Zinc finger protein 684
ZNF684 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | ZNF684, zinc finger protein 684 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | HomoloGene: 65042; GeneCards: ZNF684; OMA:ZNF684 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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![](http://upload.wikimedia.org/wikipedia/commons/thumb/5/54/ZNF684_5%27_UTR.jpg/220px-ZNF684_5%27_UTR.jpg)
Zinc finger protein 684 is a protein that in humans is encoded by the ZNF684 gene.[3]
Gene
[edit]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]
Transcript
[edit]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]
Protein
[edit]![](http://upload.wikimedia.org/wikipedia/commons/thumb/3/3a/ZNF684_3UTR.jpg/220px-ZNF684_3UTR.jpg)
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]
Regulation
[edit]Gene
[edit]Tissue Distribution
[edit]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]
Transcript
[edit]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).
Protein
[edit]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]
Homology/ evolution
[edit]![](http://upload.wikimedia.org/wikipedia/commons/thumb/4/44/KRABbox.png/220px-KRABbox.png)
![](http://upload.wikimedia.org/wikipedia/commons/thumb/e/ed/ZincFingers.png/220px-ZincFingers.png)
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.
Genus and Species | 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 |
Interacting Proteins
[edit]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]
Functions
[edit]ZNF684 physically interacts with mRNA export factors and directly binds to RNA.[23]
References
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000117010 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b c d e f g "ZNF684 zinc finger protein 684 [Homo sapiens (human)] - Gene". www.ncbi.nlm.nih.gov. National Center for Biotechnology Information (NCBI). Retrieved 2023-12-14.
- ^ a b c d "zinc finger protein 684 [Homo sapiens] - Protein". National Center for Biotechnology Information (NCBI). Retrieved 2023-12-14.
- ^ a b "Homo sapiens zinc finger protein 684 (ZNF684), mRNA". National Center for Biotechnology Information (NCBI). 2022-12-24.
- ^ "Gene: ZNF684 (ENSG00000117010) - Summary - Homo_sapiens". Ensembl genome browser 110. Retrieved 2023-12-14.
- ^ "ZNF684". www.phosphosite.org. Retrieved 2023-12-14.
- ^ Urrutia R (2003). "KRAB-containing zinc-finger repressor proteins". Genome Biology. 4 (10): 231. doi:10.1186/gb-2003-4-10-231. PMC 328446. PMID 14519192.
- ^ a b Lupo A, Cesaro E, Montano G, Zurlo D, Izzo P, Costanzo P (June 2013). "KRAB-Zinc Finger Proteins: A Repressor Family Displaying Multiple Biological Functions". Current Genomics. 14 (4): 268–278. doi:10.2174/13892029113149990002. PMC 3731817. PMID 24294107.
- ^ "Zinc finger protein 684". UniProt. Retrieved 2023-12-14.
- ^ "SAPS < Sequence Statistics < EMBL-EBI". www.ebi.ac.uk. Retrieved 2023-12-14.
- ^ Chou PY, Fasman GD (January 1979). "Prediction of the Secondary Structure of Proteins from their Amino Acid Sequence". In Meister A (ed.). Advances in Enzymology and Related Areas of Molecular Biology. Advances in Enzymology - and Related Areas of Molecular Biology. Vol. 47 (1st ed.). Wiley. pp. 45–148. doi:10.1002/9780470122921.ch2. ISBN 978-0-471-04116-0. PMID 364941. Retrieved 2023-12-14.
- ^ a b "ZNF684 protein expression summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2023-12-14.
- ^ "Expression of ZNF684 in liver cancer - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2023-12-14.
- ^ "Expression of ZNF684 in renal cancer - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2023-12-14.
- ^ a b "Subcellular - ZNF684 - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2023-12-14.
- ^ "Nucleotide BLAST: Search nucleotide databases using a nucleotide query". blast.ncbi.nlm.nih.gov. Retrieved 2023-12-14.
- ^ "Gene: ZNF684 (ENSG00000117010) - Paralogues - Homo_sapiens - Ensembl genome browser 110". useast.ensembl.org. Retrieved 2023-12-15.
- ^ "Clustal Omega < Multiple Sequence Alignment < EMBL-EBI". www.ebi.ac.uk. Retrieved 2023-12-15.
- ^ "ZNF684 protein (human)". STRING interaction network. Retrieved 2023-12-15.
- ^ "Homo sapiens tripartite motif containing 28 (TRIM28), mRNA". 2023-11-21.
- ^ "TIF1B_HUMAN". UniProt. Retrieved 2023-12-15.
- ^ Nitoiu A, Nabeel-Shah S, Farhangmehr S, Pu S, Braunschweig U, Blencowe BJ, et al. (2021-10-01), KRAB Zinc Finger protein Znf684 interacts with Nxf1 to regulate mRNA export, doi:10.1101/2021.09.29.462476, S2CID 238261558, retrieved 2023-12-15