SIR2_HUMAN
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 03-AUG-2022, entry version 199.
DE RecName: Full=NAD-dependent protein deacetylase sirtuin-2;
DE EC=2.3.1.286 {ECO:0000269|PubMed:11483616, ECO:0000269|PubMed:11812793, ECO:0000269|PubMed:16648462, ECO:0000269|PubMed:18722353, ECO:0000269|PubMed:24177535, ECO:0000269|PubMed:24940000, ECO:0000269|PubMed:25672491};
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 sheat (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 ---------------------------------------------------------------------------
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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. [Q8IXJ6-2]
DR RefSeq; XP_011524956.1; XM_011526654.1. [Q8IXJ6-2]
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 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 AlphaFoldDB; Q8IXJ6; -.
DR SMR; Q8IXJ6; -.
DR BioGRID; 116593; 120.
DR DIP; DIP-33350N; -.
DR IntAct; Q8IXJ6; 49.
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; Q8IXJ6; -.
DR PeptideAtlas; Q8IXJ6; -.
DR PRIDE; Q8IXJ6; -.
DR ProteomicsDB; 71008; -. [Q8IXJ6-1]
DR ProteomicsDB; 71009; -. [Q8IXJ6-2]
DR ProteomicsDB; 71010; -. [Q8IXJ6-3]
DR ProteomicsDB; 71011; -. [Q8IXJ6-4]
DR Antibodypedia; 2167; 593 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 CTD; 22933; -.
DR DisGeNET; 22933; -.
DR GeneCards; SIRT2; -.
DR HGNC; HGNC:10886; SIRT2.
DR HPA; ENSG00000068903; Tissue enhanced (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; FNMEKVG; -.
DR OrthoDB; 973532at2759; -.
DR PhylomeDB; Q8IXJ6; -.
DR TreeFam; TF106181; -.
DR BioCyc; MetaCyc:ENSG00000068903-MON; -.
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; 17 hits in 1098 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 157 other tissues.
DR ExpressionAtlas; Q8IXJ6; baseline and differential.
DR Genevisible; Q8IXJ6; HS.
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:UniProtKB.
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 deacetylase activity (H4-K16 specific); 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:0035729; P:cellular response to hepatocyte growth factor stimulus; IDA:UniProtKB.
DR GO; GO:0071456; P:cellular response to hypoxia; IDA:UniProtKB.
DR GO; GO:0071219; P:cellular response to molecule of bacterial origin; IDA:UniProtKB.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0048012; P:hepatocyte growth factor receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0031507; P:heterochromatin assembly; NAS:UniProtKB.
DR GO; GO:0016575; P:histone deacetylation; IDA:UniProtKB.
DR GO; GO:0070932; P:histone H3 deacetylation; IMP:UniProtKB.
DR GO; GO:0070933; P:histone H4 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:0008285; P:negative regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:1900425; P:negative regulation of defense response to bacterium; IMP: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:0061428; P:negative regulation of transcription from RNA polymerase II promoter in response to hypoxia; IMP:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; 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:0014065; P:phosphatidylinositol 3-kinase signaling; IMP: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: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; ISS:UniProtKB.
DR GO; GO:2000777; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process involved in cellular response to hypoxia; 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:0006471; P:protein ADP-ribosylation; IDA:GO_Central.
DR GO; GO:0006476; P:protein deacetylation; IDA:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; IMP:UniProtKB.
DR GO; GO:0000183; P:rDNA heterochromatin assembly; 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 assembly; NAS:UniProtKB.
DR GO; GO:0090042; P:tubulin deacetylation; IDA:UniProtKB.
DR Gene3D; 3.30.1600.10; -; 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 Pfam; PF02146; SIR2; 1.
DR PIRSF; PIRSF037938; SIR2_euk; 1.
DR SUPFAM; SSF52467; SSF52467; 1.
DR PROSITE; PS50305; SIRTUIN; 1.
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 65..340
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:0000305"
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 CDK2-
FT dependent phosphorylation. Does not inhibit interaction
FT with alpha-tubulin, HDAC6, HIF1A and the cyclin E-CDK2
FT 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: Reduces strongly 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
