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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 plays 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]
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
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]
Tertiary structure of ZNF548 was predicted using I-Tasser.[12][13]
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 human 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]
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.[23]
| Genus, Species | Common name | Order | Estimated divergence date (MYA) | Accession number[24] | 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
References
- ^ "ZNF548 Gene". www.genecards.org. Retrieved 26 September 2021.
- ^ a b "UniProtKB - Q8NEK5 (ZN548_HUMAN)". UniProt. Retrieved 30 September 2021.
- ^ a b "Homo sapiens zinc finger protein 548 (ZNF548), transcript variant 1, mRNA". NCBI. 11 December 2020.
- ^ a b "zinc finger protein 548 isoform 1 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov.
- ^ "Transcript: ZNF548-201 (ENST00000336128.12) - Protein summary - Homo_sapiens - Ensembl genome browser 104". useast.ensembl.org.
- ^ "ZNF548 Gene". www.genecards.org.
- ^ "Promoter region for human ZNF548 gene". Genomatix Software Suite.
{{cite web}}: CS1 maint: url-status (link) - ^ "Homo sapiens zinc finger protein 548 (ZNF548), transcript variant 2, mRNA". NCBI.
{{cite web}}: CS1 maint: url-status (link) - ^ "zinc finger protein 548 isoform 2 [Homo sapiens]". NCBI.
{{cite web}}: CS1 maint: url-status (link) - ^ "Zinc finger C2H2 superfamily". www.ebi.ac.uk.
- ^ "Kruppel-associated box". www.ebi.ac.uk.
- ^ J Yang, Y Zhang. I-TASSER server: new development for protein structure and function predictions, Nucleic Acids Research, 43: W174-W181, 2015.
- ^ 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.
- ^ "I-TASSER server for protein structure and function prediction". I-TASSER.
{{cite web}}: CS1 maint: url-status (link) - ^ "Compute pI/MW of ZNF548". Expasy.
{{cite web}}: CS1 maint: url-status (link) - ^ "Statistical Analysis of Protein Sequence for ZNF548". SAPS.
{{cite web}}: CS1 maint: url-status (link) - ^ "Prediction of eukaryotic protein subcellular localization using deep learning for ZNF548". DeepLoc - 1.0.
{{cite web}}: CS1 maint: url-status (link) - ^ "PSORT II Prediction for human ZNF548 protein". PSORT II.
{{cite web}}: CS1 maint: url-status (link) - ^ "Protein Abundance Database entry on ZNF548". PAXdb.
{{cite web}}: CS1 maint: url-status (link) - ^ "The Human Protein Atlas entry on ZNF548". The Human Protein Atlas.
{{cite web}}: CS1 maint: url-status (link) - ^ 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.
- ^ "ZNF548 interactions with other proteins". BioGRID 4.4.
{{cite web}}: CS1 maint: url-status (link) - ^ "Zinc fingers C2H2-type". www.genenames.org.
- ^ "BLAST of ZNF548 protein". BLAST.
{{cite web}}: CS1 maint: url-status (link)