ZFP62

Zinc Finger Protein 62, also known as "ZNF62," "ZNF755," or "ZET," is a protein that in humans is encoded by the ZFP62 gene. ZFP62 is part of the C2H2 Zinc Finger family of genes.

Gene
ZFP62 is located on chromosome 5 (5q35.5) on the minus strand, from base pair 180,826,870 to 180,861,285. It spans a total of 34,415 base pairs. The ZFP62 gene has 7 transcripts (splice variants), 5 known paralogues, and several mammalian orthologues.

Tissue expression
The ZFP62 gene is ubiquitously expressed but variable across all tissue types. The gene appears in 35 different tissue type, with the thymus, thalamus, thyroid, kidney, prostate, testes, and ovaries expressing the highest levels. Additionally, there are low levels of specificity across all human tissue types for ZFP62 compared to other human proteins, as well as low levels of cancer specificity within both cell line cancer and TGCA cancer tissues.

Protein
The most commonly recognized "cannon" ZFP62 protein is Isoform 2, which is 900 amino acids in length and contains 2 coding exons. The full protein weighs approximately 102.5 kDa. The isoelectric point of the ZFP62 protein is 9.24, meaning that the protein is negatively charged at neutral pH.

The ZFP62 protein is known to function both within RNA polymerase II cis-regulatory region sequence-specific DNA-binding and RNA polymerase II-specific DNA-binding transcription activator activity.

Composition and motifs
The most crucial compositional motif lies within the C2H2 structural zinc finger repeats. The Cys2His2 zinc finger repeats function as a binding mechanism for a zinc, or other metal ion. The structure of this motif is two ligands from a knuckle and two more from the c-terminus of a helix. It is thought that these domains are crucial to the regulation of transcription for both DNA and RNA. The ZFP62 protein contains 26 of these repeats.

There is one disordered region present between amino acids 1 and 97.

Secondary structure
The secondary structure of the ZFP62 protein is composed of a mixture of alpha-helices, beta-sheets, and turns, with alpha-helices being the most abundant secondary structure.

Tertiary structure
The tertiary structure of the ZFP62 protein appears as a double-coiled structure, with alpha-helices being twisted into a larger coiled shape. The highest confidence in this structure comes from the 26 smaller coils, correlating with the 26 zinc finger repeats that are present within the protein. This structure is consistent and nearly identical across all orthologous species.

Protein interactions
The ZFP62 protein is known to interact with many proteins, as seen in the following figures. The most common function among these proteins is that of managing RNA binding.

Among all of the proteins ZFP62 is thought to interact with, only a five that appear on multiple databases, and therefore have a higher likelihood of interaction: The KNOP1, PUM3, RBM34, RPL14, and RPL37A proteins. All of these proteins appear to have RNA binding functionality, but otherwise seem reasonably distinct from one another.

Promoter
ZFP62 has one known promoter, named EH38E2437834. EH38E2437834 spans 354 base pairs and is only associated with the ZFP62 gene. EH38E2437834 has been shown to be associated with ZFP62 through 15 different biosamples and eQTL experimentation.

Promoter-region transcription factors
There are hundreds of transcription factors that are predicted to bind the promoter region of the ZFP62 gene. The following table highlights 20 of these transcription factors, with high binding affinity.

Paralogues
In humans, the ZFP62 gene is paralogous with 5 other Zinc Finger Proteins, as seen in the following table. All five of these paralogues share similar functionality and localization to ZFP62- They are all RNA/DNA transcription factors and are primarily localized to the cell nucleus.

Orthologues
ZFP62 orthologues are only found in mammalian species. The orthologues appear primarily in placental mammals, including Primates, Rodentia, Cetacea, Chiroptera, Aritodactyla, Perissodactyla, and Carnivora.

Conservation across orthologues
Conservation is varied across orthologous species, with the least similar orthologue being from the Carnivora and Hyracoidea taxonomic groups.

Clinical significance
The ZFP62 gene has been linked to a variety of different human ailments. In a more recent study, ZFP62 has been discovered to be a potential therapeutic target for treatment of SARS-CoV-2 (COVID-19). The role of zinc finger protein as transcription factors can be utilized to target genes to participate in the removal of SARS infection. The drug that is predicted to be able to target ZFP62 is named Artenimol, which would inhibit the RNA-dependent RNA polymerase activity of ZFP62, which is known to be an effective mechanism of other COVID-19 treatment drugs.

In two other publications, ZFP62 was discovered to be a mechanism of hippocampal aging in the brain, as well as lymphoblastic leukemia. In the case of hippocampal aging, ZFP62 was found to be significantly upregulated within the hippocampus of aged patients. It is speculated that this gene, as well as another zinc finger protein named ZFP51, may be specifically related to increased neuroinflammation within the hippocampal region. Another study, completed in 2016, focusing on the deletion of terminal 5q in HOXA-positive T-cell acute lymphoblastic leukemia, found that ZFP62 was one of only eight significantly down-regulated genes. This discovery also indicates that the inhibition of ZFP62 significantly contributes to the onset of this particular form of leukemia.