Wikipedia

ZNF839

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 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.[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]

ZNF839
Identifiers
AliasesZNF839, C14orf131, zinc finger protein 839
External IDsMGI: 1920055; HomoloGene: 49541; GeneCards: ZNF839; OMA:ZNF839 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

55778

72805

Ensembl

ENSG00000022976

ENSMUSG00000021271

UniProt

A8K0R7

n/a

RefSeq (mRNA)

NM_001267827
NM_001267828
NM_018335

NM_001199785
NM_028365

RefSeq (protein)

NP_001254756
NP_001254757
NP_060805

n/a

Location (UCSC)Chr 14: 102.32 – 102.34 MbChr 12: 110.82 – 110.84 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Gene

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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

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The mRNA isoform 1 encoded by the human ZNF839 gene is 2992 nucleotides long. There are 9 isoforms of the ZNF839 mRNA. [11]

Human ZNF839 Isoform Table
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

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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

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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

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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

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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

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Interacting proteins

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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

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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

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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 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

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Orthologs

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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 Orthologs
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 Japanese 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

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Zinc finger protein 839 was found to have no paralogs.

Evolution Rate

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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.

 
ZNF839 evolution rate graph

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000022976 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021271 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "ZNF839 zinc finger protein 839 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-06.
  6. ^ a b Yang YP, Ting WC, Chen LM, Lu TL, Bao BY (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. PMC 5278659. PMID 28138309.
  7. ^ Scanlan MJ, Gordan JD, Williamson B, Stockert E, Bander NH, Jongeneel V, et al. (November 1999). "Antigens recognized by autologous antibody in patients with renal-cell carcinoma". International Journal of Cancer. 83 (4): 456–464. doi:10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5. PMID 10508479. S2CID 21839750.
  8. ^ "Alliance of Genome Resources". www.alliancegenome.org. Retrieved 2023-12-06.
  9. ^ a b "UniProt". www.uniprot.org. Retrieved 2023-12-06.
  10. ^ a b "Homo sapiens zinc finger protein 839 (ZNF839), transcript variant 1, mRNA". ncbi.nlm.nih.gov. 2022-12-29. Retrieved 2023-12-16.
  11. ^ a b "ZNF839 zinc finger protein 839 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-07.
  12. ^ Fagerberg L, Hallström BM, Oksvold P, Kampf C, Djureinovic D, Odeberg J, et al. (February 2014). "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. PMC 3916642. PMID 24309898.
  13. ^ "GDS596 / 221709_s_at". www.ncbi.nlm.nih.gov. Retrieved 2023-12-07.
  14. ^ Ishizuka M, Ohtsuka E, Inoue A, Odaka M, Ohshima H, Tamura N, et al. (September 2016). "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. PMID 27385512.
  15. ^ "Microarray Gene Detail :: Allen Brain Atlas: Human Brain". human.brain-map.org. Retrieved 2023-12-15.
  16. ^ Bu S, Lv Y, Liu Y, Qiao S, Wang H (2021). "Zinc Finger Proteins in Neuro-Related Diseases Progression". Frontiers in Neuroscience. 15: 760567. doi:10.3389/fnins.2021.760567. PMC 8637543. PMID 34867169.
  17. ^ "Expasy - Compute pI/Mw tool". web.expasy.org. Retrieved 2023-12-10.
  18. ^ 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, ISBN 978-0-12-378631-9, retrieved 2023-12-10
  19. ^ "PSORT II Prediction". psort.hgc.jp. Retrieved 2023-12-10.
  20. ^ "ZNF839 protein expression summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2023-12-10.
  21. ^ "PSICQUIC View". www.ebi.ac.uk. Retrieved 2023-12-15.
  22. ^ "YWHAE", Wikipedia, 2023-08-18, retrieved 2023-12-13
  23. ^ Falke D, Fisher MH, Juliano RL (November 2004). "Selective transcription of p53 target genes by zinc finger-p53 DNA binding domain chimeras". Biochimica et Biophysica Acta. 1681 (1): 15–27. doi:10.1016/j.bbaexp.2004.09.011. PMID 15566940.
  24. ^ a b To KK, Tong CW, Wu M, Cho WC (July 2018). "MicroRNAs in the prognosis and therapy of colorectal cancer: From bench to bedside". World Journal of Gastroenterology. 24 (27): 2949–2973. doi:10.3748/wjg.v24.i27.2949. PMC 6054943. PMID 30038463.
  25. ^ "Frontpage". www.healthtech.dtu.dk. Retrieved 2023-12-15.
  26. ^ "GPS-SUMO: Prediction of SUMOylation Sites & SUMO-interaction Motifs". sumo.biocuckoo.cn. Retrieved 2023-12-15.
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