Role of the ubiquitin-like modifier FAT10 in protein degradation and ...

Introduction
Figure 3: Two families of ubiquitin-like proteins. Ubiquitin-like modifiers (UbLs, red)
are conjugated to their target proteins in a manner analogous to that of ubiquitin.
Ubiquitin-domain proteins (UBDs) contain an integral ubiquitin-like domain (green),
but do not form conjugates. (Modified from Jentsch and Pyrowolakis, 2000).
which ultimately results in the formation of an isopeptide linkage between the
C-terminal glycine of the UbL and a lysine residue of the target protein. Many of
the enzymes involved in the conjugation of UbLs have recently been discovered,
and although the pathways appear to be for the most part distinct, there appears
to be a certain amount of enzyme sharing between different modifiers. ATG8 and
ATG12, the two UbLs involved in autophagosome formation, for example share a
single E1, ATG7, but each of them has their own E2. Conversely, two different
E1s specific for different UbLs can share the same E2; UBEL1, the E1 for ISG15,
and UBE1, the E1 for ubiquitin, both can both transfer their respective modifier
to the E2 UbcH8. Apart from FAT10, none of the other UbLs are directly involved
in the targeting of proteins for proteasomal degradation. Instead, through their
attachment, they are for example able to alter the function or subcellular local-
ization of their target protein (Welchman et al., 2005; Kerscher et al., 2006).
SUMO (Small ubiquitin-like modifier), which is perhaps the most well-studied
member of this group, exists in the form of three isoforms, SUMO-1, SUMO-
2 and SUMO-3, of which the latter two are virtually identical in sequence and
are functionally distinct from SUMO-1. Interestingly, SUMO-2/3 are the only
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