Zinc finger protein 684 is a protein that in humans is encoded by the ZNF684 gene.[1]
The zinc finger protein 684 is also known as the Kruppel-associated box protein.[2] 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.[3] [4]
Currently, there is one transcript variant encoding ZNF684. The transcript variant has five identified exon regions within ZNF684 and spans 2,019 base pairs (bp).
The ZNF684 protein in humans is 378 amino acids long. Human ZNF684 has a molecular weight of 32,945 Da and basal isoelectric point of 9.06.[5] The ZNF684 protein contains the Kruppel-associated box A (KRAB-A) domain, which functions as a transcriptional repressor.[6] 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.[7] [8] Within those domains, cystine and histidine are the primary amino acids involved in zinc ion (Zn2+) or nucleic acid binding. The human ZNF684 protein is rich in lysine and histidine, and poor in alanine.[9] Predicted secondary structures of ZNF684 demonstrate a variable number of alpha helices, beta sheets, helical turns, and coils throughout the protein.[10]
In terms of gene expression, ZNF684 has ubiquitous expression in all human tissues. Microarray data illustrates higher expression of ZNF684 within the liver.[11] This is further supported by data which depicts a decrease in ZNF684 expression in liver cells within individuals with liver cancer.[12] There was also higher expressions of ZNF684 within the kidney compared to other tissues. Evidence of decreased ZNF684 expression is observed with individuals with renal cancer.[13]
Within fetuses, the ubiquitous expression of ZNF684 gene is present in all tissues throughout the gestational period of 10 to 20 weeks. 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.
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.[14] It has also been predicted to localize within the cytoplasm.
Homologs of the ZNF684 gene have been found across eukaryotes and bacteria species.[15] Strict orthologs were only found within placental mammals. The gene is also closely related to the paralog ZFP25 in humans.[16] 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).[17] The list of the various mammalian placental species are summarized in Table 1 by their median date of divergence from Homo sapiens.
| Common Name | Taxonomic Group | Median Date of Divergence | Accession # | Sequence Length (aa) | Sequence Identity to Human Protein (%) | Sequence Similarity to Human Protein | ||
| Homo sapiens | Human | Primates | 0.0 | NP_689586.3 | 378 | 100.0 | 100.0 | |
| Pan troglodytes | Chimpanzee | Primates | 6.4 | XP_513358.3 | 378 | 98.9 | 98.9 | |
| Macaca mulatta | Rhesus monkey | Primates | 28.8 | XP_028691269.1 | 398 | 77.3 | 78.0 | |
| Tupaia chinensis | Chinese treeshrew | Scandentia | 85.0 | XP_006164992.2 | 401 | 75.9 | 82.6 | |
| Heterocephalus glaber | Naked mole-rat | Rodentia | 87.0 | XP_021105597.1 | 380 | 79.5 | 88.7 | |
| Castor canadensis | American beaver | Rodentia | 87.0 | XP_020027280.1 | 352 | 77.3 | 78.0 | |
| Oryctolagus cuniculus | Rabbit | Lagomorpha | 87.0 | XP_051713856.1 | 405 | 48.2 | 61.0 | |
| Ochotona curzoniae | Black-lipped pika | Lagomorpha | 87.0 | XP_040830236.1 | 407 | 45.5 | 61.2 | |
| Bos taurus | Cattle | Artiodactyla | 94.0 | XP_024845985.1 | 382 | 81.2 | 88.7 | |
| Balaenoptera ricei | Rices whale | Artiodactyla | 94.0 | XP_059753474.1 | 380 | 85.0 | 90.5 | |
| Ursus arctos | Brown bear | Carnivora | 94.0 | XP_057161231.1 | 380 | 86.3 | 90.8 | |
| Acinonyx jubatus | Cheetah | Carnivora | 94.0 | XP_053068190.1 | 380 | 82.9 | 89.2 | |
| Diceros bicornis minor | South-central black rhinoceros | Perissodactyla | 94.0 | XP_058409785.1 | 380 | 86.8 | 91.8 | |
| Pteropus alecto | Large flying fox | Chiroptera | 94.0 | XP_023377766.1 | 378 | 84.2 | 89.5 | |
| Myotis daubentonii | Daubentons bat | Chiroptera | 94.0 | XP_059545721.1 | 394 | 79.0 | 84.8 | |
| Condylura cristata | Star-nosed mole | Eulipotyphla | 94.0 | XP_012577988.1 | 386 | 80.3 | 87.6 | |
| Manis pentadactyla | Chinese pango | Pholidota | 94.0 | XP_057356056.1 | 409 | 74.3 | 79.2 | |
| Trichechus manatus | Florida manatee | Afrotheria | 99.0 | XP_023582938.1 | 380 | 82.1 | 88.9 | |
| Elephas maximus indicus | Elephant | Afrotheria | 99.0 | XP_049734871.1 | 392 | 76.7 | 84.8 | |
| Choloepus didactylus | Two-toed sloth | Pilosa | 99.0 | XP_037683504.1 | 399 | 79.2 | 83.2 |
Multiple interactions were detected between ZNF684 and other proteins.[18] TRIM28 is a transcription factor co-repressor that interacts with the KRAB domain.[19] TRIM28 recruits components for histone methylation and histone deacetylation, leading to changes in chromatin structure that repress gene expression.[20]
ZNF684 physically interacts with mRNA export factors and directly binds to RNA.