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. Zinc finger protein 839 is speculated to play a role in humoral immune response to cancer as a renal carcinoma antigen (NY-REN-50). This is because NY-REN-50 was found to be over expressed in cancer patients, especially those with renal carcinoma. 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.
Gene
The human ZNF839 gene is 25,326 nucleotides long and it encodes transcript variant 1 which is the longest isoform. The gene locus is 14q32.31 and it is found on the plus strand. ZNF839 consists of 8 exons, it encodes for one zinc finger repeat, and 3 disordered regions. 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. +Human ZNF839 Isoform TableIsoform NumberAccession NumbermRNA Length (nt)Protein Length (AA)Molecular Weight (kDa)1NM_018335299292787.52NM_001267827284581187.43NM_001385065284287793.54NM_001385069301780686.95NM_001385070269576181.56NM_001385071262073679.37NM_001385072221266772.48NM_001385073206261766.69NM_001385076206555160.5
Expression 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. 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. 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. The high expression of ZNF839 in the gyri of the cerebrum may be due to the regulatory involvement of zinc finger proteins in neurodevelopment.
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. 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.
Subcellular localization Zinc finger protein 839 is predicted to be localized to the nucleus due to its role as a transcription factor. The pat4 nuclear localization signal was conserved among all strict orthologs of the human zinc finger protein 839.
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). It was found that YWHAE is involved in signal transduction pathways due to its binding of phosphoserine-containing proteins. 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. 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. 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. The up-regulation of the ZNF839 gene results in decreased survival of colorectal cancer patients.
Post-translational modifications Zinc finger protein 839 has five phosphorylation sites and one sumoylation site. 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.
Evolution
Orthologs 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. +Human ZNF839 OrthologsZNF839GenusCommon nameTaxonomic groupDate of Divergence (MYA)Accession numberSequence length (aa)Sequence similarity (%)Sequence identity(%)MammalHomo sapiensHumanPrimates0NP_060805927100100Mus musculusMouseRodentia87NP_08264192161.549.8Hipposideros armigerGreat roundleaf batChiroptera94XP_01949495291660.953.2Elephas maximus indicusIndian ElephantProboscidea99XP_04975560093761.152.8Choloepus didactylusLinnaeus's two-toed slothPilosa99XP_03768773994060.452.5AvesFalco biarmicusLanner FalconFalconiformes319XP_056201354101047.634.5Serinus canariaAtlantic canaryPasseriformes319XP_03009554897446.735Manacus CandeiWhite-collared manakinPasseriformes319XP_05162557498046.734.8Coturnix japonicaJapanese quailGalliformes319XP_01572092193144.333.2ReptiliaPodarcis raffoneiAeolian wall lizardSquamata319XP_05322631577637.826.8Pogona vitticepsCentral bearded dragonSquamata319XP_02064926966937.627.3Zootoca vivparaViviparous lizardSquamata319XP_03496157277735.926.8Sceloporus undulatusEastern Fence LizardSquamata319XP_04230204269635.825.1AmphibiansMicrocaecilia unicolorTiny cayenne caecillianGymnophiona352XP_030070400113342.129.5Geotrypetes seraphiniGaboon caecillianGymnophiona352XP_033808581112641.429.2Bombina bombinaEuropean fire-bellied toadAnura352XP_05355340893738.827.6Rana temporariaCommon FrogAnura352XP_04018893196535.422.8FishCallorhinchus miliiAustralian ghostsharkChimaeriformes462XP_042194042124735.324.6Leucoraja erinaceaLittle skateRajiformes462XP_055497145125634.923.3Chiloscyllium plagiosumWhitespotted bamboo sharkOrectolobiformes462XP_043553384126933.922.9Rhincodon typusWhale sharkOrectolobiformes462XP_020377475126533.123.3
Paralogs Zinc finger protein 839 was found to have no paralogs.
Evolution Rate In addition. the ZNF839 gene is evolving at a fast rate, due to its evolution rate being close to fibrinogen alpha chain's rate than cytochrome C.
References