gene Nomenclature Committee". www.genenames.org. Retrieved 2025-08-11.
  5. ↑ "Human Gene ZNF555 (ENST00000334241.9) from GENCODE V48". genome-euro.ucsc.edu. Retrieved 2025-08-11.
  6. ↑ Arbogast S, Kotzur H, Frank C, Compagnone N, Sutra T, Pillard F, et al. (October 2022). "ANT1 overexpression models: Some similarities with facioscapulohumeral muscular dystrophy". Redox Biology. 56 102450. doi:10.1016/j.redox.2022.102450. PMC   9434167 . PMID   36030628.
  7. 1 2 Kim E, Rich J, Karoutas A, Tarlykov P, Cochet E, Malysheva D, et al. (2015-09-30). "ZNF555 protein binds to transcriptional activator site of 4qA allele and ANT1: potential implication in Facioscapulohumeral dystrophy". Nucleic Acids Research. 43 (17): 8227–8242. doi:10.1093/nar/gkv721. ISSN   0305-1048. PMC   4787827 . PMID   26184877.
  8. 1 2 3 4 5 6 7 Rich J, Bennaroch M, Notel L, Patalakh P, Alberola J, Issa F, et al. (2024-07-15). "DiPRO1 distinctly reprograms muscle and mesenchymal cancer cells". EMBO Molecular Medicine. 16 (8): 1840–1885. doi:10.1038/s44321-024-00097-z. ISSN   1757-4684. PMC   11319797 . PMID   39009887.
  9. 1 2 3 "UniProt". UniProt. Retrieved 2025-08-11.
  10. 1 2 Ecco G, Imbeault M, Trono D (August 2017). "KRAB zinc finger proteins". Development. 144 (15). Cambridge, England: 2719–2729. doi:10.1242/dev.132605. ISSN   1477-9129. PMC   7117961 . PMID   28765213.
  11. ↑ Wurmser M, Chaverot N, Madani R, Sakai H, Negroni E, Demignon J, et al. (2020-01-01). "SIX1 and SIX4 homeoproteins regulate PAX7+ progenitor cell properties during fetal epaxial myogenesis". Development dev.185975. doi:10.1242/dev.185975 (inactive 21 October 2025). ISSN   1477-9129.{{cite journal}}: CS1 maint: DOI inactive as of October 2025 (link)
  12. ↑ Maire P, Dos Santos M, Madani R, Sakakibara I, Viaut C, Wurmser M (2020-08-01). "Myogenesis control by SIX transcriptional complexes". Seminars in Cell & Developmental Biology. Differentiation of skeletal muscles. 104: 51–64. doi:10.1016/j.semcdb.2020.03.003. ISSN   1084-9521. PMID   32247726.
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