Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P62988 (Ubiquitin)
 4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ubiquitin-associated (UBA) domains are found in a large number of proteins with diverse functions involved in ubiquitination, DNA repair, and signaling pathways. Recent studies have shown that several UBA domain proteins interact with ubiquitin (Ub), specifically p62, the phosphotyrosine-independent ligand of the SH2 domain of p56(lck); HHR23A, a human nucleotide excision repair protein; and DDI1, another damage-inducible protein. NMR chemical shift mapping reveals that Ub binds specifically but weakly to a conserved hydrophobic epitope on HHR23A UBA(1) and UBA(2) and that the UBA domains bind on the hydrophobic patch on the surface of the five-stranded beta-sheet of Ub. Models of the UBA(1)-Ub and UBA(2)-Ub complexes obtained from de novo docking reveal different orientations of the UBA domains on the Ub surface compared with those obtained by homology modeling with the related CUE domains, which also bind Ub. Our results suggest that UBA domains may interact with Ub as well as other proteins in more than one way while utilizing the same binding surface.
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PMID:Specificity of the interaction between ubiquitin-associated domains and ubiquitin. 1470 25

Toxoplasma gondii is an obligate intracellular apicomplexan parasite that causes lethal diseases in immunocompromised patients. Ubiquitin-proteasome system (UPS) regulates many cellular processes by degrading ubiquitinylated proteins. The UBL-UBA shuttle protein family, which escorts the ubiquitinylated proteins to the proteasome for degradation, are crucial components of UPS. Here, we identified three UBL-UBA shuttle proteins (TGGT1_304680, DNA damage inducible protein 1, DDI1; TGGT1_295340, UV excision repair protein rad23 protein, RAD23; and TGGT1_223680, ubiquitin family protein, DSK2) localized in the cytoplasm and nucleus of T gondii. Deletion of shuttle proteins inhibited parasites growth and resulted in accumulation of ubiquitinylated proteins. Cell division of triple-gene knockout strain was asynchronous. In addition, we found that the retroviral aspartic protease activity of the nonclassical shuttle protein DDI1 was important for the virulence of Toxoplasma in mice. These results showed the critical roles of UBL-UBA shuttle proteins in regulating the degradation of ubiquitinylated proteins and cell division of T gondii.
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PMID:Toxoplasma gondii UBL-UBA shuttle proteins contribute to the degradation of ubiquitinylated proteins and are important for synchronous cell division and virulence. 3280 30