Reference on EC 2.3.1.B43 - protein-lysine desuccinylase (NAD+)
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REF. 
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Starai, V.J.; Celic, I.; Cole, R.N.; Boeke, J.D.; Escalante-Semerena, J.C.
Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of active lysine
Science
298
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2002
Salmonella enterica
Ogura, M.; Nakamura, Y.; Tanaka, D.; Zhuang, X.; Fujita, Y.; Obara, A.; Hamasaki, A.; Hosokawa, M.; Inagaki, N.
Overexpression of SIRT5 confirms its involvement in deacetylation and activation of carbamoyl phosphate synthetase 1
Biochem. Biophys. Res. Commun.
393
73-78
2010
Mus musculus (Q8K2C6)
Nakagawa, T.; Lomb, D.J.; Haigis, M.C.; Guarente, L.
SIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle
Cell
137
560-570
2009
Mus musculus (Q8K2C6)
Maurer, B.; Rumpf, T.; Scharfe, M.; Stolfa, D.A.; Schmitt, M.L.; He, W.; Verdin, E.; Sippl, W.; Jung, M.
Inhibitors of the NAD(+)-dependent protein desuccinylase and demalonylase Sirt5
ACS Med. Chem. Lett.
3
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2012
Homo sapiens (Q9NXA8)
Nakagawa, T.; Guarente, L.
Urea cycle regulation by mitochondrial sirtuin, SIRT5
Aging
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2009
Mus musculus (Q8K2C6)
Roessler, C.; Nowak, T.; Pannek, M.; Gertz, M.; Nguyen, G.T.; Scharfe, M.; Born, I.; Sippl, W.; Steegborn, C.; Schutkowski, M.
Chemical probing of the human sirtuin 5 active site reveals its substrate acyl specificity and peptide-based inhibitors
Angew. Chem. Int. Ed. Engl.
53
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2014
Homo sapiens (Q9NXA8), Homo sapiens
Lin, Z.F.; Xu, H.B.; Wang, J.Y.; Lin, Q.; Ruan, Z.; Liu, F.B.; Jin, W.; Huang, H.H.; Chen, X.
SIRT5 desuccinylates and activates SOD1 to eliminate ROS
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441
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2013
Homo sapiens (Q9NXA8), Homo sapiens
Suenkel, B.; Fischer, F.; Steegborn, C.
Inhibition of the human deacylase Sirtuin 5 by the indole GW5074
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Homo sapiens (Q9NXA8), Homo sapiens
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Lysine glutarylation is a protein posttranslational modification regulated by SIRT5
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2014
Homo sapiens (Q9NXA8)
Liu, B.; Che, W.; Zheng, C.; Liu, W.; Wen, J.; Fu, H.; Tang, K.; Zhang, J.; Xu, Y.
SIRT5: a safeguard against oxidative stress-induced apoptosis in cardiomyocytes
Cell. Physiol. Biochem.
32
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2013
Rattus norvegicus (Q68FX9)
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SIRT5 is under the control of PGC-1alpha and AMPK and is involved in regulation of mitochondrial energy metabolism
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2014
Mus musculus (Q8K2C6), Mus musculus
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Reversibly acetylated lysine residues play important roles in the enzymatic activity of Escherichia coli N-hydroxyarylamine O-acetyltransferase
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280
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2013
Escherichia coli, Escherichia coli AD494
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586
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2012
Mus musculus (Q8K2C6), Mus musculus
Matsushita, N.; Yonashiro, R.; Ogata, Y.; Sugiura, A.; Nagashima, S.; Fukuda, T.; Inatome, R.; Yanagi, S.
Distinct regulation of mitochondrial localization and stability of two human Sirt5 isoforms
Genes Cells
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2011
Homo sapiens (Q9NXA8), Homo sapiens
He, B.; Du, J.; Lin, H.
Thiosuccinyl peptides as Sirt5-specific inhibitors
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134
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Homo sapiens (Q9NXA8), Homo sapiens
Hu, L.I.; Chi, B.K.; Kuhn, M.L.; Filippova, E.V.; Walker-Peddakotla, A.J.; Bsell, K.; Becher, D.; Anderson, W.F.; Antelmann, H.; Wolfe, A.J.
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2013
Escherichia coli
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2002
Archaeoglobus fulgidus (O28597)
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Salmonella enterica
Zhou, Y.; Zhang, H.; He, B.; Du, J.; Lin, H.; Cerione, R.A.; Hao, Q.
The bicyclic intermediate structure provides insights into the desuccinylation mechanism of human sirtuin 5 (SIRT5)
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287
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2012
Homo sapiens (Q9NXA8), Homo sapiens
Feldman, J.L.; Baeza, J.; Denu, J.M.
Activation of the protein deacetylase SIRT6 by long-chain fatty acids and widespread deacylation by mammalian sirtuins
J. Biol. Chem.
288
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2013
Homo sapiens (Q9NXA8)
Baeza, J.; Dowell, J.A.; Smallegan, M.J.; Fan, J.; Amador-Noguez, D.; Khan, Z.; Denu, J.M.
Stoichiometry of site-specific lysine acetylation in an entire proteome
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289
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2014
Escherichia coli
Geng, Y.Q.; Li, T.T.; Liu, X.Y.; Li, Z.H.; Fu, Y.C.
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112
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2011
Rattus norvegicus (Q68FX9)
Madsen, A.S.; Olsen, C.A.
Substrates for efficient fluorometric screening employing the NAD-dependent sirtuin 5 lysine deacylase (KDAC) enzyme
J. Med. Chem.
55
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2012
Homo sapiens (Q9NXA8), Homo sapiens
Zhao, K.; Chai, X.; Marmorstein, R.
Structure and substrate binding properties of cobB, a Sir2 homolog protein deacetylase from Escherichia coli
J. Mol. Biol.
337
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2004
Escherichia coli (P75960), Escherichia coli
Schlicker, C.; Gertz, M.; Papatheodorou, P.; Kachholz, B.; Becker, C.F.; Steegborn, C.
Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5
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382
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2008
Homo sapiens (Q9NXA8), Homo sapiens
Szczepankiewicz, B.G.; Dai, H.; Koppetsch, K.J.; Qian, D.; Jiang, F.; Mao, C.; Perni, R.B.
Synthesis of carba-NAD and the structures of its ternary complexes with SIRT3 and SIRT5
J. Org. Chem.
77
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2012
Homo sapiens (Q9NXA8), Homo sapiens
AbouElfetouh, A.; Kuhn, M.L.; Hu, L.I.; Scholle, M.D.; Sorensen, D.J.; Sahu, A.K.; Becher, D.; Antelmann, H.; Mrksich, M.; Anderson, W.F.; Gibson, B.W.; Schilling, B.; Wolfe, A.J.
The E. coli sirtuin CobB shows no preference for enzymatic and nonenzymatic lysine acetylation substrate sites
Microbiologyopen
4
66-83
2015
Escherichia coli (P75960)
Peng, C.; Lu, Z.; Xie, Z.; Cheng, Z.; Chen, Y.; Tan, M.; Luo, H.; Zhang, Y.; He, W.; Yang, K.; Zwaans, B.M.; Tishkoff, D.; Ho, L.; Lombard, D.; He, T.C.; Dai, J.; Verdin, E.; Ye, Y.; Zhao, Y.
The first identification of lysine malonylation substrates and its regulatory enzyme
Mol. Cell. Proteomics
10
M111.012658
2011
Mus musculus (Q8K2C6)
Colak, G.; Xie, Z.; Zhu, A.Y.; Dai, L.; Lu, Z.; Zhang, Y.; Wan, X.; Chen, Y.; Cha, Y.H.; Lin, H.; Zhao, Y.; Tan, M.
Identification of lysine succinylation substrates and the succinylation regulatory enzyme CobB in Escherichia coli
Mol. Cell. Proteomics
12
3509-3520
2013
Escherichia coli
Park, J.; Chen, Y.; Tishkoff, D.X.; Peng, C.; Tan, M.; Dai, L.; Xie, Z.; Zhang, Y.; Zwaans, B.M.; Skinner, M.E.; Lombard, D.B.; Zhao, Y.
SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways
Mol. Cell.
50
919-930
2013
Mus musculus (Q8K2C6)
Li, R.; Gu, J.; Chen, Y.Y.; Xiao, C.L.; Wang, L.W.; Zhang, Z.P.; Bi, L.J.; Wei, H.P.; Wang, X.D.; Deng, J.Y.; Zhang, X.E.
CobB regulates Escherichia coli chemotaxis by deacetylating the response regulator CheY
Mol. Microbiol.
76
1162-1174
2010
Escherichia coli, Escherichia coli W3110 / ATCC 27325
Lima, B.P.; Antelmann, H.; Gronau, K.; Chi, B.K.; Becher, D.; Brinsmade, S.R.; Wolfe, A.J.
Involvement of protein acetylation in glucose-induced transcription of a stress-responsive promoter
Mol. Microbiol.
81
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2011
Escherichia coli
Lutz, M.I.; Milenkovic, I.; Regelsberger, G.; Kovacs, G.G.
Distinct patterns of sirtuin expression during progression of Alzheimer's disease
Neuromolecular Med.
16
405-414
2014
Homo sapiens (Q9NXA8)
Thao, S.; Chen, C.S.; Zhu, H.; Escalante-Semerena, J.C.
Nepsilon-lysine acetylation of a bacterial transcription factor inhibits its DNA-binding activity
PLoS One
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2010
Escherichia coli (P75960)
Fischer, F.; Gertz, M.; Suenkel, B.; Lakshminarasimhan, M.; Schutkowski, M.; Steegborn, C.
Sirt5 deacylation activities show differential sensitivities to nicotinamide inhibition
PLoS One
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Homo sapiens (Q9NXA8), Homo sapiens
Gertz, M.; Nguyen, G.T.; Fischer, F.; Suenkel, B.; Schlicker, C.; Frnzel, B.; Tomaschewski, J.; Aladini, F.; Becker, C.; Wolters, D.; Steegborn, C.
A molecular mechanism for direct sirtuin activation by resveratrol
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Homo sapiens (Q9NXA8), Homo sapiens
Ringel, A.E.; Roman, C.; Wolberger, C.
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Escherichia coli, Archaeoglobus fulgidus (O28597), Archaeoglobus fulgidus
Pacella-Ince, L.; Zander-Fox, D.L.; Lane, M.
Mitochondrial SIRT5 is present in follicular cells and is altered by reduced ovarian reserve and advanced maternal age
Reprod. Fertil. Dev.
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Homo sapiens (Q9NXA8)
Du, J.; Zhou, Y.; Su, X.; Yu, J.J.; Khan, S.; Jiang, H.; Kim, J.; Woo, J.; Kim, J.H.; Choi, B.H.; He, B.; Chen, W.; Zhang, S.; Cerione, R.A.; Auwerx, J.; Hao, Q.; Lin, H.
Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase
Science
334
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2011
Homo sapiens (Q9NXA8), Mus musculus (Q8K2C6)
Schuetz, A.; Min, J.; Antoshenko, T.; Wang, C.L.; Allali-Hassani, A.; Dong, A.; Loppnau, P.; Vedadi, M.; Bochkarev, A.; Sternglanz, R.; Plotnikov, A.N.
Structural basis of inhibition of the human NAD+-dependent deacetylase SIRT5 by suramin
Structure
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2007
Homo sapiens (Q9NXA8), Homo sapiens
Lu, W.; Zuo, Y.; Feng, Y.; Zhang, M.
SIRT5 facilitates cancer cell growth and drug resistance in non-small cell lung cancer
Tumour Biol.
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Homo sapiens (Q9NXA8), Homo sapiens
Wang, Y.; Zhu, Y.; Xing, S.; Ma, P.; Lin, D.
SIRT5 prevents cigarette smoke extract-induced apoptosis in lung epithelial cells via deacetylation of FOXO3
Cell Stress Chaperones
20
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2015
Homo sapiens
Zhou, L.; Wang, F.; Sun, R.; Chen, X.; Zhang, M.; Xu, Q.; Wang, Y.; Wang, S.; Xiong, Y.; Guan, K.L.; Yang, P.; Yu, H.; Ye, D.
SIRT5 promotes IDH2 desuccinylation and G6PD deglutarylation to enhance cellular antioxidant defense
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Mus musculus
Roessler, C.; Tueting, C.; Meleshin, M.; Steegborn, C.; Schutkowski, M.
A novel continuous assay for the deacylase sirtuin 5 and other deacetylases
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58
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Homo sapiens (Q9NXA8)
Nishida, Y.; Rardin, M.J.; Carrico, C.; He, W.; Sahu, A.K.; Gut, P.; Najjar, R.; Fitch, M.; Hellerstein, M.; Gibson, B.W.; Verdin, E.
SIRT5 regulates both cytosolic and mitochondrial protein malonylation with glycolysis as a major target
Mol. Cell
59
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2015
Mus musculus (Q8K2C6)
Yu, J.; Haldar, M.; Mallik, S.; Srivastava, D.K.
Role of the substrate specificity-defining residues of human SIRT5 in modulating the structural stability and inhibitory features of the enzyme
PLoS ONE
11
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2016
Homo sapiens (Q9NXA8), Homo sapiens
Rajabi, N.; Auth, M.; Troelsen, K.R.; Pannek, M.; Bhatt, D.P.; Fontenas, M.; Hirschey, M.D.; Steegborn, C.; Madsen, A.S.; Olsen, C.A.
Mechanism-based inhibitors of the human sirtuin 5 deacylase structure-activity relationship, biostructural, and kinetic insight
Angew. Chem. Int. Ed. Engl.
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Danio rerio (Q6DHI5), Danio rerio, Homo sapiens (Q9NXA8), Homo sapiens
Du, Y.; Hu, H.; Hua, C.; Du, K.; Wei, T.
Tissue distribution, subcellular localization, and enzymatic activity analysis of human SIRT5 isoforms
Biochem. Biophys. Res. Commun.
503
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2018
Homo sapiens (Q9NXA8), Homo sapiens
Hang, T.; Chen, W.; Wu, M.; Zhan, L.; Wang, C.; Jia, N.; Zhang, X.; Zang, J.
Structural insights into the molecular mechanism underlying Sirt5-catalyzed desuccinylation of histone peptides
Biochem. J.
476
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2019
Homo sapiens (Q9NXA8), Homo sapiens
Wang, F.; Wang, K.; Xu, W.; Zhao, S.; Ye, D.; Wang, Y.; Xu, Y.; Zhou, L.; Chu, Y.; Zhang, C.; Qin, X.; Yang, P.; Yu, H.
SIRT5 desuccinylates and activates pyruvate kinase M2 to block macrophage IL-1beta production and to prevent DSS-induced colitis in mice
Cell Rep.
19
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2017
Mus musculus (A0A1Y7VM56)
Liu, S.; Ji, S.; Yu, Z.J.; Wang, H.L.; Cheng, X.; Li, W.J.; Jing, L.; Yu, Y.; Chen, Q.; Yang, L.L.; Li, G.B.; Wu, Y.
Structure-based discovery of new selective small-molecule sirtuin 5 inhibitors
Chem. Biol. Drug Des.
91
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2018
Homo sapiens (Q9NXA8), Homo sapiens
Kumar, S.; Lombard, D.B.
Functions of the sirtuin deacylase SIRT5 in normal physiology and pathobiology
Crit. Rev. Biochem. Mol. Biol.
53
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2018
Mus musculus (A0A1Y7VM56), Homo sapiens (Q9NXA8)
Shuai, L.; Zhang, L.N.; Li, B.H.; Tang, C.L.; Wu, L.Y.; Li, J.; Li, J.Y.
SIRT5 regulates brown adipocyte differentiation and browning of subcutaneous white adipose tissue
Diabetes
68
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2019
Mus musculus (A0A1Y7VM56)
Du, Y.; Hu, H.; Qu, S.; Wang, J.; Hua, C.; Zhang, J.; Wei, P.; He, X.; Hao, J.; Liu, P.; Yang, F.; Li, T.; Wei, T.
SIRT5 deacylates metabolism-related proteins and attenuates hepatic steatosis in ob/ob mice
EBioMedicine
36
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2018
Mus musculus (A0A1Y7VM56), Mus musculus, Mus musculus C57BL/6 (A0A1Y7VM56)
Ma, Y.; Fei, X.
SIRT5 regulates pancreatic beta-cell proliferation and insulin secretion in type 2 diabetes
Exp. Therap. Med.
16
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2018
Homo sapiens (Q9NXA8), Homo sapiens
Qin, K.; Han, C.; Zhang, H.; Li, T.; Li, N.; Cao, X.
NAD+ dependent deacetylase Sirtuin 5 rescues the innate inflammatory response of endotoxin tolerant macrophages by promoting acetylation of p65
J. Autoimmun.
81
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2017
Mus musculus (Q8K2C6)
Zhang, Y.; Bharathi, S.S.; Rardin, M.J.; Lu, J.; Maringer, K.V.; Sims-Lucas, S.; Prochownik, E.V.; Gibson, B.W.; Goetzman, E.S.
Lysine desuccinylase SIRT5 binds to cardiolipin and regulates the electron transport chain
J. Biol. Chem.
292
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2017
Mus musculus (A0A1Y7VM56), Mus musculus, Homo sapiens (Q9NXA8), Homo sapiens
Hershberger, K.A.; Abraham, D.M.; Martin, A.S.; Mao, L.; Liu, J.; Gu, H.; Locasale, J.W.; Hirschey, M.D.
Sirtuin 5 is required for mouse survival in response to cardiac pressure overload
J. Biol. Chem.
292
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2017
Mus musculus (A0A1Y7VM56), Mus musculus
Yang, L.; He, Y.; Chen, Q.; Qian, S.; Wang, Z.
Design and synthesis of new 9-substituted norharmane derivatives as potential Sirt5 inhibitors
J. Heterocycl. Chem.
54
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2017
Homo sapiens (Q9NXA8)
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Kalbas, D.; Liebscher, S.; Nowak, T.; Meleshin, M.; Pannek, M.; Popp, C.; Alhalabi, Z.; Bordusa, F.; Sippl, W.; Steegborn, C.; Schutkowski, M.
Potent and selective inhibitors of human sirtuin 5
J. Med. Chem.
61
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2018
Danio rerio (Q6DHI5), Homo sapiens (Q9NXA8), Homo sapiens
Kumar, S.; Lombard, D.B.
Generation and purification of catalytically active recombinant sirtuin5 (SIRT5) protein
Methods Mol. Biol.
1436
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2016
Homo sapiens (Q9NXA8)
Greene, K.S.; Lukey, M.J.; Wang, X.; Blank, B.; Druso, J.E.; Lin, M.J.; Stalnecker, C.A.; Zhang, C.; Negron Abril, Y.; Erickson, J.W.; Wilson, K.F.; Lin, H.; Weiss, R.S.; Cerione, R.A.
SIRT5 stabilizes mitochondrial glutaminase and supports breast cancer tumorigenesis
Proc. Natl. Acad. Sci. USA
116
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2019
Homo sapiens (Q9NXA8), Homo sapiens
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