# 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.
| Isoform number | AC# | mRNA length (base pairs) | Exons | AC# | Protein Length (Amino Acids) |
| 1 | NM_001031665 | 2711 | 5 | NP_001026835 | 651 |
| 2 | NM_001202456.3 | 2570 | 4 | NP_001189385 | 651 |
| 3 | NM_001202457.3 | 2560 | 4 | NP_001189386.1 | 651 |

## 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.
| Species name | Genus | Common name | Family | Date of div. (MYA) | % Identity | % similarity | Protein length (Amino Acids) | Accession Number |
| Homo sapiens | Homo | Human | Hominidae | 0 | 100.00% | 100.00% | 651 | NP_001189386 |
| Pan paniscus | Pan | Bonobo | Hominidae | 6.4 | 88.80% | 90.00% | 598 | XP_024782426.3 |
| Pan troglodytes | Pan | Chimpanzee | Hominidae | 6.4 | 80.50% | 81.30% | 730 | XP_054528711.1 |
| Gorilla gorilla gorilla | Gorilla | Western lowland gorilla | Hominidae | 8.6 | 51.70% | 52.60% | 681 | XP_030860498.2 |
| Pongo pygmaeus | Pongo | Bornean orangutan | Hominidae | 15.2 | 86.60% | 88.30% | 642 | XP_054321989.1 |
| Pongo abelii | Pongo | Sumatran orangutan | Hominidae | 15.2 | 80.40% | 81.80% | 698 | XP_024093826.3 |
| Symphalangus syndactylus | Symphalangus | Siamang | Hylobatidae | 19.5 | 79.30% | 81.8% | 749 | XP_063471613.1 |
| Hylobates moloch | Hylobates | Silvery gibbon | Hylobatidae | 19.5 | 83.00% | 85.90% | 721 | XP_058281887.1 |
| Cercocebus atys | Cercocebus | Sooty mangabey | Cercopithecidae | 28.8 | 80.50% | 85.10% | 697 | XP_011936585.1 |
| Macaca fascicularis | Macaca | Long-tailed macaque (Crab-eating macaque) | Cercopithecidae | 28.8 | 80.80% | 85.10% | 697 | XP_005590270.3 |
| Rhinopithecus bieti | Rhinopithecus | Black snub-nosed monkey | Cercopithecidae | 28.8 | 82.00% | 86.20% | 694 | XP_017714826.1 |
| Colobus angolensis palliatus | Colobus | Angolan black-and-white colobus | Cercopithecidae | 28.8 | 82.10% | 85.80% | 641 | XP_011801561.1 |
| Papio anubis | Papio | Olive baboon | Cercopithecidae | 28.8 | 78.20% | 83.00% | 717 | XP_009193448.2 |
| Rhinopithecus roxellana | Rhinopithecus | Golden snub-nosed monkey | Cercopithecidae | 28.8 | 74.20% | 77.70% | 776 | XP_010374801.2 |
| Theropithecus gelada | Theropithecus | Gelada | Cercopithecidae | 28.8 | 77.60% | 82.10% | 695 | XP_025222771.1 |
| Macaca mulatta | Macaca | Rhesus macaque | Cercopithecidae | 28.8 | 80.80% | 85.10% | 697 | XP_014980263.2 |
| Chlorocebus sabaeus | Chlorocebus | Green monkey (Savanna monkey) | Cercopithecidae | 28.8 | 78.30% | 83.30% | 647 | XP_037847362.1 |
| Trachypithecus francoisi | Trachypithecus | François' langur | Cercopithecidae | 28.8 | 75.70% | 80.20% | 726 | XP_033084859.1 |
| Macaca nemestrina | Macaca | Southern pig-tailed macaque | Cercopithecidae | 28.8 | 65.90% | 71.00% | 721 | XP_011766059.1 |
| Mandrillus leucophaeus | Mandrillus | Drill | Cercopithecidae | 28.8 | 76.30% | 81.10% | 669 | XP_011835608.1 |
| Piliocolobus tephrosceles | Piliocolobus | Ugandan red colobus | Cercopithecidae | 28.8 | 70.20% | 73.80% | 812 | XP_023051555.1 |

### 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.