Zinc finger protein 684

Last updated

ZNF684
Identifiers
Aliases ZNF684 , zinc finger protein 684
External IDs HomoloGene: 65042; GeneCards: ZNF684; OMA:ZNF684 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_152373

n/a

RefSeq (protein)

NP_689586

n/a

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

Contents

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 ZNF684 3UTR.jpg
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. KRABbox.png
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. ZincFingers.png
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 SpeciesCommon NameTaxonomic GroupMedian Date of DivergenceAccession #Sequence Length (aa)Sequence Identity to Human Protein (%)Sequence Similarity to Human Protein ()
Homo sapiensHumanPrimates0.0NP_689586.3378100.0100.0
Pan troglodytesChimpanzeePrimates6.4XP_513358.337898.998.9
Macaca mulattaRhesus monkeyPrimates28.8XP_028691269.139877.378.0
Tupaia chinensisChinese treeshrewScandentia85.0XP_006164992.240175.982.6
Heterocephalus glaberNaked mole-ratRodentia87.0XP_021105597.138079.588.7
Castor canadensisAmerican beaverRodentia87.0XP_020027280.135277.378.0
Oryctolagus cuniculusRabbitLagomorpha87.0XP_051713856.140548.261.0
Ochotona curzoniaeBlack-lipped pikaLagomorpha87.0XP_040830236.140745.561.2
Bos taurusCattleArtiodactyla94.0XP_024845985.138281.288.7
Balaenoptera riceiRices whaleArtiodactyla94.0XP_059753474.138085.090.5
Ursus arctosBrown bearCarnivora94.0XP_057161231.138086.390.8
Acinonyx jubatusCheetahCarnivora94.0XP_053068190.138082.989.2
Diceros bicornis minorSouth-central black rhinocerosPerissodactyla94.0XP_058409785.138086.891.8
Pteropus alectoLarge flying foxChiroptera94.0XP_023377766.137884.289.5
Myotis daubentoniiDaubentons batChiroptera94.0XP_059545721.139479.084.8
Condylura cristataStar-nosed moleEulipotyphla94.0XP_012577988.138680.387.6
Manis pentadactylaChinese pangoPholidota94.0XP_057356056.140974.379.2
Trichechus manatusFlorida manateeAfrotheria99.0XP_023582938.138082.188.9
Elephas maximus indicusElephantAfrotheria99.0XP_049734871.139276.784.8
Choloepus didactylusTwo-toed slothPilosa99.0XP_037683504.139979.283.2

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". www.ncbi.nlm.nih.gov. National Center for Biotechnology Information (NCBI). Retrieved 2023-12-14.
  4. 1 2 3 4 "zinc finger protein 684 [Homo sapiens] - Protein". National Center for Biotechnology Information (NCBI). Retrieved 2023-12-14.
  5. 1 2 "Homo sapiens zinc finger protein 684 (ZNF684), mRNA". National Center for Biotechnology Information (NCBI). 2022-12-24.
  6. "Gene: ZNF684 (ENSG00000117010) - Summary - Homo_sapiens". Ensembl genome browser 110. Retrieved 2023-12-14.
  7. "ZNF684". www.phosphosite.org. Retrieved 2023-12-14.
  8. 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.
  9. 1 2 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.
  10. "Zinc finger protein 684". UniProt. Retrieved 2023-12-14.
  11. "SAPS < Sequence Statistics < EMBL-EBI". www.ebi.ac.uk. Retrieved 2023-12-14.
  12. 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.
  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. Retrieved 2023-12-15.
  21. "Homo sapiens tripartite motif containing 28 (TRIM28), mRNA". 2023-11-21.
  22. "TIF1B_HUMAN". UniProt. Retrieved 2023-12-15.
  23. 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

Further reading