E3 SUMO-protein ligase component of the SMC5-SMC6 complex, a complex involved in DNA double-strand break repair by homologous recombination (PubMed:16055714, PubMed:16810316). Is not be required for the stability of the complex (PubMed:16055714, PubMed:16810316). The complex may promote sister chromatid homologous recombination by recruiting the SMC1-SMC3 cohesin complex to double-strand breaks (PubMed:16055714, PubMed:16810316). The complex is required for telomere maintenance via recombination in ALT (alternative lengthening of telomeres) cell lines and mediates sumoylation of shelterin complex (telosome) components which is proposed to lead to shelterin complex disassembly in ALT-associated PML bodies (APBs) (PubMed:17589526). Acts as an E3 ligase mediating SUMO attachment to various proteins such as SMC6L1 and TSNAX, the shelterin complex subunits TERF1, TERF2, TINF2 and TERF2IP, RAD51AP1, and maybe the cohesin components RAD21 and STAG2 (PubMed:16055714, PubMed:16810316, PubMed:17589526, PubMed:31400850). Required for recruitment of telomeres to PML nuclear bodies (PubMed:17589526). SUMO protein-ligase activity is required for the prevention of DNA damage-induced apoptosis by facilitating DNA repair, and for formation of APBs in ALT cell lines (PubMed:17589526). Required for sister chromatid cohesion during prometaphase and mitotic progression (PubMed:19502785). Protein modification; protein sumoylation. Component of the SMC5-SMC6 complex which consists at least of SMC5, SMC6, NSMCE2, NSMCE1, NSMCE4A or EID3 and NSMCE3. Localizes to PML nuclear bodies in ALT cell lines. Sumoylated, possibly via autosumoylation. The disease is caused by variants affecting the gene represented in this entry. Belongs to the NSE2 family.