Taxonomic distribution of proteins containing UBQ domains

The UBQ domain within your query sequence starts at position 258 and ends at position 328, and its E-value is 1.31e-8.

The FF domain: a novel motif that often accompanies WW domains.

Bedford MT, Leder P
Trends Biochem Sci. 1999; 24: 264-5

The PCI domain: a common theme in three multiprotein complexes.

Hofmann K, Bucher P
Trends Biochem Sci. 1998; 23: 204-5

Introduction: evolving roles for ubiquitin in cellular regulation.

Haas AL
FASEB J. 1997; 11: 1053-4

Pathways of ubiquitin conjugation.

Haas AL, Siepmann TJ
FASEB J. 1997; 11: 1257-68

The covalent attachment of the polypeptide ubiquitin to proteins marks them for degradation by the ubiquitin/26S proteasome-dependent degradation pathway. This pathway functions in regulating many fundamental processes required for cell viability. Phylogenetic analysis of ubiquitin sequences reveals greater variability among lower eukaryotes and defines essential residues, many of which are conserved among the three ubiquitin-like proteins known to undergo parallel ligation pathways. The hierarchical design of the ubiquitin conjugation mechanism provides great flexibility for the divergent evolution of new functions mediated by this posttranslational modification. Within this hierarchy, a single ubiquitin-activating enzyme provides charged intermediates to multiple targeting pathways defined by cognate ubiquitin carrier protein (E2)/ligase (E3) pairs. Sequence analysis of E2 isozymes shows that the E2 superfamily is composed of distinct function-specific families. The apparent lack of E2/E3 specificity suggested in the literature results from the presence of multiple isozymes within many E2 families and erroneous family assignments based on incomplete data sets. Other apparent inconsistencies are explained by interfamily sequence relationships among some E2 isoforms.

Roles of ubiquitin-mediated proteolysis in cell cycle control.

Hershko A
Curr Opin Cell Biol. 1997; 9: 788-99

Selective degradation of cyclins, inhibitors of cyclin-dependent kinases and anaphase inhibitors is responsible for several major cell cycle transitions. The degradation of these cell cycle regulators is controlled by the action of ubiquitin-protein-ligase complexes, which target the regulators for degradation by the 26S proteasome. Recent results indicate that two types of multisubunit ubiquitin ligase complexes, which are connected to the protein kinase regulatory network of the cell cycle in different ways, are responsible for the specific and programmed degradation of many cell cycle regulators.

SUMO-1: wrestling with a new ubiquitin-related modifier.

Saitoh H, Pu RT, Dasso M
Trends Biochem Sci. 1997; 22: 374-6

Ubiquitin-dependent protein degradation.

Hochstrasser M
Annu Rev Genet. 1996; 30: 405-39

A growing number of cellular regulatory mechanisms are being linked to protein modification by the polypeptide ubiquitin. These include key transitions in the cell cycle, class I antigen processing, signal transduction pathways, and receptor-mediated endocytosis. In most, but not all, of these examples, ubiquitination of a protein leads to its degradation by the 26S proteasome. Following attachment of ubiquitin to a substrate and binding of the ubiquitinated protein to the proteasome, the bound substrate must be unfolded (and eventually deubiquitinated) and translocated through a narrow set of channels that leads to the proteasome interior, where the polypeptide is cleaved into short peptides. Protein ubiquitination and deubiquitination are both mediated by large enzyme families, and the proteasome itself comprises a family of related but functionally distinct particles. This diversity underlies both the high substrate specificity of the ubiquitin system and the variety of regulatory mechanisms that it serves.

The UBA domain: a sequence motif present in multiple enzyme classes of the ubiquitination pathway.

Hofmann K, Bucher P
Trends Biochem Sci. 1996; 21: 172-3

Ubiquitin in signal transduction and cell transformation.

Isaksson A, Musti AM, Bohmann D
Biochim Biophys Acta. 1996; 1288: 219-219

Since the discovery of ubiquitin-dependent protein degradation almost two decades ago, great strides have been made towards a detailed understanding of the biochemistry of this process (reviewed in [1-3]). It was, however, only in recent years that the physiological role of the ubiquitin system in signal transduction and the regulation of several cell functions started to be appreciated and experimentally addressed. As with other principal mechanisms of signal transduction, such as phosphorylation or GTP hydrolysis, much of the information regarding the role of the ubiquitin system as a component of cell regulation and signaling cascades, was gained in studies of transformation and the control of cell growth. It seems, however, that ubiquitin-dependent proteolysis, and possibly other processes that are controlled by protein ubiquitination, play a role in many aspects of cellular function from the control of differentiation to intracellular trafficking [1,3,4]. Here we will review some of the results that implicate ubiquitin-dependent proteolysis in the control of cell growth and that indicate how perturbations of ubiquitin-dependent degradation of oncogene and tumor suppressor gene products may contribute to cell transformation and oncogenesis.

The Saccharomyces cerevisiae DNA repair gene RAD23 encodes a nuclear protein containing a ubiquitin-like domain required for biological function.

Watkins JF, Sung P, Prakash L, Prakash S
Mol Cell Biol. 1993; 13: 7757-65

In eukaryotes, the posttranslational conjugation of ubiquitin to various cellular proteins marks them for degradation. Interestingly, several proteins have been reported to contain ubiquitin-like (ub-like) domains that are in fact specified by the DNA coding sequences of the proteins. The biological role of the ub-like domain in these proteins is not known; however, it has been proposed that this domain functions as a degradation signal rendering the proteins unstable. Here, we report that the product of the Saccharomyces cerevisiae RAD23 gene, which is involved in excision repair of UV-damaged DNA, bears a ub-like domain at its amino terminus. This finding has presented an opportunity to define the functional significance of this domain. We show that deletion of the ub-like domain impairs the DNA repair function of RAD23 and that this domain can be functionally substituted by the authentic ubiquitin sequence. Surprisingly, RAD23 is highly stable, and the studies reported herein indicate that its ub-like domain does not mediate protein degradation. Thus, in RAD23 at least, the ub-like domain affects protein function in a nonproteolytic manner.

The yeast ubiquitin genes: a family of natural gene fusions.

Ozkaynak E, Finley D, Solomon MJ, Varshavsky A
EMBO J. 1987; 6: 1429-39

Ubiquitin is a 76-residue protein highly conserved among eukaryotes. Conjugation of ubiquitin to intracellular proteins mediates their selective degradation in vivo. We describe a family of four ubiquitin-coding loci in the yeast Saccharomyces cerevisiae. UB11, UB12 and UB13 encode hybrid proteins in which ubiquitin is fused to unrelated ('tail') amino acid sequences. The ubiquitin coding elements of UB11 and UB12 are interrupted at identical positions by non-homologous introns. UB11 and UB12 encode identical 52-residue tails, whereas UB13 encodes a different 76-residue tail. The tail amino acid sequences are highly conserved between yeast and mammals. Each tail contains a putative metal-binding, nucleic acid-binding domain of the form Cys-X2-4-Cys-X2-15-Cys-X2-4-Cys, suggesting that these proteins may function by binding to DNA. The fourth gene, UB14, encodes a polyubiquitin precursor protein containing five ubiquitin repeats in a head-to-tail, spacerless arrangement. All four ubiquitin genes are expressed in exponentially growing cells, while in stationary-phase cells the expression of UB11 and UB12 is repressed. The UB14 gene, which is strongly inducible by starvation, high temperatures and other stresses, contains in its upstream region strong homologies to the consensus 'heat shock box' nucleotide sequence. Elsewhere we show that the essential function of the UB14 gene is to provide ubiquitin to cells under stress.