Zinc Finger 559 (ZNF559) 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 (KRAB) 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 (19p13.2) 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 (reads per thousand nucleotides of transcript length per million) 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. +IsoformTranscript VariantmRNA length (bp)Protein length (aa)5'UTR (nt)A13009602407B24675538255C34622496328D43087148407E52886112330F6273484262F7276384291F8290384431
Conceptual translation The depicted conceptual translation for ZNF559 isoform A; contains 5' UTR, protein coding sequence, and the end of the 3'UTR region. +Conceptual Translation Table SignalLocation Color/StyleC2H2 Structural Motif158-177, 185–240, 213–243, 251–299, 307–327, 363–383, 391–411, 419–439, 447–467, 475–495, 503–523, 531–551, 559–579Yellow highlightPutative Nucleic Binding site162, 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, 578Green highlightCOG508, FOG: Zn Finger221-601Blue lettering KRAB BOX pfam0135277-118Pink highlightSignal Peptide1-37Grey 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 Interactions for ZNF559ProteinName FunctionLocalizationZNF385BZinc finger 385BRole in p53/TP53-mediated apoptosis.NucleusZNF827Zinc finger 827Involved in transcriptional regulation.Nucleus, Cytosol ZNF773Zinc finger 773Involved in transcriptional regulation.Nucleus, CytosolZNF549Zinc finger 559Involved in transcriptional regulation.Nucleus, Cytosol, Cytoskeleton ZNF224Zinc finger 224Involved in transcriptional regulation as a transcriptional repressor.Nucleus, Golgi, Lysosome, Cytoskeleton, ER, Mitochondria, Extracellular, PM ZNF585AZinc finger 585AInvolved in transcriptional regulation.Nucleus, GolgiTRIM28Tripartite-motif containing 28Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs).Nucleus, Cytosol, Lysosome, ER, Mitochondrion, Cytoskeleton, Extracellular, PM, FAM98CFamily 98CInvolved in RNA binding and transcriptional regulation.Nucleus, Cytosol, ExtracellularKRBOX4Krab box 4KRAB box domain containing 4. -KRTAP10-1Keratin associated protein 10–1Structural hair-shaft protein contributing to keratin fiber formation.Cytosol, Cytoskeleton, Extracellular, PM KRTAP10-3Keratin associated protein 10–3Structural hair-shaft protein contributing to keratin fiber formation.Cytosol, Cytoskeleton, Extracellular, PM KRTAP10-5Keratin associated protein 10–5Structural hair-shaft protein contributing to keratin fiber formation.Cytosol, Cytoskeleton, Extracellular, PM SART3Squamous carcinoma antigen recognized by T cells 3Functions as an RNA-binding protein involved in pre-mRNA splicing and is a tumor-associated antigen.NucleusCABP5Calcium binding protein 5Modulate 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. +Orthologs for ZNF559SpeciesCommon NameProtein Length (aa)Similarity to Human Protein (%)Date of Divergence (MYA)Taxonomic GroupPan PiniscusBonobo602996.4Mammalia; PrimatesPongo abeliiSumatran Orangutan5669715.2Mammalia; PrimatesHylobates molochJavan Gibbon5559419.5Mammalia; PrimatesMacaca thibetanaTibetan Macaque5649528.8Mammalia; PrimatesMandrillus leucophaeusDrill5659428.8Mammalia; PrimatesPapio anubisOlive Baboon5539328.8Mammalia; PrimatesRhinopithecus roxellanaGolden Snub-nosed Monkey5369428.8Mammalia; PrimatesChlorocebus sabaeusGreen Monkey5649428.8Mammalia; PrimatesSaimiri boliviensisBolivian Squirrel Monkey5638143Mammalia; PrimatesCynocephalus volansPhilippine Colugo5597879DermopteraUrsus arctosBrown Bear5576694Carnivora (Ursidae)Neogale visonAmerican Mink56739.894Carnivora (Mustelidae)Acinonyx jubatusCheetah6825394Carnivora (Felidae)Prionailurus bengalensisLeopard Cat5746294Carnivora (Felidae)Odobenus rosmarus divergensPacific Walrus5306094Carnivora (Odobenidae)Leptonychotes weddelliiWeddel Seal5145792Carnivora (Phocidae)Neomonachus schauinslandiHawaiian Monk Seal5675995Carnivora (Phocidae)Mirounga leoninaSouthern Elephant Seal5365695Carnivora (Phocidae)Camelus bactrianusBactrian Camel6976181Aritodactyla
Paralogs According to NCBI BLAST ZNF559 in humans is characterized by two paralogs; ZNF426 and ZNF846. +Paralogs for ZNF559ParalogLocation (Chromosome)Similarity (%)ZNF4261948.14ZNF8461948.79
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 (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
References