Sirtuin/Sir2 Phylogeny, Evolutionary Considerations and Structural Conservation

Overview

Journal Mol Cells

Publisher Elsevier

Specialties Cell Biology
Molecular Biology

Date 2009 Nov 26

PMID 19936627

Citations 95

Authors

Sebastian Greiss

Anton Gartner

Affiliations

Soon will be listed here.

Abstract

The sirtuins are a protein family named after the first identified member, S. cerevisiae Sir2p. Sirtuins are protein deacetylases whose activity is dependent on NAD(+) as a cosubstrate. They are structurally defined by two central domains that together form a highly conserved catalytic center, which catalyzes the transfer of an acetyl moiety from acetyllysine to NAD(+), yielding nicotinamide, the unique metabolite O-acetyl-ADP-ribose and deacetylated lysine. One or more sirtuins are present in virtually all species from bacteria to mammals. Here we describe a phylogenetic analysis of sirtuins. Based on their phylogenetic relationship, sirtuins can be grouped into over a dozen classes and subclasses. Humans, like most vertebrates, have seven sirtuins: SIRT1-SIRT7. These function in diverse cellular pathways, regulating transcriptional repression, aging, metabolism, DNA damage responses and apoptosis. We show that these seven sirtuins arose early during animal evolution. Conserved residues cluster around the catalytic center of known sirtuin family members.

Citing Articles

Fragment Screening Reveals Novel Scaffolds against Sirtuin-2-Related Protein 1 from .

Gomes R, D Poleto M, Verli H, Almeida V, Marana S, Bender A ACS Omega. 2025; 10(4):3808-3819.

PMID: 39926558 PMC: 11799985. DOI: 10.1021/acsomega.4c09231.

Molecular Sentinels: Unveiling the Role of Sirtuins in Prostate Cancer Progression.

Chouhan S, Muhammad N, Usmani D, Khan T, Kumar A Int J Mol Sci. 2025; 26(1.

PMID: 39796040 PMC: 11720558. DOI: 10.3390/ijms26010183.

The role of acetylation in obesity-induced cardiac metabolic alterations.

Ketema E, Lopaschuk G J Pharm Pharm Sci. 2024; 27:13080.

PMID: 39109269 PMC: 11300292. DOI: 10.3389/jpps.2024.13080.

The global regulation of c-di-GMP and cAMP in bacteria.

Liu C, Shi R, Jensen M, Zhu J, Liu J, Liu X mLife. 2024; 3(1):42-56.

PMID: 38827514 PMC: 11139211. DOI: 10.1002/mlf2.12104.

Mitochondrial sirtuins: Energy dynamics and cancer metabolism.

Lee H, Yoon H Mol Cells. 2024; 47(2):100029.

PMID: 38331199 PMC: 10960136. DOI: 10.1016/j.mocell.2024.100029.

References

Gardner M, Hall N, Fung E, White O, Berriman M, Hyman R . Genome sequence of the human malaria parasite Plasmodium falciparum. Nature. 2002; 419(6906):498-511. PMC: 3836256. DOI: 10.1038/nature01097. View

Fritze C, Verschueren K, Strich R, Easton Esposito R . Direct evidence for SIR2 modulation of chromatin structure in yeast rDNA. EMBO J. 1997; 16(21):6495-509. PMC: 1170255. DOI: 10.1093/emboj/16.21.6495. View

Zhao K, Chai X, Clements A, Marmorstein R . Structure and autoregulation of the yeast Hst2 homolog of Sir2. Nat Struct Biol. 2003; 10(10):864-71. DOI: 10.1038/nsb978. View

Rosenberg M, Parkhurst S . Drosophila Sir2 is required for heterochromatic silencing and by euchromatic Hairy/E(Spl) bHLH repressors in segmentation and sex determination. Cell. 2002; 109(4):447-58. DOI: 10.1016/s0092-8674(02)00732-8. View

Hallows W, Lee S, Denu J . Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases. Proc Natl Acad Sci U S A. 2006; 103(27):10230-10235. PMC: 1480596. DOI: 10.1073/pnas.0604392103. View

Liszt G, Ford E, Kurtev M, Guarente L . Mouse Sir2 homolog SIRT6 is a nuclear ADP-ribosyltransferase. J Biol Chem. 2005; 280(22):21313-20. DOI: 10.1074/jbc.M413296200. View

van der Horst A, Tertoolen L, de Vries-Smits L, Frye R, Medema R, Burgering B . FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1). J Biol Chem. 2004; 279(28):28873-9. DOI: 10.1074/jbc.M401138200. View

Solignac M, Zhang L, Mougel F, Li B, Vautrin D, Monnerot M . The genome of Apis mellifera: dialog between linkage mapping and sequence assembly. Genome Biol. 2007; 8(3):403. PMC: 1868943. DOI: 10.1186/gb-2007-8-3-403. View

Eichinger L, Pachebat J, Glockner G, Rajandream M, Sucgang R, Berriman M . The genome of the social amoeba Dictyostelium discoideum. Nature. 2005; 435(7038):43-57. PMC: 1352341. DOI: 10.1038/nature03481. View

10.

Wang C, Chen L, Hou X, Li Z, Kabra N, Ma Y . Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage. Nat Cell Biol. 2006; 8(9):1025-31. DOI: 10.1038/ncb1468. View

11.

Srivastava M, Begovic E, Chapman J, Putnam N, Hellsten U, Kawashima T . The Trichoplax genome and the nature of placozoans. Nature. 2008; 454(7207):955-60. DOI: 10.1038/nature07191. View

12.

Klar A, Fogel S, MacLeod K . MAR1-a Regulator of the HMa and HMalpha Loci in SACCHAROMYCES CEREVISIAE. Genetics. 1979; 93(1):37-50. PMC: 1217836. DOI: 10.1093/genetics/93.1.37. View

13.

Brunet A, Sweeney L, Sturgill J, Chua K, Greer P, Lin Y . Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science. 2004; 303(5666):2011-5. DOI: 10.1126/science.1094637. View

14.

Tanno M, Sakamoto J, Miura T, Shimamoto K, Horio Y . Nucleocytoplasmic shuttling of the NAD+-dependent histone deacetylase SIRT1. J Biol Chem. 2007; 282(9):6823-32. DOI: 10.1074/jbc.M609554200. View

15.

Oberdoerffer P, Michan S, McVay M, Mostoslavsky R, Vann J, Park S . SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging. Cell. 2008; 135(5):907-18. PMC: 2853975. DOI: 10.1016/j.cell.2008.10.025. View

16.

Smith J, Brachmann C, Celic I, Kenna M, Muhammad S, Starai V . A phylogenetically conserved NAD+-dependent protein deacetylase activity in the Sir2 protein family. Proc Natl Acad Sci U S A. 2000; 97(12):6658-63. PMC: 18692. DOI: 10.1073/pnas.97.12.6658. View

17.

Rogina B, Helfand S . Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc Natl Acad Sci U S A. 2004; 101(45):15998-6003. PMC: 528752. DOI: 10.1073/pnas.0404184101. View

18.

Pettersen E, Goddard T, Huang C, Couch G, Greenblatt D, Meng E . UCSF Chimera--a visualization system for exploratory research and analysis. J Comput Chem. 2004; 25(13):1605-12. DOI: 10.1002/jcc.20084. View

19.

Yeung F, Hoberg J, Ramsey C, Keller M, Jones D, Frye R . Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J. 2004; 23(12):2369-80. PMC: 423286. DOI: 10.1038/sj.emboj.7600244. View

20.

Min J, Landry J, Sternglanz R, Xu R . Crystal structure of a SIR2 homolog-NAD complex. Cell. 2001; 105(2):269-79. DOI: 10.1016/s0092-8674(01)00317-8. View