Ubiquitin functional diversity

Haas, A. L., Bright, P. M., and Jackson, V. E. Functional diversity among putative E2 isozymes in the mechanism of ubiquitin-histone ligation./. Biol. Chem. 1988, 363, 13268-75. 

Varadan, R., Assealg, M., Haririnia, A., Raasi, S., Pickart, C., and Fushman, D. Solution conformation of Lys63-linked di-ubiquitin chain provides clues to functional diversity of polyubiquitin signaling, J Biol Chem, 2003, 8, 7055-63. 

Both WD- and Kelch-repeat P-propellers are modular in nature. The P-propeller module can be present alone or at the amino- or carboxy-terminus of proteins that contain other structural motifs. The most common accompanying structural motifr mediate dimerization or oligomerization, or association with cuUin-based ubiquitin E3 ligases (Table 2). In addition, examples have been found of proteins that contain two (or possibly more) P-propellers coimected by linkers. The variety of modular contexts of P-propellers reflects the functional diversity of the proteins that contain them. 

The mechanistically and functionally complex N-end rule pathway (Fig. 2) is but one of many distinct pathways of the Ub system. The vast functional range of this system stems from the enormous diversity of its physiological substrates. In other words, it is the constitutive or conditional degradation of many specific proteins (cyclins, transcription factors, components of signal transduction pathways, damaged proteins) by ubiquitin-dependent pathways that underlies the involvement of the Ub system in just about every biological circuit in a living cell (5, 6, 9). 

Harvey, K. F., and Kumar, S. (1999). Nedd4-like proteins an emerging family of ubiquitin-protein ligases implicated in diverse cellular functions. Trends Cell Biol 9,166-9. 

Sequence analysis showed that a diverse set of proteins with unrelated functions to TRAFs appear to contain the TRAF-G domain. These include meprins, a family of extracellular metalloproteases (Uren and Vaux, 1996), MUL, the product of the causative gene in Mulibrey Nanism syndrome, USP7 (HAUSP), an ubiquitin protease, and SPOP, a POZ (poxvirus and zinc finger) domain-containing protein (Zapata et al, 2001). Because of its similarities with meprins, TRAF-G domain was also dubbed meprin- and TRAF-homology (MATH) domain (Uren and Vaux, 1996). 

The ubiquitin-proteasome pathway is a finely tuned system, coordinating the function of multiple diverse components to enable the highly specified... 

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