ID SIR2_HUMAN Reviewed; 389 AA. AC Q8IXJ6; A8K3V1; B2RB45; O95889; Q924Y7; Q9P0G8; Q9UNT0; Q9Y6E9; U5TP13; DT 31-OCT-2003, integrated into UniProtKB/Swiss-Prot. DT 31-OCT-2003, sequence version 2. DT 27-MAR-2024, entry version 208. DE RecName: Full=NAD-dependent protein deacetylase sirtuin-2; DE EC=2.3.1.286 {ECO:0000255|PROSITE-ProRule:PRU00236, ECO:0000269|PubMed:11483616, ECO:0000269|PubMed:11812793, ECO:0000269|PubMed:16648462, ECO:0000269|PubMed:18722353, ECO:0000269|PubMed:24177535}; DE AltName: Full=NAD-dependent protein defatty-acylase sirtuin-2 {ECO:0000305}; DE EC=2.3.1.- {ECO:0000269|PubMed:25704306, ECO:0000269|PubMed:29239724, ECO:0000269|PubMed:32103017}; DE AltName: Full=Regulatory protein SIR2 homolog 2; DE AltName: Full=SIR2-like protein 2; GN Name=SIRT2; Synonyms=SIR2L, SIR2L2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND MUTAGENESIS RP OF HIS-187. RC TISSUE=Testis; RX PubMed=10381378; DOI=10.1006/bbrc.1999.0897; RA Frye R.A.; RT "Characterization of five human cDNAs with homology to the yeast SIR2 gene: RT Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP- RT ribosyltransferase activity."; RL Biochem. Biophys. Res. Commun. 260:273-279(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=10393250; DOI=10.1016/s0378-1119(99)00162-6; RA Afshar G., Murnane J.P.; RT "Characterization of a human gene with sequence homology to Saccharomyces RT cerevisiae SIR2."; RL Gene 234:161-168(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=12065666; DOI=10.1046/j.1471-4159.2002.00847.x; RA De Smet C., Nishimori H., Furnari F.B., Boegler O., Huang H.-J.S., RA Cavenee W.K.; RT "A novel seven transmembrane receptor induced during the early steps of RT astrocyte differentiation identified by differential expression."; RL J. Neurochem. 81:575-588(2002). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), ALTERNATIVE SPLICING (ISOFORMS 1 RP AND 2), FUNCTION IN DEACETYLATION (ISOFORMS 1 AND 2), CATALYTIC ACTIVITY, RP LACK OF DEACETYLATION (ISOFORM 5), INTERACTION WITH EP300 (ISOFORMS 1; 2 RP AND 5), AND SUBCELLULAR LOCATION (ISOFORMS 1; 2 AND 5). RX PubMed=24177535; DOI=10.1016/j.jmb.2013.10.027; RA Rack J.G., Vanlinden M.R., Lutter T., Aasland R., Ziegler M.; RT "Constitutive nuclear localization of an alternatively spliced sirtuin-2 RT isoform."; RL J. Mol. Biol. 426:1677-1691(2014). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RA Lennerz V., Fatho M., Gentilini C., Lifke A., Woelfel C., Woelfel T.; RT "Response of autologous T cells to a human melanoma is dominated by RT individual mutant antigens."; RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Adrenal gland; RX PubMed=10931946; DOI=10.1073/pnas.160270997; RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J., RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., RA Chen M.-D., Chen J.-L.; RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis RT and full-length cDNA cloning."; RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Brain, and Lung; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 22-389 (ISOFORM 4). RC TISSUE=Brain; RA Mei G., Yu W., Gibbs R.A.; RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases. RN [11] RP SUBCELLULAR LOCATION. RX PubMed=11226170; DOI=10.1093/emboj/20.1.197; RA Perrod S., Cockell M.M., Laroche T., Renauld H., Ducrest A.L., Bonnard C., RA Gasser S.M.; RT "A cytosolic NAD-dependent deacetylase, Hst2p, can modulate nucleolar and RT telomeric silencing in yeast."; RL EMBO J. 20:197-209(2001). RN [12] RP INHIBITION BY SIRTINOL; A3 AND M15, CATALYTIC ACTIVITY, AND ACTIVITY RP REGULATION. RX PubMed=11483616; DOI=10.1074/jbc.m106779200; RA Grozinger C.M., Chao E.D., Blackwell H.E., Moazed D., Schreiber S.L.; RT "Identification of a class of small molecule inhibitors of the sirtuin RT family of NAD-dependent deacetylases by phenotypic screening."; RL J. Biol. Chem. 276:38837-38843(2001). RN [13] RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-187. RX PubMed=11812793; DOI=10.1074/jbc.m111830200; RA Borra M.T., O'Neill F.J., Jackson M.D., Marshall B.L., Verdin E., RA Foltz K.R., Denu J.M.; RT "Conserved enzymatic production and biological effect of O-acetyl-ADP- RT ribose by silent information regulator 2-like NAD+-dependent RT deacetylases."; RL J. Biol. Chem. 277:12632-12641(2002). RN [14] RP FUNCTION IN DEACETYLATION OF TUBULIN, SUBCELLULAR LOCATION, INTERACTION RP WITH HDAC6, AND MUTAGENESIS OF ASN-168 AND HIS-187. RX PubMed=12620231; DOI=10.1016/s1097-2765(03)00038-8; RA North B.J., Marshall B.L., Borra M.T., Denu J.M., Verdin E.; RT "The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin RT deacetylase."; RL Mol. Cell 11:437-444(2003). RN [15] RP FUNCTION AS REGULATOR OF CELL CYCLE PROGRESSION, SUBCELLULAR LOCATION, RP DEVELOPMENTAL STAGE, PHOSPHORYLATION, UBIQUITINATION, AND MUTAGENESIS OF RP HIS-187. RX PubMed=12697818; DOI=10.1128/mcb.23.9.3173-3185.2003; RA Dryden S.C., Nahhas F.A., Nowak J.E., Goustin A.-S., Tainsky M.A.; RT "Role for human SIRT2 NAD-dependent deacetylase activity in control of RT mitotic exit in the cell cycle."; RL Mol. Cell. Biol. 23:3173-3185(2003). RN [16] RP TISSUE SPECIFICITY. RX PubMed=12963026; DOI=10.1016/j.bbrc.2003.08.029; RA Hiratsuka M., Inoue T., Toda T., Kimura N., Shirayoshi Y., Kamitani H., RA Watanabe T., Ohama E., Tahimic C.G.T., Kurimasa A., Oshimura M.; RT "Proteomics-based identification of differentially expressed genes in human RT gliomas: down-regulation of SIRT2 gene."; RL Biochem. Biophys. Res. Commun. 309:558-566(2003). RN [17] RP INTERACTION WITH HOXA10. RX PubMed=15213244; DOI=10.1093/jb/mvh084; RA Bae N.S., Swanson M.J., Vassilev A., Howard B.H.; RT "Human histone deacetylase SIRT2 interacts with the homeobox transcription RT factor HOXA10."; RL J. Biochem. 135:695-700(2004). RN [18] RP SUBCELLULAR LOCATION. RX PubMed=16079181; DOI=10.1091/mbc.e05-01-0033; RA Michishita E., Park J.Y., Burneskis J.M., Barrett J.C., Horikawa I.; RT "Evolutionarily conserved and nonconserved cellular localizations and RT functions of human SIRT proteins."; RL Mol. Biol. Cell 16:4623-4635(2005). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [20] RP FUNCTION IN DEACETYLATION OF HISTONE H4 AND H3, CATALYTIC ACTIVITY, RP SUBUNIT, AND SUBCELLULAR LOCATION. RX PubMed=16648462; DOI=10.1101/gad.1412706; RA Vaquero A., Scher M.B., Lee D.H., Sutton A., Cheng H.L., Alt F.W., RA Serrano L., Sternglanz R., Reinberg D.; RT "SirT2 is a histone deacetylase with preference for histone H4 Lys 16 RT during mitosis."; RL Genes Dev. 20:1256-1261(2006). RN [21] RP FUNCTION AS REGULATOR IN CELL CYCLE PROGRESSION, PHOSPHORYLATION AT SER-368 RP BY CDK1, DEPHOSPHORYLATION AT SER-368 BY CDC14A AND CDC14B, SUBCELLULAR RP LOCATION, AND MUTAGENESIS OF HIS-187 AND SER-368. RX PubMed=17488717; DOI=10.1074/jbc.m702990200; RA North B.J., Verdin E.; RT "Mitotic regulation of SIRT2 by cyclin-dependent kinase 1-dependent RT phosphorylation."; RL J. Biol. Chem. 282:19546-19555(2007). RN [22] RP INTERACTION WITH HDAC6 (ISOFORMS 1 AND 2), PHOSPHORYLATION AT SER-372 AND RP SER-368, UBIQUITINATION, AND MUTAGENESIS OF SER-53; SER-98; SER-100; RP HIS-187; SER-279; THR-280; SER-311; TYR-315; SER-364; SER-368 AND SER-372. RX PubMed=17516032; DOI=10.1007/s11010-007-9478-6; RA Nahhas F., Dryden S.C., Abrams J., Tainsky M.A.; RT "Mutations in SIRT2 deacetylase which regulate enzymatic activity but not RT its interaction with HDAC6 and tubulin."; RL Mol. Cell. Biochem. 303:221-230(2007). RN [23] RP FUNCTION IN AXONAL DEGENERATION. RX PubMed=17574768; DOI=10.1016/j.neuroscience.2007.04.059; RA Suzuki K., Koike T.; RT "Mammalian Sir2-related protein (SIRT) 2-mediated modulation of resistance RT to axonal degeneration in slow Wallerian degeneration mice: a crucial role RT of tubulin deacetylation."; RL Neuroscience 147:599-612(2007). RN [24] RP FUNCTION AS REGULATOR OF MITOTIC CELL CYCLE CHECKPOINT, SUBCELLULAR RP LOCATION, NUCLEOCYTOPLASMIC SHUTTLING, INDUCTION, TISSUE SPECIFICITY, AND RP MUTAGENESIS OF GLN-167; ASN-168 AND HIS-187. RX PubMed=16909107; DOI=10.1038/sj.onc.1209857; RA Inoue T., Hiratsuka M., Osaki M., Yamada H., Kishimoto I., Yamaguchi S., RA Nakano S., Katoh M., Ito H., Oshimura M.; RT "SIRT2, a tubulin deacetylase, acts to block the entry to chromosome RT condensation in response to mitotic stress."; RL Oncogene 26:945-957(2007). RN [25] RP FUNCTION AS REGULATOR IN CELL CYCLE PROGRESSION, INTERACTION WITH AURKA, RP SUBCELLULAR LOCATION, NUCLEOCYTOPLASMIC SHUTTLING, AND MUTAGENESIS OF RP HIS-187. RX PubMed=17726514; DOI=10.1371/journal.pone.0000784; RA North B.J., Verdin E.; RT "Interphase nucleo-cytoplasmic shuttling and localization of SIRT2 during RT mitosis."; RL PLoS ONE 2:E784-E784(2007). RN [26] RP FUNCTION IN DEACETYLATION OF TP53, FUNCTION IN REGULATION OF TP53, AND RP INTERACTION WITH YWHAB AND YWHAG. RX PubMed=18249187; DOI=10.1016/j.bbrc.2008.01.114; RA Jin Y.H., Kim Y.J., Kim D.W., Baek K.H., Kang B.Y., Yeo C.Y., Lee K.Y.; RT "Sirt2 interacts with 14-3-3 beta/gamma and down-regulates the activity of RT p53."; RL Biochem. Biophys. Res. Commun. 368:690-695(2008). RN [27] RP INTERACTION WITH EP300, ACETYLATION BY EP300, ACTIVITY REGULATION, AND RP CATALYTIC ACTIVITY. RX PubMed=18722353; DOI=10.1016/j.bbrc.2008.08.042; RA Han Y., Jin Y.H., Kim Y.J., Kang B.Y., Choi H.J., Kim D.W., Yeo C.Y., RA Lee K.Y.; RT "Acetylation of Sirt2 by p300 attenuates its deacetylase activity."; RL Biochem. Biophys. Res. Commun. 375:576-580(2008). RN [28] RP FUNCTION IN STRESS RESPONSE, AND INDUCTION BY STRESS. RX PubMed=18640115; DOI=10.1016/j.febslet.2008.07.016; RA Lynn E.G., McLeod C.J., Gordon J.P., Bao J., Sack M.N.; RT "SIRT2 is a negative regulator of anoxia-reoxygenation tolerance via RT regulation of 14-3-3 zeta and BAD in H9c2 cells."; RL FEBS Lett. 582:2857-2862(2008). RN [29] RP FUNCTION IN DEACETYLATION OF ALPHA-TUBULIN AND HISTONE, FUNCTION IN RP REGULATION OF CELL MOTILITY, INTERACTION WITH CDK5R1; CDK5 AND CYCLIN RP E-CDK2 COMPLEX, PHOSPHORYLATION AT SER-368 BY CDK2 AND CDK5, AND RP MUTAGENESIS OF SER-368. RX PubMed=18332217; DOI=10.1083/jcb.200707126; RA Pandithage R., Lilischkis R., Harting K., Wolf A., Jedamzik B., RA Luscher-Firzlaff J., Vervoorts J., Lasonder E., Kremmer E., Knoll B., RA Luscher B.; RT "The regulation of SIRT2 function by cyclin-dependent kinases affects cell RT motility."; RL J. Cell Biol. 180:915-929(2008). RN [30] RP FUNCTION IN DEACETYLATION OF EP300 AND ALPHA-TUBULIN, FUNCTION IN RP REGULATION OF EP300, AND SUBCELLULAR LOCATION. RX PubMed=18995842; DOI=10.1016/j.molcel.2008.09.018; RA Black J.C., Mosley A., Kitada T., Washburn M., Carey M.; RT "The SIRT2 deacetylase regulates autoacetylation of p300."; RL Mol. Cell 32:449-455(2008). RN [31] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [32] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [33] RP FUNCTION AS REGULATOR OF MITOTIC CELL CYCLE CHECKPOINT. RX PubMed=19282667; DOI=10.4161/cc.8.8.8245; RA Inoue T., Nakayama Y., Yamada H., Li Y.C., Yamaguchi S., Osaki M., RA Kurimasa A., Hiratsuka M., Katoh M., Oshimura M.; RT "SIRT2 downregulation confers resistance to microtubule inhibitors by RT prolonging chronic mitotic arrest."; RL Cell Cycle 8:1279-1291(2009). RN [34] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [35] RP FUNCTION IN DEACETYLATION OF HISTONE H3. RX PubMed=20587414; DOI=10.1074/jbc.m110.149393; RA Vempati R.K., Jayani R.S., Notani D., Sengupta A., Galande S., Haldar D.; RT "p300-mediated acetylation of histone H3 lysine 56 functions in DNA damage RT response in mammals."; RL J. Biol. Chem. 285:28553-28564(2010). RN [36] RP FUNCTION IN DEACETYLATION OF RELA, FUNCTION IN REGULATION OF RELA ACTIVITY, RP INTERACTION WITH RELA, AND SUBCELLULAR LOCATION. RX PubMed=21081649; DOI=10.1242/jcs.073783; RA Rothgiesser K.M., Erener S., Waibel S., Luscher B., Hottiger M.O.; RT "SIRT2 regulates NF-kappaB dependent gene expression through deacetylation RT of p65 Lys310."; RL J. Cell Sci. 123:4251-4258(2010). RN [37] RP FUNCTION IN DEACETYLATION OF FOXO1, FUNCTION IN AUTOPHAGY, AND INTERACTION RP WITH FOXO1. RX PubMed=20543840; DOI=10.1038/ncb2069; RA Zhao Y., Yang J., Liao W., Liu X., Zhang H., Wang S., Wang D., Feng J., RA Yu L., Zhu W.G.; RT "Cytosolic FoxO1 is essential for the induction of autophagy and tumour RT suppressor activity."; RL Nat. Cell Biol. 12:665-675(2010). RN [38] RP FUNCTION IN DEACETYLATION OF CDC20 AND FZR1, FUNCTION AS A TUMOR RP SUPPRESSOR, TISSUE SPECIFICITY, AND MUTAGENESIS OF HIS-187. RX PubMed=22014574; DOI=10.1016/j.ccr.2011.09.004; RA Kim H.S., Vassilopoulos A., Wang R.H., Lahusen T., Xiao Z., Xu X., Li C., RA Veenstra T.D., Li B., Yu H., Ji J., Wang X.W., Park S.H., Cha Y.I., RA Gius D., Deng C.X.; RT "SIRT2 maintains genome integrity and suppresses tumorigenesis through RT regulating APC/C activity."; RL Cancer Cell 20:487-499(2011). RN [39] RP TISSUE SPECIFICITY. RX PubMed=21791548; DOI=10.1093/hmg/ddr326; RA Maxwell M.M., Tomkinson E.M., Nobles J., Wizeman J.W., Amore A.M., RA Quinti L., Chopra V., Hersch S.M., Kazantsev A.G.; RT "The Sirtuin 2 microtubule deacetylase is an abundant neuronal protein that RT accumulates in the aging CNS."; RL Hum. Mol. Genet. 20:3986-3996(2011). RN [40] RP FUNCTION IN DEACETYLATION OF PCK1, POSSIBLE FUNCTION IN REGULATION OF BLOOD RP GLUCOSE HOMEOSTASIS, AND INDUCTION BY GLUCOSE. RX PubMed=21726808; DOI=10.1016/j.molcel.2011.04.028; RA Jiang W., Wang S., Xiao M., Lin Y., Zhou L., Lei Q., Xiong Y., Guan K.L., RA Zhao S.; RT "Acetylation regulates gluconeogenesis by promoting PEPCK1 degradation via RT recruiting the UBR5 ubiquitin ligase."; RL Mol. Cell 43:33-44(2011). RN [41] RP FUNCTION IN DEACETYLATION OF PARD3, AND INTERACTION WITH PARD3. RX PubMed=21949390; DOI=10.1073/pnas.1104969108; RA Beirowski B., Gustin J., Armour S.M., Yamamoto H., Viader A., North B.J., RA Michan S., Baloh R.H., Golden J.P., Schmidt R.E., Sinclair D.A., Auwerx J., RA Milbrandt J.; RT "Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through RT polarity protein Par-3/atypical protein kinase C (aPKC) signaling."; RL Proc. Natl. Acad. Sci. U.S.A. 108:E952-961(2011). RN [42] RP FUNCTION IN DEACETYLATION OF EIF5A. RX PubMed=22771473; DOI=10.1016/j.febslet.2012.06.042; RA Ishfaq M., Maeta K., Maeda S., Natsume T., Ito A., Yoshida M.; RT "Acetylation regulates subcellular localization of eukaryotic translation RT initiation factor 5A (eIF5A)."; RL FEBS Lett. 586:3236-3241(2012). RN [43] RP FUNCTION IN AUTOPHAGY, AND SUBCELLULAR LOCATION. RX PubMed=22819792; DOI=10.1016/j.neuint.2012.07.010; RA Gal J., Bang Y., Choi H.J.; RT "SIRT2 interferes with autophagy-mediated degradation of protein aggregates RT in neuronal cells under proteasome inhibition."; RL Neurochem. Int. 61:992-1000(2012). RN [44] RP REVIEW, AND FUNCTION AS A TUMOR SUPPRESSOR. RX PubMed=22943040; RA Park S.H., Zhu Y., Ozden O., Kim H.S., Jiang H., Deng C.X., Gius D., RA Vassilopoulos A.; RT "SIRT2 is a tumor suppressor that connects aging, acetylome, cell cycle RT signaling, and carcinogenesis."; RL Transl. Cancer Res. 1:15-21(2012). RN [45] RP INTERACTION WITH MAPK1/ERK2 AND MAPK3/ERK1. RX PubMed=23806683; DOI=10.1016/j.bbrc.2013.06.053; RA Choi Y.H., Kim H., Lee S.H., Jin Y.H., Lee K.Y.; RT "ERK1/2 regulates SIRT2 deacetylase activity."; RL Biochem. Biophys. Res. Commun. 437:245-249(2013). RN [46] RP FUNCTION IN DEACETYLATION OF HISTONE H4K16 AND KMT5A, FUNCTION IN RP REGULATION OF KMT5A ACTIVITY; H4K20 METHYLATION; CELL CYCLE PROGRESSION AND RP GENOMIC STABILITY, INTERACTION WITH KMT5A, SUBCELLULAR LOCATION, AND MASS RP SPECTROMETRY. RX PubMed=23468428; DOI=10.1101/gad.211342.112; RA Serrano L., Martinez-Redondo P., Marazuela-Duque A., Vazquez B.N., RA Dooley S.J., Voigt P., Beck D.B., Kane-Goldsmith N., Tong Q., Rabanal R.M., RA Fondevila D., Munoz P., Kruger M., Tischfield J.A., Vaquero A.; RT "The tumor suppressor SirT2 regulates cell cycle progression and genome RT stability by modulating the mitotic deposition of H4K20 methylation."; RL Genes Dev. 27:639-653(2013). RN [47] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-368, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [48] RP FUNCTION. RX PubMed=23932781; DOI=10.1016/j.molcel.2013.07.002; RA Lin R., Tao R., Gao X., Li T., Zhou X., Guan K.L., Xiong Y., Lei Q.Y.; RT "Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and RT tumor growth."; RL Mol. Cell 51:506-518(2013). RN [49] RP FUNCTION IN DEACETYLATION OF HISTONE H3K18, FUNCTION IN LISTERIA INFECTION, RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASN-168. RX PubMed=23908241; DOI=10.1126/science.1238858; RA Eskandarian H.A., Impens F., Nahori M.A., Soubigou G., Coppee J.Y., RA Cossart P., Hamon M.A.; RT "A role for SIRT2-dependent histone H3K18 deacetylation in bacterial RT infection."; RL Science 341:1238858-1238858(2013). RN [50] RP FUNCTION IN HISTONE H4 DEACETYLATION, FUNCTION IN REGULATION OF VEGFA RP EXPRESSION AND ANGIOGENESIS, CATALYTIC ACTIVITY, AND INTERACTION WITH RP SARS1. RX PubMed=24940000; DOI=10.7554/elife.02349; RA Shi Y., Xu X., Zhang Q., Fu G., Mo Z., Wang G.S., Kishi S., Yang X.L.; RT "tRNA synthetase counteracts c-Myc to develop functional vasculature."; RL Elife 3:E02349-E02349(2014). RN [51] RP FUNCTION IN DEACETYLATION OF G6PD, FUNCTION IN REGULATION OF G6PD ACTIVITY, RP INTERACTION WITH G6PD, AND MUTAGENESIS OF ASN-168. RX PubMed=24769394; DOI=10.1002/embj.201387224; RA Wang Y.P., Zhou L.S., Zhao Y.Z., Wang S.W., Chen L.L., Liu L.X., Ling Z.Q., RA Hu F.J., Sun Y.P., Zhang J.Y., Yang C., Yang Y., Xiong Y., Guan K.L., RA Ye D.; RT "Regulation of G6PD acetylation by KAT9/SIRT2 modulates NADPH homeostasis RT and cell survival during oxidative stress."; RL EMBO J. 33:1304-1320(2014). RN [52] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23; SER-25 AND SER-27, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [53] RP FUNCTION IN DEACETYLATION OF HIF1A, FUNCTION IN REGULATION OF HIF1A RP STABILITY, INTERACTION WITH HIF1A, MUTAGENESIS OF HIS-187, SUBCELLULAR RP LOCATION, AND MASS SPECTROMETRY. RX PubMed=24681946; DOI=10.1038/onc.2014.76; RA Seo K.S., Park J.H., Heo J.Y., Jing K., Han J., Min K.N., Kim C., Koh G.Y., RA Lim K., Kang G.Y., Uee Lee J., Yim Y.H., Shong M., Kwak T.H., Kweon G.R.; RT "SIRT2 regulates tumour hypoxia response by promoting HIF-1alpha RT hydroxylation."; RL Oncogene 34:1354-1362(2015). RN [54] RP INTERACTION WITH BEX4, AND MUTAGENESIS OF HIS-187. RX PubMed=27512957; DOI=10.1038/cddis.2016.240; RA Lee J.K., Lee J., Go H., Lee C.G., Kim S., Kim H.S., Cho H., Choi K.S., RA Ha G.H., Lee C.W.; RT "Oncogenic microtubule hyperacetylation through BEX4-mediated sirtuin 2 RT inhibition."; RL Cell Death Dis. 7:E2336-E2336(2016). RN [55] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-187. RX PubMed=29239724; DOI=10.7554/elife.32436; RA Jing H., Zhang X., Wisner S.A., Chen X., Spiegelman N.A., Linder M.E., RA Lin H.; RT "SIRT2 and lysine fatty acylation regulate the transforming activity of K- RT Ras4a."; RL Elife 6:0-0(2017). RN [56] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=32103017; DOI=10.1038/s41467-020-14893-x; RA Kosciuk T., Price I.R., Zhang X., Zhu C., Johnson K.N., Zhang S., RA Halaby S.L., Komaniecki G.P., Yang M., DeHart C.J., Thomas P.M., RA Kelleher N.L., Fromme J.C., Lin H.; RT "NMT1 and NMT2 are lysine myristoyltransferases regulating the ARF6 GTPase RT cycle."; RL Nat. Commun. 11:1067-1067(2020). RN [57] RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 34-356 IN COMPLEX WITH ZINC, AND RP MUTAGENESIS OF ARG-97; GLN-167; ASN-168; ASP-170 AND HIS-187. RX PubMed=11427894; DOI=10.1038/89668; RA Finnin M.S., Donigian J.R., Pavletich N.P.; RT "Structure of the histone deacetylase SIRT2."; RL Nat. Struct. Biol. 8:621-625(2001). RN [58] RP X-RAY CRYSTALLOGRAPHY (1.63 ANGSTROMS) OF 34-356 IN COMPLEX WITH NAD ANALOG RP AND ZINC. RX PubMed=23454361; DOI=10.1016/j.jsb.2013.02.012; RA Moniot S., Schutkowski M., Steegborn C.; RT "Crystal structure analysis of human Sirt2 and its ADP-ribose complex."; RL J. Struct. Biol. 182:136-143(2013). RN [59] {ECO:0007744|PDB:4L3O} RP X-RAY CRYSTALLOGRAPHY (2.52 ANGSTROMS) OF 55-356 IN COMPLEX WITH PEPTIDE RP INHIBITOR AND ZINC, ACTIVITY REGULATION, CATALYTIC ACTIVITY, AND RP MUTAGENESIS OF GLU-116; GLU-120; PHE-244; GLN-265; SER-271 AND ASP-294. RX PubMed=24389023; DOI=10.1016/j.str.2013.12.001; RA Yamagata K., Goto Y., Nishimasu H., Morimoto J., Ishitani R., Dohmae N., RA Takeda N., Nagai R., Komuro I., Suga H., Nureki O.; RT "Structural basis for potent inhibition of SIRT2 deacetylase by a RT macrocyclic peptide inducing dynamic structural change."; RL Structure 22:345-352(2014). RN [60] {ECO:0007744|PDB:4RMG, ECO:0007744|PDB:4RMH, ECO:0007744|PDB:4RMI, ECO:0007744|PDB:4RMJ} RP X-RAY CRYSTALLOGRAPHY (1.42 ANGSTROMS) OF 56-356 IN COMPLEX WITH NAD AND RP ZINC, CATALYTIC ACTIVITY, AND COFACTOR. RX PubMed=25672491; DOI=10.1038/ncomms7263; RA Rumpf T., Schiedel M., Karaman B., Roessler C., North B.J., Lehotzky A., RA Olah J., Ladwein K.I., Schmidtkunz K., Gajer M., Pannek M., Steegborn C., RA Sinclair D.A., Gerhardt S., Ovadi J., Schutkowski M., Sippl W., Einsle O., RA Jung M.; RT "Selective Sirt2 inhibition by ligand-induced rearrangement of the active RT site."; RL Nat. Commun. 6:6263-6263(2015). RN [61] {ECO:0007744|PDB:4R8M} RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 38-356 IN COMPLEX WITH ZINC, RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=25704306; DOI=10.1038/srep08529; RA Teng Y.B., Jing H., Aramsangtienchai P., He B., Khan S., Hu J., Lin H., RA Hao Q.; RT "Efficient demyristoylase activity of SIRT2 revealed by kinetic and RT structural studies."; RL Sci. Rep. 5:8529-8529(2015). CC -!- FUNCTION: NAD-dependent protein deacetylase, which deacetylates CC internal lysines on histone and alpha-tubulin as well as many other CC proteins such as key transcription factors (PubMed:24177535, CC PubMed:12620231, PubMed:16648462, PubMed:18249187, PubMed:18332217, CC PubMed:18995842, PubMed:20587414, PubMed:21081649, PubMed:20543840, CC PubMed:22014574, PubMed:21726808, PubMed:21949390, PubMed:22771473, CC PubMed:23468428, PubMed:23908241, PubMed:24940000, PubMed:24769394, CC PubMed:24681946). Participates in the modulation of multiple and CC diverse biological processes such as cell cycle control, genomic CC integrity, microtubule dynamics, cell differentiation, metabolic CC networks, and autophagy (PubMed:24177535, PubMed:12620231, CC PubMed:16648462, PubMed:18249187, PubMed:18332217, PubMed:18995842, CC PubMed:20587414, PubMed:21081649, PubMed:20543840, PubMed:22014574, CC PubMed:21726808, PubMed:21949390, PubMed:22771473, PubMed:23468428, CC PubMed:23908241, PubMed:24940000, PubMed:24769394, PubMed:24681946). CC Plays a major role in the control of cell cycle progression and genomic CC stability (PubMed:12697818, PubMed:17488717, PubMed:16909107, CC PubMed:17726514, PubMed:19282667, PubMed:23468428). Functions in the CC antephase checkpoint preventing precocious mitotic entry in response to CC microtubule stress agents, and hence allowing proper inheritance of CC chromosomes (PubMed:12697818, PubMed:17488717, PubMed:16909107, CC PubMed:17726514, PubMed:19282667, PubMed:23468428). Positively CC regulates the anaphase promoting complex/cyclosome (APC/C) ubiquitin CC ligase complex activity by deacetylating CDC20 and FZR1, then allowing CC progression through mitosis (PubMed:22014574). Associates both with CC chromatin at transcriptional start sites (TSSs) and enhancers of active CC genes (PubMed:23468428). Plays a role in cell cycle and chromatin CC compaction through epigenetic modulation of the regulation of histone CC H4 'Lys-20' methylation (H4K20me1) during early mitosis CC (PubMed:23468428). Specifically deacetylates histone H4 at 'Lys-16' CC (H4K16ac) between the G2/M transition and metaphase enabling H4K20me1 CC deposition by KMT5A leading to ulterior levels of H4K20me2 and H4K20me3 CC deposition throughout cell cycle, and mitotic S-phase progression CC (PubMed:23468428). Deacetylates KMT5A modulating KMT5A chromatin CC localization during the mitotic stress response (PubMed:23468428). CC Deacetylates also histone H3 at 'Lys-57' (H3K56ac) during the mitotic CC G2/M transition (PubMed:20587414). Upon bacterium Listeria CC monocytogenes infection, deacetylates 'Lys-18' of histone H3 in a CC receptor tyrosine kinase MET- and PI3K/Akt-dependent manner, thereby CC inhibiting transcriptional activity and promoting late stages of CC listeria infection (PubMed:23908241). During oocyte meiosis CC progression, may deacetylate histone H4 at 'Lys-16' (H4K16ac) and CC alpha-tubulin, regulating spindle assembly and chromosome alignment by CC influencing microtubule dynamics and kinetochore function CC (PubMed:24940000). Deacetylates histone H4 at 'Lys-16' (H4K16ac) at the CC VEGFA promoter and thereby contributes to regulate expression of VEGFA, CC a key regulator of angiogenesis (PubMed:24940000). Deacetylates alpha- CC tubulin at 'Lys-40' and hence controls neuronal motility, CC oligodendroglial cell arbor projection processes and proliferation of CC non-neuronal cells (PubMed:18332217, PubMed:18995842). Phosphorylation CC at Ser-368 by a G1/S-specific cyclin E-CDK2 complex inactivates SIRT2- CC mediated alpha-tubulin deacetylation, negatively regulating cell CC adhesion, cell migration and neurite outgrowth during neuronal CC differentiation (PubMed:17488717). Deacetylates PARD3 and participates CC in the regulation of Schwann cell peripheral myelination formation CC during early postnatal development and during postinjury remyelination CC (PubMed:21949390). Involved in several cellular metabolic pathways CC (PubMed:20543840, PubMed:21726808, PubMed:24769394). Plays a role in CC the regulation of blood glucose homeostasis by deacetylating and CC stabilizing phosphoenolpyruvate carboxykinase PCK1 activity in response CC to low nutrient availability (PubMed:21726808). Acts as a key regulator CC in the pentose phosphate pathway (PPP) by deacetylating and activating CC the glucose-6-phosphate G6PD enzyme, and therefore, stimulates the CC production of cytosolic NADPH to counteract oxidative damage CC (PubMed:24769394). Maintains energy homeostasis in response to nutrient CC deprivation as well as energy expenditure by inhibiting adipogenesis CC and promoting lipolysis (PubMed:20543840). Attenuates adipocyte CC differentiation by deacetylating and promoting FOXO1 interaction to CC PPARG and subsequent repression of PPARG-dependent transcriptional CC activity (PubMed:20543840). Plays a role in the regulation of lysosome- CC mediated degradation of protein aggregates by autophagy in neuronal CC cells (PubMed:20543840). Deacetylates FOXO1 in response to oxidative CC stress or serum deprivation, thereby negatively regulating FOXO1- CC mediated autophagy (PubMed:20543840). Deacetylates a broad range of CC transcription factors and co-regulators regulating target gene CC expression. Deacetylates transcriptional factor FOXO3 stimulating the CC ubiquitin ligase SCF(SKP2)-mediated FOXO3 ubiquitination and CC degradation (By similarity). Deacetylates HIF1A and therefore promotes CC HIF1A degradation and inhibition of HIF1A transcriptional activity in CC tumor cells in response to hypoxia (PubMed:24681946). Deacetylates RELA CC in the cytoplasm inhibiting NF-kappaB-dependent transcription CC activation upon TNF-alpha stimulation (PubMed:21081649). Inhibits CC transcriptional activation by deacetylating p53/TP53 and EP300 CC (PubMed:18249187, PubMed:18995842). Deacetylates also EIF5A CC (PubMed:22771473). Functions as a negative regulator on oxidative CC stress-tolerance in response to anoxia-reoxygenation conditions CC (PubMed:24769394). Plays a role as tumor suppressor (PubMed:22014574). CC In addition to protein deacetylase activity, also has activity toward CC long-chain fatty acyl groups and mediates protein-lysine CC demyristoylation and depalmitoylation of target proteins, such as ARF6 CC and KRAS, thereby regulating their association with membranes CC (PubMed:25704306, PubMed:29239724, PubMed:32103017). CC {ECO:0000250|UniProtKB:Q8VDQ8, ECO:0000269|PubMed:12620231, CC ECO:0000269|PubMed:12697818, ECO:0000269|PubMed:16648462, CC ECO:0000269|PubMed:16909107, ECO:0000269|PubMed:17488717, CC ECO:0000269|PubMed:17574768, ECO:0000269|PubMed:17726514, CC ECO:0000269|PubMed:18249187, ECO:0000269|PubMed:18332217, CC ECO:0000269|PubMed:18640115, ECO:0000269|PubMed:18722353, CC ECO:0000269|PubMed:18995842, ECO:0000269|PubMed:19282667, CC ECO:0000269|PubMed:20543840, ECO:0000269|PubMed:20587414, CC ECO:0000269|PubMed:21081649, ECO:0000269|PubMed:21726808, CC ECO:0000269|PubMed:21949390, ECO:0000269|PubMed:22014574, CC ECO:0000269|PubMed:22771473, ECO:0000269|PubMed:22819792, CC ECO:0000269|PubMed:23468428, ECO:0000269|PubMed:23908241, CC ECO:0000269|PubMed:23932781, ECO:0000269|PubMed:24177535, CC ECO:0000269|PubMed:24681946, ECO:0000269|PubMed:24769394, CC ECO:0000269|PubMed:24940000, ECO:0000269|PubMed:25704306, CC ECO:0000269|PubMed:29239724, ECO:0000269|PubMed:32103017}. CC -!- FUNCTION: [Isoform 1]: Deacetylates EP300, alpha-tubulin and histone H3 CC and H4. {ECO:0000269|PubMed:24177535}. CC -!- FUNCTION: [Isoform 2]: Deacetylates EP300, alpha-tubulin and histone H3 CC and H4. {ECO:0000269|PubMed:24177535}. CC -!- FUNCTION: [Isoform 5]: Lacks deacetylation activity, at least toward CC known SIRT2 targets. {ECO:0000269|PubMed:24177535}. CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + N(6)-acetyl-L-lysyl-[protein] + NAD(+) = 2''-O-acetyl- CC ADP-D-ribose + L-lysyl-[protein] + nicotinamide; CC Xref=Rhea:RHEA:43636, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10731, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:61930, ChEBI:CHEBI:83767; CC EC=2.3.1.286; Evidence={ECO:0000255|PROSITE-ProRule:PRU00236, CC ECO:0000269|PubMed:11483616, ECO:0000269|PubMed:11812793, CC ECO:0000269|PubMed:16648462, ECO:0000269|PubMed:18722353, CC ECO:0000269|PubMed:24177535, ECO:0000269|PubMed:24389023, CC ECO:0000269|PubMed:24940000, ECO:0000269|PubMed:25672491}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + N(6)-tetradecanoyl-L-lysyl-[protein] + NAD(+) = 2''-O- CC tetradecanoyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide; CC Xref=Rhea:RHEA:70567, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:15437, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:141129, ChEBI:CHEBI:189674; CC Evidence={ECO:0000269|PubMed:25704306, ECO:0000269|PubMed:32103017}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70568; CC Evidence={ECO:0000269|PubMed:25704306, ECO:0000269|PubMed:32103017}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + N(6)-hexadecanoyl-L-lysyl-[protein] + NAD(+) = 2''-O- CC hexadecanoyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide; CC Xref=Rhea:RHEA:70563, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:14175, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:138936, ChEBI:CHEBI:189673; CC Evidence={ECO:0000269|PubMed:29239724}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70564; CC Evidence={ECO:0000269|PubMed:29239724}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:25672491, ECO:0000269|PubMed:25704306}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:25672491, CC ECO:0000269|PubMed:25704306}; CC -!- ACTIVITY REGULATION: Inhibited by Sirtinol, A3 and M15 small molecules CC (PubMed:11483616). Inhibited by nicotinamide. Inhibited by a CC macrocyclic peptide inhibitor S2iL5 (PubMed:24389023). Inhibited by CC EP300-induced acetylation (PubMed:18722353). CC {ECO:0000269|PubMed:11483616, ECO:0000269|PubMed:18722353, CC ECO:0000269|PubMed:24389023}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=19 uM for an peptide acetylated on lysine CC {ECO:0000269|PubMed:25704306}; CC KM=0.24 uM for an peptide myristoylated on lysine CC {ECO:0000269|PubMed:25704306}; CC Note=kcat is 0.275 sec(-1) with a peptide acetylated on lysine as CC substrate (PubMed:25704306). kcat is 0.018 sec(-1) with a peptide CC myristoylated on lysine as substrate (PubMed:25704306). CC {ECO:0000269|PubMed:25704306}; CC -!- SUBUNIT: Interacts with CDC20, FOXO3 and FZR1. Associates with CC microtubules in primary cortical mature neurons (By similarity). CC Homotrimer. Isoform 1 and isoform 2 interact (via both phosphorylated, CC unphosphorylated, active or inactive forms) with HDAC6; the interaction CC is necessary for the complex to interact with alpha-tubulin, suggesting CC that these proteins belong to a large complex that deacetylates the CC cytoskeleton. Interacts with FOXO1; the interaction is disrupted upon CC serum-starvation or oxidative stress, leading to increased level of CC acetylated FOXO1 and induction of autophagy. Interacts with RELA; the CC interaction occurs in the cytoplasm and is increased in a TNF-alpha- CC dependent manner. Interacts with HOXA10; the interaction is direct. CC Interacts with YWHAB and YWHAG; the interactions occur in a AKT- CC dependent manner and increase SIRT2-dependent TP53 deacetylation. CC Interacts with MAPK1/ERK2 and MAPK3/ERK1; the interactions increase CC SIRT2 stability and deacetylation activity. Interacts (phosphorylated CC form) with KMT5A isoform 2; the interaction is direct, stimulates CC KMT5A-mediated methyltransferase activity on histone at 'Lys-20' CC (H4K20me1) and is increased in a H(2)O(2)-induced oxidative stress- CC dependent manner. Interacts with G6PD; the interaction is enhanced by CC H(2)O(2) treatment. Interacts with a G1/S-specific cyclin E-CDK2 CC complex. Interacts with AURKA, CDK5R1 (p35 form) and CDK5 and HIF1A. CC Isoform 1, isoform 2 and isoform 5 interact (via C-terminus region) CC with EP300 (PubMed:24177535). Interacts with the tRNA ligase SARS1; CC recruited to the VEGFA promoter via interaction with SARS1 CC (PubMed:24940000). Interacts with BEX4; negatively regulates alpha- CC tubulin deacetylation by SIRT2 (PubMed:27512957). {ECO:0000250, CC ECO:0000250|UniProtKB:Q8VDQ8, ECO:0000269|PubMed:11427894, CC ECO:0000269|PubMed:12620231, ECO:0000269|PubMed:15213244, CC ECO:0000269|PubMed:16648462, ECO:0000269|PubMed:17726514, CC ECO:0000269|PubMed:18249187, ECO:0000269|PubMed:18332217, CC ECO:0000269|PubMed:18722353, ECO:0000269|PubMed:20543840, CC ECO:0000269|PubMed:21081649, ECO:0000269|PubMed:21949390, CC ECO:0000269|PubMed:23454361, ECO:0000269|PubMed:23468428, CC ECO:0000269|PubMed:23806683, ECO:0000269|PubMed:24177535, CC ECO:0000269|PubMed:24389023, ECO:0000269|PubMed:24681946, CC ECO:0000269|PubMed:24769394, ECO:0000269|PubMed:24940000, CC ECO:0000269|PubMed:27512957}. CC -!- INTERACTION: CC Q8IXJ6; O60566: BUB1B; NbExp=3; IntAct=EBI-477232, EBI-1001438; CC Q8IXJ6; O60729: CDC14B; NbExp=2; IntAct=EBI-477232, EBI-970231; CC Q8IXJ6; P11413: G6PD; NbExp=3; IntAct=EBI-477232, EBI-4289891; CC Q8IXJ6; Q92831: KAT2B; NbExp=4; IntAct=EBI-477232, EBI-477430; CC Q8IXJ6; Q04206: RELA; NbExp=2; IntAct=EBI-477232, EBI-73886; CC Q8IXJ6; Q9BYB0: SHANK3; NbExp=2; IntAct=EBI-477232, EBI-1752330; CC Q8IXJ6-2; Q12834: CDC20; NbExp=2; IntAct=EBI-5240785, EBI-367462; CC Q8IXJ6-2; Q9UM11: FZR1; NbExp=2; IntAct=EBI-5240785, EBI-724997; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12697818, CC ECO:0000269|PubMed:16079181, ECO:0000269|PubMed:16648462, CC ECO:0000269|PubMed:17726514, ECO:0000269|PubMed:20543840, CC ECO:0000269|PubMed:23908241, ECO:0000269|PubMed:24177535}. Cytoplasm, CC perinuclear region {ECO:0000250|UniProtKB:Q8VDQ8}. Cytoplasm CC {ECO:0000269|PubMed:12697818, ECO:0000269|PubMed:16079181, CC ECO:0000269|PubMed:16648462, ECO:0000269|PubMed:17726514, CC ECO:0000269|PubMed:20543840, ECO:0000269|PubMed:23908241, CC ECO:0000269|PubMed:24681946}. Cytoplasm, cytoskeleton CC {ECO:0000269|PubMed:12620231}. Cytoplasm, cytoskeleton, microtubule CC organizing center, centrosome {ECO:0000269|PubMed:17488717, CC ECO:0000269|PubMed:17726514}. Cytoplasm, cytoskeleton, microtubule CC organizing center, centrosome, centriole {ECO:0000269|PubMed:17726514}. CC Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:17488717}. Midbody CC {ECO:0000269|PubMed:17726514}. Chromosome {ECO:0000269|PubMed:16648462, CC ECO:0000269|PubMed:23468428}. Perikaryon CC {ECO:0000250|UniProtKB:Q8VDQ8}. Cell projection CC {ECO:0000250|UniProtKB:Q8VDQ8}. Cell projection, growth cone CC {ECO:0000250|UniProtKB:Q8VDQ8}. Myelin membrane CC {ECO:0000250|UniProtKB:Q8VDQ8}. Note=Localizes in the cytoplasm during CC most of the cell cycle except in the G2/M transition and during CC mitosis, where it is localized in association with chromatin and CC induces deacetylation of histone at 'Lys-16' (H4K16ac) CC (PubMed:17726514, PubMed:23468428). Colocalizes with KMT5A at mitotic CC foci (PubMed:23468428). Colocalizes with CDK1 at centrosome during CC prophase and splindle fibers during metaphase (PubMed:17488717). CC Colocalizes with Aurora kinase AURKA at centrosome during early CC prophase and in the centrioles and growing mitotic spindle throughout CC metaphase (PubMed:17488717). Colocalizes with Aurora kinase AURKB CC during cytokinesis with the midbody (PubMed:17488717). Colocalizes with CC microtubules (PubMed:12620231). Detected in perinuclear foci that may CC be aggresomes containing misfolded, ubiquitinated proteins (By CC similarity). Shuttles between the cytoplasm and the nucleus through the CC CRM1 export pathway (PubMed:17726514). Colocalizes with EP300 in the CC nucleus (PubMed:24177535). Translocates to the nucleus and chromatin CC upon bacterium Listeria monocytogenes infection in interphase cells CC (PubMed:23908241). Deacetylates FOXO3 in the cytoplasm (By similarity). CC Colocalizes with PLP1 in internodal regions, at paranodal axoglial CC junction and Schmidt-Lanterman incisures of myelin sheath (By CC similarity). Colocalizes with CDK5R1 in the perikaryon, neurites and CC growth cone of hippocampal neurons (By similarity). Colocalizes with CC alpha-tubulin in neuronal growth cone (By similarity). Localizes in the CC cytoplasm and nucleus of germinal vesicle (GV) stage oocytes (By CC similarity). Colocalizes with alpha-tubulin on the meiotic spindle as CC the oocytes enter into metaphase, and also during meiotic anaphase and CC telophase, especially with the midbody (By similarity). Colocalizes CC with PARD3 in internodal region of axons (By similarity). Colocalizes CC with acetylated alpha-tubulin in cell projection processes during CC primary oligodendrocyte precursor (OLP) differentiation (By CC similarity). {ECO:0000250|UniProtKB:Q8VDQ8, CC ECO:0000269|PubMed:12620231, ECO:0000269|PubMed:17488717, CC ECO:0000269|PubMed:17726514, ECO:0000269|PubMed:23468428, CC ECO:0000269|PubMed:23908241, ECO:0000269|PubMed:24177535}. CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm CC {ECO:0000269|PubMed:24177535}. Nucleus {ECO:0000269|PubMed:24177535}. CC Note=Predominantly localized in the cytoplasmic. CC {ECO:0000269|PubMed:24177535}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm CC {ECO:0000269|PubMed:24177535}. Nucleus {ECO:0000269|PubMed:24177535}. CC Note=Predominantly localized in the cytoplasmic. CC {ECO:0000269|PubMed:24177535}. CC -!- SUBCELLULAR LOCATION: [Isoform 5]: Cytoplasm CC {ECO:0000269|PubMed:24177535}. Nucleus {ECO:0000269|PubMed:24177535}. CC Note=Predominantly localized in the nucleus. CC {ECO:0000269|PubMed:24177535}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=Q8IXJ6-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8IXJ6-2; Sequence=VSP_008724; CC Name=3; CC IsoId=Q8IXJ6-3; Sequence=VSP_008726; CC Name=4; CC IsoId=Q8IXJ6-4; Sequence=VSP_008727, VSP_008728; CC Name=5; CC IsoId=Q8IXJ6-5; Sequence=VSP_055328; CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed in heart, liver and skeletal CC muscle, weakly expressed in the cortex. Isoform 2 is strongly expressed CC in the cortex, weakly expressed in heart and liver. Weakly expressed in CC several malignancies including breast, liver, brain, kidney and CC prostate cancers compared to normal tissues. Weakly expressed in glioma CC cell lines compared to normal brain tissues (at protein level). Widely CC expressed. Highly expressed in heart, brain and skeletal muscle, while CC it is weakly expressed in placenta and lung. Down-regulated in many CC gliomas suggesting that it may act as a tumor suppressor gene in human CC gliomas possibly through the regulation of microtubule network. CC {ECO:0000269|PubMed:10381378, ECO:0000269|PubMed:10393250, CC ECO:0000269|PubMed:12963026, ECO:0000269|PubMed:16909107, CC ECO:0000269|PubMed:21791548, ECO:0000269|PubMed:22014574}. CC -!- DEVELOPMENTAL STAGE: Peaks during mitosis. After mitosis, it is CC probably degraded by the 26S proteasome. {ECO:0000269|PubMed:12697818}. CC -!- INDUCTION: Up-regulated in response to low levels of glucose and CC anoxia-reoxygenation stress. Up-regulated by trichostatin A. Down- CC regulated in response to high levels of glucose. Down-regulated by CC histone deacetylation in several tumors. {ECO:0000269|PubMed:16909107, CC ECO:0000269|PubMed:18640115, ECO:0000269|PubMed:21726808}. CC -!- PTM: Phosphorylated at phosphoserine and phosphothreonine. CC Phosphorylated at Ser-368 by a mitotic kinase CDK1/cyclin B at the G2/M CC transition; phosphorylation regulates the delay in cell-cycle CC progression. Phosphorylated at Ser-368 by a mitotic kinase G1/S- CC specific cyclin E/Cdk2 complex; phosphorylation inactivates SIRT2- CC mediated alpha-tubulin deacetylation and thereby negatively regulates CC cell adhesion, cell migration and neurite outgrowth during neuronal CC differentiation. Phosphorylated by cyclin A/Cdk2 and p35-Cdk5 complexes CC and to a lesser extent by the cyclin D3/Cdk4 and cyclin B/Cdk1, in CC vitro. Dephosphorylated at Ser-368 by CDC14A and CDC14B around early CC anaphase. {ECO:0000269|PubMed:12697818, ECO:0000269|PubMed:17488717, CC ECO:0000269|PubMed:17516032, ECO:0000269|PubMed:18332217}. CC -!- PTM: Acetylated by EP300; acetylation leads both to the decreased of CC SIRT2-mediated alpha-tubulin deacetylase activity and SIRT2-mediated CC down-regulation of TP53 transcriptional activity. CC {ECO:0000269|PubMed:18722353}. CC -!- PTM: Ubiquitinated. {ECO:0000269|PubMed:12697818, CC ECO:0000269|PubMed:17516032}. CC -!- SIMILARITY: Belongs to the sirtuin family. Class I subfamily. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAD45971.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAF67015.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF083107; AAD40850.2; -; mRNA. DR EMBL; AF095714; AAD45971.1; ALT_INIT; mRNA. DR EMBL; AY030277; AAK51133.1; -; mRNA. DR EMBL; KF032391; AGZ02589.1; -; mRNA. DR EMBL; AJ505014; CAD43717.1; -; mRNA. DR EMBL; AF160214; AAF67015.1; ALT_FRAME; mRNA. DR EMBL; AK290716; BAF83405.1; -; mRNA. DR EMBL; AK314492; BAG37092.1; -; mRNA. DR EMBL; CH471126; EAW56833.1; -; Genomic_DNA. DR EMBL; CH471126; EAW56835.1; -; Genomic_DNA. DR EMBL; BC003012; AAH03012.1; -; mRNA. DR EMBL; BC003547; AAH03547.1; -; mRNA. DR EMBL; AF131800; AAD20046.1; -; mRNA. DR CCDS; CCDS12523.1; -. [Q8IXJ6-1] DR CCDS; CCDS46069.1; -. [Q8IXJ6-2] DR RefSeq; NP_001180215.1; NM_001193286.1. DR RefSeq; NP_036369.2; NM_012237.3. [Q8IXJ6-1] DR RefSeq; NP_085096.1; NM_030593.2. [Q8IXJ6-2] DR RefSeq; XP_006723174.1; XM_006723111.1. DR RefSeq; XP_011524956.1; XM_011526654.1. DR RefSeq; XP_011524957.1; XM_011526655.1. [Q8IXJ6-5] DR PDB; 1J8F; X-ray; 1.70 A; A/B/C=34-356. DR PDB; 3ZGO; X-ray; 1.63 A; A/B/C=34-356. DR PDB; 3ZGV; X-ray; 2.27 A; A/B=34-356. DR PDB; 4L3O; X-ray; 2.52 A; A/B/C/D=55-356. DR PDB; 4R8M; X-ray; 2.10 A; A/B=38-356. DR PDB; 4RMG; X-ray; 1.88 A; A=56-356. DR PDB; 4RMH; X-ray; 1.42 A; A=56-356. DR PDB; 4RMI; X-ray; 1.45 A; A=56-356. DR PDB; 4RMJ; X-ray; 1.87 A; A/B=56-356. DR PDB; 4X3O; X-ray; 1.50 A; A=52-355. DR PDB; 4X3P; X-ray; 1.80 A; A=52-355. DR PDB; 4Y6L; X-ray; 1.60 A; A/B=52-356. DR PDB; 4Y6O; X-ray; 1.60 A; A/B=52-356. DR PDB; 4Y6Q; X-ray; 1.90 A; A/B/C/D=52-356. DR PDB; 5D7O; X-ray; 1.63 A; A/B=50-356. DR PDB; 5D7P; X-ray; 1.76 A; A/B=56-356. DR PDB; 5D7Q; X-ray; 2.01 A; A/B=56-356. DR PDB; 5DY4; X-ray; 1.77 A; A=56-356. DR PDB; 5DY5; X-ray; 1.95 A; A=56-356. DR PDB; 5FYQ; X-ray; 3.00 A; A/B=1-356. DR PDB; 5G4C; X-ray; 2.10 A; A/B=34-356. DR PDB; 5MAR; X-ray; 1.89 A; A/B=56-356. DR PDB; 5MAT; X-ray; 2.07 A; A/C=56-356. DR PDB; 5Y0Z; X-ray; 2.00 A; A/B=52-356. DR PDB; 5Y5N; X-ray; 2.30 A; A=32-356. DR PDB; 5YQL; X-ray; 1.60 A; A=56-356. DR PDB; 5YQM; X-ray; 1.74 A; A=56-356. DR PDB; 5YQN; X-ray; 1.60 A; A=56-356. DR PDB; 5YQO; X-ray; 1.48 A; A=56-356. DR PDB; 6L65; X-ray; 1.80 A; A=50-355. DR PDB; 6L66; X-ray; 2.17 A; A=52-355. DR PDB; 6L71; X-ray; 2.11 A; A=52-355. DR PDB; 6L72; X-ray; 2.50 A; A=52-355. DR PDB; 6NR0; X-ray; 2.45 A; A/B=38-356. DR PDB; 6QCN; X-ray; 2.23 A; A/B=55-356. DR PDB; 7BOS; X-ray; 1.70 A; A=52-356. DR PDB; 7BOT; X-ray; 1.70 A; A=52-356. DR PDB; 8OWZ; X-ray; 1.65 A; A=56-356. DR PDBsum; 1J8F; -. DR PDBsum; 3ZGO; -. DR PDBsum; 3ZGV; -. DR PDBsum; 4L3O; -. DR PDBsum; 4R8M; -. DR PDBsum; 4RMG; -. DR PDBsum; 4RMH; -. DR PDBsum; 4RMI; -. DR PDBsum; 4RMJ; -. DR PDBsum; 4X3O; -. DR PDBsum; 4X3P; -. DR PDBsum; 4Y6L; -. DR PDBsum; 4Y6O; -. DR PDBsum; 4Y6Q; -. DR PDBsum; 5D7O; -. DR PDBsum; 5D7P; -. DR PDBsum; 5D7Q; -. DR PDBsum; 5DY4; -. DR PDBsum; 5DY5; -. DR PDBsum; 5FYQ; -. DR PDBsum; 5G4C; -. DR PDBsum; 5MAR; -. DR PDBsum; 5MAT; -. DR PDBsum; 5Y0Z; -. DR PDBsum; 5Y5N; -. DR PDBsum; 5YQL; -. DR PDBsum; 5YQM; -. DR PDBsum; 5YQN; -. DR PDBsum; 5YQO; -. DR PDBsum; 6L65; -. DR PDBsum; 6L66; -. DR PDBsum; 6L71; -. DR PDBsum; 6L72; -. DR PDBsum; 6NR0; -. DR PDBsum; 6QCN; -. DR PDBsum; 7BOS; -. DR PDBsum; 7BOT; -. DR PDBsum; 8OWZ; -. DR AlphaFoldDB; Q8IXJ6; -. DR SMR; Q8IXJ6; -. DR BioGRID; 116593; 144. DR DIP; DIP-33350N; -. DR IntAct; Q8IXJ6; 50. DR MINT; Q8IXJ6; -. DR STRING; 9606.ENSP00000249396; -. DR BindingDB; Q8IXJ6; -. DR ChEMBL; CHEMBL4462; -. DR DrugBank; DB15493; Cambinol. DR DrugCentral; Q8IXJ6; -. DR GuidetoPHARMACOLOGY; 2708; -. DR iPTMnet; Q8IXJ6; -. DR PhosphoSitePlus; Q8IXJ6; -. DR BioMuta; SIRT2; -. DR DMDM; 38258608; -. DR EPD; Q8IXJ6; -. DR jPOST; Q8IXJ6; -. DR MassIVE; Q8IXJ6; -. DR MaxQB; Q8IXJ6; -. DR PaxDb; 9606-ENSP00000249396; -. DR PeptideAtlas; Q8IXJ6; -. DR ProteomicsDB; 71008; -. [Q8IXJ6-1] DR ProteomicsDB; 71009; -. [Q8IXJ6-2] DR ProteomicsDB; 71010; -. [Q8IXJ6-3] DR ProteomicsDB; 71011; -. [Q8IXJ6-4] DR Pumba; Q8IXJ6; -. DR Antibodypedia; 2167; 668 antibodies from 47 providers. DR DNASU; 22933; -. DR Ensembl; ENST00000249396.12; ENSP00000249396.7; ENSG00000068903.21. [Q8IXJ6-1] DR Ensembl; ENST00000392081.6; ENSP00000375931.2; ENSG00000068903.21. [Q8IXJ6-2] DR Ensembl; ENST00000634533.2; ENSP00000489602.1; ENSG00000283100.2. [Q8IXJ6-1] DR Ensembl; ENST00000635478.1; ENSP00000488940.1; ENSG00000283100.2. [Q8IXJ6-2] DR GeneID; 22933; -. DR KEGG; hsa:22933; -. DR MANE-Select; ENST00000249396.12; ENSP00000249396.7; NM_012237.4; NP_036369.2. DR UCSC; uc002ojt.3; human. [Q8IXJ6-1] DR AGR; HGNC:10886; -. DR CTD; 22933; -. DR DisGeNET; 22933; -. DR GeneCards; SIRT2; -. DR HGNC; HGNC:10886; SIRT2. DR HPA; ENSG00000068903; Group enriched (brain, skeletal muscle, tongue). DR MIM; 604480; gene. DR neXtProt; NX_Q8IXJ6; -. DR OpenTargets; ENSG00000068903; -. DR PharmGKB; PA35786; -. DR VEuPathDB; HostDB:ENSG00000068903; -. DR eggNOG; KOG2682; Eukaryota. DR GeneTree; ENSGT00940000157514; -. DR HOGENOM; CLU_023643_7_4_1; -. DR InParanoid; Q8IXJ6; -. DR OMA; QRPGPRC; -. DR OrthoDB; 10545at2759; -. DR PhylomeDB; Q8IXJ6; -. DR TreeFam; TF106181; -. DR BioCyc; MetaCyc:ENSG00000068903-MONOMER; -. DR BRENDA; 2.3.1.286; 2681. DR PathwayCommons; Q8IXJ6; -. DR Reactome; R-HSA-2995383; Initiation of Nuclear Envelope (NE) Reformation. DR SABIO-RK; Q8IXJ6; -. DR SignaLink; Q8IXJ6; -. DR SIGNOR; Q8IXJ6; -. DR BioGRID-ORCS; 22933; 18 hits in 1176 CRISPR screens. DR ChiTaRS; SIRT2; human. DR EvolutionaryTrace; Q8IXJ6; -. DR GeneWiki; SIRT2; -. DR GenomeRNAi; 22933; -. DR Pharos; Q8IXJ6; Tchem. DR PRO; PR:Q8IXJ6; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q8IXJ6; Protein. DR Bgee; ENSG00000068903; Expressed in C1 segment of cervical spinal cord and 159 other cell types or tissues. DR ExpressionAtlas; Q8IXJ6; baseline and differential. DR GO; GO:0005814; C:centriole; IDA:UniProtKB. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0005677; C:chromatin silencing complex; NAS:UniProtKB. DR GO; GO:0005694; C:chromosome; IDA:UniProtKB. DR GO; GO:0000781; C:chromosome, telomeric region; IEA:GOC. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0097386; C:glial cell projection; ISS:UniProtKB. DR GO; GO:0030426; C:growth cone; IEA:UniProtKB-SubCell. DR GO; GO:0000792; C:heterochromatin; ISS:UniProtKB. DR GO; GO:0044224; C:juxtaparanode region of axon; ISS:UniProtKB. DR GO; GO:0043219; C:lateral loop; ISS:UniProtKB. DR GO; GO:0072687; C:meiotic spindle; ISS:UniProtKB. DR GO; GO:0005874; C:microtubule; IDA:UniProtKB. DR GO; GO:0030496; C:midbody; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl. DR GO; GO:0072686; C:mitotic spindle; IDA:UniProtKB. DR GO; GO:0043209; C:myelin sheath; ISS:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0033010; C:paranodal junction; ISS:UniProtKB. DR GO; GO:0033270; C:paranode region of axon; ISS:UniProtKB. DR GO; GO:0043204; C:perikaryon; ISS:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0043220; C:Schmidt-Lanterman incisure; ISS:UniProtKB. DR GO; GO:0005819; C:spindle; IDA:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB. DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB. DR GO; GO:0035035; F:histone acetyltransferase binding; IPI:UniProtKB. DR GO; GO:0004407; F:histone deacetylase activity; IDA:UniProtKB. DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB. DR GO; GO:0003950; F:NAD+ ADP-ribosyltransferase activity; IDA:GO_Central. DR GO; GO:0070403; F:NAD+ binding; IDA:UniProtKB. DR GO; GO:0017136; F:NAD-dependent histone deacetylase activity; IDA:UniProtKB. DR GO; GO:0046970; F:NAD-dependent histone H4K16 deacetylase activity; IDA:UniProtKB. DR GO; GO:0034979; F:NAD-dependent protein deacetylase activity; IDA:UniProtKB. DR GO; GO:0140773; F:NAD-dependent protein demyristoylase activity; IDA:UniProtKB. DR GO; GO:0140774; F:NAD-dependent protein depalmitoylase activity; IDA:UniProtKB. DR GO; GO:0033558; F:protein lysine deacetylase activity; IDA:UniProtKB. DR GO; GO:0042903; F:tubulin deacetylase activity; IDA:UniProtKB. DR GO; GO:0043130; F:ubiquitin binding; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0044242; P:cellular lipid catabolic process; ISS:UniProtKB. DR GO; GO:0061433; P:cellular response to caloric restriction; ISS:UniProtKB. DR GO; GO:0071872; P:cellular response to epinephrine stimulus; ISS:UniProtKB. DR GO; GO:0071456; P:cellular response to hypoxia; IDA:UniProtKB. DR GO; GO:0034599; P:cellular response to oxidative stress; ISS:UniProtKB. DR GO; GO:0040029; P:epigenetic regulation of gene expression; IMP:UniProtKB. DR GO; GO:0031507; P:heterochromatin formation; NAS:UniProtKB. DR GO; GO:0016575; P:histone deacetylation; IDA:UniProtKB. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW. DR GO; GO:0007084; P:mitotic nuclear membrane reassembly; TAS:Reactome. DR GO; GO:0022011; P:myelination in peripheral nervous system; ISS:UniProtKB. DR GO; GO:0010507; P:negative regulation of autophagy; IMP:UniProtKB. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045599; P:negative regulation of fat cell differentiation; ISS:UniProtKB. DR GO; GO:1900226; P:negative regulation of NLRP3 inflammasome complex assembly; IEA:Ensembl. DR GO; GO:0070446; P:negative regulation of oligodendrocyte progenitor proliferation; ISS:UniProtKB. DR GO; GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; ISS:UniProtKB. DR GO; GO:0042177; P:negative regulation of protein catabolic process; IMP:UniProtKB. DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; ISS:UniProtKB. DR GO; GO:0045843; P:negative regulation of striated muscle tissue development; IDA:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0044546; P:NLRP3 inflammasome complex assembly; IEA:Ensembl. DR GO; GO:0034983; P:peptidyl-lysine deacetylation; IDA:UniProtKB. DR GO; GO:0051987; P:positive regulation of attachment of spindle microtubules to kinetochore; ISS:UniProtKB. DR GO; GO:0051781; P:positive regulation of cell division; ISS:UniProtKB. DR GO; GO:0043388; P:positive regulation of DNA binding; ISS:UniProtKB. DR GO; GO:1900119; P:positive regulation of execution phase of apoptosis; ISS:UniProtKB. DR GO; GO:0045723; P:positive regulation of fatty acid biosynthetic process; IDA:UniProt. DR GO; GO:0045836; P:positive regulation of meiotic nuclear division; ISS:UniProtKB. DR GO; GO:1900195; P:positive regulation of oocyte maturation; ISS:UniProtKB. DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR GO; GO:0006476; P:protein deacetylation; IDA:UniProtKB. DR GO; GO:0000183; P:rDNA heterochromatin formation; NAS:UniProtKB. DR GO; GO:0051726; P:regulation of cell cycle; IMP:UniProtKB. DR GO; GO:0007096; P:regulation of exit from mitosis; NAS:UniProtKB. DR GO; GO:0031641; P:regulation of myelination; ISS:UniProtKB. DR GO; GO:0042325; P:regulation of phosphorylation; NAS:UniProtKB. DR GO; GO:0051775; P:response to redox state; NAS:UniProtKB. DR GO; GO:0021762; P:substantia nigra development; HEP:UniProtKB. DR GO; GO:0031509; P:subtelomeric heterochromatin formation; NAS:UniProtKB. DR GO; GO:0090042; P:tubulin deacetylation; IDA:UniProtKB. DR CDD; cd01408; SIRT1; 1. DR Gene3D; 3.30.1600.10; SIR2/SIRT2 'Small Domain; 1. DR Gene3D; 3.40.50.1220; TPP-binding domain; 1. DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom. DR InterPro; IPR003000; Sirtuin. DR InterPro; IPR026591; Sirtuin_cat_small_dom_sf. DR InterPro; IPR017328; Sirtuin_class_I. DR InterPro; IPR026590; Ssirtuin_cat_dom. DR PANTHER; PTHR11085:SF10; NAD-DEPENDENT PROTEIN DEACETYLASE SIRTUIN-2; 1. DR PANTHER; PTHR11085; NAD-DEPENDENT PROTEIN DEACYLASE SIRTUIN-5, MITOCHONDRIAL-RELATED; 1. DR Pfam; PF02146; SIR2; 1. DR PIRSF; PIRSF037938; SIR2_euk; 1. DR SUPFAM; SSF52467; DHS-like NAD/FAD-binding domain; 1. DR PROSITE; PS50305; SIRTUIN; 1. DR Genevisible; Q8IXJ6; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Autophagy; Cell cycle; KW Cell division; Cell membrane; Cell projection; Chromosome; Cytoplasm; KW Cytoskeleton; Differentiation; Immunity; Innate immunity; Meiosis; KW Membrane; Metal-binding; Microtubule; Mitosis; NAD; Neurodegeneration; KW Neurogenesis; Nucleus; Phosphoprotein; Reference proteome; Transcription; KW Transcription regulation; Transferase; Ubl conjugation; Zinc. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330" FT CHAIN 2..389 FT /note="NAD-dependent protein deacetylase sirtuin-2" FT /id="PRO_0000110258" FT DOMAIN 57..338 FT /note="Deacetylase sirtuin-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236" FT REGION 1..34 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 351..389 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 41..51 FT /note="Nuclear export signal" FT COMPBIAS 374..389 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 187 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236" FT BINDING 85..89 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:25672491, FT ECO:0007744|PDB:4RMG" FT BINDING 95..97 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:25672491, FT ECO:0007744|PDB:4RMG" FT BINDING 167..170 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:25672491, FT ECO:0007744|PDB:4RMG" FT BINDING 195 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236, FT ECO:0000269|PubMed:11427894, ECO:0000269|PubMed:23454361, FT ECO:0000269|PubMed:24389023, ECO:0000269|PubMed:25672491, FT ECO:0000269|PubMed:25704306, ECO:0007744|PDB:4R8M" FT BINDING 200 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236, FT ECO:0000269|PubMed:11427894, ECO:0000269|PubMed:23454361, FT ECO:0000269|PubMed:24389023, ECO:0000269|PubMed:25672491, FT ECO:0000269|PubMed:25704306, ECO:0007744|PDB:4R8M" FT BINDING 221 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236, FT ECO:0000269|PubMed:11427894, ECO:0000269|PubMed:23454361, FT ECO:0000269|PubMed:24389023, ECO:0000269|PubMed:25672491, FT ECO:0000269|PubMed:25704306, ECO:0007744|PDB:4R8M" FT BINDING 224 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236, FT ECO:0000269|PubMed:11427894, ECO:0000269|PubMed:23454361, FT ECO:0000269|PubMed:24389023, ECO:0000269|PubMed:25672491, FT ECO:0000269|PubMed:25704306, ECO:0007744|PDB:4R8M" FT BINDING 262..263 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:25672491, FT ECO:0007744|PDB:4RMG" FT BINDING 286..288 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:25672491, FT ECO:0007744|PDB:4RMG" FT BINDING 324 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:25672491, FT ECO:0007744|PDB:4RMG" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:19413330" FT MOD_RES 23 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 25 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 27 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 53 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q5RJQ4" FT MOD_RES 100 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q5RJQ4" FT MOD_RES 207 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q5RJQ4" FT MOD_RES 368 FT /note="Phosphoserine; by CDK2 and CDK5" FT /evidence="ECO:0000269|PubMed:17488717, FT ECO:0000269|PubMed:17516032, ECO:0000269|PubMed:18332217, FT ECO:0007744|PubMed:23186163" FT MOD_RES 372 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:17516032" FT VAR_SEQ 1..38 FT /note="MAEPDPSHPLETQAGKVQEAQDSDSDSEGGAAGGEADM -> MPLAECPSCR FT CLSSFRSV (in isoform 3)" FT /evidence="ECO:0000303|Ref.5" FT /id="VSP_008726" FT VAR_SEQ 1..37 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10393250, FT ECO:0000303|PubMed:10931946, ECO:0000303|PubMed:12065666, FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334" FT /id="VSP_008724" FT VAR_SEQ 6..76 FT /note="PSHPLETQAGKVQEAQDSDSDSEGGAAGGEADMDFLRNLFSQTLSLGSQKER FT LLDELTLEGVARYMQSERC -> R (in isoform 5)" FT /evidence="ECO:0000303|PubMed:24177535" FT /id="VSP_055328" FT VAR_SEQ 266..271 FT /note="VQPFAS -> GRGLAG (in isoform 4)" FT /evidence="ECO:0000303|Ref.10" FT /id="VSP_008727" FT VAR_SEQ 272..389 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|Ref.10" FT /id="VSP_008728" FT MUTAGEN 53 FT /note="S->A: Reduces deacetylase activity." FT /evidence="ECO:0000269|PubMed:17516032" FT MUTAGEN 97 FT /note="R->A: No effect on deacetylase activity." FT /evidence="ECO:0000269|PubMed:11427894" FT MUTAGEN 98 FT /note="S->A: Inhibits deacetylase activity." FT /evidence="ECO:0000269|PubMed:17516032" FT MUTAGEN 100 FT /note="S->A: Reduces deacetylase activity." FT /evidence="ECO:0000269|PubMed:17516032" FT MUTAGEN 116 FT /note="E->A: Reduces binding for the peptide inhibitor FT S2iL5." FT /evidence="ECO:0000269|PubMed:24389023" FT MUTAGEN 120 FT /note="E->A: Reduces binding for the peptide inhibitor FT S2iL5." FT /evidence="ECO:0000269|PubMed:24389023" FT MUTAGEN 167 FT /note="Q->A: Reduces deacetylase activity. Inhibits the FT block of entry to chromosome condensation and subsequent FT hyperploidy cell formation in response to mitotic stress; FT when associated with A-168 and A-187." FT /evidence="ECO:0000269|PubMed:11427894, FT ECO:0000269|PubMed:16909107" FT MUTAGEN 168 FT /note="N->A: Abolishes deacetylation of alpha-tubulin. FT Inhibits deacetylation of histone H3 at 'Lys-18'. Inhibits FT the block of entry to chromosome condensation and FT subsequent hyperploidy cell formation in response to FT mitotic stress; when associated with A-167 and A-187." FT /evidence="ECO:0000269|PubMed:11427894, FT ECO:0000269|PubMed:12620231, ECO:0000269|PubMed:16909107, FT ECO:0000269|PubMed:23908241, ECO:0000269|PubMed:24769394" FT MUTAGEN 170 FT /note="D->A,N: Reduces deacetylase activity." FT /evidence="ECO:0000269|PubMed:11427894" FT MUTAGEN 187 FT /note="H->Y,A: Inhibits deacetylase activity toward FT histone, alpha-tubulin, FZR1 and CDC20. No effect on FT CDK2-dependent phosphorylation. Does not inhibit FT interaction with alpha-tubulin, HDAC6, HIF1A and the cyclin FT E-CDK2 complex. Inhibits interaction with BEX4 and KMT5A. FT Abolishes deacetylation, dimeric formation and enzymatic FT activity increase of G6PD. Prevents histone H4 methylation FT at 'Lys-20'(H4K20me1) in metaphase chromosomes. Inhibits FT the block of entry to chromosome condensation and FT subsequent hyperploidy cell formation in response to FT mitotic stress; when associated with A-167 and A-168. FT Strongly reduced activity toward long-chain fatty acyl FT groups." FT /evidence="ECO:0000269|PubMed:10381378, FT ECO:0000269|PubMed:11427894, ECO:0000269|PubMed:11812793, FT ECO:0000269|PubMed:12620231, ECO:0000269|PubMed:12697818, FT ECO:0000269|PubMed:16909107, ECO:0000269|PubMed:17488717, FT ECO:0000269|PubMed:17516032, ECO:0000269|PubMed:17726514, FT ECO:0000269|PubMed:22014574, ECO:0000269|PubMed:24681946, FT ECO:0000269|PubMed:27512957, ECO:0000269|PubMed:29239724" FT MUTAGEN 244 FT /note="F->A: Strongly reduces binding for the peptide FT inhibitor S2iL5." FT /evidence="ECO:0000269|PubMed:24389023" FT MUTAGEN 265 FT /note="Q->A: Reduces binding for the peptide inhibitor FT S2iL5." FT /evidence="ECO:0000269|PubMed:24389023" FT MUTAGEN 271 FT /note="S->A: Reduces binding for the peptide inhibitor FT S2iL5." FT /evidence="ECO:0000269|PubMed:24389023" FT MUTAGEN 279 FT /note="S->A: Reduces deacetylase activity." FT /evidence="ECO:0000269|PubMed:17516032" FT MUTAGEN 280 FT /note="T->A: Reduces deacetylase activity." FT /evidence="ECO:0000269|PubMed:17516032" FT MUTAGEN 294 FT /note="D->A: Reduces binding for the peptide inhibitor FT S2iL5." FT /evidence="ECO:0000269|PubMed:24389023" FT MUTAGEN 311 FT /note="S->A: Reduces deacetylase activity." FT /evidence="ECO:0000269|PubMed:17516032" FT MUTAGEN 315 FT /note="Y->A: Reduces deacetylase activity." FT /evidence="ECO:0000269|PubMed:17516032" FT MUTAGEN 364 FT /note="S->A: Abolishes CDK2-dependent phosphorylation." FT /evidence="ECO:0000269|PubMed:17516032" FT MUTAGEN 368 FT /note="S->A: Does not affect deacetylase activity. FT Abolishes CDK2-dependent phosphorylation. Inhibits cellular FT proliferation delay in the early metaphase to prevent FT chromosomal instability. Does not inhibit interaction with FT a cyclin E-CDK2 complex. Does not inhibit interaction with FT HDAC6 and ubiquitination. Inhibits cell adhesion and FT migration and neurite outgrowth. Inhibits deacetylase FT activity; when associated with A-372." FT /evidence="ECO:0000269|PubMed:17488717, FT ECO:0000269|PubMed:17516032, ECO:0000269|PubMed:18332217" FT MUTAGEN 368 FT /note="S->D: Abolishes CDK2-dependent phosphorylation. FT Inhibits interaction with a cyclin E-CDK2 complex. Reduces FT strongly histone deacetylation activity." FT /evidence="ECO:0000269|PubMed:17488717, FT ECO:0000269|PubMed:17516032, ECO:0000269|PubMed:18332217" FT MUTAGEN 368 FT /note="S->E: Abolishes CDK2-dependent phosphorylation." FT /evidence="ECO:0000269|PubMed:17488717, FT ECO:0000269|PubMed:17516032, ECO:0000269|PubMed:18332217" FT MUTAGEN 372 FT /note="S->A: Reduces phosphorylation. Does not inhibit FT interaction with HDAC6, ubiquitination and deacetylase FT activity. Inhibits deacetylase activity; when associated FT with A-368." FT /evidence="ECO:0000269|PubMed:17516032" FT CONFLICT 199 FT /note="S -> N (in Ref. 6)" FT /evidence="ECO:0000305" FT CONFLICT 219 FT /note="P -> L (in Ref. 5; CAD43717)" FT /evidence="ECO:0000305" FT HELIX 35..45 FT /evidence="ECO:0007829|PDB:3ZGO" FT STRAND 60..63 FT /evidence="ECO:0007829|PDB:4RMH" FT HELIX 64..71 FT /evidence="ECO:0007829|PDB:4RMH" FT STRAND 73..75 FT /evidence="ECO:0007829|PDB:6L66" FT STRAND 79..83 FT /evidence="ECO:0007829|PDB:4RMH" FT HELIX 85..87 FT /evidence="ECO:0007829|PDB:4RMH" FT HELIX 89..91 FT /evidence="ECO:0007829|PDB:4RMH" FT STRAND 96..98 FT /evidence="ECO:0007829|PDB:4RMI" FT HELIX 99..101 FT /evidence="ECO:0007829|PDB:4RMH" FT HELIX 103..105 FT /evidence="ECO:0007829|PDB:4X3O" FT HELIX 108..110 FT /evidence="ECO:0007829|PDB:4X3O" FT HELIX 115..119 FT /evidence="ECO:0007829|PDB:4RMH" FT HELIX 121..126 FT /evidence="ECO:0007829|PDB:4RMH" FT HELIX 129..138 FT /evidence="ECO:0007829|PDB:4RMH" FT STRAND 139..142 FT /evidence="ECO:0007829|PDB:3ZGO" FT HELIX 147..157 FT /evidence="ECO:0007829|PDB:4RMH" FT STRAND 161..166 FT /evidence="ECO:0007829|PDB:4RMH" FT HELIX 172..175 FT /evidence="ECO:0007829|PDB:4RMH" FT HELIX 180..182 FT /evidence="ECO:0007829|PDB:4RMH" FT STRAND 183..185 FT /evidence="ECO:0007829|PDB:4RMH" FT STRAND 188..196 FT /evidence="ECO:0007829|PDB:4RMH" FT TURN 198..200 FT /evidence="ECO:0007829|PDB:4RMH" FT STRAND 203..205 FT /evidence="ECO:0007829|PDB:4RMH" FT HELIX 206..215 FT /evidence="ECO:0007829|PDB:4RMH" FT TURN 222..224 FT /evidence="ECO:0007829|PDB:4RMH" FT STRAND 227..232 FT /evidence="ECO:0007829|PDB:4RMH" FT HELIX 241..250 FT /evidence="ECO:0007829|PDB:4RMH" FT TURN 251..253 FT /evidence="ECO:0007829|PDB:4RMI" FT STRAND 255..261 FT /evidence="ECO:0007829|PDB:4RMH" FT STRAND 264..266 FT /evidence="ECO:0007829|PDB:5Y0Z" FT HELIX 269..275 FT /evidence="ECO:0007829|PDB:4RMH" FT STRAND 282..288 FT /evidence="ECO:0007829|PDB:4RMH" FT TURN 295..297 FT /evidence="ECO:0007829|PDB:4X3O" FT HELIX 301..303 FT /evidence="ECO:0007829|PDB:5DY4" FT STRAND 309..311 FT /evidence="ECO:0007829|PDB:4RMH" FT STRAND 316..322 FT /evidence="ECO:0007829|PDB:4RMH" FT HELIX 324..334 FT /evidence="ECO:0007829|PDB:4RMH" FT HELIX 338..353 FT /evidence="ECO:0007829|PDB:4RMH" SQ SEQUENCE 389 AA; 43182 MW; A392442A8F6316F1 CRC64; MAEPDPSHPL ETQAGKVQEA QDSDSDSEGG AAGGEADMDF LRNLFSQTLS LGSQKERLLD ELTLEGVARY MQSERCRRVI CLVGAGISTS AGIPDFRSPS TGLYDNLEKY HLPYPEAIFE ISYFKKHPEP FFALAKELYP GQFKPTICHY FMRLLKDKGL LLRCYTQNID TLERIAGLEQ EDLVEAHGTF YTSHCVSASC RHEYPLSWMK EKIFSEVTPK CEDCQSLVKP DIVFFGESLP ARFFSCMQSD FLKVDLLLVM GTSLQVQPFA SLISKAPLST PRLLINKEKA GQSDPFLGMI MGLGGGMDFD SKKAYRDVAW LGECDQGCLA LAELLGWKKE LEDLVRREHA SIDAQSGAGV PNPSTSASPK KSPPPAKDEA RTTEREKPQ //