Table 2.
SOD1 lysine-modified sites. Summary of SOD1 lysine-modified sites described in this paper, including acetylation, succinylation, sumoylation, ubiquitination, and glycation.
| Species | Residue | Modification | Modifying Enzyme (if known); Potential Location of PTM | Significance | Reference |
|---|---|---|---|---|---|
| human | Lys70 | acetylation | SIRT1; nucleus, cytoplasm, mitochondrion | inactivates ROS scavenging activity, deacetylated by SIRT1, may help sensitize cancer cells to genotoxic agents | Lin, 2015 |
| human | Lys122 | succinylation | SIRT5; mitochondrion, cytoplasm, nucleus | inactivates ROS scavenging activity, desuccinylated by SIRT5 | Lin, 2013 |
| human | Lys122 | acetylation/succinylation | SIRT5 (desuccinylation); mitochondrion, cytoplasm, nucleus | inhibits SOD1's anti-respiratory activity, succinyl-mimetics cause decreased growth and less healthy mitochondria in HCT116 cells, does not affect ROS scavenging activity | Banks, 2017 |
| human | Lys122 | acetylation | acetylated SOD1 found in distinct regions of adult central nervous system | Kaliszewski, 2016 | |
| human | general | acetylation | treatment with aspirin increases SOD1 acetylation and decreases A4V SOD1 amyloidogenesis | Abdolvahabi, 2015 | |
| human | Lys9 | sumoylation | SUMO-1 modification observed but function not yet known | Niikura, 2014 | |
| human | Lys75 | sumoylation | SUMO-1 modification increases SOD1 stability and propensity to aggregate; sumoylation increases further after aggregation of SOD1 | Fei, 2006 | |
| SUMO-3 modification also increases SOD1 stability and propensity to aggregate | Niikura, 2014 | ||||
| yeast | Lys18, Lys69 | sumoylation | unknown | Zhou, 2004 | |
| human | Lys136 | ubiquitination | ubiquitination occurs after formation of the aggregates and may occur on additional lysines as well | Basso, 2006 | |
| human | unknown | ubiquitination | colocalizes with SOD1 aggregates in patients with fALS | Kato, 1997 | |
| human | unknown | ubiquitination | colocalizes with SOD1 aggregates in G85R and G93A SOD1 transgenic mice; Stieber et al. postulates this may be a result of the ubiquitin-proteasome pathway being unable to handle degradation of the aggregates | Bruijn, 1997; Stieber, 2000 | |
| human | unknown | ubiquitination | intact single neuronal cells demonstrated that G93A and G85R SOD1 had increased ubiquitination and colocalization with Hsp70; did not cause proteasomal dysfunction so chaperone depletion may be a cause of mutant SOD1 toxicity | Ganesan, 2008 | |
| human | Lys3, Lys9, Lys30, Lys36, Lys122, Lys128 | glycation | Lys122, Lys128 most critical for enzymatic deactivation | Fujii, 1996 | |
| human | unknown | glycation | does not promote amyloid formation in fALS but may cause cytotoxicity through another pathway | Sirangelo, 2016 |