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NAD-dependent protein deacetylase sirtuin-2 (EC 3.5.1.-) (Regulatory protein SIR2 homolog 2) (SIR2-like protein 2)

 SIR2_HUMAN              Reviewed;         389 AA.
Q8IXJ6; A8K3V1; B2RB45; O95889; Q924Y7; Q9P0G8; Q9UNT0; Q9Y6E9;
U5TP13;
31-OCT-2003, integrated into UniProtKB/Swiss-Prot.
31-OCT-2003, sequence version 2.
25-OCT-2017, entry version 169.
RecName: Full=NAD-dependent protein deacetylase sirtuin-2;
EC=3.5.1.- {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};
AltName: Full=Regulatory protein SIR2 homolog 2;
AltName: Full=SIR2-like protein 2;
Name=SIRT2; Synonyms=SIR2L, SIR2L2;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND
MUTAGENESIS OF HIS-187.
TISSUE=Testis;
PubMed=10381378; DOI=10.1006/bbrc.1999.0897;
Frye R.A.;
"Characterization of five human cDNAs with homology to the yeast SIR2
gene: Sir2-like proteins (sirtuins) metabolize NAD and may have
protein ADP-ribosyltransferase activity.";
Biochem. Biophys. Res. Commun. 260:273-279(1999).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, AND
TISSUE SPECIFICITY.
PubMed=10393250; DOI=10.1016/S0378-1119(99)00162-6;
Afshar G., Murnane J.P.;
"Characterization of a human gene with sequence homology to
Saccharomyces cerevisiae SIR2.";
Gene 234:161-168(1999).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
PubMed=12065666; DOI=10.1046/j.1471-4159.2002.00847.x;
De Smet C., Nishimori H., Furnari F.B., Boegler O., Huang H.-J.S.,
Cavenee W.K.;
"A novel seven transmembrane receptor induced during the early steps
of astrocyte differentiation identified by differential expression.";
J. Neurochem. 81:575-588(2002).
[4]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), ALTERNATIVE SPLICING (ISOFORMS
1 AND 2), FUNCTION IN DEACETYLATION (ISOFORMS 1 AND 2), CATALYTIC
ACTIVITY, LACK OF DEACETYLATION (ISOFORM 5), INTERACTION WITH EP300
(ISOFORMS 1; 2 AND 5), AND SUBCELLULAR LOCATION (ISOFORMS 1; 2 AND 5).
PubMed=24177535; DOI=10.1016/j.jmb.2013.10.027;
Rack J.G., Vanlinden M.R., Lutter T., Aasland R., Ziegler M.;
"Constitutive nuclear localization of an alternatively spliced
sirtuin-2 isoform.";
J. Mol. Biol. 426:1677-1691(2014).
[5]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
Lennerz V., Fatho M., Gentilini C., Lifke A., Woelfel C., Woelfel T.;
"Response of autologous T cells to a human melanoma is dominated by
individual mutant antigens.";
Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
TISSUE=Adrenal gland;
PubMed=10931946; DOI=10.1073/pnas.160270997;
Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H.,
Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J.,
Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M.,
Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.;
"Gene expression profiling in the human hypothalamus-pituitary-adrenal
axis and full-length cDNA cloning.";
Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
TISSUE=Brain, and Lung;
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[8]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[9]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
TISSUE=Lung;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[10]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 22-389 (ISOFORM 4).
TISSUE=Brain;
Mei G., Yu W., Gibbs R.A.;
Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
[11]
SUBCELLULAR LOCATION.
PubMed=11226170; DOI=10.1093/emboj/20.1.197;
Perrod S., Cockell M.M., Laroche T., Renauld H., Ducrest A.L.,
Bonnard C., Gasser S.M.;
"A cytosolic NAD-dependent deacetylase, Hst2p, can modulate nucleolar
and telomeric silencing in yeast.";
EMBO J. 20:197-209(2001).
[12]
INHIBITION BY SIRTINOL; A3 AND M15, CATALYTIC ACTIVITY, AND ENZYME
REGULATION.
PubMed=11483616; DOI=10.1074/jbc.M106779200;
Grozinger C.M., Chao E.D., Blackwell H.E., Moazed D., Schreiber S.L.;
"Identification of a class of small molecule inhibitors of the sirtuin
family of NAD-dependent deacetylases by phenotypic screening.";
J. Biol. Chem. 276:38837-38843(2001).
[13]
CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-187.
PubMed=11812793; DOI=10.1074/jbc.M111830200;
Borra M.T., O'Neill F.J., Jackson M.D., Marshall B.L., Verdin E.,
Foltz K.R., Denu J.M.;
"Conserved enzymatic production and biological effect of O-acetyl-ADP-
ribose by silent information regulator 2-like NAD+-dependent
deacetylases.";
J. Biol. Chem. 277:12632-12641(2002).
[14]
FUNCTION IN DEACETYLATION OF TUBULIN, SUBCELLULAR LOCATION,
INTERACTION WITH HDAC6, AND MUTAGENESIS OF ASN-168 AND HIS-187.
PubMed=12620231; DOI=10.1016/S1097-2765(03)00038-8;
North B.J., Marshall B.L., Borra M.T., Denu J.M., Verdin E.;
"The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin
deacetylase.";
Mol. Cell 11:437-444(2003).
[15]
FUNCTION AS REGULATOR OF CELL CYCLE PROGRESSION, SUBCELLULAR LOCATION,
DEVELOPMENTAL STAGE, PHOSPHORYLATION, UBIQUITINATION, AND MUTAGENESIS
OF HIS-187.
PubMed=12697818; DOI=10.1128/MCB.23.9.3173-3185.2003;
Dryden S.C., Nahhas F.A., Nowak J.E., Goustin A.-S., Tainsky M.A.;
"Role for human SIRT2 NAD-dependent deacetylase activity in control of
mitotic exit in the cell cycle.";
Mol. Cell. Biol. 23:3173-3185(2003).
[16]
TISSUE SPECIFICITY.
PubMed=12963026; DOI=10.1016/j.bbrc.2003.08.029;
Hiratsuka M., Inoue T., Toda T., Kimura N., Shirayoshi Y.,
Kamitani H., Watanabe T., Ohama E., Tahimic C.G.T., Kurimasa A.,
Oshimura M.;
"Proteomics-based identification of differentially expressed genes in
human gliomas: down-regulation of SIRT2 gene.";
Biochem. Biophys. Res. Commun. 309:558-566(2003).
[17]
INTERACTION WITH HOXA10.
PubMed=15213244; DOI=10.1093/jb/mvh084;
Bae N.S., Swanson M.J., Vassilev A., Howard B.H.;
"Human histone deacetylase SIRT2 interacts with the homeobox
transcription factor HOXA10.";
J. Biochem. 135:695-700(2004).
[18]
SUBCELLULAR LOCATION.
PubMed=16079181; DOI=10.1091/mbc.E05-01-0033;
Michishita E., Park J.Y., Burneskis J.M., Barrett J.C., Horikawa I.;
"Evolutionarily conserved and nonconserved cellular localizations and
functions of human SIRT proteins.";
Mol. Biol. Cell 16:4623-4635(2005).
[19]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
Mann M.;
"Global, in vivo, and site-specific phosphorylation dynamics in
signaling networks.";
Cell 127:635-648(2006).
[20]
FUNCTION IN DEACETYLATION OF HISTONE H4 AND H3, CATALYTIC ACTIVITY,
SUBUNIT, AND SUBCELLULAR LOCATION.
PubMed=16648462; DOI=10.1101/gad.1412706;
Vaquero A., Scher M.B., Lee D.H., Sutton A., Cheng H.L., Alt F.W.,
Serrano L., Sternglanz R., Reinberg D.;
"SirT2 is a histone deacetylase with preference for histone H4 Lys 16
during mitosis.";
Genes Dev. 20:1256-1261(2006).
[21]
FUNCTION AS REGULATOR IN CELL CYCLE PROGRESSION, PHOSPHORYLATION AT
SER-368 BY CDK1, DEPHOSPHORYLATION AT SER-368 BY CDC14A AND CDC14B,
SUBCELLULAR LOCATION, AND MUTAGENESIS OF HIS-187 AND SER-368.
PubMed=17488717; DOI=10.1074/jbc.M702990200;
North B.J., Verdin E.;
"Mitotic regulation of SIRT2 by cyclin-dependent kinase 1-dependent
phosphorylation.";
J. Biol. Chem. 282:19546-19555(2007).
[22]
INTERACTION WITH HDAC6 (ISOFORMS 1 AND 2), PHOSPHORYLATION AT SER-372
AND SER-368, UBIQUITINATION, AND MUTAGENESIS OF SER-53; SER-98;
SER-100; HIS-187; SER-279; THR-280; SER-311; TYR-315; SER-364; SER-368
AND SER-372.
PubMed=17516032; DOI=10.1007/s11010-007-9478-6;
Nahhas F., Dryden S.C., Abrams J., Tainsky M.A.;
"Mutations in SIRT2 deacetylase which regulate enzymatic activity but
not its interaction with HDAC6 and tubulin.";
Mol. Cell. Biochem. 303:221-230(2007).
[23]
FUNCTION IN AXONAL DEGENERATION.
PubMed=17574768; DOI=10.1016/j.neuroscience.2007.04.059;
Suzuki K., Koike T.;
"Mammalian Sir2-related protein (SIRT) 2-mediated modulation of
resistance to axonal degeneration in slow Wallerian degeneration mice:
a crucial role of tubulin deacetylation.";
Neuroscience 147:599-612(2007).
[24]
FUNCTION AS REGULATOR OF MITOTIC CELL CYCLE CHECKPOINT, SUBCELLULAR
LOCATION, NUCLEOCYTOPLASMIC SHUTTLING, INDUCTION, TISSUE SPECIFICITY,
AND MUTAGENESIS OF GLN-167; ASN-168 AND HIS-187.
PubMed=16909107; DOI=10.1038/sj.onc.1209857;
Inoue T., Hiratsuka M., Osaki M., Yamada H., Kishimoto I.,
Yamaguchi S., Nakano S., Katoh M., Ito H., Oshimura M.;
"SIRT2, a tubulin deacetylase, acts to block the entry to chromosome
condensation in response to mitotic stress.";
Oncogene 26:945-957(2007).
[25]
FUNCTION AS REGULATOR IN CELL CYCLE PROGRESSION, INTERACTION WITH
AURKA, SUBCELLULAR LOCATION, NUCLEOCYTOPLASMIC SHUTTLING, AND
MUTAGENESIS OF HIS-187.
PubMed=17726514; DOI=10.1371/journal.pone.0000784;
North B.J., Verdin E.;
"Interphase nucleo-cytoplasmic shuttling and localization of SIRT2
during mitosis.";
PLoS ONE 2:E784-E784(2007).
[26]
FUNCTION IN DEACETYLATION OF TP53, FUNCTION IN REGULATION OF TP53, AND
INTERACTION WITH YWHAB AND YWHAG.
PubMed=18249187; DOI=10.1016/j.bbrc.2008.01.114;
Jin Y.H., Kim Y.J., Kim D.W., Baek K.H., Kang B.Y., Yeo C.Y.,
Lee K.Y.;
"Sirt2 interacts with 14-3-3 beta/gamma and down-regulates the
activity of p53.";
Biochem. Biophys. Res. Commun. 368:690-695(2008).
[27]
INTERACTION WITH EP300, ACETYLATION BY EP300, ENZYME REGULATION, AND
CATALYTIC ACTIVITY.
PubMed=18722353; DOI=10.1016/j.bbrc.2008.08.042;
Han Y., Jin Y.H., Kim Y.J., Kang B.Y., Choi H.J., Kim D.W., Yeo C.Y.,
Lee K.Y.;
"Acetylation of Sirt2 by p300 attenuates its deacetylase activity.";
Biochem. Biophys. Res. Commun. 375:576-580(2008).
[28]
FUNCTION IN STRESS RESPONSE, AND INDUCTION BY STRESS.
PubMed=18640115; DOI=10.1016/j.febslet.2008.07.016;
Lynn E.G., McLeod C.J., Gordon J.P., Bao J., Sack M.N.;
"SIRT2 is a negative regulator of anoxia-reoxygenation tolerance via
regulation of 14-3-3 zeta and BAD in H9c2 cells.";
FEBS Lett. 582:2857-2862(2008).
[29]
FUNCTION IN DEACETYLATION OF ALPHA-TUBULIN AND HISTONE, FUNCTION IN
REGULATION OF CELL MOTILITY, INTERACTION WITH CDK5R1; CDK5 AND CYCLIN
E-CDK2 COMPLEX, PHOSPHORYLATION AT SER-368 BY CDK2 AND CDK5, AND
MUTAGENESIS OF SER-368.
PubMed=18332217; DOI=10.1083/jcb.200707126;
Pandithage R., Lilischkis R., Harting K., Wolf A., Jedamzik B.,
Luscher-Firzlaff J., Vervoorts J., Lasonder E., Kremmer E., Knoll B.,
Luscher B.;
"The regulation of SIRT2 function by cyclin-dependent kinases affects
cell motility.";
J. Cell Biol. 180:915-929(2008).
[30]
FUNCTION IN DEACETYLATION OF EP300 AND ALPHA-TUBULIN, FUNCTION IN
REGULATION OF EP300, AND SUBCELLULAR LOCATION.
PubMed=18995842; DOI=10.1016/j.molcel.2008.09.018;
Black J.C., Mosley A., Kitada T., Washburn M., Carey M.;
"The SIRT2 deacetylase regulates autoacetylation of p300.";
Mol. Cell 32:449-455(2008).
[31]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=18669648; DOI=10.1073/pnas.0805139105;
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
Elledge S.J., Gygi S.P.;
"A quantitative atlas of mitotic phosphorylation.";
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
[32]
ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS
SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=19413330; DOI=10.1021/ac9004309;
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
Mohammed S.;
"Lys-N and trypsin cover complementary parts of the phosphoproteome in
a refined SCX-based approach.";
Anal. Chem. 81:4493-4501(2009).
[33]
FUNCTION AS REGULATOR OF MITOTIC CELL CYCLE CHECKPOINT.
PubMed=19282667; DOI=10.4161/cc.8.8.8245;
Inoue T., Nakayama Y., Yamada H., Li Y.C., Yamaguchi S., Osaki M.,
Kurimasa A., Hiratsuka M., Katoh M., Oshimura M.;
"SIRT2 downregulation confers resistance to microtubule inhibitors by
prolonging chronic mitotic arrest.";
Cell Cycle 8:1279-1291(2009).
[34]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Leukemic T-cell;
PubMed=19690332; DOI=10.1126/scisignal.2000007;
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
Rodionov V., Han D.K.;
"Quantitative phosphoproteomic analysis of T cell receptor signaling
reveals system-wide modulation of protein-protein interactions.";
Sci. Signal. 2:RA46-RA46(2009).
[35]
FUNCTION IN DEACETYLATION OF HISTONE H3.
PubMed=20587414; DOI=10.1074/jbc.M110.149393;
Vempati R.K., Jayani R.S., Notani D., Sengupta A., Galande S.,
Haldar D.;
"p300-mediated acetylation of histone H3 lysine 56 functions in DNA
damage response in mammals.";
J. Biol. Chem. 285:28553-28564(2010).
[36]
FUNCTION IN DEACETYLATION OF RELA, FUNCTION IN REGULATION OF RELA
ACTIVITY, INTERACTION WITH RELA, AND SUBCELLULAR LOCATION.
PubMed=21081649; DOI=10.1242/jcs.073783;
Rothgiesser K.M., Erener S., Waibel S., Luscher B., Hottiger M.O.;
"SIRT2 regulates NF-kappaB dependent gene expression through
deacetylation of p65 Lys310.";
J. Cell Sci. 123:4251-4258(2010).
[37]
FUNCTION IN DEACETYLATION OF FOXO1, FUNCTION IN AUTOPHAGY, AND
INTERACTION WITH FOXO1.
PubMed=20543840; DOI=10.1038/ncb2069;
Zhao Y., Yang J., Liao W., Liu X., Zhang H., Wang S., Wang D.,
Feng J., Yu L., Zhu W.G.;
"Cytosolic FoxO1 is essential for the induction of autophagy and
tumour suppressor activity.";
Nat. Cell Biol. 12:665-675(2010).
[38]
FUNCTION IN DEACETYLATION OF CDC20 AND FZR1, FUNCTION AS A TUMOR
SUPPRESSOR, TISSUE SPECIFICITY, AND MUTAGENESIS OF HIS-187.
PubMed=22014574; DOI=10.1016/j.ccr.2011.09.004;
Kim H.S., Vassilopoulos A., Wang R.H., Lahusen T., Xiao Z., Xu X.,
Li C., Veenstra T.D., Li B., Yu H., Ji J., Wang X.W., Park S.H.,
Cha Y.I., Gius D., Deng C.X.;
"SIRT2 maintains genome integrity and suppresses tumorigenesis through
regulating APC/C activity.";
Cancer Cell 20:487-499(2011).
[39]
TISSUE SPECIFICITY.
PubMed=21791548; DOI=10.1093/hmg/ddr326;
Maxwell M.M., Tomkinson E.M., Nobles J., Wizeman J.W., Amore A.M.,
Quinti L., Chopra V., Hersch S.M., Kazantsev A.G.;
"The Sirtuin 2 microtubule deacetylase is an abundant neuronal protein
that accumulates in the aging CNS.";
Hum. Mol. Genet. 20:3986-3996(2011).
[40]
FUNCTION IN DEACETYLATION OF PCK1, POSSIBLE FUNCTION IN REGULATION OF
BLOOD GLUCOSE HOMEOSTASIS, AND INDUCTION BY GLUCOSE.
PubMed=21726808; DOI=10.1016/j.molcel.2011.04.028;
Jiang W., Wang S., Xiao M., Lin Y., Zhou L., Lei Q., Xiong Y.,
Guan K.L., Zhao S.;
"Acetylation regulates gluconeogenesis by promoting PEPCK1 degradation
via recruiting the UBR5 ubiquitin ligase.";
Mol. Cell 43:33-44(2011).
[41]
FUNCTION IN DEACETYLATION OF PARD3, AND INTERACTION WITH PARD3.
PubMed=21949390; DOI=10.1073/pnas.1104969108;
Beirowski B., Gustin J., Armour S.M., Yamamoto H., Viader A.,
North B.J., Michan S., Baloh R.H., Golden J.P., Schmidt R.E.,
Sinclair D.A., Auwerx J., Milbrandt J.;
"Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through
polarity protein Par-3/atypical protein kinase C (aPKC) signaling.";
Proc. Natl. Acad. Sci. U.S.A. 108:E952-961(2011).
[42]
FUNCTION IN DEACETYLATION OF EIF5A.
PubMed=22771473; DOI=10.1016/j.febslet.2012.06.042;
Ishfaq M., Maeta K., Maeda S., Natsume T., Ito A., Yoshida M.;
"Acetylation regulates subcellular localization of eukaryotic
translation initiation factor 5A (eIF5A).";
FEBS Lett. 586:3236-3241(2012).
[43]
FUNCTION IN AUTOPHAGY, AND SUBCELLULAR LOCATION.
PubMed=22819792; DOI=10.1016/j.neuint.2012.07.010;
Gal J., Bang Y., Choi H.J.;
"SIRT2 interferes with autophagy-mediated degradation of protein
aggregates in neuronal cells under proteasome inhibition.";
Neurochem. Int. 61:992-1000(2012).
[44]
REVIEW, AND FUNCTION AS A TUMOR SUPPRESSOR.
PubMed=22943040;
Park S.H., Zhu Y., Ozden O., Kim H.S., Jiang H., Deng C.X., Gius D.,
Vassilopoulos A.;
"SIRT2 is a tumor suppressor that connects aging, acetylome, cell
cycle signaling, and carcinogenesis.";
Transl. Cancer Res. 1:15-21(2012).
[45]
INTERACTION WITH MAPK1/ERK2 AND MAPK3/ERK1.
PubMed=23806683; DOI=10.1016/j.bbrc.2013.06.053;
Choi Y.H., Kim H., Lee S.H., Jin Y.H., Lee K.Y.;
"ERK1/2 regulates SIRT2 deacetylase activity.";
Biochem. Biophys. Res. Commun. 437:245-249(2013).
[46]
FUNCTION IN DEACETYLATION OF HISTONE H4K16 AND KMT5A, FUNCTION IN
REGULATION OF KMT5A ACTIVITY; H4K20 METHYLATION; CELL CYCLE
PROGRESSION AND GENOMIC STABILITY, INTERACTION WITH KMT5A, SUBCELLULAR
LOCATION, AND MASS SPECTROMETRY.
PubMed=23468428; DOI=10.1101/gad.211342.112;
Serrano L., Martinez-Redondo P., Marazuela-Duque A., Vazquez B.N.,
Dooley S.J., Voigt P., Beck D.B., Kane-Goldsmith N., Tong Q.,
Rabanal R.M., Fondevila D., Munoz P., Kruger M., Tischfield J.A.,
Vaquero A.;
"The tumor suppressor SirT2 regulates cell cycle progression and
genome stability by modulating the mitotic deposition of H4K20
methylation.";
Genes Dev. 27:639-653(2013).
[47]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-368, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma, and Erythroleukemia;
PubMed=23186163; DOI=10.1021/pr300630k;
Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
Mohammed S.;
"Toward a comprehensive characterization of a human cancer cell
phosphoproteome.";
J. Proteome Res. 12:260-271(2013).
[48]
FUNCTION.
PubMed=23932781; DOI=10.1016/j.molcel.2013.07.002;
Lin R., Tao R., Gao X., Li T., Zhou X., Guan K.L., Xiong Y., Lei Q.Y.;
"Acetylation stabilizes ATP-citrate lyase to promote lipid
biosynthesis and tumor growth.";
Mol. Cell 51:506-518(2013).
[49]
FUNCTION IN DEACETYLATION OF HISTONE H3K18, FUNCTION IN LISTERIA
INFECTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASN-168.
PubMed=23908241; DOI=10.1126/science.1238858;
Eskandarian H.A., Impens F., Nahori M.A., Soubigou G., Coppee J.Y.,
Cossart P., Hamon M.A.;
"A role for SIRT2-dependent histone H3K18 deacetylation in bacterial
infection.";
Science 341:1238858-1238858(2013).
[50]
FUNCTION IN HISTONE H4 DEACETYLATION, FUNCTION IN REGULATION OF VEGFA
EXPRESSION AND ANGIOGENESIS, CATALYTIC ACTIVITY, AND INTERACTION WITH
SARS.
PubMed=24940000;
Shi Y., Xu X., Zhang Q., Fu G., Mo Z., Wang G.S., Kishi S., Yang X.L.;
"tRNA synthetase counteracts c-Myc to develop functional
vasculature.";
Elife 3:E02349-E02349(2014).
[51]
FUNCTION IN DEACETYLATION OF G6PD, FUNCTION IN REGULATION OF G6PD
ACTIVITY, INTERACTION WITH G6PD, AND MUTAGENESIS OF ASN-168.
PubMed=24769394; DOI=10.1002/embj.201387224;
Wang Y.P., Zhou L.S., Zhao Y.Z., Wang S.W., Chen L.L., Liu L.X.,
Ling Z.Q., Hu F.J., Sun Y.P., Zhang J.Y., Yang C., Yang Y., Xiong Y.,
Guan K.L., Ye D.;
"Regulation of G6PD acetylation by KAT9/SIRT2 modulates NADPH
homeostasis and cell survival during oxidative stress.";
EMBO J. 33:1304-1320(2014).
[52]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23; SER-25 AND SER-27,
AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Liver;
PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
Wang L., Ye M., Zou H.;
"An enzyme assisted RP-RPLC approach for in-depth analysis of human
liver phosphoproteome.";
J. Proteomics 96:253-262(2014).
[53]
FUNCTION IN DEACETYLATION OF HIF1A, FUNCTION IN REGULATION OF HIF1A
STABILITY, INTERACTION WITH HIF1A, MUTAGENESIS OF HIS-187, SUBCELLULAR
LOCATION, AND MASS SPECTROMETRY.
PubMed=24681946; DOI=10.1038/onc.2014.76;
Seo K.S., Park J.H., Heo J.Y., Jing K., Han J., Min K.N., Kim C.,
Koh G.Y., Lim K., Kang G.Y., Uee Lee J., Yim Y.H., Shong M.,
Kwak T.H., Kweon G.R.;
"SIRT2 regulates tumour hypoxia response by promoting HIF-1alpha
hydroxylation.";
Oncogene 34:1354-1362(2015).
[54]
INTERACTION WITH BEX4, AND MUTAGENESIS OF HIS-187.
PubMed=27512957; DOI=10.1038/cddis.2016.240;
Lee J.K., Lee J., Go H., Lee C.G., Kim S., Kim H.S., Cho H.,
Choi K.S., Ha G.H., Lee C.W.;
"Oncogenic microtubule hyperacetylation through BEX4-mediated sirtuin
2 inhibition.";
Cell Death Dis. 7:E2336-E2336(2016).
[55]
X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 34-356 IN COMPLEX WITH ZINC,
AND MUTAGENESIS OF ARG-97; GLN-167; ASN-168; ASP-170 AND HIS-187.
PubMed=11427894; DOI=10.1038/89668;
Finnin M.S., Donigian J.R., Pavletich N.P.;
"Structure of the histone deacetylase SIRT2.";
Nat. Struct. Biol. 8:621-625(2001).
[56]
X-RAY CRYSTALLOGRAPHY (1.63 ANGSTROMS) OF 34-356 IN COMPLEX WITH NAD
ANALOG AND ZINC.
PubMed=23454361; DOI=10.1016/j.jsb.2013.02.012;
Moniot S., Schutkowski M., Steegborn C.;
"Crystal structure analysis of human Sirt2 and its ADP-ribose
complex.";
J. Struct. Biol. 182:136-143(2013).
[57]
X-RAY CRYSTALLOGRAPHY (2.52 ANGSTROMS) OF 55-356 IN COMPLEX WITH
PEPTIDE INHIBITOR AND ZINC, ENZYME REGULATION, CATALYTIC ACTIVITY, AND
MUTAGENESIS OF GLU-116; GLU-120; PHE-244; GLN-265; SER-271 AND
ASP-294.
PubMed=24389023; DOI=10.1016/j.str.2013.12.001;
Yamagata K., Goto Y., Nishimasu H., Morimoto J., Ishitani R.,
Dohmae N., Takeda N., Nagai R., Komuro I., Suga H., Nureki O.;
"Structural basis for potent inhibition of SIRT2 deacetylase by a
macrocyclic peptide inducing dynamic structural change.";
Structure 22:345-352(2014).
[58] {ECO:0000244|PDB:4RMG, ECO:0000244|PDB:4RMH, ECO:0000244|PDB:4RMI, ECO:0000244|PDB:4RMJ}
X-RAY CRYSTALLOGRAPHY (1.42 ANGSTROMS) OF 56-356 IN COMPLEX WITH NAD
AND ZINC, CATALYTIC ACTIVITY, AND COFACTOR.
PubMed=25672491; DOI=10.1038/ncomms7263;
Rumpf T., Schiedel M., Karaman B., Roessler C., North B.J.,
Lehotzky A., Olah J., Ladwein K.I., Schmidtkunz K., Gajer M.,
Pannek M., Steegborn C., Sinclair D.A., Gerhardt S., Ovadi J.,
Schutkowski M., Sippl W., Einsle O., Jung M.;
"Selective Sirt2 inhibition by ligand-induced rearrangement of the
active site.";
Nat. Commun. 6:6263-6263(2015).
-!- FUNCTION: NAD-dependent protein deacetylase, which deacetylates
internal lysines on histone and alpha-tubulin as well as many
other proteins such as key transcription factors (PubMed:24177535,
PubMed:12620231, PubMed:16648462, PubMed:18249187,
PubMed:18332217, PubMed:18995842, PubMed:20587414,
PubMed:21081649, PubMed:20543840, PubMed:22014574,
PubMed:21726808, PubMed:21949390, PubMed:22771473,
PubMed:23468428, PubMed:23908241, PubMed:24940000,
PubMed:24769394, PubMed:24681946). Participates in the modulation
of multiple and diverse biological processes such as cell cycle
control, genomic integrity, microtubule dynamics, cell
differentiation, metabolic networks, and autophagy. Plays a major
role in the control of cell cycle progression and genomic
stability. Functions in the antephase checkpoint preventing
precocious mitotic entry in response to microtubule stress agents,
and hence allowing proper inheritance of chromosomes. Positively
regulates the anaphase promoting complex/cyclosome (APC/C)
ubiquitin ligase complex activity by deacetylating CDC20 and FZR1,
then allowing progression through mitosis. Associates both with
chromatin at transcriptional start sites (TSSs) and enhancers of
active genes. Plays a role in cell cycle and chromatin compaction
through epigenetic modulation of the regulation of histone H4
'Lys-20' methylation (H4K20me1) during early mitosis. Specifically
deacetylates histone H4 at 'Lys-16' (H4K16ac) between the G2/M
transition and metaphase enabling H4K20me1 deposition by KMT5A
leading to ulterior levels of H4K20me2 and H4K20me3 deposition
throughout cell cycle, and mitotic S-phase progression
(PubMed:23468428). Deacetylates KMT5A modulating KMT5A chromatin
localization during the mitotic stress response (PubMed:23468428).
Deacetylates also histone H3 at 'Lys-57' (H3K56ac) during the
mitotic G2/M transition. Upon bacterium Listeria monocytogenes
infection, deacetylates 'Lys-18' of histone H3 in a receptor
tyrosine kinase MET- and PI3K/Akt-dependent manner, thereby
inhibiting transcriptional activity and promoting late stages of
listeria infection (PubMed:23908241). During oocyte meiosis
progression, may deacetylate histone H4 at 'Lys-16' (H4K16ac) and
alpha-tubulin, regulating spindle assembly and chromosome
alignment by influencing microtubule dynamics and kinetochore
function. Deacetylates histone H4 at 'Lys-16' (H4K16ac) at the
VEGFA promoter and thereby contributes to regulate expression of
VEGFA, a key regulator of angiogenesis (PubMed:24940000).
Deacetylates alpha-tubulin at 'Lys-40' and hence controls neuronal
motility, oligodendroglial cell arbor projection processes and
proliferation of non-neuronal cells. Phosphorylation at Ser-368 by
a G1/S-specific cyclin E-CDK2 complex inactivates SIRT2-mediated
alpha-tubulin deacetylation, negatively regulating cell adhesion,
cell migration and neurite outgrowth during neuronal
differentiation. Deacetylates PARD3 and participates in the
regulation of Schwann cell peripheral myelination formation during
early postnatal development and during postinjury remyelination.
Involved in several cellular metabolic pathways. Plays a role in
the regulation of blood glucose homeostasis by deacetylating and
stabilizing phosphoenolpyruvate carboxykinase PCK1 activity in
response to low nutrient availability. Acts as a key regulator in
the pentose phosphate pathway (PPP) by deacetylating and
activating the glucose-6-phosphate G6PD enzyme, and therefore,
stimulates the production of cytosolic NADPH to counteract
oxidative damage. Maintains energy homeostasis in response to
nutrient deprivation as well as energy expenditure by inhibiting
adipogenesis and promoting lipolysis. Attenuates adipocyte
differentiation by deacetylating and promoting FOXO1 interaction
to PPARG and subsequent repression of PPARG-dependent
transcriptional activity. Plays a role in the regulation of
lysosome-mediated degradation of protein aggregates by autophagy
in neuronal cells. Deacetylates FOXO1 in response to oxidative
stress or serum deprivation, thereby negatively regulating FOXO1-
mediated autophagy (PubMed:20543840). Deacetylates a broad range
of transcription factors and co-regulators regulating target gene
expression. Deacetylates transcriptional factor FOXO3 stimulating
the ubiquitin ligase SCF(SKP2)-mediated FOXO3 ubiquitination and
degradation (By similarity). Deacetylates HIF1A and therefore
promotes HIF1A degradation and inhibition of HIF1A transcriptional
activity in tumor cells in response to hypoxia (PubMed:24681946).
Deacetylates RELA in the cytoplasm inhibiting NF-kappaB-dependent
transcription activation upon TNF-alpha stimulation. Inhibits
transcriptional activation by deacetylating p53/TP53 and EP300
(PubMed:18249187). Deacetylates also EIF5A (PubMed:22771473).
Functions as a negative regulator on oxidative stress-tolerance in
response to anoxia-reoxygenation conditions. Plays a role as tumor
suppressor (PubMed:22014574). {ECO:0000250|UniProtKB:Q8VDQ8,
ECO:0000269|PubMed:12620231, ECO:0000269|PubMed:12697818,
ECO:0000269|PubMed:16648462, ECO:0000269|PubMed:16909107,
ECO:0000269|PubMed:17488717, ECO:0000269|PubMed:17574768,
ECO:0000269|PubMed:17726514, ECO:0000269|PubMed:18249187,
ECO:0000269|PubMed:18332217, ECO:0000269|PubMed:18640115,
ECO:0000269|PubMed:18722353, ECO:0000269|PubMed:18995842,
ECO:0000269|PubMed:19282667, ECO:0000269|PubMed:20543840,
ECO:0000269|PubMed:20587414, ECO:0000269|PubMed:21081649,
ECO:0000269|PubMed:21726808, ECO:0000269|PubMed:21949390,
ECO:0000269|PubMed:22014574, ECO:0000269|PubMed:22771473,
ECO:0000269|PubMed:22819792, ECO:0000269|PubMed:23468428,
ECO:0000269|PubMed:23908241, ECO:0000269|PubMed:23932781,
ECO:0000269|PubMed:24177535, ECO:0000269|PubMed:24681946,
ECO:0000269|PubMed:24769394, ECO:0000269|PubMed:24940000}.
-!- FUNCTION: Isoform 1: Deacetylates EP300, alpha-tubulin and histone
H3 and H4. {ECO:0000269|PubMed:24177535}.
-!- FUNCTION: Isoform 2: Deacetylates EP300, alpha-tubulin and histone
H3 and H4. {ECO:0000269|PubMed:24177535}.
-!- FUNCTION: Isoform 5: Lacks deacetylation activity.
{ECO:0000269|PubMed:24177535}.
-!- CATALYTIC ACTIVITY: NAD(+) + an acetylprotein = nicotinamide + O-
acetyl-ADP-ribose + a protein. {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,
ECO:0000269|PubMed:24389023, ECO:0000269|PubMed:24940000,
ECO:0000269|PubMed:25672491}.
-!- COFACTOR:
Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
Evidence={ECO:0000269|PubMed:25672491};
Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:25672491};
-!- ENZYME REGULATION: Inhibited by Sirtinol, A3 and M15 small
molecules (PubMed:11483616). Inhibited by nicotinamide. Inhibited
by a macrocyclic peptide inhibitor S2iL5 (PubMed:24389023).
Inhibited by EP300-induced acetylation (PubMed:18722353).
{ECO:0000269|PubMed:11483616, ECO:0000269|PubMed:18722353,
ECO:0000269|PubMed:24389023}.
-!- SUBUNIT: Interacts with CDC20, FOXO3 and FZR1. Associates with
microtubules in primary cortical mature neurons (By similarity).
Homotrimer. Isoform 1 and isoform 2 interact (via both
phosphorylated, unphosphorylated, active or inactive forms) with
HDAC6; the interaction is necessary for the complex to interact
with alpha-tubulin, suggesting that these proteins belong to a
large complex that deacetylates the cytoskeleton. Interacts with
FOXO1; the interaction is disrupted upon serum-starvation or
oxidative stress, leading to increased level of acetylated FOXO1
and induction of autophagy. Interacts with RELA; the interaction
occurs in the cytoplasm and is increased in a TNF-alpha-dependent
manner. Interacts with HOXA10; the interaction is direct.
Interacts with YWHAB and YWHAG; the interactions occur in a AKT-
dependent manner and increase SIRT2-dependent TP53 deacetylation.
Interacts with MAPK1/ERK2 and MAPK3/ERK1; the interactions
increase SIRT2 stability and deacetylation activity. Interacts
(phosphorylated form) with KMT5A isoform 2; the interaction is
direct, stimulates KMT5A-mediated methyltransferase activity on
histone at 'Lys-20' (H4K20me1) and is increased in a H(2)O(2)-
induced oxidative stress-dependent manner. Interacts with G6PD;
the interaction is enhanced by H(2)O(2) treatment. Interacts with
a G1/S-specific cyclin E-CDK2 complex. Interacts with AURKA,
CDK5R1 (p35 form) and CDK5 and HIF1A. Isoform 1, isoform 2 and
isoform 5 interact (via C-terminus region) with EP300
(PubMed:24177535). Interacts with the tRNA ligase SARS; recruited
to the VEGFA promoter via interaction with SARS (PubMed:24940000).
Interacts with BEX4; negatively regulates alpha-tubulin
deacetylation by SIRT2 (PubMed:27512957). {ECO:0000250,
ECO:0000250|UniProtKB:Q8VDQ8, ECO:0000269|PubMed:11427894,
ECO:0000269|PubMed:12620231, ECO:0000269|PubMed:15213244,
ECO:0000269|PubMed:16648462, ECO:0000269|PubMed:17726514,
ECO:0000269|PubMed:18249187, ECO:0000269|PubMed:18332217,
ECO:0000269|PubMed:18722353, ECO:0000269|PubMed:20543840,
ECO:0000269|PubMed:21081649, ECO:0000269|PubMed:21949390,
ECO:0000269|PubMed:23454361, ECO:0000269|PubMed:23468428,
ECO:0000269|PubMed:23806683, ECO:0000269|PubMed:24177535,
ECO:0000269|PubMed:24389023, ECO:0000269|PubMed:24681946,
ECO:0000269|PubMed:24769394, ECO:0000269|PubMed:24940000,
ECO:0000269|PubMed:27512957}.
-!- INTERACTION:
O60566:BUB1B; NbExp=3; IntAct=EBI-477232, EBI-1001438;
O60729:CDC14B; NbExp=2; IntAct=EBI-477232, EBI-970231;
Q12834:CDC20; NbExp=2; IntAct=EBI-5240785, EBI-367462;
Q9UM11:FZR1; NbExp=2; IntAct=EBI-5240785, EBI-724997;
P11413:G6PD; NbExp=3; IntAct=EBI-477232, EBI-4289891;
Q92831:KAT2B; NbExp=4; IntAct=EBI-477232, EBI-477430;
Q04206:RELA; NbExp=2; IntAct=EBI-477232, EBI-73886;
Q9Y572:RIPK3; NbExp=2; IntAct=EBI-477232, EBI-298250;
-!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm, perinuclear region.
Cytoplasm. Cytoplasm, cytoskeleton. Cytoplasm, cytoskeleton,
microtubule organizing center, centrosome. Cytoplasm,
cytoskeleton, microtubule organizing center, centrosome,
centriole. Cytoplasm, cytoskeleton, spindle. Midbody. Chromosome.
Perikaryon {ECO:0000250}. Cell projection {ECO:0000250}. Cell
projection, growth cone {ECO:0000250}. Myelin membrane
{ECO:0000250}. Note=Deacetylates FOXO3 in the cytoplasm.
Colocalizes with PLP1 in internodal regions, at paranodal axoglial
junction and Schmidt-Lanterman incisures of myelin sheat.
Colocalizes with CDK5R1 in the perikaryon, neurites and growth
cone of hippocampal neurons. Colocalizes with alpha-tubulin in
neuronal growth cone. Localizes in the cytoplasm and nucleus of
germinal vesicle (GV) stage oocytes. Colocalizes with alpha-
tubulin on the meiotic spindle as the oocytes enter into
metaphase, and also during meiotic anaphase and telophase,
especially with the midbody. Colocalizes with PARD3 in internodal
region of axons. Colocalizes with acetylated alpha-tubulin in cell
projection processes during primary oligodendrocyte precursor
(OLP) differentiation (By similarity). Localizes in the cytoplasm
during most of the cell cycle except in the G2/M transition and
during mitosis, where it is localized in association with
chromatin and induces deacetylation of histone at 'Lys-16'
(H4K16ac). Colocalizes with KMT5A at mitotic foci. Colocalizes
with CDK1 at centrosome during prophase and splindle fibers during
metaphase. Colocalizes with Aurora kinase AURKA at centrosome
during early prophase and in the centrioles and growing mitotic
spindle throughout metaphase. Colocalizes with Aurora kinase AURKB
during cytokinesis with the midbody. Colocalizes with
microtubules. Detected in perinuclear foci that may be aggresomes
containing misfolded, ubiquitinated proteins. Shuttles between the
cytoplasm and the nucleus through the CRM1 export pathway.
Colocalizes with EP300 in the nucleus. Translocates to the nucleus
and chromatin upon bacterium Listeria monocytogenes infection in
interphase cells. {ECO:0000250}.
-!- SUBCELLULAR LOCATION: Isoform 1: Cytoplasm
{ECO:0000269|PubMed:24177535}. Nucleus
{ECO:0000269|PubMed:24177535}. Note=Predominantly localized in the
cytoplasmic.
-!- SUBCELLULAR LOCATION: Isoform 2: Cytoplasm
{ECO:0000269|PubMed:24177535}. Nucleus
{ECO:0000269|PubMed:24177535}. Note=Predominantly localized in the
cytoplasmic.
-!- SUBCELLULAR LOCATION: Isoform 5: Cytoplasm
{ECO:0000269|PubMed:24177535}. Nucleus
{ECO:0000269|PubMed:24177535}. Note=Predominantly localized in the
nucleus.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=5;
Name=1;
IsoId=Q8IXJ6-1; Sequence=Displayed;
Name=2;
IsoId=Q8IXJ6-2; Sequence=VSP_008724;
Name=3;
IsoId=Q8IXJ6-3; Sequence=VSP_008726;
Note=No experimental confirmation available.;
Name=4;
IsoId=Q8IXJ6-4; Sequence=VSP_008727, VSP_008728;
Note=No experimental confirmation available.;
Name=5;
IsoId=Q8IXJ6-5; Sequence=VSP_055328;
Note=Lacks deacetylase activity, at least toward known SIRT2
targets.;
-!- TISSUE SPECIFICITY: Isoform 1 is expressed in heart, liver and
skeletal muscle, weakly expressed in the cortex. Isoform 2 is
strongly expressed in the cortex, weakly expressed in heart and
liver. Weakly expressed in several malignancies including breast,
liver, brain, kidney and prostate cancers compared to normal
tissues. Weakly expressed in glioma cell lines compared to normal
brain tissues (at protein level). Widely expressed. Highly
expressed in heart, brain and skeletal muscle, while it is weakly
expressed in placenta and lung. Down-regulated in many gliomas
suggesting that it may act as a tumor suppressor gene in human
gliomas possibly through the regulation of microtubule network.
{ECO:0000269|PubMed:10381378, ECO:0000269|PubMed:10393250,
ECO:0000269|PubMed:12963026, ECO:0000269|PubMed:16909107,
ECO:0000269|PubMed:21791548, ECO:0000269|PubMed:22014574}.
-!- DEVELOPMENTAL STAGE: Peaks during mitosis. After mitosis, it is
probably degraded by the 26S proteasome.
{ECO:0000269|PubMed:12697818}.
-!- INDUCTION: Up-regulated in response to low levels of glucose and
anoxia-reoxygenation stress. Up-regulated by trichostatin A. Down-
regulated in response to high levels of glucose. Down-regulated by
histone deacetylation in several tumors.
{ECO:0000269|PubMed:16909107, ECO:0000269|PubMed:18640115,
ECO:0000269|PubMed:21726808}.
-!- PTM: Phosphorylated at phosphoserine and phosphothreonine.
Phosphorylated at Ser-368 by a mitotic kinase CDK1/cyclin B at the
G2/M transition; phosphorylation regulates the delay in cell-cycle
progression. Phosphorylated at Ser-368 by a mitotic kinase G1/S-
specific cyclin E/Cdk2 complex; phosphorylation inactivates SIRT2-
mediated alpha-tubulin deacetylation and thereby negatively
regulates cell adhesion, cell migration and neurite outgrowth
during neuronal differentiation. Phosphorylated by cyclin A/Cdk2
and p35-Cdk5 complexes and to a lesser extent by the cyclin
D3/Cdk4 and cyclin B/Cdk1, in vitro. Dephosphorylated at Ser-368
by CDC14A and CDC14B around early anaphase.
{ECO:0000269|PubMed:12697818, ECO:0000269|PubMed:17488717,
ECO:0000269|PubMed:17516032, ECO:0000269|PubMed:18332217}.
-!- PTM: Acetylated by EP300; acetylation leads both to the decreased
of SIRT2-mediated alpha-tubulin deacetylase activity and SIRT2-
mediated down-regulation of TP53 transcriptional activity.
{ECO:0000269|PubMed:18722353}.
-!- PTM: Ubiquitinated. {ECO:0000269|PubMed:12697818,
ECO:0000269|PubMed:17516032}.
-!- SIMILARITY: Belongs to the sirtuin family. Class I subfamily.
{ECO:0000305}.
-!- SEQUENCE CAUTION:
Sequence=AAD45971.1; Type=Erroneous initiation; Evidence={ECO:0000305};
Sequence=AAF67015.1; Type=Frameshift; Positions=Several; Evidence={ECO:0000305};
-----------------------------------------------------------------------
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EMBL; AF083107; AAD40850.2; -; mRNA.
EMBL; AF095714; AAD45971.1; ALT_INIT; mRNA.
EMBL; AY030277; AAK51133.1; -; mRNA.
EMBL; KF032391; AGZ02589.1; -; mRNA.
EMBL; AJ505014; CAD43717.1; -; mRNA.
EMBL; AF160214; AAF67015.1; ALT_FRAME; mRNA.
EMBL; AK290716; BAF83405.1; -; mRNA.
EMBL; AK314492; BAG37092.1; -; mRNA.
EMBL; CH471126; EAW56833.1; -; Genomic_DNA.
EMBL; CH471126; EAW56835.1; -; Genomic_DNA.
EMBL; BC003012; AAH03012.1; -; mRNA.
EMBL; BC003547; AAH03547.1; -; mRNA.
EMBL; AF131800; AAD20046.1; -; mRNA.
CCDS; CCDS12523.1; -. [Q8IXJ6-1]
CCDS; CCDS46069.1; -. [Q8IXJ6-2]
RefSeq; NP_001180215.1; NM_001193286.1.
RefSeq; NP_036369.2; NM_012237.3. [Q8IXJ6-1]
RefSeq; NP_085096.1; NM_030593.2. [Q8IXJ6-2]
RefSeq; XP_006723174.1; XM_006723111.1. [Q8IXJ6-2]
RefSeq; XP_011524956.1; XM_011526654.1. [Q8IXJ6-2]
RefSeq; XP_011524957.1; XM_011526655.1. [Q8IXJ6-5]
UniGene; Hs.466693; -.
PDB; 1J8F; X-ray; 1.70 A; A/B/C=34-356.
PDB; 3ZGO; X-ray; 1.63 A; A/B/C=34-356.
PDB; 3ZGV; X-ray; 2.27 A; A/B=34-356.
PDB; 4L3O; X-ray; 2.52 A; A/B/C/D=55-356.
PDB; 4R8M; X-ray; 2.10 A; A/B=38-356.
PDB; 4RMG; X-ray; 1.88 A; A=56-356.
PDB; 4RMH; X-ray; 1.42 A; A=56-356.
PDB; 4RMI; X-ray; 1.45 A; A=56-356.
PDB; 4RMJ; X-ray; 1.87 A; A/B=56-356.
PDB; 4X3O; X-ray; 1.50 A; A=52-355.
PDB; 4X3P; X-ray; 1.80 A; A=52-355.
PDB; 4Y6L; X-ray; 1.60 A; A/B=52-356.
PDB; 4Y6O; X-ray; 1.60 A; A/B=52-356.
PDB; 4Y6Q; X-ray; 1.90 A; A/B/C/D=52-356.
PDB; 5D7O; X-ray; 1.63 A; A/B=50-356.
PDB; 5D7P; X-ray; 1.76 A; A/B=56-356.
PDB; 5D7Q; X-ray; 2.01 A; A/B=56-356.
PDB; 5DY4; X-ray; 1.77 A; A=56-356.
PDB; 5DY5; X-ray; 1.95 A; A=56-356.
PDB; 5FYQ; X-ray; 3.00 A; A/B=1-356.
PDB; 5G4C; X-ray; 2.10 A; A/B=34-356.
PDB; 5MAR; X-ray; 1.89 A; A/B=56-356.
PDB; 5MAT; X-ray; 2.07 A; A/C=56-356.
PDB; 5Y5N; X-ray; 2.30 A; A=32-356.
PDBsum; 1J8F; -.
PDBsum; 3ZGO; -.
PDBsum; 3ZGV; -.
PDBsum; 4L3O; -.
PDBsum; 4R8M; -.
PDBsum; 4RMG; -.
PDBsum; 4RMH; -.
PDBsum; 4RMI; -.
PDBsum; 4RMJ; -.
PDBsum; 4X3O; -.
PDBsum; 4X3P; -.
PDBsum; 4Y6L; -.
PDBsum; 4Y6O; -.
PDBsum; 4Y6Q; -.
PDBsum; 5D7O; -.
PDBsum; 5D7P; -.
PDBsum; 5D7Q; -.
PDBsum; 5DY4; -.
PDBsum; 5DY5; -.
PDBsum; 5FYQ; -.
PDBsum; 5G4C; -.
PDBsum; 5MAR; -.
PDBsum; 5MAT; -.
PDBsum; 5Y5N; -.
ProteinModelPortal; Q8IXJ6; -.
SMR; Q8IXJ6; -.
BioGrid; 116593; 65.
DIP; DIP-33350N; -.
IntAct; Q8IXJ6; 29.
MINT; MINT-3037896; -.
STRING; 9606.ENSP00000249396; -.
BindingDB; Q8IXJ6; -.
ChEMBL; CHEMBL4462; -.
GuidetoPHARMACOLOGY; 2708; -.
iPTMnet; Q8IXJ6; -.
PhosphoSitePlus; Q8IXJ6; -.
BioMuta; SIRT2; -.
DMDM; 38258608; -.
EPD; Q8IXJ6; -.
MaxQB; Q8IXJ6; -.
PaxDb; Q8IXJ6; -.
PeptideAtlas; Q8IXJ6; -.
PRIDE; Q8IXJ6; -.
DNASU; 22933; -.
Ensembl; ENST00000249396; ENSP00000249396; ENSG00000068903. [Q8IXJ6-1]
Ensembl; ENST00000392081; ENSP00000375931; ENSG00000068903. [Q8IXJ6-2]
Ensembl; ENST00000634533; ENSP00000489602; ENSG00000283100. [Q8IXJ6-1]
Ensembl; ENST00000635478; ENSP00000488940; ENSG00000283100. [Q8IXJ6-2]
GeneID; 22933; -.
KEGG; hsa:22933; -.
UCSC; uc002ojt.3; human. [Q8IXJ6-1]
CTD; 22933; -.
DisGeNET; 22933; -.
EuPathDB; HostDB:ENSG00000068903.19; -.
GeneCards; SIRT2; -.
HGNC; HGNC:10886; SIRT2.
HPA; CAB004573; -.
HPA; HPA011165; -.
MIM; 604480; gene.
neXtProt; NX_Q8IXJ6; -.
OpenTargets; ENSG00000068903; -.
PharmGKB; PA35786; -.
eggNOG; KOG2682; Eukaryota.
eggNOG; COG0846; LUCA.
GeneTree; ENSGT00870000136486; -.
HOVERGEN; HBG057095; -.
InParanoid; Q8IXJ6; -.
KO; K11412; -.
PhylomeDB; Q8IXJ6; -.
TreeFam; TF106181; -.
SABIO-RK; Q8IXJ6; -.
SIGNOR; Q8IXJ6; -.
ChiTaRS; SIRT2; human.
EvolutionaryTrace; Q8IXJ6; -.
GeneWiki; SIRT2; -.
GenomeRNAi; 22933; -.
PRO; PR:Q8IXJ6; -.
Proteomes; UP000005640; Chromosome 19.
Bgee; ENSG00000068903; -.
CleanEx; HS_SIRT2; -.
ExpressionAtlas; Q8IXJ6; baseline and differential.
Genevisible; Q8IXJ6; HS.
GO; GO:0005814; C:centriole; IDA:UniProtKB.
GO; GO:0005813; C:centrosome; IDA:UniProtKB.
GO; GO:0005677; C:chromatin silencing complex; NAS:UniProtKB.
GO; GO:0005694; C:chromosome; IDA:UniProtKB.
GO; GO:0000781; C:chromosome, telomeric region; IEA:GOC.
GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
GO; GO:0005829; C:cytosol; IDA:UniProtKB.
GO; GO:0097386; C:glial cell projection; ISS:UniProtKB.
GO; GO:0030426; C:growth cone; IEA:UniProtKB-SubCell.
GO; GO:0044224; C:juxtaparanode region of axon; ISS:UniProtKB.
GO; GO:0043219; C:lateral loop; ISS:UniProtKB.
GO; GO:0072687; C:meiotic spindle; ISS:UniProtKB.
GO; GO:0005874; C:microtubule; IDA:UniProtKB.
GO; GO:0030496; C:midbody; IDA:UniProtKB.
GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
GO; GO:0072686; C:mitotic spindle; IDA:UniProtKB.
GO; GO:0043209; C:myelin sheath; ISS:UniProtKB.
GO; GO:0005720; C:nuclear heterochromatin; ISS:UniProtKB.
GO; GO:0005730; C:nucleolus; IDA:HPA.
GO; GO:0005634; C:nucleus; IDA:UniProtKB.
GO; GO:0033010; C:paranodal junction; ISS:UniProtKB.
GO; GO:0033270; C:paranode region of axon; ISS:UniProtKB.
GO; GO:0043204; C:perikaryon; ISS:UniProtKB.
GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
GO; GO:0005886; C:plasma membrane; IDA:HPA.
GO; GO:0043220; C:Schmidt-Lanterman incisure; ISS:UniProtKB.
GO; GO:0005819; C:spindle; IDA:UniProtKB.
GO; GO:0048487; F:beta-tubulin binding; IEA:Ensembl.
GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
GO; GO:0035035; F:histone acetyltransferase binding; IPI:UniProtKB.
GO; GO:0004407; F:histone deacetylase activity; IDA:UniProtKB.
GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB.
GO; GO:0070403; F:NAD+ binding; IDA:UniProtKB.
GO; GO:0017136; F:NAD-dependent histone deacetylase activity; IDA:UniProtKB.
GO; GO:0046970; F:NAD-dependent histone deacetylase activity (H4-K16 specific); IDA:UniProtKB.
GO; GO:0034979; F:NAD-dependent protein deacetylase activity; IDA:UniProtKB.
GO; GO:0033558; F:protein deacetylase activity; IDA:UniProtKB.
GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB.
GO; GO:0042903; F:tubulin deacetylase activity; IDA:UniProtKB.
GO; GO:0043130; F:ubiquitin binding; IDA:UniProtKB.
GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
GO; GO:0044242; P:cellular lipid catabolic process; ISS:UniProtKB.
GO; GO:0061433; P:cellular response to caloric restriction; ISS:UniProtKB.
GO; GO:0071872; P:cellular response to epinephrine stimulus; ISS:UniProtKB.
GO; GO:0035729; P:cellular response to hepatocyte growth factor stimulus; IDA:UniProtKB.
GO; GO:0071456; P:cellular response to hypoxia; IDA:UniProtKB.
GO; GO:0071219; P:cellular response to molecule of bacterial origin; IDA:UniProtKB.
GO; GO:0034599; P:cellular response to oxidative stress; ISS:UniProtKB.
GO; GO:0006342; P:chromatin silencing; NAS:UniProtKB.
GO; GO:0000183; P:chromatin silencing at rDNA; NAS:UniProtKB.
GO; GO:0006348; P:chromatin silencing at telomere; NAS:UniProtKB.
GO; GO:0016458; P:gene silencing; NAS:UniProtKB.
GO; GO:0048012; P:hepatocyte growth factor receptor signaling pathway; IDA:UniProtKB.
GO; GO:0016575; P:histone deacetylation; IDA:UniProtKB.
GO; GO:0070932; P:histone H3 deacetylation; IMP:UniProtKB.
GO; GO:0070933; P:histone H4 deacetylation; IDA:UniProtKB.
GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
GO; GO:0022011; P:myelination in peripheral nervous system; ISS:UniProtKB.
GO; GO:0010507; P:negative regulation of autophagy; IMP:UniProtKB.
GO; GO:0008285; P:negative regulation of cell proliferation; IMP:UniProtKB.
GO; GO:1900425; P:negative regulation of defense response to bacterium; IMP:UniProtKB.
GO; GO:0045599; P:negative regulation of fat cell differentiation; ISS:UniProtKB.
GO; GO:1900226; P:negative regulation of NLRP3 inflammasome complex assembly; IEA:Ensembl.
GO; GO:0070446; P:negative regulation of oligodendrocyte progenitor proliferation; ISS:UniProtKB.
GO; GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; ISS:UniProtKB.
GO; GO:0042177; P:negative regulation of protein catabolic process; IMP:UniProtKB.
GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; ISS:UniProtKB.
GO; GO:0045843; P:negative regulation of striated muscle tissue development; IDA:UniProtKB.
GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
GO; GO:0061428; P:negative regulation of transcription from RNA polymerase II promoter in response to hypoxia; IMP:UniProtKB.
GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
GO; GO:0034983; P:peptidyl-lysine deacetylation; IDA:UniProtKB.
GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IMP:UniProtKB.
GO; GO:0051987; P:positive regulation of attachment of spindle microtubules to kinetochore; ISS:UniProtKB.
GO; GO:0051781; P:positive regulation of cell division; ISS:UniProtKB.
GO; GO:0043388; P:positive regulation of DNA binding; ISS:UniProtKB.
GO; GO:1900119; P:positive regulation of execution phase of apoptosis; ISS:UniProtKB.
GO; GO:0045836; P:positive regulation of meiotic nuclear division; ISS:UniProtKB.
GO; GO:1900195; P:positive regulation of oocyte maturation; ISS:UniProtKB.
GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
GO; GO:2000777; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process involved in cellular response to hypoxia; IMP:UniProtKB.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; ISS:UniProtKB.
GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
GO; GO:0006471; P:protein ADP-ribosylation; NAS:UniProtKB.
GO; GO:0006476; P:protein deacetylation; IDA:UniProtKB.
GO; GO:0043491; P:protein kinase B signaling; IMP:UniProtKB.
GO; GO:0051726; P:regulation of cell cycle; IMP:UniProtKB.
GO; GO:0007096; P:regulation of exit from mitosis; NAS:UniProtKB.
GO; GO:0031641; P:regulation of myelination; ISS:UniProtKB.
GO; GO:0042325; P:regulation of phosphorylation; NAS:UniProtKB.
GO; GO:0051775; P:response to redox state; NAS:UniProtKB.
GO; GO:1901026; P:ripoptosome assembly involved in necroptotic process; IEA:Ensembl.
GO; GO:0021762; P:substantia nigra development; IEP:UniProtKB.
GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
GO; GO:0090042; P:tubulin deacetylation; IDA:UniProtKB.
Gene3D; 3.40.50.1220; -; 1.
InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
InterPro; IPR003000; Sirtuin.
InterPro; IPR017328; Sirtuin_class_I.
InterPro; IPR026590; Ssirtuin_cat_dom.
Pfam; PF02146; SIR2; 1.
PIRSF; PIRSF037938; SIR2_euk; 1.
SUPFAM; SSF52467; SSF52467; 1.
PROSITE; PS50305; SIRTUIN; 1.
1: Evidence at protein level;
3D-structure; Acetylation; Alternative splicing; Autophagy;
Cell cycle; Cell division; Cell membrane; Cell projection; Chromosome;
Complete proteome; Cytoplasm; Cytoskeleton; Differentiation;
Hydrolase; Immunity; Innate immunity; Meiosis; Membrane;
Metal-binding; Microtubule; Mitosis; NAD; Neurodegeneration;
Neurogenesis; Nucleus; Phosphoprotein; Reference proteome;
Transcription; Transcription regulation; Ubl conjugation; Zinc.
INIT_MET 1 1 Removed. {ECO:0000244|PubMed:19413330}.
CHAIN 2 389 NAD-dependent protein deacetylase
sirtuin-2.
/FTId=PRO_0000110258.
DOMAIN 65 340 Deacetylase sirtuin-type.
{ECO:0000255|PROSITE-ProRule:PRU00236}.
NP_BIND 85 89 NAD. {ECO:0000244|PDB:4RMG,
ECO:0000269|PubMed:25672491}.
NP_BIND 95 97 NAD. {ECO:0000244|PDB:4RMG,
ECO:0000269|PubMed:25672491}.
NP_BIND 167 170 NAD. {ECO:0000244|PDB:4RMG,
ECO:0000269|PubMed:25672491}.
NP_BIND 262 263 NAD. {ECO:0000244|PDB:4RMG,
ECO:0000269|PubMed:25672491}.
NP_BIND 286 288 NAD. {ECO:0000244|PDB:4RMG,
ECO:0000269|PubMed:25672491}.
REGION 116 120 Peptide inhibitor binding.
REGION 232 301 Peptide inhibitor binding.
MOTIF 41 51 Nuclear export signal.
ACT_SITE 187 187 Proton acceptor. {ECO:0000305}.
METAL 195 195 Zinc. {ECO:0000255|PROSITE-
ProRule:PRU00236,
ECO:0000269|PubMed:11427894,
ECO:0000269|PubMed:23454361,
ECO:0000269|PubMed:24389023,
ECO:0000269|PubMed:25672491}.
METAL 200 200 Zinc. {ECO:0000255|PROSITE-
ProRule:PRU00236,
ECO:0000269|PubMed:11427894,
ECO:0000269|PubMed:23454361,
ECO:0000269|PubMed:24389023,
ECO:0000269|PubMed:25672491}.
METAL 221 221 Zinc. {ECO:0000255|PROSITE-
ProRule:PRU00236,
ECO:0000269|PubMed:11427894,
ECO:0000269|PubMed:23454361,
ECO:0000269|PubMed:24389023,
ECO:0000269|PubMed:25672491}.
METAL 224 224 Zinc. {ECO:0000255|PROSITE-
ProRule:PRU00236,
ECO:0000269|PubMed:11427894,
ECO:0000269|PubMed:23454361,
ECO:0000269|PubMed:24389023,
ECO:0000269|PubMed:25672491}.
BINDING 324 324 NAD; via amide nitrogen.
{ECO:0000244|PDB:4RMG,
ECO:0000269|PubMed:25672491}.
MOD_RES 2 2 N-acetylalanine.
{ECO:0000244|PubMed:19413330}.
MOD_RES 23 23 Phosphoserine.
{ECO:0000244|PubMed:24275569}.
MOD_RES 25 25 Phosphoserine.
{ECO:0000244|PubMed:24275569}.
MOD_RES 27 27 Phosphoserine.
{ECO:0000244|PubMed:24275569}.
MOD_RES 53 53 Phosphoserine.
{ECO:0000250|UniProtKB:Q5RJQ4}.
MOD_RES 100 100 Phosphoserine.
{ECO:0000250|UniProtKB:Q5RJQ4}.
MOD_RES 207 207 Phosphoserine.
{ECO:0000250|UniProtKB:Q5RJQ4}.
MOD_RES 368 368 Phosphoserine; by CDK2 and CDK5.
{ECO:0000244|PubMed:23186163,
ECO:0000269|PubMed:17488717,
ECO:0000269|PubMed:17516032,
ECO:0000269|PubMed:18332217}.
MOD_RES 372 372 Phosphoserine.
{ECO:0000269|PubMed:17516032}.
VAR_SEQ 1 38 MAEPDPSHPLETQAGKVQEAQDSDSDSEGGAAGGEADM ->
MPLAECPSCRCLSSFRSV (in isoform 3).
{ECO:0000303|Ref.5}.
/FTId=VSP_008726.
VAR_SEQ 1 37 Missing (in isoform 2).
{ECO:0000303|PubMed:10393250,
ECO:0000303|PubMed:10931946,
ECO:0000303|PubMed:12065666,
ECO:0000303|PubMed:14702039,
ECO:0000303|PubMed:15489334}.
/FTId=VSP_008724.
VAR_SEQ 6 76 PSHPLETQAGKVQEAQDSDSDSEGGAAGGEADMDFLRNLFS
QTLSLGSQKERLLDELTLEGVARYMQSERC -> R (in
isoform 5).
{ECO:0000303|PubMed:24177535}.
/FTId=VSP_055328.
VAR_SEQ 266 271 VQPFAS -> GRGLAG (in isoform 4).
{ECO:0000303|Ref.10}.
/FTId=VSP_008727.
VAR_SEQ 272 389 Missing (in isoform 4).
{ECO:0000303|Ref.10}.
/FTId=VSP_008728.
MUTAGEN 53 53 S->A: Reduces deacetylase activity.
{ECO:0000269|PubMed:17516032}.
MUTAGEN 97 97 R->A: No effect on deacetylase activity.
{ECO:0000269|PubMed:11427894}.
MUTAGEN 98 98 S->A: Inhibits deacetylase activity.
{ECO:0000269|PubMed:17516032}.
MUTAGEN 100 100 S->A: Reduces deacetylase activity.
{ECO:0000269|PubMed:17516032}.
MUTAGEN 116 116 E->A: Reduces binding for the peptide
inhibitor S2iL5.
{ECO:0000269|PubMed:24389023}.
MUTAGEN 120 120 E->A: Reduces binding for the peptide
inhibitor S2iL5.
{ECO:0000269|PubMed:24389023}.
MUTAGEN 167 167 Q->A: Reduces deacetylase activity.
Inhibits the block of entry to chromosome
condensation and subsequent hyperploidy
cell formation in response to mitotic
stress; when associated with A-168 and A-
187. {ECO:0000269|PubMed:11427894,
ECO:0000269|PubMed:16909107}.
MUTAGEN 168 168 N->A: Abolishes deacetylation of alpha-
tubulin. Inhibits deacetylation of
histone H3 at 'Lys-18'. Inhibits the
block of entry to chromosome condensation
and subsequent hyperploidy cell formation
in response to mitotic stress; when
associated with A-167 and A-187.
{ECO:0000269|PubMed:11427894,
ECO:0000269|PubMed:12620231,
ECO:0000269|PubMed:16909107,
ECO:0000269|PubMed:23908241,
ECO:0000269|PubMed:24769394}.
MUTAGEN 170 170 D->A,N: Reduces deacetylase activity.
{ECO:0000269|PubMed:11427894}.
MUTAGEN 187 187 H->Y,A: Inhibits deacetylase activity
toward histone, alpha-tubulin, FZR1 and
CDC20. No effect on CDK2-dependent
phosphorylation. Does not inhibit
interaction with alpha-tubulin, HDAC6,
HIF1A and the cyclin E-CDK2 complex.
Inhibits interaction with BEX4 and KMT5A.
Abolishes deacetylation, dimeric
formation and enzymatic activity increase
of G6PD. Prevents histone H4 methylation
at 'Lys-20'(H4K20me1) in metaphase
chromosomes. Inhibits the block of entry
to chromosome condensation and subsequent
hyperploidy cell formation in response to
mitotic stress; when associated with A-
167 and A-168.
{ECO:0000269|PubMed:10381378,
ECO:0000269|PubMed:11427894,
ECO:0000269|PubMed:11812793,
ECO:0000269|PubMed:12620231,
ECO:0000269|PubMed:12697818,
ECO:0000269|PubMed:16909107,
ECO:0000269|PubMed:17488717,
ECO:0000269|PubMed:17516032,
ECO:0000269|PubMed:17726514,
ECO:0000269|PubMed:22014574,
ECO:0000269|PubMed:24681946,
ECO:0000269|PubMed:27512957}.
MUTAGEN 244 244 F->A: Reduces strongly binding for the
peptide inhibitor S2iL5.
{ECO:0000269|PubMed:24389023}.
MUTAGEN 265 265 Q->A: Reduces binding for the peptide
inhibitor S2iL5.
{ECO:0000269|PubMed:24389023}.
MUTAGEN 271 271 S->A: Reduces binding for the peptide
inhibitor S2iL5.
{ECO:0000269|PubMed:24389023}.
MUTAGEN 279 279 S->A: Reduces deacetylase activity.
{ECO:0000269|PubMed:17516032}.
MUTAGEN 280 280 T->A: Reduces deacetylase activity.
{ECO:0000269|PubMed:17516032}.
MUTAGEN 294 294 D->A: Reduces binding for the peptide
inhibitor S2iL5.
{ECO:0000269|PubMed:24389023}.
MUTAGEN 311 311 S->A: Reduces deacetylase activity.
{ECO:0000269|PubMed:17516032}.
MUTAGEN 315 315 Y->A: Reduces deacetylase activity.
{ECO:0000269|PubMed:17516032}.
MUTAGEN 364 364 S->A: Abolishes CDK2-dependent
phosphorylation.
{ECO:0000269|PubMed:17516032}.
MUTAGEN 368 368 S->A: Does not affect deacetylase
activity. Abolishes CDK2-dependent
phosphorylation. Inhibits cellular
proliferation delay in the early
metaphase to prevent chromosomal
instability. Does not inhibit interaction
with a cyclin E-CDK2 complex. Does not
inhibit interaction with HDAC6 and
ubiquitination. Inhibits cell adhesion
and migration and neurite outgrowth.
Inhibits deacetylase activity; when
associated with A-372.
{ECO:0000269|PubMed:17488717,
ECO:0000269|PubMed:17516032,
ECO:0000269|PubMed:18332217}.
MUTAGEN 368 368 S->D: Abolishes CDK2-dependent
phosphorylation. Inhibits interaction
with a cyclin E-CDK2 complex. Reduces
strongly histone deacetylation activity.
{ECO:0000269|PubMed:17488717,
ECO:0000269|PubMed:17516032,
ECO:0000269|PubMed:18332217}.
MUTAGEN 368 368 S->E: Abolishes CDK2-dependent
phosphorylation.
{ECO:0000269|PubMed:17488717,
ECO:0000269|PubMed:17516032,
ECO:0000269|PubMed:18332217}.
MUTAGEN 372 372 S->A: Reduces phosphorylation. Does not
inhibit interaction with HDAC6,
ubiquitination and deacetylase activity.
Inhibits deacetylase activity; when
associated with A-368.
{ECO:0000269|PubMed:17516032}.
CONFLICT 199 199 S -> N (in Ref. 6). {ECO:0000305}.
CONFLICT 219 219 P -> L (in Ref. 5; CAD43717).
{ECO:0000305}.
HELIX 35 45 {ECO:0000244|PDB:3ZGO}.
STRAND 60 63 {ECO:0000244|PDB:4RMH}.
HELIX 64 71 {ECO:0000244|PDB:4RMH}.
STRAND 73 75 {ECO:0000244|PDB:3ZGV}.
STRAND 79 83 {ECO:0000244|PDB:4RMH}.
HELIX 85 87 {ECO:0000244|PDB:4RMH}.
HELIX 89 91 {ECO:0000244|PDB:4RMH}.
STRAND 96 98 {ECO:0000244|PDB:4RMI}.
HELIX 99 101 {ECO:0000244|PDB:4RMH}.
HELIX 103 105 {ECO:0000244|PDB:4X3O}.
HELIX 108 110 {ECO:0000244|PDB:4X3O}.
HELIX 115 119 {ECO:0000244|PDB:4RMH}.
HELIX 121 126 {ECO:0000244|PDB:4RMH}.
HELIX 129 138 {ECO:0000244|PDB:4RMH}.
STRAND 139 142 {ECO:0000244|PDB:3ZGO}.
HELIX 147 157 {ECO:0000244|PDB:4RMH}.
STRAND 161 166 {ECO:0000244|PDB:4RMH}.
HELIX 172 175 {ECO:0000244|PDB:4RMH}.
HELIX 180 182 {ECO:0000244|PDB:4RMH}.
STRAND 183 185 {ECO:0000244|PDB:4RMH}.
STRAND 188 196 {ECO:0000244|PDB:4RMH}.
TURN 198 200 {ECO:0000244|PDB:4RMH}.
STRAND 203 205 {ECO:0000244|PDB:4RMH}.
HELIX 206 215 {ECO:0000244|PDB:4RMH}.
TURN 222 224 {ECO:0000244|PDB:4RMH}.
STRAND 227 232 {ECO:0000244|PDB:4RMH}.
HELIX 241 250 {ECO:0000244|PDB:4RMH}.
TURN 251 253 {ECO:0000244|PDB:4RMI}.
STRAND 255 261 {ECO:0000244|PDB:4RMH}.
HELIX 269 275 {ECO:0000244|PDB:4RMH}.
STRAND 282 288 {ECO:0000244|PDB:4RMH}.
TURN 295 297 {ECO:0000244|PDB:4X3O}.
HELIX 301 303 {ECO:0000244|PDB:5DY4}.
STRAND 309 311 {ECO:0000244|PDB:4RMH}.
STRAND 316 322 {ECO:0000244|PDB:4RMH}.
HELIX 324 334 {ECO:0000244|PDB:4RMH}.
HELIX 338 353 {ECO:0000244|PDB:4RMH}.
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


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