Zinc finger protein 684

Zinc finger protein 684 is a protein that in humans is encoded by the ZNF684 gene.^[3]

The zinc finger protein 684 is also known as the Kruppel-associated box protein.^[4] Within humans, the ZNF684 gene is found on the plus strand at 1q34.2, spanning 16,594 nucleotides from 40,548,167 to 40,531,573.^[5][6]

Currently, there is one transcript variant encoding ZNF684.^[3] The transcript variant has five identified exon regions within ZNF684 and spans 2,019 base pairs (bp).^[5]

The ZNF684 protein in humans is 378 amino acids long.^[4] Human ZNF684 has a molecular weight of 32,945 Da and basal isoelectric point of 9.06.^[7] The ZNF684 protein contains the Kruppel-associated box A (KRAB-A) domain, which functions as a transcriptional repressor.^[4][8] Within the ZNF684 protein, there are 8 C2H2 zinc finger structural motif (zf-C2H2) domain, which are known to bind either zinc ions or nucleic acid.^[4][9][10] Within those domains, cystine and histidine are the primary amino acids involved in zinc ion (Zn²⁺) or nucleic acid binding.^[9] The human ZNF684 protein is rich in lysine and histidine, and poor in alanine.^[11] Predicted secondary structures of ZNF684 demonstrate a variable number of alpha helices, beta sheets, helical turns, and coils throughout the protein.^[12]

In terms of gene expression, ZNF684 has ubiquitous expression in all human tissues.^[3] Microarray data illustrates higher expression of ZNF684 within the liver.^[3][13] This is further supported by data which depicts a decrease in ZNF684 expression in liver cells within individuals with liver cancer.^[14] There was also higher expressions of ZNF684 within the kidney compared to other tissues.^[3][13] Evidence of decreased ZNF684 expression is observed with individuals with renal cancer.^[15]

Within fetuses, the ubiquitous expression of ZNF684 gene is present in all tissues throughout the gestational period of 10 to 20 weeks.^[3] There is a higher level of expression of ZNF684 in the heart at 20 weeks of gestation, and a decreased level of expression in kidneys at 20 week of gestation.^[3]

Using RNAfold, minimum free energy structures were created based on the extended 5' and 3' untranslated region (UTR) in the human sequence (Figure 1-2).

It is predicted that ZNF684 localizes within the nucleus, which aligns with the protein's known functions as a transcription factor.^[16] It has also been predicted to localize within the cytoplasm.^[16]

Homologs of the ZNF684 gene have been found across eukaryotes and bacteria species.^[17] Strict orthologs were only found within placental mammals. The gene is also closely related to the paralog ZFP25 in humans.^[18] Across the various species in which ZNF684 strict ortholog is present, conservation of C2H2 binding sites and the Kruppel-associated box is apparent (Figure 3-4).^[19] The list of the various mammalian placental species are summarized in Table 1 by their median date of divergence from Homo sapiens.

Multiple interactions were detected between ZNF684 and other proteins.^[20] TRIM28 is a transcription factor co-repressor that interacts with the KRAB domain.^[21] TRIM28 recruits components for histone methylation and histone deacetylation, leading to changes in chromatin structure that repress gene expression.^[22]

ZNF684 physically interacts with mRNA export factors and directly binds to RNA.^[23]