3.4.22.B74	evolution	the enzyme belongs to the SENP/ULP protease family	732884	
3.4.22.B74	malfunction	cells lacking SENP6 show defects in spindle assembly and metaphase chromosome congression. A subset of proteins becomes undetectable on inner kinetochores after SENP6 depletion, particularly the CENP-H/I/K complex	715706	
3.4.22.B74	malfunction	depletion of SENP6 results in accumulation of endogenous SUMO-2/3 and SUMO-1 conjugates, and in accumulation of SUMO and promyelocytic leukemia protein in an increased number of promyelocytic leukemia nuclear bodies. Although SENP6 depletion drastically increases the size of promyelocytic leukemia nuclear bodies, the organizational structure of the body is not affected	716169	
3.4.22.B74	additional information	active site loop1 insertion is the determinant for the SUMO2/3 activity and specificity of SENP6, role of the SENP6/7-loop1 insertion in chain dismantling	732884	
3.4.22.B74	physiological function	overexpression of SENP6 in RAW264.7 cells significantly decreases the LPS-induced release of proinflammatory proteins, TNF-alpha, IL-6 and IFN-gamma, while depletion of SENP6 in RAW264.7 cells significantly increases these proteins. In LPS-treated RAW264.7 cells, chloroquine dose-dependently decreases the levels of microRNA-669n, which bound to 3'-UTR of SENP6 mRNA to inhibit its translation. Overexpression of microR-669n decreases SENP6, resulting in increased production of TNF-alpha, IL-6 and IFN-gamma in RAW264.7 cells, while depletion of microR-669n increases SENP6	752453	
3.4.22.B74	physiological function	postnatal loss of SENP6 causes premature aging. osteochondroprogenitor-specific SENP6 knockout mice exhibit smaller skeletons, with elevated apoptosis and cell senescence in osteochondroprogenitors and chondrocytes. In Senp6-/- cells, the two most significantly elevated pathways are p53 signaling and senescence-associated secreted phenotypes, and Trp53 loss partially rescues the skeletal and cellular phenotypes caused by Senp6 loss. SENP6 interacts with, desumoylates, and stabilizes TRIM28, suppressing p53 activity	754848	
3.4.22.B74	physiological function	SENP6 is essential for inner kinetochore assembly. Balanced activities of SENP6 and RNF4 control vertebrate kinetochore assembly through SUMO-targeted destabilization of inner plate components	715706