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ZNF839

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This is an old revision of this page, as edited by Biology AD (talk | contribs) at 20:58, 15 December 2023 (←Created page with '== ZNF839 == 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.<ref>{{Cite web |title=ZNF839 zinc finger protein 839 [Homo sapiens (human)] - Gene - NCBI |url=https://www.ncbi.nlm.nih.gov/gene/55778 |access-date=2023-12-06 |website=www.ncbi.nlm.nih.gov}}</ref> Zinc finger protein 839 is speculated to pay a role in hummoral immune response...'). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

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ZNF839

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.[1] Zinc finger protein 839 is speculated to pay a role in hummoral 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.[2] [3] 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.[4][5]

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.[6] The gene locus is 14q32.31 and it is found on the plus strand.[6] ZNF839 consists of 8 exons, it encodes for one zinc finger repeat, and 3 disordered regions.[5] 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 is 2992 nucleotides long. There are 9 isoforms of the ZNF839 mRNA. [7]

Isoform Number Accession Number mRNA Length (nt) Protein Length (AA) Molecular Weight (kDa)
1 NM_018335 2992 927 87.5
2 NM_001267827 2845 811 87.4
3 NM_001385065 2842 877 93.5
4 NM_001385069 3017 806 86.9
5 NM_001385070 2695 761 81.5
6 NM_001385071 2620 736 79.3
7 NM_001385072 2212 667 72.4
8 NM_001385073 2062 617 66.6
9 NM_001385076 2065 551 60.5

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.[7][8][9] 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.[10] 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.[11] The high expression of ZNF839 in the gyri of the cerebrum may be due to the regulatory involvement of zinc finger proteins in neurodevelopment.[12]

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.[13] 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.[14]

Subcellular Localization

Zinc finger protein 839 is predicted to be localized to the nucleus due to its role as a transcription factor.[15][16] 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. Also, the prevalence of negative and positive charges is mostly found in the coils.

Function

Interacting Proteins

Zinc finger protein 839 was 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).[17] It was found that YWHAE  is involved in signal transduction pathways due to its binding of phosphoserine-containing proteins.[18] 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.[19] 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

There has also been a relationship found between colorectal cancer patient survival and human ZNF839 expression.[20] 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.[2] The up-regulation of the ZNF839 gene results in decreased survival of colorectal cancer patients.[20]

Post-Translational Modifications

Zinc finger protein 839 has five phosphorylation sites and one sumoylation site.[21][22] 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 schematic illustration showing phosphorylation sites (phos), sumoylation sites (sumo), negative charge cluster (NCC), positive charge cluster (PCC), C2H2 zinc finger, conserved alpha-helix region, and nuclear localization signal (NLS).

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.

ZNF839 Genus Common Name Taxonomic Group Date of Divergence (MYA) Accession Number Sequence Length (aa) Sequence Similarity (%) Sequence Identity(%)
Mammal Homo sapiens Human Primates 0 NP_060805 927 100 100
Mus musculus Mouse Rodentia 87 NP_082641 921 61.5 49.8
Hipposideros armiger Great roundleaf bat Chiroptera 94 XP_019494952 916 60.9 53.2
Elephas maximus indicus Indian Elephant Proboscidea 99 XP_049755600 937 61.1 52.8
Choloepus didactylus Linneaus’s two-toed sloth Pilosa 99 XP_037687739 940 60.4 52.5
Aves Falco biarmicus Lanner Falcon Falconiformes 319 XP_056201354 1010 47.6 34.5
Serinus canaria Atlantic canary Passeriformes 319 XP_030095548 974 46.7 35
Manacus Candei White-collared manakin Passeriformes 319 XP_051625574 980 46.7 34.8
Coturnix japonica Japnese quail Galliformes 319 XP_015720921 931 44.3 33.2
Reptilia Podarcis raffonei Aeolian wall lizard Squamata 319 XP_053226315 776 37.8 26.8
Pogona vitticeps Central bearded dragon Squamata 319 XP_020649269 669 37.6 27.3
Zootoca vivpara Viviparous lizard Squamata 319 XP_034961572 777 35.9 26.8
Sceloporus undulatus Eastern Fence Lizard Squamata 319 XP_042302042 696 35.8 25.1
Amphibians Microcaecilia unicolor Tiny cayenne caecillian Gymnophiona 352 XP_030070400 1133 42.1 29.5
Geotrypetes seraphini Gaboon caecillian Gymnophiona 352 XP_033808581 1126 41.4 29.2
Bombina bombina European fire-bellied toad Anura 352 XP_053553408 937 38.8 27.6
Rana temporaria Common Frog Anura 352 XP_040188931 965 35.4 22.8
Fish Callorhinchus milii Australian ghostshark Chimaeriformes 462 XP_042194042 1247 35.3 24.6
Leucoraja erinacea Little skate Rajiformes 462 XP_055497145 1256 34.9 23.3
Chiloscyllium plagiosum Whitespotted bamboo shark Orectolobiformes 462 XP_043553384 1269 33.9 22.9
Rhincodon typus Whale shark Orectolobiformes 462 XP_020377475 1265 33.1 23.3

Paralogs

Zinc finger protein 839 was found to have no paralogs. This sandbox is in the article namespace. Either move this page into your userspace, or remove the {{User sandbox}} template.

  1. ^ "ZNF839 zinc finger protein 839 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-06.
  2. ^ a b Yang, Ying-Pi; Ting, Wen-Chien; Chen, Lu-Min; Lu, Te-Ling; Bao, Bo-Ying (2017-01-01). "Polymorphisms in MicroRNA Binding Sites Predict Colorectal Cancer Survival". International Journal of Medical Sciences. 14 (1): 53–57. doi:10.7150/ijms.17027. ISSN 1449-1907. PMC 5278659. PMID 28138309.{{cite journal}}: CS1 maint: PMC format (link)
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  7. ^ a b "ZNF839 zinc finger protein 839 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-07.
  8. ^ Fagerberg, Linn; Hallström, Björn M.; Oksvold, Per; Kampf, Caroline; Djureinovic, Dijana; Odeberg, Jacob; Habuka, Masato; Tahmasebpoor, Simin; Danielsson, Angelika; Edlund, Karolina; Asplund, Anna; Sjöstedt, Evelina; Lundberg, Emma; Szigyarto, Cristina Al-Khalili; Skogs, Marie (2014-02). "Analysis of the Human Tissue-specific Expression by Genome-wide Integration of Transcriptomics and Antibody-based Proteomics". Molecular & Cellular Proteomics. 13 (2): 397–406. doi:10.1074/mcp.m113.035600. ISSN 1535-9476. PMC 3916642. PMID 24309898. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
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  10. ^ Ishizuka, Masamichi; Ohtsuka, Eri; Inoue, Atsuto; Odaka, Mirei; Ohshima, Hirotaka; Tamura, Norihisa; Yoshida, Kaoru; Sako, Norihisa; Baba, Tadashi; Kashiwabara, Shin‐ichi; Okabe, Masaru; Noguchi, Junko; Hagiwara, Hiromi (2016-09). "Abnormal spermatogenesis and male infertility in testicular zinc finger protein Zfp318 ‐knockout mice". Development, Growth & Differentiation. 58 (7): 600–608. doi:10.1111/dgd.12301. ISSN 0012-1592. {{cite journal}}: Check date values in: |date= (help)
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