ZNF684
Identifiers
AliasesZNF684, zinc finger protein 684
External IDsHomoloGene: 65042 GeneCards: ZNF684
Orthologs
SpeciesHumanMouse
Entrez

127396

n/a

Ensembl

ENSG00000117010

n/a

UniProt

Q5T5D7

n/a

RefSeq (mRNA)

NM_152373

n/a

RefSeq (protein)

NP_689586

n/a

Location (UCSC)Chr 1: 40.53 – 40.55 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human
Figure 1. Human ZNF684 5' UTR Secondary Structure

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

Gene

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

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

Figure 2. Human ZNF684 3' UTR Secondary Structure

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

Gene

Tissue Distribution

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

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

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

Figure 3. ZNF684 multiple sequence alignment of the Kruppel-associated box across 20 different placental species.
Figure 4. ZNF684 multiple sequence alignment of zinc finger domains across 20 different placental mammals.

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.

Table 1. ZNF684 Isoform 1 Strict Ortholog Table Across Placental Mammals
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

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

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

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000117010 - Ensembl, May 2017
  2. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. 1 2 3 4 5 6 7 "ZNF684 zinc finger protein 684 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-14.
  4. 1 2 3 4 "zinc finger protein 684 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-14.
  5. 1 2 "Homo sapiens zinc finger protein 684 (ZNF684), mRNA". 2022-12-24. {{cite journal}}: Cite journal requires |journal= (help)
  6. ↑ "Gene: ZNF684 (ENSG00000117010) - Summary - Homo_sapiens - Ensembl genome browser 110". useast.ensembl.org. Retrieved 2023-12-14.
  7. ↑ www.phosphosite.org https://www.phosphosite.org/overviewExecuteAction?id=3509849. Retrieved 2023-12-14. {{cite web}}: Missing or empty |title= (help)
  8. ↑ Urrutia, Raul (2003). "KRAB-containing zinc-finger repressor proteins". Genome Biology. 4 (10): 231. doi:10.1186/gb-2003-4-10-231. ISSN 1465-6906. PMC 328446. PMID 14519192.
  9. 1 2 Lupo, Angelo; Cesaro, Elena; Montano, Giorgia; Zurlo, Diana; Izzo, Paola; Costanzo, Paola (June 2013). "KRAB-Zinc Finger Proteins: A Repressor Family Displaying Multiple Biological Functions". Current Genomics. 14 (4): 268–278. doi:10.2174/13892029113149990002. ISSN 1389-2029. PMC 3731817. PMID 24294107.
  10. ↑ "UniProt". www.uniprot.org. Retrieved 2023-12-14.
  11. ↑ "SAPS < Sequence Statistics < EMBL-EBI". www.ebi.ac.uk. Retrieved 2023-12-14.
  12. ↑ Chou, Peter Y.; Fasman, Gerald D. (January 1979), Meister, Alton (ed.), Prediction of the Secondary Structure of Proteins from their Amino Acid Sequence, Advances in Enzymology - and Related Areas of Molecular Biology, vol. 47 (1 ed.), Wiley, pp. 45–148, doi:10.1002/9780470122921.ch2, ISBN 978-0-471-04116-0, PMID 364941, retrieved 2023-12-14
  13. 1 2 "ZNF684 protein expression summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2023-12-14.
  14. ↑ "Expression of ZNF684 in liver cancer - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2023-12-14.
  15. ↑ "Expression of ZNF684 in renal cancer - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2023-12-14.
  16. 1 2 "Subcellular - ZNF684 - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2023-12-14.
  17. ↑ "Nucleotide BLAST: Search nucleotide databases using a nucleotide query". blast.ncbi.nlm.nih.gov. Retrieved 2023-12-14.
  18. ↑ "Gene: ZNF684 (ENSG00000117010) - Paralogues - Homo_sapiens - Ensembl genome browser 110". useast.ensembl.org. Retrieved 2023-12-15.
  19. ↑ "Clustal Omega < Multiple Sequence Alignment < EMBL-EBI". www.ebi.ac.uk. Retrieved 2023-12-15.
  20. ↑ "ZNF684 protein (human) - STRING interaction network". string-db.org. Retrieved 2023-12-15.
  21. ↑ "Homo sapiens tripartite motif containing 28 (TRIM28), mRNA". 2023-11-21. {{cite journal}}: Cite journal requires |journal= (help)
  22. ↑ "UniProt". www.uniprot.org. Retrieved 2023-12-15.
  23. ↑ Nitoiu, Alexandra; Nabeel-Shah, Syed; Farhangmehr, Shaghayegh; Pu, Shuye; Braunschweig, Ulrich; Blencowe, Benjamin J.; Greenblatt, Jack F. (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

Further reading

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