SUHW4

SUHW4

SUHW4

Protein-coding gene in the species Homo sapiens


Zinc finger protein 280D, also known as Suppressor Of Hairy Wing Homolog 4, SUWH4, Zinc Finger Protein 634, ZNF634, or KIAA1584, is a protein that in humans is encoded by the ZNF280D gene located on chromosome 15q21.3.[4][5]

Quick Facts ZNF280D, Identifiers ...

Gene

There are a total of 24 possible exons in any variant of the ZNF280D gene.[6] ZNF280D is oriented on the minus strand of Chromosome 15 and spans 288.396 kb.[7] Surrounding genes at the same locus include TEX9, HMGB1P33, MNS1, LOC645877, and LOC145783.[8]

Chromosomal location of the ZNF280D gene in humans with surrounding local genes
Chromosome 15 Location

mRNA

At least 24 spliced variants have been identified.[9] There are 7 probable alternative promoters. The mRNAs appear to differ by truncation of the 5' end, truncation of the 3' end, presence or absence of 12 cassette exons, overlapping exons with different boundaries, splicing versus retention of 5 introns.[9] The longest splice form contains 4428 bp.[10]

Most abundant alternative splice forms of ZNF280D mRNA.

Protein

Composition and Domains

Multiple sequence alignment of orthologs for DUF4195 reveals low conservation.
Multiple sequence alignment of orthologs for five zinc finger domains reveals high conservation.

The ZNF280D protein is 979 amino acids in length.[11] The protein contains a domain of unknown function (DUF4195) spanning from amino acid 45 to amino acid 230.[11] DUF4195 (pfam13826) is a family that is found at the N-terminus of metazoan proteins that carry PHD-like zinc-finger domains; the function is unknown.[12] ZNF280D protein also contains five highly conserved Cys2His2-type zinc finger domains.[13] Zinc fingers have the ability to bind DNA, which supports the speculative role of ZNF280D as a transcription factor.[14] The protein has a weight of approximately 109.3 kdal.[15] Charge cluster analysis reveals a negative charge cluster near the N-terminus from amino acids 16-43.[15] Charge clusters are associated with functional domains of cellular transcription factors, providing further support for ZNF280D as a possible transcription factor.[16]

Interactions

ZNF280D has been experimentally determined to interact with CBX5 and CBX3 proteins.[17] These proteins both play a role in the formation of heterochromatin, which presents a possible functional role of ZNF280D as a transcriptional repressor.[18][19]

SNPs

There are a number of SNPs that have been observed in the human population.[20] The image below lists some of the most frequently occurring.

Frequently observed SNPs in human genome.

Regulation

mRNA Level

Human ZNF280D promoter region and predicted transcription factor binding sites.

A number of transcription factors are predicted to bind to the predicted promoter region.[21]

Protein Level

ZNF280D protein contains 66 serine, 17 threonine, and 6 tyrosine residues all of which are potential phosphorylation sites.[22]

Candidate phosphorylation sites in human ZNF280D protein.

The glycine residue at position 2 is a probable candidate for N-terminal acetylation.[23] There are seven probable sumoylation sites.[24]

Probable sumoylation sites in ZNF280D protein.

Expression

GEO Profile expression analysis of ZNF280D protein in human tissues.

ZNF280D is ubiquitously expressed at relatively low levels throughout almost all tissues in the human body.[25]

In one study, the expression of ZNF280D was compared between endothelial progenitor cells in cord blood and peripheral blood. The results show that expression was significantly higher in cord blood. This supports a possible involvement of ZNF280D in embryonic development or cell differentiation.[26]

Expression data for ZNF280D in endothelial progenitor cells from cord blood and adult peripheral blood.

Evolution

A number of orthologs and distant homologs have been identified for the human ZNF280D protein. There are also four paralogs to ZNF280D in the human genome.[27]

More information Protein Name, Species ...
More information Paralog Name, Accession Number ...

References

  1. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  2. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. "Genetic Testing Registry". NCBI. Retrieved 7 May 2014.
  4. "GeneCards". Retrieved 7 May 2014.
  5. "pfam13836: DUF4195". NCBI. Retrieved 7 May 2014.
  6. "Q6N043 (Z280D_HUMAN)". UniProt. Retrieved 7 May 2014.
  7. Klug A (October 1999). "Zinc finger peptides for the regulation of gene expression". Journal of Molecular Biology. 293 (2): 215–8. doi:10.1006/jmbi.1999.3007. PMID 10529348.
  8. Brendel, Voker. "SAPS Statistical Analysis of PS". SDSC Workbench. Retrieved 7 May 2014.[permanent dead link]
  9. Brendel V, Karlin S (August 1989). "Association of charge clusters with functional domains of cellular transcription factors". Proceedings of the National Academy of Sciences of the United States of America. 86 (15): 5698–702. Bibcode:1989PNAS...86.5698B. doi:10.1073/pnas.86.15.5698. PMC 297697. PMID 2569737.
  10. "STRING input ZNF280D (Homo sapiens)". STRING. Retrieved 10 May 2014.
  11. "CBX5 [Homo sapiens]". NCBI. Retrieved 10 May 2014.
  12. "CBX3 [Homo sapiens]". NCBI. Retrieved 10 May 2014.
  13. "Genomatix". Genomatix. Retrieved 7 May 2014.
  14. Blom N, Gammeltoft S, Brunak S (December 1999). "Sequence and structure-based prediction of eukaryotic protein phosphorylation sites". Journal of Molecular Biology. 294 (5): 1351–62. doi:10.1006/jmbi.1999.3310. PMID 10600390.
  15. Kiemer, Lars (2005). "NetAcet: Prediction of N-terminal acetylation sites". Bioinformatics. 21 (7). NetAcet: 1269–1270. doi:10.1093/bioinformatics/bti130. PMID 15539450. Retrieved 7 May 2014.
  16. "SUMOplot™ Analysis Program". Retrieved 7 May 2014.
  17. "GDS596 / 221213_s_at / ZNF280D". GEO Profile. NCBI. Retrieved 7 May 2014.
  18. "NCBI Basic Local Alignment Search Tool". NCBI. Retrieved 10 May 2014.
  19. "TimeTree". TimeTree. Retrieved 10 May 2014.

Further reading


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