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E TOMVPSHV-( VNMVPSHV-S raMIPAHV-

IERVPYKV-P [JPSSIPHEV-■SSIPATV-tlPHCVDKNV-S rSAVRSSV-E ISKAPLST-SfpGEVNUKC-'EE1PRKV-; [■PCWPKSI-P

3FVHEAKLHO-. 3FVHEAK1HG-A ,ÏKN—A HANKD—A ÏVKDSG-

VAKZKG-Ad iIVKQRG~GA] ILALAHG-T IAKKAG-

228 SGPRFIHHAHMKK-228 SGYC§VNHAHMQN-KH 237 SGYRPILTAWBKK-LH

228 SGPRFIHHAHMKK-228 SGYC§VNHAHMQN-KH 237 SGYRPILTAWBKK-LH

Fig. 1. (A) Sequence alignment of a wide variety of Sir2 proteins from eukaryotic and prokaryotic sources. Alignments are courtesy of the CLUSTAL W server at the BCM search launcher (Baylor College of Medicine) and are shaded with Boxshade, using default parameters. Abbreviations are as follows: eukaryotes include SceS2, 5. cerevisiae Sir2; SceHl-4, S. cerevisiae Hstl-4; Klact, Kluyveromyces lactis Sir2; CalS2, Candida albicans Sir2; Cele3, Caenorhabiditis elegans Sir2; Dmela, Drosophila melanogaster; HsapA-F, human Sir2A-F; CalH2, Candida albicans Hst2; Lmajo, Leishmania major; Tbruc, Trypanosoma brucei. Prokaryotes and archaea include Ecoli, Escherichia coli; Styph, Salmonella typhimurium; Aacti, Actinobacillus actinomycetecomitans; Hpylo, Helicobacter pylori; Phori, Pyrococcus horikoshii; Aaeol, Aquifex aeolius; Afull and Aful2, Archaeoglolobus fulgidus Sir2-Afl,2; Mtube, Mycobacterium tuberculosis; SpoH4, Schizosaccharomyces pombe Hst4; Tmari, Thermotoga maritima, Scoel, Streptomyces coelicolor; Bsubt, Bacillus subtilis; Saure, Staphylococcus aureus. The human Sir2 proteins have also been referred to with an alternative nomenclature by R. A. Frye, Biochem. Biophys. Res. Commun. 273, 793 (2000). Sir2A = SIRT2; Sir2B = SIRT1; Sir2C = SIRT4; Sir2D = SIRT3;Sir2F = SIRT6. (B) Sequence alignment of a wide variety of Sir2 proteins from archaea and prokaryotes only.

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