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A novel conserved family of Macro-like domains—putative new players in ADP-ribosylation signaling

Dudkiewicz, Malgorzata and Pawlowski, Krzysztof LU (2019) In PeerJ 2019(5).
Abstract

The presence of many completely uncharacterized proteins, even in well-studied organisms such as humans, seriously hampers a full understanding of the functioning of living cells. One such example is the human protein C12ORF4, which belongs to the DUF2362 family, present in many eukaryotic lineages and conserved in metazoans. The only functional information available on C12ORF4 (Chromosome 12 Open Reading Frame 4) is its involvement in mast cell degranulation and its being a genetic cause of autosomal intellectual disability. Bioinformatics analysis of the DUF2362 family provides strong evidence that it is a novel member of the Macro clan/superfamily. Sequence similarity analysis versus other representatives of the Macro superfamily of... (More)

The presence of many completely uncharacterized proteins, even in well-studied organisms such as humans, seriously hampers a full understanding of the functioning of living cells. One such example is the human protein C12ORF4, which belongs to the DUF2362 family, present in many eukaryotic lineages and conserved in metazoans. The only functional information available on C12ORF4 (Chromosome 12 Open Reading Frame 4) is its involvement in mast cell degranulation and its being a genetic cause of autosomal intellectual disability. Bioinformatics analysis of the DUF2362 family provides strong evidence that it is a novel member of the Macro clan/superfamily. Sequence similarity analysis versus other representatives of the Macro superfamily of ADP-ribose-binding proteins and mapping sequence conservation on predicted three-dimensional structure provides hypotheses regarding the molecular function for members of the DUF2362 family. For example, the available functional data suggest a possible role for C12ORF4 in ADP-ribosylation signaling in asthma and related inflammatory diseases. This novel family appears to be a likely novel ADP-ribosylation “reader” and “eraser,” a previously unnoticed putative new player in cell signaling by this emerging post-translational modification.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Bioinformatics, DUF2362, Intellectual disability, Macrodomain ADP-ribosilation, Novel enzyme families, Protein structure prediction, Uncharacterized proteins
in
PeerJ
volume
2019
issue
5
article number
e6863
publisher
PeerJ
external identifiers
  • pmid:31106069
  • scopus:85074231693
ISSN
2167-8359
DOI
10.7717/peerj.6863
language
English
LU publication?
yes
id
d805d09e-db2c-4e33-846a-f1fe8fb961c0
date added to LUP
2019-11-19 17:02:28
date last changed
2024-02-16 01:20:31
@article{d805d09e-db2c-4e33-846a-f1fe8fb961c0,
  abstract     = {{<p>The presence of many completely uncharacterized proteins, even in well-studied organisms such as humans, seriously hampers a full understanding of the functioning of living cells. One such example is the human protein C12ORF4, which belongs to the DUF2362 family, present in many eukaryotic lineages and conserved in metazoans. The only functional information available on C12ORF4 (Chromosome 12 Open Reading Frame 4) is its involvement in mast cell degranulation and its being a genetic cause of autosomal intellectual disability. Bioinformatics analysis of the DUF2362 family provides strong evidence that it is a novel member of the Macro clan/superfamily. Sequence similarity analysis versus other representatives of the Macro superfamily of ADP-ribose-binding proteins and mapping sequence conservation on predicted three-dimensional structure provides hypotheses regarding the molecular function for members of the DUF2362 family. For example, the available functional data suggest a possible role for C12ORF4 in ADP-ribosylation signaling in asthma and related inflammatory diseases. This novel family appears to be a likely novel ADP-ribosylation “reader” and “eraser,” a previously unnoticed putative new player in cell signaling by this emerging post-translational modification.</p>}},
  author       = {{Dudkiewicz, Malgorzata and Pawlowski, Krzysztof}},
  issn         = {{2167-8359}},
  keywords     = {{Bioinformatics; DUF2362; Intellectual disability; Macrodomain ADP-ribosilation; Novel enzyme families; Protein structure prediction; Uncharacterized proteins}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{5}},
  publisher    = {{PeerJ}},
  series       = {{PeerJ}},
  title        = {{A novel conserved family of Macro-like domains—putative new players in ADP-ribosylation signaling}},
  url          = {{http://dx.doi.org/10.7717/peerj.6863}},
  doi          = {{10.7717/peerj.6863}},
  volume       = {{2019}},
  year         = {{2019}},
}