SUMOylation

Small Ubiquitin-like MOdifiers (SUMOs) are a family of 3 proteins (SUMO1,2,3) that are reversibly conjugated to lysine residues of target proteins via a glycine-lysine isopeptide bond (reviewed in Hay 2013, Hannoun et al. 2010, Gareau and Lima 2010, Wilkinson and Henley 2010, Wang and Dasso 2009). Proteomic methods have yielded estimates of hundreds of target proteins. Targets are mostly located in the nucleus and therefore SUMOylation disproportionately affects gene expression.<br>SUMOs are initially translated as proproteins possessing extra amino acid residues at the C-terminus which are removed by the SUMO processing endoproteases SENP1,2,5 (Hay 2007). Different SENPs have significantly different efficiencies with different SUMOs. The processing exposes a glycine residue at the C-terminus that is activated by ATP-dependent thiolation at cysteine-173 of UBA2 in a complex with SAE1, the E1 complex. The SUMO is transferred from E1 to cysteine-93 of a single E2 enzyme, UBC9 (UBE2I). UBC9 with or, in some cases, without an E3 ligase conjugates the glycine C-terminus of SUMO to an epsilon amino group of a lysine residue on the target protein. SUMO2 and SUMO3 may then be further polymerized, forming chains. SUMO1 is unable to form polymers.<br> Conjugated SUMO can act as a biinding site for proteins possessing SUMO interaction motifs (SIMs) and can also directly affect the formation of complexes between the target protein and other proteins.<br>Conjugated SUMOs are removed by cleavage of the isopeptide bond by processing enzymes SENP1,2,3,5. The processing enzymes SENP6 and SENP7 edit chains of SUMO2 and SUMO3.

小泛素样修饰因子（SUMOs）是一组由三种蛋白质（SUMO1、2、3）组成的家族，它们通过甘氨酸-赖氨酸异肽键可逆地结合到目标蛋白的赖氨酸残基上（参见 Hay 2013，Hannoun 等 2010，Gareau 和 Lima 2010，Wilkinson 和 Henley 2010，Wang 和 Dasso 2009 的综述）。蛋白质组学方法估计，目标蛋白的数量达数百种。这些目标蛋白主要定位于细胞核中，因此SUMO化对基因表达的影响尤为显著。SUMOs最初作为具有额外氨基酸残基的蛋白质前体在C端翻译，随后由SUMO加工内肽酶SENP1、2、5（Hay 2007）去除这些残基。不同的SENP对不同的SUMOs具有显著不同的加工效率。加工过程暴露出C端的甘氨酸残基，该残基在含有SAE1的E1复合物中，通过ATP依赖性的巯基化作用激活UBA2蛋白上的半胱氨酸-173。SUMO随后从E1转移到单个E2酶UBC9（UBE2I）的半胱氨酸-93。UBC9（在某些情况下，也可能不与E3连接酶结合）将SUMO的C端甘氨酸与目标蛋白赖氨酸残基的ε氨基结合。SUMO2和SUMO3随后可以进一步聚合成链。SUMO1无法形成聚合物。结合的SUMO可以作为具有SUMO相互作用基序（SIMs）的蛋白质的结合位点，并且也可以直接影响目标蛋白与其他蛋白之间的复合物形成。结合的SUMOs通过加工酶SENP1、2、3、5切割异肽键被移除。加工酶SENP6和SENP7编辑SUMO2和SUMO3的链。