SMC5
Domain
The flexible hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of SMC6, forming a V-shaped heterodimer.
Function
Core component of the SMC5-SMC6 complex, a complex involved in repair of DNA double-strand breaks by homologous recombination. The complex may promote sister chromatid homologous recombination by recruiting the SMC1-SMC3 cohesin complex to double-strand breaks. 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). Required for recruitment of telomeres to PML nuclear bodies. Required for sister chromatid cohesion during prometaphase and mitotic progression; the function seems to be independent of SMC6. SMC5-SMC6 complex may prevent transcription of episomal DNA, such as circular viral DNA genome (PubMed:26983541).
Involvement in disease
Atelis syndrome 2
ATELS2
A form of Atelis syndrome, an autosomal recessive neurodevelopmental disorder characterized by mild to severe developmental delay, learning difficulties, microcephaly, and growth restriction with short stature. Additional features include anemia, skin hyperpigmentation, ocular anomalies, congenital heart defects, and mild skeletal abnormalities. Death in childhood may occur. Patient cells show spontaneous chromosome breakage and chromosomal anomalies, hallmarked by segmented and dicentric chromosomes and mosaic variegated hyperploidy.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Sumoylated.
Ubiquitinated.
(Microbial infection) SMC5-SMC6 complex is degraded by the activity of Hepatitis B X protein.
Sequence Similarities
Belongs to the SMC family. SMC5 subfamily.
Tissue Specificity
Widely expressed (PubMed:11408570). Strongly expressed in testis (PubMed:11408570).
Cellular localization
- Nucleus
- Chromosome
- Nucleus
- PML body
- Chromosome
- Telomere
- Associates with chromatin (PubMed:25931565). Colocalizes with SMC6 on the X-Y chromosome pair within the sex vesicle during late pachytene/diplotene (By similarity). Localizes to PML nuclear bodies in ALT cell lines (PubMed:17589526). Accumulates with RAD18 and the SLF1-SLF2 complex at replication-coupled DNA interstrand repair and DNA double-strand breaks (DSBs) sites on chromatin in a ubiquitin-dependent manner (PubMed:25931565).
Alternative names
KIAA0594, SMC5L1, SMC5, Structural maintenance of chromosomes protein 5, SMC protein 5, SMC-5, hSMC5