Systematic identification of novel protein domain families associated with nuclear functions

European Molecular Biology Laboratory, 69114 Heidelberg, Germany.
Genome Research (Impact Factor: 14.63). 02/2002; 12(1):47-56.
Source: PubMed


A systematic computational analysis of protein sequences containing known nuclear domains led to the identification of 28 novel domain families. This represents a 26% increase in the starting set of 107 known nuclear domain families used for the analysis. Most of the novel domains are present in all major eukaryotic lineages, but 3 are species specific. For about 500 of the 1200 proteins that contain these new domains, nuclear localization could be inferred, and for 700, additional features could be predicted. For example, we identified a new domain, likely to have a role downstream of the unfolded protein response; a nematode-specific signalling domain; and a widespread domain, likely to be a noncatalytic homolog of ubiquitin-conjugating enzymes.

Download full-text


Available from: Tobias Doerks, Jun 03, 2014
  • Source
    • "In 2000, the first GEM, a model of Escherichia coli MG1655, was reported (Edwards and Palsson, 2000). A few years later, a yeast GEM was published (Doerks et al., 2002), thus initiating a new era for systems biology. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Genome-scale metabolic models (GEMs) have become a popular tool for systems biology, and they have been used in many fields such as industrial biotechnology and systems medicine. Since more and more studies are being conducted using GEMs, they have recently received considerable attention. In this review, we introduce the basic concept of GEMs and provide an overview of their applications in biotechnology, systems medicine, and some other fields. In addition, we describe the general principle of the applications and analyses built on GEMs. The purpose of this review is to introduce the application of GEMs in biological analysis and to promote its wider use by biologists.
    Full-text · Article · Dec 2015 · Frontiers in Physiology
  • Source
    • "The HOIP subunit of LUBAC possesses multiple domains, and although the roles of most of the domains have been clarified, the function of the PUB (PNGase/UBA or UBX) domain (amino acids 51– 144) in the N-terminal region of HOIP has remained unclear (Tokunaga 2013). The PUB domain is found in several proteins including PNGase and Ubxd1 and is a highly conserved domain in protozoans, plants, and animals (Suzuki et al. 2001;Doerks et al. 2002;Allen et al. 2006;Madsen et al. 2009). PUB domains have been shown to associate with the valosin-containing protein (VCP), an AAA-type ATPase complex (Allen et al. 2006;Zhao et al. 2007;Madsen et al. 2009). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Linear ubiquitin chains generated by the linear ubiquitin chain assembly complex (LUBAC) play an important role in NF-κB activation. However, the regulation of linear ubiquitin chain generation by LUBAC is not well characterized. Here, we identified two deubiquitinating enzymes (DUBs), ovarian tumor DUB with linear linkage specificity (OTULIN/Gumby/FAM105B) and cylindromatosis (CYLD) that can cleave linear polyubiquitin chains and interact with LUBAC via the N-terminal PNGase/UBA or UBX (PUB) domain of HOIP, a catalytic subunit of LUBAC. HOIP interacts with both CYLD and OTULIN even in unstimulated cells. The interaction of CYLD and OTULIN with HOIP synergistically suppresses LUBAC-mediated linear polyubiquitination and NF-κB activation. Moreover, introduction of a HOIP mutant unable to bind either deubiquitinase into HOIP-null cells augments the activation of NF-κB by TNF-α stimulation. Thus, the interactions between these two deubiquitinases and the LUBAC ubiquitin ligase are involved in controlling the extent of TNF-α-induced NF-κB activation in cells by fine-tuning the generation of linear ubiquitin chains by LUBAC. The interaction of HOIP with OTULIN is also involved in OTULIN suppressing the canonical Wnt signaling pathway activation by LUBAC. Our observations provide molecular insights into the roles of ligase-deubiquitinase interactions in regulating molecular events resulting from linear ubiquitin conjugation.
    Preview · Article · Jan 2014 · Genes to Cells
  • Source
    • "The RWD domain of Gcn2 is related to the ubiquitin-conjugating enzymes (UBC) domain, forming the clade of Ubiquitin-conjugating enzyme/RWD-like domain (InterPro IPR016135, [65]), predicted to have a function in protein–protein interaction [66]. RWD domains including the Gcn2 RWD domain, however, lack the catalytic cysteine residue critical for ubiquitin-conjugating activity [66]. The structure of the GCN2 RWD domain has been solved by NMR [63]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Figure optionsDownload full-size imageDownload high-quality image (266 K)Download as PowerPoint slide
    Full-text · Article · Jan 2014 · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Show more