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ZFP62

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ZFP62
Identifiers
AliasesZFP62, ZET, ZNF755, ZFP62 zinc finger protein
External IDsOMIM: 610281; MGI: 99662; HomoloGene: 40686; GeneCards: ZFP62; OMA:ZFP62 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

643836

22720

Ensembl

ENSG00000196670

ENSMUSG00000046311

UniProt

Q8NB50

Q8C827

RefSeq (mRNA)

NM_001172638
NM_152283

RefSeq (protein)
Location (UCSC)Chr 5: 180.85 – 180.86 MbChr 11: 49.09 – 49.11 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Zinc Finger Protein 62, also known as "ZNF62," "ZNF755," or "ZET," is a protein that in humans is encoded by the ZFP62 gene.[5] ZFP62 is part of the C2H2 Zinc Finger family of genes. [6]

Gene

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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. [5] The ZFP62 gene has 7 transcripts (splice variants), 5 known paralogues, and several mammalian orthologues.

Tissue expression

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The ZFP62 gene is ubiquitously expressed but variable across all tissue types.[7] 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. [8]

Protein

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The most commonly recognized "cannon" ZFP62 protein is Isoform 2, which is 900 amino acids in length and contains 2 coding exons.[9] The full protein weighs approximately 102.5 kDa. [10] The isoelectric point of the ZFP62 protein is 9.24, meaning that the protein is negatively charged at neutral pH. [11]

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.[12]

The predicted tertiary structure of the ZFP62 protein in humans, as generated by AlphaFold. [13]

Composition and motifs

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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.[14] 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. [15] The ZFP62 protein contains 26 of these repeats. [16]

There is one disordered region present between amino acids 1 and 97. [16]

A table of the protein interactions of the ZFP62 protein in humans. This data was compiled from the STRING Database. [17] Interacting proteins are organized by highest to lowest scores, from 0.769 to 0.477 respectively.

Secondary structure

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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.[18] [19] [20]

Tertiary structure

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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.[21]

A table detailing the interactions between ZFP62 and other proteins in humans. This data was compiled from the IntAct Database. [22] Interacting proteins are organized by highest to lowest MI scores, from 0.4 to 0.35 respectively, and then alphabetically.

This structure is consistent and nearly identical across all orthologous species.[23] [24] [25]

Protein interactions

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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. [17] [22]

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.[26] [27] [28] [29] [30]

A table highlighting transcription factors within the promoter region of the ZFP62 gene in humans. Generated using data from UCSC Genome Browser. [31] Inclusion of the transcription factors were based on highest matrix scores, the presence of the sequence within the excerpt, the sequence's similarity to its known sequence, and the repetition of the sequence within the excerpt.

Regulation

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Promoter

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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.[32]

Promoter-region transcription factors

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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. [33] [31]

Homology and evolution

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Paralogues

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In humans, the ZFP62 gene is paralogous with 5 other Zinc Finger Proteins, as seen in the following table.[34] 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. [35][36][37][38][39]

Human ZFP62 Paralogues
Gene Symbol Full Gene Name Gene Location NCBI Gene ID
ZNF648 [35] Zinc Finger Protein 648 1q25.3 127665
ZNF808 [36] Zinc Finger Protein 808 19q13.41 388558
ZNF664 [37] Zinc Finger Protein 664 12q24.31 144348
ZNF721 [38] Zinc Finger Protein 721 4p16.3 170960
ZNF485 [39] Zinc Finger Protein 648 10q11.21 220992
A table comparing members of each taxonomic group that the ZFP62 gene appears in, compared to the Homo sapiens ZFP62 protein. Generated using NCBI and NCBI Orthologue Viewer. [7] [40] All species are mammalian in nature and therefore colored based on their Taxonomic Group. The table is organized based on the “Divergence” category. If two species had the same estimated date of “Divergence,” the table was then sorted by “Sequence Identity.”

Orthologues

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ZFP62 orthologues are only found in mammalian species. The orthologues appear primarily in placental mammals, including Primates, Rodentia, Cetacea, Chiroptera, Aritodactyla, Perissodactyla, and Carnivora.[40]

Conservation across orthologues

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Conservation is varied across orthologous species, with the least similar orthologue being from the Carnivora and Hyracoidea taxonomic groups.[40] [41]

Clinical significance

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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.[42]

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.[43] 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. [44]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000196670 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000046311 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b "Gene: ZFP62 (ENSG00000196670) - Summary - Homo_sapiens - Ensembl genome browser 110". useast.ensembl.org. Retrieved 2023-12-07.
  6. ^ "UniProt". www.uniprot.org. Retrieved 2023-12-07.
  7. ^ a b "ZFP62 ZFP62 zinc finger protein [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-15.
  8. ^ "Expression of ZFP62 in cancer - Summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2023-12-15.
  9. ^ "Transcript: ENST00000502412.2 (ZFP62-201) - Summary - Homo_sapiens - Ensembl genome browser 110". useast.ensembl.org. Retrieved 2023-12-07.
  10. ^ "UniProt- ZFP62". www.uniprot.org. Retrieved 2023-12-07.
  11. ^ "Expasy - Compute pI/Mw tool". web.expasy.org. Retrieved 2023-12-17.
  12. ^ "Gene: ZFP62 (ENSG00000196670) - GO: Molecular function - Homo_sapiens - Ensembl genome browser 110". useast.ensembl.org. Retrieved 2023-12-07.
  13. ^ "AlphaFold Protein Structure Database". alphafold.ebi.ac.uk. Retrieved 2023-12-17.
  14. ^ Pabo CO, Peisach E, Grant RA (June 2001). "Design and selection of novel Cys2His2 zinc finger proteins". Annual Review of Biochemistry. 70 (1): 313–340. doi:10.1146/annurev.biochem.70.1.313. PMID 11395410.
  15. ^ Krishna SS, Majumdar I, Grishin NV (January 2003). "Structural classification of zinc fingers: survey and summary". Nucleic Acids Research. 31 (2): 532–550. doi:10.1093/nar/gkg161. PMC 140525. PMID 12527760.
  16. ^ a b "zinc finger protein 62 homolog isoform 2 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-07.
  17. ^ a b "ZFP62 protein (human) - STRING interaction network". version-12-0.string-db.org. Retrieved 2023-12-17.
  18. ^ "DeepLoc 2.0 - DTU Health Tech - Bioinformatic Services". services.healthtech.dtu.dk. Retrieved 2023-12-15.
  19. ^ Kumar PT. "CFSSP: Chou & Fasman Secondary Structure Prediction Server". www.biogem.org. Retrieved 2023-12-15.
  20. ^ "Ali2D- Bioinformatics Toolkit". toolkit.tuebingen.mpg.de. Retrieved 2023-12-15.
  21. ^ "AlphaFold Protein Structure Database - ZFP62 (Homo sapiens)". alphafold.ebi.ac.uk. Retrieved 2023-12-17.
  22. ^ a b "IntAct Portal". www.ebi.ac.uk. Retrieved 2023-12-17.
  23. ^ "AlphaFold Protein Structure Database - ZFP62 (Rattus norvegicus)". alphafold.ebi.ac.uk. Retrieved 2023-12-17.
  24. ^ "AlphaFold Protein Structure Database - ZFP62 (Bos taurus)". alphafold.ebi.ac.uk. Retrieved 2023-12-17.
  25. ^ "AlphaFold Protein Structure Database - ZFP62 (Pongo abelii)". alphafold.ebi.ac.uk. Retrieved 2023-12-17.
  26. ^ "KNOP1 lysine rich nucleolar protein 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-18.
  27. ^ "PUM3 pumilio RNA binding family member 3 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-18.
  28. ^ "RBM34 RNA binding motif protein 34 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-18.
  29. ^ "RPL14 ribosomal protein L14 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-18.
  30. ^ "RPL37A ribosomal protein L37a [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-18.
  31. ^ a b "UCSC Genome Browser Home". genome.ucsc.edu. Retrieved 2023-12-17.
  32. ^ "SCREEN: Search Candidate Regulatory Elements by ENCODE". screen.encodeproject.org. Retrieved 2023-12-17.
  33. ^ "SCREEN: Search Candidate Regulatory Elements by ENCODE". screen.encodeproject.org. Retrieved 2023-12-18.
  34. ^ "Gene: ZFP62 (ENSG00000196670) - Paralogues - Homo_sapiens - Ensembl genome browser 110". useast.ensembl.org. Retrieved 2023-12-15.
  35. ^ a b "ZNF648 zinc finger protein 648 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-15.
  36. ^ a b "ZNF808 zinc finger protein 808 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-15.
  37. ^ a b "ZNF664 zinc finger protein 664 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-15.
  38. ^ a b "ZNF721 zinc finger protein 721 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-15.
  39. ^ a b "ZNF485 zinc finger protein 485 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-15.
  40. ^ a b c "ZFP62 orthologs". NCBI. Retrieved 2023-12-18.
  41. ^ "EMBOSS Needle < Pairwise Sequence Alignment < EMBL-EBI". www.ebi.ac.uk. Retrieved 2023-12-18.
  42. ^ Xenos A, Malod-Dognin N, Zambrana C, Pržulj N (January 2023). "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. PMC 9863794. PMID 36674947.
  43. ^ Su X, Xie L, Li J, Tian X, Lin B, Chen M (2023-03-23). "Exploring molecular signatures related to the mechanism of aging in different brain regions by integrated bioinformatics". Frontiers in Molecular Neuroscience. 16: 1133106. doi:10.3389/fnmol.2023.1133106. PMC 10076559. PMID 37033380.
  44. ^ La Starza R, Barba G, Demeyer S, Pierini V, Di Giacomo D, Gianfelici V, et al. (August 2016). "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. PMC 4967574. PMID 27151989.
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