User:Maddlerr/ZFP62
ZFP62
[edit]Zinc Finger Protein 62, also known as "ZNF62," "ZNF755," or "ZET," is a protein that in humans is encoded by the ZFP62 gene. [1] ZFP62 is part of the C2H2 Zinc Finger family of genes. [2]
Gene
[edit]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. [1] The ZFP62 gene has 7 transcripts (splice variants), 5 known paralogues, and several mammalian orthologues. The orthologues appear primarily in placental mammals, including Primates, Rodentia, Cetacea, Chiroptera, Aritodactyla, Perissodactyla, and Carnivora.
Tissue Expression
[edit]The ZFP62 gene is ubiquitously expressed but variable across all tissue types. [3] 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. [4]
Protein
[edit]The most commonly used ZFP62 protein is Isoform 2, which is 900 amino acids in length and contains 2 coding exons. [5] The full protein weighs approximately 102.5 kDa. [6]
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. [7]
Composition and Motifs
[edit]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. [8] 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. [9] The ZFP62 protein contains 26 of these repeats. [10]
There is one disordered region present between amino acids 1 and 97. [10]
Secondary Structure
[edit]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. [11][12][13]
Tertiary Structure
[edit]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.
Protein Interactions
[edit]The ZFP62 protein is known to interact with many other proteins, as seen in Figure _. The most common function among these proteins is that of managing RNA binding.
Regulation
[edit]Promoter
[edit]Promoter-Region Transcription Factors
[edit]Homology and Evolution
[edit]Paralogues
[edit]In humans, the ZFP62 gene is paralogous with 5 other Zinc Finger Proteins, as seen in the following table. [14] 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. [15][16][17][18][19]
| Gene Symbol | Full Gene Name | Gene Location | NCBI Gene ID |
|---|---|---|---|
| ZNF648 [15] | Zinc Finger Protein 648 | 1q25.3 | 127665 |
| ZNF808 [16] | Zinc Finger Protein 808 | 19q13.41 | 388558 |
| ZNF664 [17] | Zinc Finger Protein 664 | 12q24.31 | 144348 |
| ZNF721 [18] | Zinc Finger Protein 721 | 4p16.3 | 170960 |
| ZNF485 [19] | Zinc Finger Protein 648 | 10q11.21 | 220992 |
Orthologues
[edit]ZFP62 homologues are only found in mammalian species, specifically
Conservation Across Orthologues
[edit]Clinical Significance
[edit]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 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. [20]
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. [21] A 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 finding also points towards the suppression of ZFP62 playing a large role in the development of this specific type of leukemia. [22]
Evolutionary History
[edit]- ^ a b "Gene: ZFP62 (ENSG00000196670) - Summary - Homo_sapiens - Ensembl genome browser 110". useast.ensembl.org. Retrieved 2023-12-07.
- ^ "UniProt". www.uniprot.org. Retrieved 2023-12-07.
- ^ "ZFP62 ZFP62 zinc finger protein [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-15.
- ^ "Expression of ZFP62 in cancer - Summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2023-12-15.
- ^ "Transcript: ENST00000502412.2 (ZFP62-201) - Summary - Homo_sapiens - Ensembl genome browser 110". useast.ensembl.org. Retrieved 2023-12-07.
- ^ "UniProt- ZFP62". www.uniprot.org. Retrieved 2023-12-07.
- ^ "Gene: ZFP62 (ENSG00000196670) - GO: Molecular function - Homo_sapiens - Ensembl genome browser 110". useast.ensembl.org. Retrieved 2023-12-07.
- ^ Pabo, Carl O.; Peisach, Ezra; Grant, Robert A. (2001-06). "Design and Selection of Novel Cys 2 His 2 Zinc Finger Proteins". Annual Review of Biochemistry. 70 (1): 313–340. doi:10.1146/annurev.biochem.70.1.313. ISSN 0066-4154.
{{cite journal}}: Check date values in:|date=(help) - ^ Krishna, S. S. (2003-01-15). "Structural classification of zinc fingers: SURVEY AND SUMMARY". Nucleic Acids Research. 31 (2): 532–550. doi:10.1093/nar/gkg161. PMC 140525. PMID 12527760.
{{cite journal}}: CS1 maint: PMC format (link) - ^ a b "zinc finger protein 62 homolog isoform 2 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-07.
- ^ "DeepLoc 2.0 - DTU Health Tech - Bioinformatic Services". services.healthtech.dtu.dk. Retrieved 2023-12-15.
- ^ Kumar, Prof. T. Ashok. "CFSSP: Chou & Fasman Secondary Structure Prediction Server". www.biogem.org. Retrieved 2023-12-15.
- ^ "Ali2D- Bioinformatics Toolkit". toolkit.tuebingen.mpg.de. Retrieved 2023-12-15.
- ^ "Gene: ZFP62 (ENSG00000196670) - Paralogues - Homo_sapiens - Ensembl genome browser 110". useast.ensembl.org. Retrieved 2023-12-15.
- ^ a b "ZNF648 zinc finger protein 648 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-15.
- ^ a b "ZNF808 zinc finger protein 808 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-15.
- ^ a b "ZNF664 zinc finger protein 664 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-15.
- ^ a b "ZNF721 zinc finger protein 721 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-15.
- ^ a b "ZNF485 zinc finger protein 485 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-15.
- ^ Xenos, Alexandros; Malod-Dognin, Noël; Zambrana, Carme; Pržulj, Nataša (2023-01-11). "Integrated Data Analysis Uncovers New COVID-19 Related Genes and Potential Drug Re-Purposing Candidates". International Journal of Molecular Sciences. 24 (2): 1431. doi:10.3390/ijms24021431. ISSN 1422-0067. PMC 9863794. PMID 36674947.
{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link) - ^ Su, Xie; Xie, Lu; Li, Jing; Tian, Xinyue; Lin, Bing; Chen, Menghua (2023-03-23). "Exploring molecular signatures related to the mechanism of aging in different brain regions by integrated bioinformatics". Frontiers in Molecular Neuroscience. 16. doi:10.3389/fnmol.2023.1133106. ISSN 1662-5099. PMC 10076559. PMID 37033380.
{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link) - ^ La Starza, R.; Barba, G.; Demeyer, S.; Pierini, V.; Di Giacomo, D.; Gianfelici, V.; Schwab, C.; Matteucci, C.; Vicente, C.; Cools, J.; Messina, M.; Crescenzi, B.; Chiaretti, S.; Foa, R.; Basso, G. (2016-08-01). "Deletions of the long arm of chromosome 5 define subgroups of T-cell acute lymphoblastic leukemia". Haematologica. 101 (8): 951–958. doi:10.3324/haematol.2016.143875. ISSN 0390-6078.