ZNF559
Zinc Finger 559 is a protein which in humans is encoded by the ZNF559 gene. ZNF559 is a member of the Krüppel C2H2-type zinc finger protein family, characterized by its 13 C2H2-type zinc finger repeats. These motifs enable the protein to bind DNA in a sequence-specific manner, facilitating transcriptional regulation. Additionally, ZNF559 contains a Krüppel-associated box domain at its N-terminus, a common feature in many zinc finger proteins. The KRAB domain is known to mediate transcriptional repression by interacting with corepressor proteins, such as TRIM28, thereby silencing target gene expression. ZNF559 activity is localized to the nucleus, where it contributes to transcriptional regulation through protein and DNA interactions.
Gene
ZNF559 is located on chromosome 19 on the plus strand spanning 72 base pairs. ZNF559 is surrounded by other ZNF genes such as ZNF699 and ZNF177. ZNF559 has six exons.Expression
ZNF559 gene expression is ubiquitous and high across many tissues. Some of the tissues with the highest expression above 4.0 RPKM were the endometrium, lymph node, prostate, spleen, testis, thyroid, and urinary bladder.mRNA
There are eight known transcript variants and six isoforms for human ZNF559.| Isoform | Transcript Variant | mRNA length | Protein length | 5'UTR |
| A | 1 | 3009 | 602 | 407 |
| B | 2 | 4675 | 538 | 255 |
| C | 3 | 4622 | 496 | 328 |
| D | 4 | 3087 | 148 | 407 |
| E | 5 | 2886 | 112 | 330 |
| F | 6 | 2734 | 84 | 262 |
| F | 7 | 2763 | 84 | 291 |
| F | 8 | 2903 | 84 | 431 |
Conceptual translation
The depicted conceptual translation for ZNF559 isoform A; contains 5' UTR, protein coding sequence, and the end of the 3'UTR region.| Signal | Location | Color/Style |
| C2H2 Structural Motif | 158-177, 185–240, 213–243, 251–299, 307–327, 363–383, 391–411, 419–439, 447–467, 475–495, 503–523, 531–551, 559–579 | Yellow highlight |
| Putative Nucleic Binding site | 162, 164, 166, 168, 169, 172, 173, 176, 190, 192, 196, 197, 200, 201, 258, 260, 262, 263, 266, 267, 270, 396, 398, 400, 402, 403, 406, 407, 410, 424, 426, 430, 431, 434, 435, 438, 452, 454, 456, 458, 459, 462, 463, 466, 508, 510, 512, 514, 515, 518, 519, 522, 536, 538, 542, 546, 547, 550, 564, 568, 570, 571, 574, 575, 578 | Green highlight |
| COG508, FOG: Zn Finger | 221-601 | Blue lettering |
| KRAB BOX pfam01352 | 77-118 | Pink highlight |
| Signal Peptide | 1-37 | Grey lettering |
Protein
For ZNF559 human isoform A has an isolelectric point of 8.9 and a molecular weight of 69kD. According to SAPS tool the amino acid composition is rich in cysteine, histidine, arginine, and lysine, which is typical for DNA binding proteins. The cysteine spacing gives results to 13 C2H2 zinc finger motifs. There are three globular domains and five regions of disorder.Protein interaction
According to STRING many proteins are found to interact with ZNF559 related to transcription regulation and keratin.| Protein | Name | Function | Localization |
| ZNF385B | Zinc finger 385B | Role in p53/TP53-mediated apoptosis. | Nucleus |
| ZNF827 | Zinc finger 827 | Involved in transcriptional regulation. | Nucleus, Cytosol |
| ZNF773 | Zinc finger 773 | Involved in transcriptional regulation. | Nucleus, Cytosol |
| ZNF549 | Zinc finger 559 | Involved in transcriptional regulation. | Nucleus, Cytosol, Cytoskeleton |
| ZNF224 | Zinc finger 224 | Involved in transcriptional regulation as a transcriptional repressor. | Nucleus, Golgi, Lysosome, Cytoskeleton, ER, Mitochondria, Extracellular, PM |
| ZNF585A | Zinc finger 585A | Involved in transcriptional regulation. | Nucleus, Golgi |
| TRIM28 | Tripartite-motif containing 28 | Nuclear corepressor for KRAB domain-containing zinc finger proteins. | Nucleus, Cytosol, Lysosome, ER, Mitochondrion, Cytoskeleton, Extracellular, PM, |
| FAM98C | Family 98C | Involved in RNA binding and transcriptional regulation. | Nucleus, Cytosol, Extracellular |
| KRBOX4 | Krab box 4 | KRAB box domain containing 4. | - |
| KRTAP10-1 | Keratin associated protein 10–1 | Structural hair-shaft protein contributing to keratin fiber formation. | Cytosol, Cytoskeleton, Extracellular, PM |
| KRTAP10-3 | Keratin associated protein 10–3 | Structural hair-shaft protein contributing to keratin fiber formation. | Cytosol, Cytoskeleton, Extracellular, PM |
| KRTAP10-5 | Keratin associated protein 10–5 | Structural hair-shaft protein contributing to keratin fiber formation. | Cytosol, Cytoskeleton, Extracellular, PM |
| SART3 | Squamous carcinoma antigen recognized by T cells 3 | Functions as an RNA-binding protein involved in pre-mRNA splicing and is a tumor-associated antigen. | Nucleus |
| CABP5 | Calcium binding protein 5 | Modulate L-type calcium channels, neurotransmitter vesicle endocytosis/exocytosis, and support neuronal signalling. | Cytosol, Nucleus |
Evolution
Orthologs
According to NBBI BLAST, the ZNF559 protein appears to be primate specific, with orthologs detected only in primates. ZNF559 orthologs are present in mammals and carnivores. No orthologs were detected in monotremes, marsupials, reptiles, birds, amphibians, or fish.| Species | Common Name | Protein Length | Similarity to Human Protein | Date of Divergence | Taxonomic Group |
| Pan Piniscus | Bonobo | 602 | 99 | 6.4 | Mammalia; Primates |
| Pongo abelii | Sumatran Orangutan | 566 | 97 | 15.2 | Mammalia; Primates |
| Hylobates moloch | Javan Gibbon | 555 | 94 | 19.5 | Mammalia; Primates |
| Macaca thibetana | Tibetan Macaque | 564 | 95 | 28.8 | Mammalia; Primates |
| Mandrillus leucophaeus | Drill | 565 | 94 | 28.8 | Mammalia; Primates |
| Papio anubis | Olive Baboon | 553 | 93 | 28.8 | Mammalia; Primates |
| Rhinopithecus roxellana | Golden Snub-nosed Monkey | 536 | 94 | 28.8 | Mammalia; Primates |
| Chlorocebus sabaeus | Green Monkey | 564 | 94 | 28.8 | Mammalia; Primates |
| Saimiri boliviensis | Bolivian Squirrel Monkey | 563 | 81 | 43 | Mammalia; Primates |
| Cynocephalus volans | Philippine Colugo | 559 | 78 | 79 | Dermoptera |
| Ursus arctos | Brown Bear | 557 | 66 | 94 | Carnivora |
| Neogale vison | American Mink | 567 | 39.8 | 94 | Carnivora |
| Acinonyx jubatus | Cheetah | 682 | 53 | 94 | Carnivora |
| Prionailurus bengalensis | Leopard Cat | 574 | 62 | 94 | Carnivora |
| Odobenus rosmarus divergens | Pacific Walrus | 530 | 60 | 94 | Carnivora |
| Leptonychotes weddellii | Weddel Seal | 514 | 57 | 92 | Carnivora |
| Neomonachus schauinslandi | Hawaiian Monk Seal | 567 | 59 | 95 | Carnivora |
| Mirounga leonina | Southern Elephant Seal | 536 | 56 | 95 | Carnivora |
| Camelus bactrianus | Bactrian Camel | 697 | 61 | 81 | Aritodactyla |
Paralogs
According to NCBI BlAST ZNF559 in humans is characterized by two paralogs; ZNF426 and ZNF846.| Paralog | Location | Similarity |
| ZNF426 | 19 | 48.14 |
| ZNF846 | 19 | 48.79 |
Clinical significance
ZNF559 was identified as a gene that becomes silenced by promoter DNA methylation in gastric cancer. Treatment with a demethylating agent restored its expression in cancer cells, and methylation of ZNF559 was also detected in primary gastric tumors, suggesting its potential role in gastric carcinogenesis.In a Waldenström's Macroglobulinemia study, ZNF559 was found to be overexpressed in CD138+ malignant cells compared to healthy donor cells. This suggests that ZNF559 may play a role in transcriptional regulation within the malignant plasma cell compartment of WM