Biology:ZNF559
Expression
ZNF559 gene expression is ubiquitous and high across many tissues.[1] Some of the tissues with the highest expression above 4.0 RPKM (reads per thousand nucleotides of transcript length per million) were the endometrium, lymph node, prostate, spleen, testis, thyroid, and urinary bladder.[2]
mRNA
There are eight known transcript variants and six isoforms for human ZNF559.[3]
| Isoform | Transcript Variant | mRNA length (bp) | Protein length (aa) | 5'UTR (nt) |
|---|---|---|---|---|
| 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.[4] According to SAPS tool the amino acid composition is rich in cysteine, histidine, arginine, and lysine, which is typical for DNA binding proteins.[5] 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.[6]
| 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 (KRAB-ZFPs). | 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.[7] 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 (aa) | Similarity to Human Protein (%) | Date of Divergence (MYA) | 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 (Ursidae) |
| Neogale vison | American Mink | 567 | 39.8 | 94 | Carnivora (Mustelidae) |
| Acinonyx jubatus | Cheetah | 682 | 53 | 94 | Carnivora (Felidae) |
| Prionailurus bengalensis | Leopard Cat | 574 | 62 | 94 | Carnivora (Felidae) |
| Odobenus rosmarus divergens | Pacific Walrus | 530 | 60 | 94 | Carnivora (Odobenidae) |
| Leptonychotes weddellii | Weddel Seal | 514 | 57 | 92 | Carnivora (Phocidae) |
| Neomonachus schauinslandi | Hawaiian Monk Seal | 567 | 59 | 95 | Carnivora (Phocidae) |
| Mirounga leonina | Southern Elephant Seal | 536 | 56 | 95 | Carnivora (Phocidae) |
| Camelus bactrianus | Bactrian Camel | 697 | 61 | 81 | Aritodactyla |
Paralogs
According to NCBI BlAST ZNF559 in humans is characterized by two paralogs;[7] ZNF426 and ZNF846.
| Paralog | Location (Chromosome) | 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.[8]
In a Waldenström's Macroglobulinemia (WM) 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[9]
References
- ↑ "ZNF559 Gene Expression - Gene - NCBI". https://www.ncbi.nlm.nih.gov/gene/84527/?report=expression&bioproject=PRJNA270632.
- ↑ "Homo sapiens (ID 270632) - BioProject - NCBI". https://www.ncbi.nlm.nih.gov/bioproject/PRJNA270632/.
- ↑ "ZNF559 zinc finger protein 559 [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/84527.
- ↑ "Expasy - Error". https://web.expasy.org/cgi-bin/compute_pi/pi_tool.cgi.
- ↑ "Job Dispatcher homepage | EMBL-EBI" (in en). https://www.ebi.ac.uk/jdispatcher/.
- ↑ "error ... STRING: functional protein association networks". https://string-db.org/cgi/network?taskId=bYTulal6EhvV&sessionId=bv1CiIsBNF2o.
- ↑ 7.0 7.1 "BLAST: Basic Local Alignment Search Tool". https://blast.ncbi.nlm.nih.gov/Blast.cgi.
- ↑ "Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray". Cancer Science 97 (1): 64–71. January 2006. doi:10.1111/j.1349-7006.2006.00136.x. PMID 16367923.
- ↑ "Comprehensive Molecular Characterization of Malignant and Microenvironmental Cells in Waldenstrom's Macroglobulinemia by Gene Expression Profiling.". Blood 110 (11): 3174. 2007-11-16. doi:10.1182/blood.v110.11.3174.3174. ISSN 0006-4971. https://doi.org/10.1182/blood.v110.11.3174.3174.
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