Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.3.2.19 (ubiquitin-protein ligase)
 799 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several proteins with significant identity to ubiquitin have been characterized recently. In contrast to ubiquitin's main role in targeting proteins for degradation, a described function of one family of ubiquitin-related proteins, the Rub family, is to serve as a stable post-translational modification of a complex involved in the G1-to-S cell cycle transition. Rub proteins have been found in animals, plants, and fungi and consist of 76 residues with 52-63% identity to ubiquitin. In this study three different RUB proteins within the plant Arabidopsis are identified; two differ by only 1 amino acid, while the third is only 77.6% identical to the other two. Genes encoding all three are expressed in multiple organs. In addition, we report the crystal structure of higher plant RUB1 at 1.7-A resolution to help elucidate the functional differences between Rub and ubiquitin. RUB1 contains a single globular domain with a flexible COOH-terminal extension. The overall RUB1 structure is very similar to ubiquitin. The majority of the amino acid differences between RUB1 and ubiquitin map to the surface. These changes alter the electrostatic surface potential in two regions and likely confer specificity between ubiquitin and RUB1 and their ubiquitin-activating enzyme (E1) or E1-like activating enzymes.
 ...
PMID:The rub family of ubiquitin-like proteins. Crystal structure of Arabidopsis rub1 and expression of multiple rubs in Arabidopsis. 985 29

Selective protein degradation by the ubiquitin-proteosome pathway has recently emerged as a powerful regulatory mechanism in a wide variety of cellular processes. Ubiquitin conjugation requires the sequential activity of three enzymes or protein complexes called the ubiquitin-activating enzyme (E1), the ubiquitin-conjugating enzyme (E2), and the ubiquitin-protein ligase (E3). In most eukaryotes, there are a small number of similar E1 isoforms without apparent functional specificity. The specific selection of target proteins is accomplished by the E2 and E3 proteins. One of the best-characterized families of E3s are the SCF complexes. The SCF is composed of a cullin (Cdc53), SKP1, RBX1 and one member of a large family of proteins called F-box proteins. The function of the F-box protein is to interact with target proteins. In some cases, the stability of the F-box protein may regulate activity of the SCF complex. In addition, post-translational modification of the cullin subunit by the ubiquitin-like protein RUB/NEDD8 appears to regulate SCF function. In plants, the SCF has so far been implicated in floral development, circadian clock, and response to the plant growth regulators auxin and jasmonic acid.
 ...
PMID:F-box proteins and protein degradation: an emerging theme in cellular regulation. 1111 56

Many aspects of eukaryotic development depend on regulated protein degradation by the ubiquitin-proteasome pathway. This highly conserved pathway promotes covalent attachment of ubiquitin to protein substrates through the sequential action of three enzymes called a ubiquitin-activating enzyme (E1), a ubiquitin-conjugating enzyme (E2), and a ubiquitin-protein ligase (E3). Most ubiquitinated proteins are then targeted for degradation by the 26S proteasome. Recent studies have also shown that the ubiquitin-related protein RUB/Nedd8 and the proteasome-related COP9 signalosome complex cooperate with the ubiquitin-proteasome pathway to promote protein degradation. Most of these components are conserved in all three eukaryotic kingdoms. However, the known targets of the pathway in plants, and the developmental processes they regulate, are specific to the plant kingdom.
 ...
PMID:Plant development: regulation by protein degradation. 1216 44