- Source: ZNF816
Zinc Finger Protein 816 (ZNF816) is a protein encoded by the ZNF816 gene, located on chromosome 19 in humans.
Gene
The ZNF816 gene is located on the minus-strand of chromosome 19, cytogenetic band 19q13.41. It spans 35,746 base pairs, from 52,927,135 to 52,962,881, containing 5 exons.
Transcripts
ZNF816 has three transcript variants, the longest is 2,711 base pairs, with 5 exons. The other two have 4 exons, while all three isoforms encode 651 amino acids. The molecular weight and isoelectric point of is consistent across all three isoforms.
Proteins
The product protein of the ZNF816 gene is 651 amino acids in length, with a predicted molecular weight of 75.7 kDa and an isoelectric point of 9.44.
= Domains
=ZNF816 has a Krüppel-associated box, which is characterized by a KRAB domain and an array of fifteen C2H2 Zinc fingers. This domain suppresses transcription by recruiting co-repressor proteins, which create heterochromatin, blocking RNA polymerase from accessing the gene. The amino acid sequence includes six disordered regions, and eight protein binding sites.
= Structure
=The predicted secondary structure of ZNF816 from AlphaFold consists of mainly alpha helices, from the C2H2 zinc finger motifs. The tertiary structure of ZNF816 was predicted by iTasser and annotated (Icn3D) according to the characteristics of other zinc finger proteins and prominent domains.
Gene Level Regulation
ZNF816 shows a moderately variable expression pattern, with detectable levels in most tissues. While some tissues, like the adrenal gland, testes, thyroid, and salivary gland, exhibit relatively higher expression, ZNF816 is generally expressed across a wide range of tissues.
= RNA-Seq Data
=RNA-seq data confirm that ZNF816 is broadly expressed at varying levels across tissues. In normal tissues, it shows moderate to high mRNA levels, suggesting consistent transcriptional activity. Data from 20 human tissues further support the gene's widespread expression, with some variability in transcription levels.
= In Situ Hybridization
=In situ hybridization results from the Allen Brain Atlas confirm widespread expression across human brain regions, including the hippocampus, cortex, and cerebellum.
= Protein Localization and Abundance
=Immunohistochemistry data show ZNF816 protein is localized in the nucleus (95.7%) across various human tissues. It is seen to be expressed at high levels relative to other proteins.
Homology/Evolution
= Paralogs
=ZNF816 has several paralogs within the zinc finger protein family. Its closest paralog is ZNF813, which shares 69.74% sequence identity. A more distant paralog is ZNF836, with 52.03% identity. These paralogs likely maintain similar roles in transcriptional regulation, reflecting the conserved functions characteristic of zinc finger proteins.
= Orthologs
=Orthologs of human ZNF816 are highly conserved in mammals, specifically primates. The closest ortholog is found in the Bonobo (Pan paniscus), with 88.8% identity, indicating strong conservation within the Hominidae family. The most divergent ortholog is found in the Olive Baboon (Papio anubis), with 78.2% identity, reflecting moderate divergence within primates. Orthologs are absent in non-mammalian species.
= Evolutionary Rate
=ZNF816 is evolving relatively slowly, as its rate of divergence is not significantly higher than that of Cytochrome C, a highly conserved protein, and is notably slower than proteins like Fibrinogen Alpha, indicating its functional conservation across species.
= Distant Homologs
=While ZNF816 is not present in non-mammalian species, distant homologs containing its zinc finger domains can be found in other vertebrates, including birds and fish.
Interacting Proteins
ZNF816 interacts with several proteins involved in similar cellular processes. It binds with TRIM28, ZNF813, ZNF845, and ZNF468, all of which are linked to transcriptional regulation, indicating that ZNF816 likely plays a role in controlling gene expression. Additionally, CUL3, DCAF1, TRIM39, TRIM37, and RNF219 are involved in ubiquitination and protein degradation, suggesting that ZNF816 may help regulate protein turnover through the ubiquitin-proteasome pathway. TRIM28, TRIM39, and VPRBP are also associated with DNA repair, further supporting the idea that ZNF816 contributes to maintaining genomic stability. These interactions emphasize ZNF816's involvement in transcriptional regulation, protein degradation, and DNA repair.
Clinical Significance
Disease Association
Although direct disease associations are still being explored, ZNF816 is considered a potential candidate for diseases such as emphysema, MRKH syndrome, and early-onset psoriasis due to the relationship of the diseases to variants in the gene.