Lys68

Site Information
NLNVTEEkYQEALAK SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 461133

In vivo Characterization
Methods used to characterize site in vivo:	immunoassay ( 11 ) , immunoprecipitation ( 1 , 2 , 4 , 5 , 6 , 9 , 10 , 11 ) , mass spectrometry ( 15 , 16 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ) , mass spectrometry (in vitro) ( 14 ) , modification-specific antibody ( 4 , 5 , 8 , 10 , 11 , 12 , 13 , 14 , 18 ) , mutation of modification site ( 1 , 2 , 4 , 6 , 9 , 10 , 12 , 14 , 18 ) , western blotting ( 1 , 2 , 4 , 5 , 6 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 18 )
Disease tissue studied:	breast cancer ( 1 , 4 , 6 , 11 ) , leukemia ( 9 , 22 , 23 , 24 ) , acute myelogenous leukemia ( 9 ) , chronic myelogenous leukemia ( 22 , 23 , 24 ) , liver cancer ( 27 , 28 ) , hepatocellular carcinoma ( 27 , 28 ) , lung cancer ( 15 ) , non-small cell lung adenocarcinoma ( 15 ) , ventricular tachycardia ( 19 , 20 , 21 ) , DKD ( 2 )
Relevant cell line - cell type - tissue:	'brain, midbrain' ( 10 ) , A549 (pulmonary) ( 15 , 26 ) , breast ( 11 ) , cardiac-heart ( 13 , 19 , 21 ) , E.coli (bacterial) ( 14 ) , HEK293T (epithelial) ( 14 , 18 ) , HeLa (cervical) ( 16 ) , HepG2 (hepatic) ( 27 , 28 ) , HK-2 (renal tubule cell) ( 2 ) , hUCB-MSCs ( 8 ) , Jurkat (T lymphocyte) ( 26 ) , K562 (erythroid) ( 22 , 23 , 24 ) , liver ( 25 ) , macrophage-bone marrow ( 12 ) , macrophage-peritoneum ( 9 ) , MCF-7 (breast cell) ( 1 , 4 , 6 , 11 ) , MDA-MB-231 (breast cell) ( 11 ) , MEF (fibroblast) ( 1 ) , MN9D ('neuron, mesencephalic') ( 10 ) , mononuclear-blood ( 5 ) , preosteoclast ( 12 ) , T47D (breast cell) ( 1 , 6 ) , THP1 (myeloid) ( 9 )

Upstream Regulation
Regulatory protein:	ER-alpha (human) ( 11 ) , SIRT1 (human) ( 18 ) , SIRT2 (human) ( 18 ) , SIRT4 (human) ( 18 ) , SIRT5 (human) ( 18 ) , SIRT6 (human) ( 18 ) , SIRT7 (human) ( 18 )
Treatments:	17-beta-estradiol ( 11 ) , adriamycin ( 1 ) , amino_acid_starvation ( 18 ) , antimycin_A ( 14 ) , cisplatin ( 1 ) , DMNQ ( 18 ) , ephrin_B2 ( 8 ) , faslodex ( 11 ) , glucose_starvation ( 18 ) , MnTMPyP ( 14 ) , nicotinamide ( 6 , 8 , 18 ) , siRNA ( 8 , 9 , 11 , 12 , 18 ) , trichostatin_A ( 6 , 18 )

Downstream Regulation
Effects of modification on SOD2:	activity, inhibited ( 8 ) , enzymatic activity, altered ( 14 ) , enzymatic activity, inhibited ( 2 , 5 , 9 , 10 , 11 , 12 , 18 ) , intracellular localization ( 1 ) , protein conformation ( 6 , 14 ) , protein stabilization ( 4 )
Effects of modification on biological processes:	carcinogenesis, induced ( 1 , 4 , 6 ) , cell cycle regulation ( 8 ) , cell differentiation, induced ( 12 ) , cell differentiation, inhibited ( 4 ) , cell growth, induced ( 1 , 6 ) , transcription, induced ( 4 , 12 )

Disease / Diagnostics Relevance
Relevant diseases:	breast cancer ( 4 , 11 ) , DKD ( 2 ) , Parkinson's disease ( 10 )

References
1	Gao Y, et al. (2021) MnSOD Lysine 68 acetylation leads to cisplatin and doxorubicin resistance due to aberrant mitochondrial metabolism. Int J Biol Sci 17, 1203-1216 33867840 Curated Info
2	Lv T, et al. (2021) General Control of Amino Acid Synthesis 5-Like 1-Mediated Acetylation of Manganese Superoxide Dismutase Regulates Oxidative Stress in Diabetic Kidney Disease. Oxid Med Cell Longev 2021, 6691226 33680286 Curated Info
3	Cao Y, et al. (2020) Quercetin promotes in vitro maturation of oocytes from humans and aged mice. Cell Death Dis 11, 965 33177495 Curated Info
4	He C, et al. (2019) SOD2 acetylation on lysine 68 promotes stem cell reprogramming in breast cancer. Proc Natl Acad Sci U S A 116, 23534-23541 31591207 Curated Info
5	He J, et al. (2019) Inhibition of Mitochondrial Oxidative Damage Improves Reendothelialization Capacity of Endothelial Progenitor Cells via SIRT3 (Sirtuin 3)-Enhanced SOD2 (Superoxide Dismutase 2) Deacetylation in Hypertension. Arterioscler Thromb Vasc Biol 39, 1682-1698 31189433 Curated Info
6	Zhu Y, et al. (2019) Lysine 68 acetylation directs MnSOD as a tetrameric detoxification complex versus a monomeric tumor promoter. Nat Commun 10, 2399 31160585 Curated Info
7	Minhas PS, et al. (2018) Macrophage de novo NAD⁺ synthesis specifies immune function in aging and inflammation. Nat Immunol 30478397 Curated Info
8	Jung YH, et al. (2017) EphB2 signaling-mediated Sirt3 expression reduces MSC senescence by maintaining mitochondrial ROS homeostasis. Free Radic Biol Med 110, 368-380 28687409 Curated Info
9	Traba J, et al. (2017) Prolonged fasting suppresses mitochondrial NLRP3 inflammasome assembly and activation via SIRT3-mediated activation of superoxide dismutase 2. J Biol Chem 292, 12153-12164 28584055 Curated Info
10	Shi H, et al. (2017) Sirt3 protects dopaminergic neurons from mitochondrial oxidative stress. Hum Mol Genet 26, 1915-1926 28369333 Curated Info
11	Lone MU, et al. (2017) Physical interaction of estrogen receptor with MnSOD: implication in mitochondrial O2(.-) upregulation and mTORC2 potentiation in estrogen-responsive breast cancer cells. Oncogene 36, 1829-1839 27721400 Curated Info
12	Kim H, et al. (2017) SOD2 and Sirt3 Control Osteoclastogenesis by Regulating Mitochondrial ROS. J Bone Miner Res 32, 397-406 27540894 Curated Info
13	Stram AR, et al. (2017) Progressive mitochondrial protein lysine acetylation and heart failure in a model of Friedreich's ataxia cardiomyopathy. PLoS One 12, e0178354 28542596 Curated Info
14	Lu J, et al. (2015) Novel mechanisms for superoxide-scavenging activity of human manganese superoxide dismutase determined by the K68 key acetylation site. Free Radic Biol Med 85, 114-26 25908444 Curated Info
15	Wu Q, et al. (2015) Suberoylanilide hydroxamic acid treatment reveals crosstalks among proteome, ubiquitylome and acetylome in non-small cell lung cancer A549 cell line. Sci Rep 5, 9520 25825284 Curated Info
16	Weinert BT, et al. (2013) Lysine succinylation is a frequently occurring modification in prokaryotes and eukaryotes and extensively overlaps with acetylation. Cell Rep 4, 842-51 23954790 Curated Info
17	Beli P, et al. (2012) Proteomic Investigations Reveal a Role for RNA Processing Factor THRAP3 in the DNA Damage Response. Mol Cell 46, 212-25 22424773 Curated Info
18	Chen Y, et al. (2011) Tumour suppressor SIRT3 deacetylates and activates manganese superoxide dismutase to scavenge ROS. EMBO Rep 12, 534-41 21566644 Curated Info
19	Li Y (2010) CST Curation Set: 10377; Year: 2010; Biosample/Treatment: tissue, heart/untreated; Disease: ventricular tachycardia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: acK Antibodies Used to Purify Peptides prior to LCMS: Acetylated-Lysine (Ac-K2-100) Rabbit mAb Cat#: 9814, PTMScan(R) Acetyl-Lys Motif (Ac-K) Immunoaffinity Beads Cat#: 1989 Curated Info
20	Li Y (2010) CST Curation Set: 10325; Year: 2010; Biosample/Treatment: tissue, heart/untreated; Disease: ventricular tachycardia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: acK Antibodies Used to Purify Peptides prior to LCMS: Acetylated-Lysine (Ac-K2-100) Rabbit mAb Cat#: 9814, PTMScan(R) Acetyl-Lys Motif (Ac-K) Immunoaffinity Beads Cat#: 1989 Curated Info
21	Li Y (2010) CST Curation Set: 10354; Year: 2010; Biosample/Treatment: tissue, heart/untreated; Disease: ventricular tachycardia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: acK Antibodies Used to Purify Peptides prior to LCMS: Acetylated-Lysine (Ac-K2-100) Rabbit mAb Cat#: 9814, PTMScan(R) Acetyl-Lys Motif (Ac-K) Immunoaffinity Beads Cat#: 1989 Curated Info
22	Moritz A (2010) CST Curation Set: 9922; Year: 2010; Biosample/Treatment: cell line, K-562/untreated; Disease: chronic myelogenous leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: acK Curated Info
23	Moritz A (2010) CST Curation Set: 9818; Year: 2010; Biosample/Treatment: cell line, K-562/untreated; Disease: chronic myelogenous leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: acK Curated Info
24	Moritz A (2010) CST Curation Set: 9817; Year: 2010; Biosample/Treatment: cell line, K-562/untreated; Disease: chronic myelogenous leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: acK Curated Info
25	Zhao S, et al. (2010) Regulation of cellular metabolism by protein lysine acetylation. Science 327, 1000-4 20167786 Curated Info
26	Choudhary C, et al. (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325, 834-40 19608861 Curated Info
27	Mitchell J (2005) CST Curation Set: 867; Year: 2005; Biosample/Treatment: cell line, HepG2/TSA; Disease: hepatocellular carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: acK Curated Info
28	Mitchell J (2005) CST Curation Set: 870; Year: 2005; Biosample/Treatment: cell line, HepG2/TSA; Disease: hepatocellular carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: acK Curated Info