Biology:ZNF548

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example
ZNF548 schematic illustration made with DOG 2.0. Blue represents the KRAB domain while pink represents the 11 zinc fingers found in the human ZNF548 protein that is 545 amino acids long.

Zinc Finger Protein 548 (ZNF548) is a human protein encoded by the ZNF548 gene which is located on chromosome 19.[1] It is found in the nucleus and is hypothesized to play a role in the regulation of transcription by RNA Polymerase II. It belongs to the Krüppel C2H2-type zinc-finger protein family as it contains many zinc-finger repeats.[2]

Gene

This protein coding gene is 4987 bp long and encodes transcript variant 1 which is the longest ZNF548 isoform.[3][4] It is found on chromosome 19; its exact position is 19q13.43 in the plus strand. The gene has 4 exons which encode for a Kruppel associated box (KRAB domain) and 11 zinc finger repeats.[5][6]

Promoter

The promoter of the ZNF548 gene is 1198 bases long and is located at 57388850 - 57390047 on chromosome 19. The promoter region is conserved in 6 orthologs: Rhesus macaque (rhesus monkey), Pan troglodytes (chimpanzee), Oryctolagus cuniculus (European rabbit), Equus caballus (horse), Canis lupus familiaris (dog) and Sus scrofa (pig).[7]

Transcript

Conceptual translation of the Human ZNF548 isoform 1 protein. DNA sequence at the beginning is the 5' UTR while DNA sequence at the end is the 3' UTR. Below the DNA sequence the amino acids encoded by each codon are shown. Annotations in the figure include: an upstream in-frame stop, start and stop codons, exon boundaries, amino acids missing in ZNF548 isoform 2, the KRAB domain, the 11 zinc fingers which are also annotated as internal repeats, zinc finger double domains, zinc binding sites, putative nucleic acid binding sites, poly-A signals and poly-A sites.

Transcript variant 1 is the longest transcript and encodes the longest protein isoform (ZNF548 isoform 1) which is 545 amino acids long.[3][4] Transcript variant 2 is missing exon 2 and encodes ZNF548 isoform 2 which is 533 amino acids long.[8][9]

Protein

ZNF548 belongs to the Kruppel C2H2-type zinc finger protein family as it contains 11 Cys2His2-type zinc finger repeats.[2] Each zinc finger has a conserved ββα structure where a zinc atom is fixed by C2H2 residues. ZNF548 is able to attach to the DNA at a 44 bp long sequence through its C2H2 Zn motifs, each binding to 4 DNA bases.[10] The protein also contains a Kruppel-associated box (KRAB) which is a domain found at the N terminus and contains multiple charged amino acids. This domain plays a role in transcription; it binds to the RING-B box-coiled coil (RBCC) domain of the KAP-1/TIF1-beta co-repressor.[11]

ZNF548 tertiary structure predicted by I-Tasser.[12] The structure was edited in iCn3D so the orange color represents the KRAB domain while blue represents the 11 zinc fingers found in the human ZNF548 protein.

Tertiary structure of ZNF548 was predicted using I-Tasser.[13][14]

ZNF548 has a molecular weight of 64 kDa and a predicted isoelectric point of 8.21.[15] Compositional analysis of ZNF548 revealed that Alanine was found at a lower percentage than expected while Histidine was found at a much higher percentage than expected in the human ZNF548.[16]

Subcellular expression

The protein is found in the nucleus and could also be detected in the cytoplasm or the mitochondria.[17][18]

Tissue expression

ZNF548 expression in humans is relatively low compared to other proteins.[19] It has low tissue specificity; it is expressed and detected in all human tissues.[20]

Interactions with other proteins

Interaction of the human ZNF548 protein with the Nuclear distribution protein nudE-like 1 (NDEL1) and the Disrupted in schizophrenia 1 (DISC1) proteins has been experimentally validated using the two hybrid fragment pooling approach.[21] Leucine rich repeat containing 36 (LRRC36), Myotubularin 1 (MTM1), Myotubularin related protein 4 (MTMR4) and RNA binding motif protein 39 (RBM39) have also been detected to interact with the ZNF548 protein through Affinity Capture-Mass Spectrometry.[22]

Function

ZNF548 has been associated with gene expression as it can bind to nucleic acids as well as zinc ions. Based on the function of other KRAB-ZNF proteins it is hypothesized that it plays a role in the regulation of transcription of protein-encoding genes transcribed by RNA Polymerase II. Specifically it is a DNA-binding transcription factor that enhances or inhibits the transcription of certain genes that are transcribed by RNA Polymerase II. It has the ability to bind to a transcription factor recognition sequence that is on the same strand (cis) as the transcription start site via its zinc-fingers and become part of the KRAB-ZNF/KAP complex in the nucleoplasm. KRAB-ZNF proteins are known to be repressors. Therefore, when a KRAB-ZNF protein, such as ZNF548, is bound to DNA and simultaneously binds to the KAP1 co-repressor through its KRAB domain, various enzymes, such as histone deacetylases, histone methyltransferases and heterochromatin proteins, are recruited in order to compact the chromatin structure and consequently prevent transcription.[1][2][4][23][24][25]

Homologs

Orthologs

Orthologs of the ZNF548 protein have been found conserved across different orders of mammals only. This is line with the fact that C2H2-like fold groups are very common in mammalian transcription factors.[26]

The KRAB domain as well as the zinc finger repeats are highly conserved across orthologs.

ZNF548 Ortholog table
Genus, Species Common name Order Estimated divergence date (MYA) Accession number[27] Sequence length (aa) Sequence similarity to human protein (%)
Homo sapiens Human Primates 0 NP_001166244.1 545 100
Pan troglodytes Chimpanzee Primates 6.7 XP_003316775.1 545 99.3
Rhinopithecus roxellana Golden snub-nosed monkey Primates 29.44 XP_010385311.1 545 97.8
Cercocebus atys Sooty mangabey Primates 29.44 XP_011931548.1 545 97.6
Trachypithecus francoisi François' langur Primates 29.44 XP_033080506.1 545 97.8
Oryctolagus cuniculus European rabbit Lagomorpha 90 XP_017193400.1 532 84.2
Marmota monax Groundhog Rodentia 90 KAF7471703.1 546 84.9
Ictidomys tridecemlineatus Thirteen-lined ground squirrel Rodentia 90 XP_013221367.2 546 84.9
Octodon degus Common degu Rodentia 90 XP_012368689.1 548 81.1
Castor canadensis North American beaver Rodentia 90 XP_020025721.1 545 76
Heterocephalus glaber Naked mole-rat Rodentia 90 XP_012921729.1 599 77.1
Enhydra lutris kenyoni Sea otter Carnivora 96 XP_022347780.1 583 76
Leptonychotes weddellii Weddell seal Carnivora 96 XP_030883405.1 634 66.4
Ailuropoda melanoleuca Giant panda Carnivora 96 XP_034495390.1 630 65.6
Equus przewalskii Przewalski's horse Perissodactyla 96 XP_008522443.1 579 71.4
Ceratotherium simum simum Southern white rhinoceros Perissodactyla 96 XP_014649872.1 578 71.1
Physeter catodon Sperm whale Artiodactyla 96 XP_023972760.1 589 72.5
Balaenoptera musculus Blue whale Artiodactyla 96 XP_036688369.1 592 72.3
Lipotes vexillifer Baiji Artiodactyla 96 XP_007457531.1 582 72.1
Bos taurus Cattle Artiodactyla 96 NP_001193737.1 581 70.3
Pteropus alecto Black flying fox Chiroptera 96 XP_024905354.1 678 64.1

Paralogs

ZNF548 has 25 paralogous proteins in human as seen in the table below.

ZNF548 Paralog Table
Protein name Accession number Sequence similarity to human ZNF548 protein (%)
ZNF548 NP_001166244.1 100
ZIK1 NP_001010879.2 57.6
ZNF792 NP_787068.3 56.2
ZNF419 NP_001091961.1 56.2
ZNF154 NP_001078853.1 55.3
ZNF256 NP_005764.2 54.7
ZNF549 NP_001186224.2 52.9
ZNF586 NP_060122.2 52.7
ZNF773 NP_940944.1 52.2
ZNF418 NP_001303956.1 51.6
ZNF480 NP_653285.2 51.6
ZNF551 NP_612356.2 50.7
ZNF304 NP_001277247.1 50.3
ZNF583 NP_001153332.1 49.2
ZNF570 NP_001287922.1 48.9
ZNF772 NP_001019767.1 48.6
ZNF587B NP_001363152.1 48.6
ZNF79 NP_009066.2 48.4
ZNF8 NP_066575.2 46.4
ZNF584 NP_775819.1 46
ZNF561 NP_689502.2 45.8
ZNF552 NP_079038.2 43
ZNF610 NP_001154897.1 42.6
ZNF793 NP_001013681.2 41.7
ZNF562 NP_001123503.1 41
ZNF691 NP_001229668.1 31.5

Clinical Significance

ZNF548 was identified as a gene in meta-virus signature (MVS) which can be used to distinguish individuals with viral infections from those with bacterial infections as well as from healthy individuals.[28]

ZNF548 microRNA expression can act as a marker to diagnose ovarian cancer.[29] ZNF548 blood gene expression biomarker can also be used as a marker for suicidality.[30]

References

  1. ↑ 1.0 1.1 "ZNF548 Gene". https://www.genecards.org/cgi-bin/carddisp.pl?gene=ZNF548. 
  2. ↑ 2.0 2.1 2.2 "UniProtKB - Q8NEK5 (ZN548_HUMAN)". https://www.uniprot.org/uniprot/Q8NEK5#function. 
  3. ↑ 3.0 3.1 Homo sapiens zinc finger protein 548 (ZNF548), transcript variant 1, mRNA. 11 December 2020. https://www.ncbi.nlm.nih.gov/nuccore/NM_001172773.2. 
  4. ↑ 4.0 4.1 4.2 "zinc finger protein 548 isoform 1 [Homo sapiens - Protein - NCBI"]. https://www.ncbi.nlm.nih.gov/protein/289666756. 
  5. ↑ "Transcript: ZNF548-201 (ENST00000336128.12) - Protein summary - Homo_sapiens - Ensembl genome browser 104". http://useast.ensembl.org/Homo_sapiens/Transcript/ProteinSummary?g=ENSG00000188785;r=19:57389854-57402992;t=ENST00000336128. 
  6. ↑ "ZNF548 Gene". https://www.genecards.org/cgi-bin/carddisp.pl?gene=ZNF548. 
  7. ↑ "Promoter region for human ZNF548 gene". https://www.genomatix.de/cgi-bin/eldorado/eldorado.pl?s=d51bcdb36fcf9ebaf336786862f78ca0;SHOW_ANNOTATION=ZNF17---TRAPPC2B---Z;ELDORADO_VERSION=E36R2011. 
  8. ↑ Homo sapiens zinc finger protein 548 (ZNF548), transcript variant 2, mRNA. 18 December 2020. https://www.ncbi.nlm.nih.gov/nuccore/NM_152909.4. 
  9. ↑ "zinc finger protein 548 isoform 2 [Homo sapiens"]. https://www.ncbi.nlm.nih.gov/protein/NP_690873.2. 
  10. ↑ "Zinc finger C2H2 superfamily". http://www.ebi.ac.uk/interpro/entry/InterPro/IPR036236/. 
  11. ↑ "Kruppel-associated box". http://www.ebi.ac.uk/interpro/entry/InterPro/IPR001909/. 
  12. ↑ "I-TASSER server for protein structure and function prediction". https://zhanggroup.org/I-TASSER/. 
  13. ↑ J Yang, Y Zhang. I-TASSER server: new development for protein structure and function predictions, Nucleic Acids Research, 43: W174-W181, 2015.
  14. ↑ C Zhang, PL Freddolino, Y Zhang. COFACTOR: improved protein function prediction by combining structure, sequence and protein–protein interaction information. Nucleic Acids Research, 45: W291-W299, 2017.
  15. ↑ "Compute pI/MW of ZNF548". https://www.expasy.org/resources/compute-pi-mw. 
  16. ↑ "Statistical Analysis of Protein Sequence for ZNF548". https://www.ebi.ac.uk/Tools/seqstats/saps/. 
  17. ↑ "Prediction of eukaryotic protein subcellular localization using deep learning for ZNF548". https://services.healthtech.dtu.dk/service.php?DeepLoc-1.0. 
  18. ↑ "PSORT II Prediction for human ZNF548 protein". https://psort.hgc.jp/form2.html. 
  19. ↑ "Protein Abundance Database entry on ZNF548". https://pax-db.org/protein/1852017. 
  20. ↑ "The Human Protein Atlas entry on ZNF548". https://www.proteinatlas.org/ENSG00000188785-ZNF548. 
  21. ↑ Sügis E, Dauvillier J, Leontjeva A, et al. HENA, heterogeneous network-based data set for Alzheimer's disease. Scientific Data. 2019 Aug;6(1):151. doi:10.1038/s41597-019-0152-0. PMID: 31413325; PMCID: PMC6694132.
  22. ↑ "ZNF548 interactions with other proteins". https://thebiogrid.org/127076/summary/homo-sapiens/znf548.html. 
  23. ↑ Gaudet, P., Livstone, M. S., Lewis, S. E., & Thomas, P. D. (2011). Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in Bioinformatics, 12(5), 449–462. doi:10.1093/bib/bbr042
  24. ↑ Reactome entry on Transcription regulation [https://reactome.org/PathwayBrowser/#/R-HSA-212436&FLG=Q8NEK5]
  25. ↑ Reactome entry on KRAB-ZNF/KAP interaction [https://reactome.org/content/detail/R-HSA-975040]
  26. ↑ "Zinc fingers C2H2-type". https://www.genenames.org/data/genegroup/#!/group/28. 
  27. ↑ "BLAST of ZNF548 protein". https://blast.ncbi.nlm.nih.gov/Blast.cgi. 
  28. ↑ Andres-Terre, M. (2018). Exploring the Heterogeneity of Immune Response to Viral and Bacterial Infection. ProQuest Dissertations Publishing.
  29. ↑ Aboutalebi, H., et al. (2020). The diagnostic, prognostic and therapeutic potential of circulating microRNAs in ovarian cancer. The International Journal of Biochemistry & Cell Biology, 124, 105765. doi:10.1016/j.biocel.2020.105765
  30. ↑ Levey, D. et al. (2016). Towards understanding and predicting suicidality in women: Biomarkers and clinical risk assessment. Molecular Psychiatry, 21(6), 768–785. doi:10.1038/mp.2016.31



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