ZNF839 or zinc finger protein 839 is a protein which in humans is encoded by the ZNF839 gene. It is located on the long arm of chromosome 14.[5] Zinc finger protein 839 is speculated to play a role in humoral immune response to cancer as a renal carcinomaantigen (NY-REN-50). This is because NY-REN-50 was found to be over expressed in cancer patients, especially those with renal carcinoma.[6][7] Zinc finger protein 839 also plays a role in transcription regulation by metal-ion binding since it binds to DNA via C2H2-type zinc finger repeats.[8][9]
Gene
Zinc finger protein 839 conceptual translation with annotations depicting important domains, signals, and conserved sites.
The human ZNF839 gene is 25,326 nucleotides long and it encodes transcript variant 1 which is the longest isoform.[10] The gene locus is 14q32.31 and it is found on the plus strand.[10] ZNF839 consists of 8 exons, it encodes for one zinc finger repeat, and 3 disordered regions.[9] The transcript variant 2 (isoform 2) is missing exon 1 so it has a downstream start codon.
mRNA/transcript
The mRNA isoform 1 encoded by the human ZNF839 gene is 2992 nucleotides long. There are 9 isoforms of the ZNF839 mRNA. [11]
It has been found that there is high expression of ZNF839 in the testis, specifically the seminiferous tubules, after RNA-sequencing analysis of various human tissues.[11][12][13] The high expression of the human ZNF839 gene in the testis may be due to its C2H2-zinc finger role in transcriptional regulation during spermatogenesis.[14] Thus, zinc finger protein 839 role's as a transcription factor may be essential in regulating spermatogenesis. There is also high expression of zinc finger protein 839 in the various regions of the gyri in the brain.[15] The high expression of ZNF839 in the gyri of the cerebrum may be due to the regulatory involvement of zinc finger proteins in neurodevelopment.[16]
ZNF839 Expression in Various Regions of the Brain. The bright red areas represent high ZNF839 expression. The following gyri have high ZNF839 expression and high z-scores: short insular gyri, postcentral gyrus, fusiform gyrus, and parolfactory gyri. These images were annotated with the help of Allen Brain Atlas.
Protein
The human zinc finger protein 839, isoform 1, has 927 amino acids and holds a molecular weight of 87.5 kDa. The predicted isoelectric point of zinc finger protein 839 is 6.18.[17] This protein contains one zinc finger and one domain of unknown function (DUF) between amino acids 123-290. In isoforms 2-9, there is variability in the location of the DUF. The C2H2 zinc fingers in zinc finger protein 839 consist of cysteine and histidine residues that are conserved.[18]
Subcellular localization
Zinc finger protein 839 is predicted to be localized to the nucleus due to its role as a transcription factor.[19][20] The pat4 nuclear localization signal was conserved among all strict orthologs of the human zinc finger protein 839.
Zinc Finger Protein 839 Tertiary Structure. This structure was elucidated and annotated with the help of AlphaFold and iCN3D.
Tertiary structure
The human zinc finger protein 839 tertiary structure is predicted to have 5 alpha helices, one beta-sheet, and the rest of the protein consists of coils. Two of the alpha helices were found in two phosphorylation sites. The prevalence of negative and positive charges is mostly found in the coils.
Function
Interacting proteins
Zinc finger protein 839 was found to have the following interacting proteins: TP53 (Tumor Protein p53), YWHAE (14-3-3 Protein Epsilon), YWHAZ (Tyrosine-3-monooxygenase), APP (amyloid beta precursor protein).[21] It was found that YWHAE is involved in signal transduction pathways due to its binding of phosphoserine-containing proteins.[22] Zinc finger protein 839 has many phosphorylation sites on serine residues since phosphorylation is one of the significant post-translational modifications that was found in ZNF839. Thus, YWHAE is able to interact with zinc finger protein 839 since it has multiple phosphoserines after post-translational modification. In addition, it was found that when a C2H2-zinc finger and p53 DNA binding domain fusion transcription factor was created, it increased the transcription of gene downstream of p53 such as p21, whose function is to arrest cell cycle in response to DNA damage.[23] Thus, TP53 and zinc finger protein 839 may interact to transcribe genes necessary for DNA damage response or tumor suppression. Overall, it was observed that there is a pattern of zinc finger protein 839 interactions with tumor suppressor proteins and signal transduction regulators. Thus, zinc finger protein may significantly play a role in tumor suppression and regulation of cellular pathways such as cell division.
Clinical significance
A relationship has been found between colorectal cancer patient survival and human ZNF839 expression.[24] The appearance of rs11704 single nucleotide polymorphism (SNP) in the miRNA binding site of the 3’ UTR within ZNF839 mRNA resulted in loss of miRNA binding site and leads to up-regulation of the human ZNF839 gene.[6] The up-regulation of the ZNF839 gene results in decreased survival of colorectal cancer patients.[24]
Post-translational modifications
Zinc finger protein 839 has five phosphorylation sites and one sumoylation site.[25][26] The kinases involved in the phosphorylation of zinc finger protein 839 include: Protein Kinase C, Casein Kinase II, and Casein Kinase I. These kinases play a role in activating transcription of genes involved in DNA repair, cell growth, and cell proliferation.
Zinc finger protein 839 is found only in vertebrates, not invertebrates. Zinc finger protein 839 is found in the following vertebrates: mammals, birds, reptiles, amphibians, and fish. Zinc Finger Protein 839 was approximately found to have first appeared in fish 462 million years ago. The sequence length for Japanese quail, white-collared manakin, lanner falcon, atlantic canary, central bearded dragon, and aeolian wall lizard have been trimmed for an accurate sequence identity.
^Isalan M (2013-01-01), "Zinc Fingers", in Lennarz WJ, Lane MD (eds.), Encyclopedia of Biological Chemistry (Second Edition), Waltham: Academic Press, pp. 575–579, ISBN978-0-12-378631-9, retrieved 2023-12-10
