NSMCE2

This gene encodes a member of a family of E3 small ubiquitin-related modifier (SUMO) ligases that mediates the attachment of a SUMO protein to proteins involved in nuclear transport, transcription, chromosome segregation and DNA repair. The encoded protein is part of the structural maintenance of chromosomes (SMC) 5/6 complex which plays a key role genome maintenance, facilitating chromosome segregation and suppressing mitotic recombination. A knockout of the orthologous mouse gene is lethal prior to embryonic day 10.5. Naturally occurring mutations in this gene, that abolish the SUMO ligase activity, are associated with primordial dwarfism and extreme insulin resistance.

NSE2/MMS21 HOMOLOG, SMC5-SMC6 COMPLEX SUMO LIGASE

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).

Cell cycleIEA:UniProtKB-KW
Cell divisionIEA:UniProtKB-KW
Cellular senescenceManual Assertion Based On ExperimentIMP:UniProtKB
Double-strand break repair via homologous recombinationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of maintenance of mitotic sister chromatid cohesionManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of mitotic metaphase/anaphase transitionManual Assertion Based On ExperimentIMP:UniProtKB
Protein sumoylationManual Assertion Based On ExperimentIBA:GO_Central
Regulation of telomere maintenance1 PublicationIC:ComplexPortal
Telomere maintenance via recombinationManual Assertion Based On ExperimentIMP:UniProtKB

Nucleus
Chromosome, telomere
Nucleus, PML body
Localizes to PML nuclear bodies in ALT cell lines.

Seckel syndrome 10 (SCKL10):
A form of Seckel syndrome, a rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and mental retardation.

Sumoylated, possibly via autosumoylation.