3rd2
From Proteopedia
NIP45 SUMO-like Domain 2
Structural highlights
Function[NF2IP_HUMAN] In T-helper 2 (Th2) cells, regulates the magnitude of NFAT-driven transcription of a specific subset of cytokine genes, including IL3, IL4, IL5 and IL13, but not IL2. Recruits PRMT1 to the IL4 promoter; this leads to enhancement of histone H4 'Arg-3'-methylation and facilitates subsequent histone acetylation at the IL4 locus, thus promotes robust cytokine expression (By similarity). Down-regulates formation of poly-SUMO chains by UBE2I/UBC9 (By similarity). Publication Abstract from PubMedGlobal sumoylation, SUMO chain formation and genome stabilization are all outputs generated by a limited repertoire of enzymes. Mechanisms driving selectivity for each of these processes are largely uncharacterized. Here, through crystallographic analyses we show that the SUMO E2 Ubc9 forms a non-covalent complex with a SUMO-like domain of Rad60 (SLD2). Ubc9:SLD2 and Ubc9:SUMO non-covalent complexes are structurally analogous, suggesting that differential recruitment of Ubc9 by SUMO or Rad60 provides a novel means for such selectivity. Indeed, deconvoluting Ubc9 function by disrupting either the Ubc9:SLD2 or Ubc9:SUMO non-covalent complex reveals distinct roles in facilitating sumoylation. Ubc9:SLD2 acts in the Nse2 SUMO E3 ligase-dependent pathway for DNA repair, whereas Ubc9:SUMO instead promotes global sumoylation and chain formation, via the Pli1 E3 SUMO ligase. Moreover, this Pli1-dependent SUMO chain formation causes the genome instability phenotypes of SUMO-targeted ubiquitin ligase (STUbL) mutants. Overall, we determine that unexpectedly, Ubc9 non-covalent partner choice dictates the role of sumoylation in distinct cellular pathways. DNA Repair and Global Sumoylation are Regulated by Distinct Ubc9 Non-covalent Complexes.,Prudden J, Perry JJ, Nie M, Vashisht AA, Arvai AS, Hitomi C, Guenther G, Wohlschlegel JA, Tainer JA, Boddy MN Mol Cell Biol. 2011 Mar 28. PMID:21444718[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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