SIR2_MOUSE
ID SIR2_MOUSE Reviewed; 389 AA.
AC Q8VDQ8; E9PXF5; Q9CXS5; Q9EQ18; Q9ERJ9; U5TP50;
DT 31-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=NAD-dependent protein deacetylase sirtuin-2;
DE EC=2.3.1.286 {ECO:0000269|PubMed:17521387, ECO:0000269|PubMed:17574768, ECO:0000269|PubMed:17681146, ECO:0000269|PubMed:21841822};
DE AltName: Full=NAD-dependent protein defatty-acylase sirtuin-2 {ECO:0000305};
DE EC=2.3.1.- {ECO:0000250|UniProtKB:Q8IXJ6};
DE AltName: Full=Regulatory protein SIR2 homolog 2;
DE AltName: Full=SIR2-like protein 2;
DE Short=mSIR2L2;
GN Name=Sirt2; Synonyms=Sir2l2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), AND SUBCELLULAR
RP LOCATION.
RC STRAIN=129/Ola;
RX PubMed=11056054; DOI=10.1006/geno.2000.6360;
RA Yang Y.H., Chen Y.H., Zhang C.Y., Nimmakayalu M.A., Ward D.C., Weissman S.;
RT "Cloning and characterization of two mouse genes with homology to the yeast
RT sir2 gene.";
RL Genomics 69:355-369(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND ALTERNATIVE SPLICING (ISOFORMS
RP 1 AND 2).
RC TISSUE=Brain;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Mammary tumor;
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 [6]
RP PROTEIN SEQUENCE OF 43-55; 58-69; 79-125; 137-153; 164-174; 213-253;
RP 276-282 AND 348-371, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=C57BL/6J, and OF1; TISSUE=Brain, and Hippocampus;
RA Lubec G., Klug S., Kang S.U., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [8]
RP FUNCTION IN DEACETYLATION OF FOXO3, CATALYTIC ACTIVITY, FUNCTION IN
RP REGULATION OF FOXO3 ACTIVITY, INTERACTION WITH FOXO3, SUBCELLULAR LOCATION,
RP MUTAGENESIS OF HIS-187, AND INDUCTION BY CALORIC RESTRICTION AND OXIDATIVE
RP STRESS.
RX PubMed=17521387; DOI=10.1111/j.1474-9726.2007.00304.x;
RA Wang F., Nguyen M., Qin F.X., Tong Q.;
RT "SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric
RT restriction.";
RL Aging Cell 6:505-514(2007).
RN [9]
RP FUNCTION IN DEACETYLATION OF FOXO1, CATALYTIC ACTIVITY, FUNCTION IN
RP INHIBITION OF ADIPOCYTE DIFFERENTIATION, INTERACTION WITH FOXO1, INDUCTION,
RP AND TISSUE SPECIFICITY.
RX PubMed=17681146; DOI=10.1016/j.cmet.2007.07.003;
RA Jing E., Gesta S., Kahn C.R.;
RT "SIRT2 regulates adipocyte differentiation through FoxO1
RT acetylation/deacetylation.";
RL Cell Metab. 6:105-114(2007).
RN [10]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17634366; DOI=10.1523/jneurosci.1254-07.2007;
RA Werner H.B., Kuhlmann K., Shen S., Uecker M., Schardt A., Dimova K.,
RA Orfaniotou F., Dhaunchak A., Brinkmann B.G., Mobius W., Guarente L.,
RA Casaccia-Bonnefil P., Jahn O., Nave K.A.;
RT "Proteolipid protein is required for transport of sirtuin 2 into CNS
RT myelin.";
RL J. Neurosci. 27:7717-7730(2007).
RN [11]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16933150; DOI=10.1007/s11064-006-9127-6;
RA Southwood C.M., Peppi M., Dryden S., Tainsky M.A., Gow A.;
RT "Microtubule deacetylases, SirT2 and HDAC6, in the nervous system.";
RL Neurochem. Res. 32:187-195(2007).
RN [12]
RP FUNCTION IN DEACETYLATION OF TUBULIN, CATALYTIC ACTIVITY, FUNCTION IN
RP AXONAL DEGENERATION, AND SUBCELLULAR LOCATION.
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 [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [14]
RP INTERACTION WITH CDK5, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
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 [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [16]
RP FUNCTION IN DEACETYLATION OF FOXO1, FUNCTION IN INHIBITION OF ADIPOCYTE
RP DIFFERENTIATION, INTERACTION WITH FOXO1, SUBCELLULAR LOCATION, AND
RP INDUCTION BY CALORIC RESTRICTION.
RX PubMed=19037106; DOI=10.1091/mbc.e08-06-0647;
RA Wang F., Tong Q.;
RT "SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and
RT enhancing FOXO1's repressive interaction with PPARgamma.";
RL Mol. Biol. Cell 20:801-808(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23; SER-25; THR-27; SER-368
RP AND SER-372, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [18]
RP FUNCTION IN DEACETYLATION OF CDC20 AND FZR1, POSSIBLE FUNCTION AS A TUMOR
RP SUPPRESSOR, INTERACTION WITH AURKA; CDC20 AND FZR1, DISRUPTION PHENOTYPE,
RP AND SUBCELLULAR LOCATION.
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 [19]
RP ALTERNATIVE SPLICING (ISOFORMS 1; 2 AND 4), FUNCTION IN DEACETYLATION OF
RP ALPHA-TUBULIN (ISOFORMS 1; 2 AND 4), ASSOCIATION WITH ALPHA-TUBULIN
RP (ISOFORMS 2 AND 4), SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP INDUCTION.
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 [20]
RP FUNCTION IN REGULATION OF PERIPHERAL MYELINATION, CONDITIONAL KNOCKOUT IN
RP SCHWANN CELL, TISSUE SPECIFICITY, AND INDUCTION.
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 [21]
RP FUNCTION IN DEACETYLATION OF FOXO3, CATALYTIC ACTIVITY, FUNCTION IN
RP REGULATION OF FOXO3 ACTIVITY, AND MUTAGENESIS OF HIS-187.
RX PubMed=21841822; DOI=10.1038/onc.2011.347;
RA Wang F., Chan C.H., Chen K., Guan X., Lin H.K., Tong Q.;
RT "Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-mediated FOXO3
RT ubiquitination and degradation.";
RL Oncogene 31:1546-1557(2012).
RN [22]
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 [23]
RP FUNCTION AS A TUMOR SUPPRESSOR, DISRUPTION PHENOTYPE, AND SUBCELLULAR
RP LOCATION.
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 [24]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=24460154; DOI=10.3109/00016489.2013.861928;
RA Takumida M., Takumida H., Anniko M.;
RT "Localization of sirtuins in the mouse inner ear.";
RL Acta Oto-Laryngol. 134:331-338(2014).
RN [25]
RP FUNCTION IN DEACETYLATION OF HISTONE H4 AND ALPHA-TUBULIN, FUNCTION IN
RP OOCYTE MEIOSIS, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=24334550; DOI=10.1096/fj.13-244111;
RA Zhang L., Hou X., Ma R., Moley K., Schedl T., Wang Q.;
RT "Sirt2 functions in spindle organization and chromosome alignment in mouse
RT oocyte meiosis.";
RL FASEB J. 28:1435-1445(2014).
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:17521387,
CC PubMed:17681146, PubMed:17574768, PubMed:19037106, PubMed:22014574,
CC PubMed:21791548, PubMed:21841822, PubMed:24334550). Participates in the
CC modulation of multiple and diverse biological processes such as cell
CC cycle control, genomic integrity, microtubule dynamics, cell
CC differentiation, metabolic networks, and autophagy. Plays a major role
CC in the control of cell cycle progression and genomic stability.
CC Functions in the antephase checkpoint preventing precocious mitotic
CC entry in response to microtubule stress agents, and hence allowing
CC proper inheritance of chromosomes. Positively regulates the anaphase
CC promoting complex/cyclosome (APC/C) ubiquitin ligase complex activity
CC by deacetylating CDC20 and FZR1, then allowing progression through
CC mitosis. Associates both with chromatin at transcriptional start sites
CC (TSSs) and enhancers of active genes. Plays a role in cell cycle and
CC chromatin compaction through epigenetic modulation of the regulation of
CC histone H4 'Lys-20' methylation (H4K20me1) during early mitosis.
CC Specifically deacetylates histone H4 at 'Lys-16' (H4K16ac) between the
CC G2/M transition and metaphase enabling H4K20me1 deposition by KMT5A
CC leading to ulterior levels of H4K20me2 and H4K20me3 deposition
CC throughout cell cycle, and mitotic S-phase progression. Deacetylates
CC KMT5A modulating KMT5A chromatin localization during the mitotic stress
CC response. Deacetylates also histone H3 at 'Lys-57' (H3K56ac) during the
CC mitotic G2/M transition. During oocyte meiosis progression, may
CC deacetylate histone H4 at 'Lys-16' (H4K16ac) and alpha-tubulin,
CC regulating spindle assembly and chromosome alignment by influencing
CC microtubule dynamics and kinetochore function. Deacetylates histone H4
CC at 'Lys-16' (H4K16ac) at the VEGFA promoter and thereby contributes to
CC regulate expression of VEGFA, a key regulator of angiogenesis.
CC Deacetylates alpha-tubulin at 'Lys-40' and hence controls neuronal
CC motility, oligodendroglial cell arbor projection processes and
CC proliferation of non-neuronal cells (PubMed:17574768, PubMed:21791548).
CC Phosphorylation at Ser-368 by a G1/S-specific cyclin E-CDK2 complex
CC inactivates SIRT2-mediated alpha-tubulin deacetylation, negatively
CC regulating cell adhesion, cell migration and neurite outgrowth during
CC neuronal differentiation. Deacetylates PARD3 and participates in the
CC regulation of Schwann cell peripheral myelination formation during
CC early postnatal development and during postinjury remyelination.
CC Involved in several cellular metabolic pathways. Plays a role in the
CC regulation of blood glucose homeostasis by deacetylating and
CC stabilizing phosphoenolpyruvate carboxykinase PCK1 activity in response
CC to low nutrient availability. Acts as a key regulator in the pentose
CC phosphate pathway (PPP) by deacetylating and activating the glucose-6-
CC phosphate G6PD enzyme, and therefore, stimulates the production of
CC cytosolic NADPH to counteract oxidative damage. Maintains energy
CC homeostasis in response to nutrient deprivation as well as energy
CC expenditure by inhibiting adipogenesis and promoting lipolysis.
CC Attenuates adipocyte differentiation by deacetylating and promoting
CC FOXO1 interaction to PPARG and subsequent repression of PPARG-dependent
CC transcriptional activity (PubMed:17681146, PubMed:19037106). Plays a
CC role in the regulation of lysosome-mediated degradation of protein
CC aggregates by autophagy in neuronal cells (PubMed:17681146,
CC PubMed:19037106). Deacetylates FOXO1 in response to oxidative stress or
CC serum deprivation, thereby negatively regulating FOXO1-mediated
CC autophagy (PubMed:17681146, PubMed:19037106). Deacetylates a broad
CC range of 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 (PubMed:17521387, PubMed:21841822). Deacetylates HIF1A and
CC therefore promotes HIF1A degradation and inhibition of HIF1A
CC transcriptional activity in tumor cells in response to hypoxia.
CC Deacetylates RELA in the cytoplasm inhibiting NF-kappaB-dependent
CC transcription activation upon TNF-alpha stimulation. Inhibits
CC transcriptional activation by deacetylating p53/TP53 and EP300.
CC Deacetylates also EIF5A. Functions as a negative regulator on oxidative
CC stress-tolerance in response to anoxia-reoxygenation conditions. Plays
CC a role as tumor suppressor (PubMed:22014574, PubMed:23468428). In
CC 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 (By
CC similarity). {ECO:0000250|UniProtKB:Q8IXJ6,
CC ECO:0000269|PubMed:17521387, ECO:0000269|PubMed:17574768,
CC ECO:0000269|PubMed:17681146, ECO:0000269|PubMed:19037106,
CC ECO:0000269|PubMed:21791548, ECO:0000269|PubMed:21841822,
CC ECO:0000269|PubMed:21949390, ECO:0000269|PubMed:22014574,
CC ECO:0000269|PubMed:23468428, ECO:0000269|PubMed:24334550}.
CC -!- FUNCTION: [Isoform 1]: Deacetylates alpha-tubulin.
CC {ECO:0000269|PubMed:21791548}.
CC -!- FUNCTION: [Isoform 2]: Deacetylates alpha-tubulin.
CC {ECO:0000269|PubMed:21791548}.
CC -!- FUNCTION: [Isoform 4]: Deacetylates alpha-tubulin.
CC {ECO:0000269|PubMed:21791548}.
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:17521387, ECO:0000269|PubMed:17574768,
CC ECO:0000269|PubMed:17681146, ECO:0000269|PubMed:21841822};
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:0000250|UniProtKB:Q8IXJ6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70568;
CC Evidence={ECO:0000250|UniProtKB:Q8IXJ6};
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:0000250|UniProtKB:Q8IXJ6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70564;
CC Evidence={ECO:0000250|UniProtKB:Q8IXJ6};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q8IXJ6};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q8IXJ6};
CC -!- ACTIVITY REGULATION: Inhibited by Sirtinol, A3 and M15 small molecules.
CC Inhibited by nicotinamide. Inhibited by a macrocyclic peptide inhibitor
CC S2iL5. Inhibited by EP300-induced acetylation (By similarity).
CC {ECO:0000250|UniProtKB:Q8IXJ6}.
CC -!- SUBUNIT: Interacts with CDC20, FOXO3 and FZR1 (PubMed:17521387,
CC PubMed:22014574). Associates with microtubule in primary cortical
CC mature neurons (By similarity). Homotrimer. Interacts (via both
CC phosphorylated, unphosphorylated, active or inactive forms) with HDAC6;
CC the interaction is necessary for the complex to interact with alpha-
CC tubulin, suggesting that these proteins belong to a large complex that
CC deacetylates the cytoskeleton. Interacts with FOXO1; the interaction is
CC disrupted upon serum-starvation or oxidative stress, leading to
CC increased level of acetylated FOXO1 and induction of autophagy
CC (PubMed:17681146, PubMed:19037106). 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 Interacts with the tRNA ligase SARS1; recruited to the VEGFA promoter
CC via interaction with SARS1 (By similarity). Isoform 2 and isoform 4
CC associate with microtubules in primary cortical mature neurons.
CC Interacts with BEX4; negatively regulates alpha-tubulin deacetylation
CC by SIRT2 (By similarity). {ECO:0000250|UniProtKB:Q8IXJ6,
CC ECO:0000269|PubMed:17521387, ECO:0000269|PubMed:17681146,
CC ECO:0000269|PubMed:18332217, ECO:0000269|PubMed:19037106,
CC ECO:0000269|PubMed:22014574}.
CC -!- INTERACTION:
CC Q8VDQ8; Q9JJ66: Cdc20; NbExp=2; IntAct=EBI-911012, EBI-2551389;
CC Q8VDQ8; Q9R1K5: Fzr1; NbExp=2; IntAct=EBI-911012, EBI-5238560;
CC Q8VDQ8; O14965: AURKA; Xeno; NbExp=5; IntAct=EBI-911012, EBI-448680;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19037106,
CC ECO:0000269|PubMed:24334550, ECO:0000269|PubMed:24460154}. Cytoplasm
CC {ECO:0000269|PubMed:11056054, ECO:0000269|PubMed:17521387,
CC ECO:0000269|PubMed:17681146, ECO:0000269|PubMed:19037106,
CC ECO:0000269|PubMed:24334550, ECO:0000269|PubMed:24460154}. Cytoplasm,
CC perinuclear region {ECO:0000269|PubMed:16933150}. Perikaryon
CC {ECO:0000269|PubMed:16933150}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q8IXJ6}. Cell projection
CC {ECO:0000269|PubMed:16933150}. Cell projection, growth cone
CC {ECO:0000269|PubMed:18332217}. Myelin membrane
CC {ECO:0000269|PubMed:16933150}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250|UniProtKB:Q8IXJ6}.
CC Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:24334550}.
CC Chromosome {ECO:0000250|UniProtKB:Q8IXJ6}. Midbody
CC {ECO:0000269|PubMed:24334550}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome, centriole
CC {ECO:0000250|UniProtKB:Q8IXJ6}. 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). Colocalizes
CC with KMT5A at mitotic foci. Colocalizes with CDK1 at centrosome during
CC prophase and splindle fibers during metaphase. Colocalizes with Aurora
CC kinase AURKA at centrosome during early prophase and in the centrioles
CC and growing mitotic spindle throughout metaphase. Colocalizes with
CC Aurora kinase AURKB during cytokinesis with the midbody. Colocalizes
CC with microtubules (By similarity). Deacetylates FOXO3 in the cytoplasm
CC (PubMed:17521387). Colocalizes with PLP1 in internodal regions of
CC myelin sheat, at paranodal axoglial junction and Schmidt-Lanterman
CC incisures (PubMed:16933150). Colocalizes with CDK5R1 in the perikaryon,
CC neurites and growth cone of hippocampal neurons (PubMed:16933150).
CC Colocalizes with alpha-tubulin in neuronal growth cone
CC (PubMed:18332217). Localizes in the cytoplasm and nucleus of germinal
CC vesicle (GV) stage oocytes (PubMed:24334550). Colocalizes with alpha-
CC tubulin on the meiotic spindle as the oocytes enter into metaphase, and
CC also during meiotic anaphase and telophase, especially with the midbody
CC (PubMed:24334550). {ECO:0000250|UniProtKB:Q8IXJ6,
CC ECO:0000269|PubMed:16933150, ECO:0000269|PubMed:17521387,
CC ECO:0000269|PubMed:18332217, ECO:0000269|PubMed:24334550}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=SIRT2.1;
CC IsoId=Q8VDQ8-1; Sequence=Displayed;
CC Name=2; Synonyms=SIRT2.2;
CC IsoId=Q8VDQ8-2; Sequence=VSP_008729;
CC Name=3;
CC IsoId=Q8VDQ8-3; Sequence=VSP_055330;
CC Name=4; Synonyms=SIRT2.3;
CC IsoId=Q8VDQ8-4; Sequence=VSP_055329;
CC -!- TISSUE SPECIFICITY: Isoform 1 is weakly expressed in the cortex at
CC postnatal(P) days P1, P3 and P7, and increases progressively between
CC P17 and older adult cortex. Isoform 1 is also expressed in heart, liver
CC and skeletal muscle, weakly expressed in the striatum and spinal cord.
CC Isoform 2 is not expressed in the cortex at P1, P3 and P7, and
CC increases strongly and progressively between P17 and older adult
CC cortex. Isoform 2 is also expressed in the heart, liver, striatum and
CC spinal cord. Isoform 4 is weakly expressed in older adult cortex and
CC spinal cords. Expressed in the cortex. Expressed in postnatal sciatic
CC nerves during myelination and during remyelination after nerve injury.
CC Expressed in neurons, oligodendrocytes, Schwann cells, Purkinje cells
CC and in astrocytes of white matter. Strongly expressed in preadipocytes
CC compared with differentiated adipocytes. Expressed in cerebellar
CC granule cells. Expressed in the inner ear: in the cochlea, expressed in
CC types I and V fibrocytes in the spiral ligament (SL) and slightly in
CC stria vascularis (SV); in the organ of Corti, expressed in some
CC supporting cells; in the crista ampullaris, expressed in spiral
CC ganglion cells; also expressed in the endolymphatic sac (ES) epithelial
CC cells (at protein level). Expressed in the brain, spinal cord, optic
CC nerve and hippocampus. Strongly expressed in 6-8 week-old ovulated
CC meiosis II oocytes and weakly expressed in 45-58 week-old ovulated
CC meiosis II oocytes. Expressed in the cochlea, vestibule and acoustic
CC nerve of the inner ear. {ECO:0000269|PubMed:16933150,
CC ECO:0000269|PubMed:17634366, ECO:0000269|PubMed:17681146,
CC ECO:0000269|PubMed:18332217, ECO:0000269|PubMed:21791548,
CC ECO:0000269|PubMed:21949390, ECO:0000269|PubMed:24334550,
CC ECO:0000269|PubMed:24460154}.
CC -!- DEVELOPMENTAL STAGE: Isoform 1 is expressed in the cortex at 15.5 dpc.
CC Isoform 2 is not detected in the cortex at 15.5 dpc (at protein level).
CC -!- INDUCTION: Up-regulated in response to caloric restriction in white and
CC brown adipose tissues. Up-regulated during cold exposure and down-
CC regulated in higher ambient temperature in brown adipose tissue. Up-
CC regulated after beta-adrenergic agonist (isoproterenol) treatment in
CC white adipose tissue (at protein level). Up-regulated in response to
CC caloric restriction in adipose tissue and kidney. Up-regulated in
CC response to oxidative stress. Up-regulated during postnatal sciatic
CC nerve myelination development and axonal regeneration. Down-regulated
CC during preadipocyte differentiation. Down-regulated in Schwann
CC dedifferentiated cells during Wallerian degeneration. Isoform 1 is up-
CC regulated upon differentiation to a neuron-like phenotype.
CC {ECO:0000269|PubMed:17521387, ECO:0000269|PubMed:17681146,
CC ECO:0000269|PubMed:19037106, ECO:0000269|PubMed:21791548,
CC ECO:0000269|PubMed:21949390}.
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 (By similarity). {ECO:0000250|UniProtKB:Q8IXJ6}.
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:0000250|UniProtKB:Q8IXJ6}.
CC -!- PTM: Ubiquitinated. {ECO:0000250|UniProtKB:Q8IXJ6}.
CC -!- DISRUPTION PHENOTYPE: Tissue-specific knockout of SIRT2 in Schwann
CC cells of early postnatal mice leads to a transient delay in
CC myelination, a reduction in the nerve conduction velocity and
CC hyperacetylation of PARD3. The number of dividing Schwann cells in the
CC developing nerve and alpha-tubulin acetylation are normal
CC (PubMed:21949390). Mutant mice embryo grow normally and new born are
CC healthy. Embryonic fibroblasts (MEFs) display reduced cell
CC proliferation capacity, centrosome amplification and mitotic cell
CC death. Nude mice inoculated with immortalized MEFs from mutant mice
CC developed tumors. Adult mutant mice exhibit genomic instability and
CC chromosomal aberrations, such as double-strand breaks (DSBs), with a
CC gender-specific spectrum of tumorigenesis; females develop primarily
CC mammary tumors and males develop tumors in several organs, including
CC the liver, lung, pancreas, stomach, duodenum and prostate. Drastic
CC increases of histone H4K16 acetylation and decreases of both histone
CC methylation (H4K20me1) in metaphasic chromosomes and histone
CC methylations (H4K20me2/3) in late M/early G1 but also throughout all
CC phases of the cell cycle (PubMed:23468428).
CC {ECO:0000269|PubMed:21949390, ECO:0000269|PubMed:22014574,
CC ECO:0000269|PubMed:23468428}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class I subfamily.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF299337; AAG39256.1; -; mRNA.
DR EMBL; AF302272; AAG32038.1; -; Genomic_DNA.
DR EMBL; AF302265; AAG32038.1; JOINED; Genomic_DNA.
DR EMBL; AF302266; AAG32038.1; JOINED; Genomic_DNA.
DR EMBL; AF302267; AAG32038.1; JOINED; Genomic_DNA.
DR EMBL; AF302268; AAG32038.1; JOINED; Genomic_DNA.
DR EMBL; AF302269; AAG32038.1; JOINED; Genomic_DNA.
DR EMBL; AF302270; AAG32038.1; JOINED; Genomic_DNA.
DR EMBL; AF302271; AAG32038.1; JOINED; Genomic_DNA.
DR EMBL; AK014042; BAB29128.1; -; mRNA.
DR EMBL; KF032392; AGZ02590.1; -; mRNA.
DR EMBL; AC171210; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC021439; AAH21439.1; -; mRNA.
DR CCDS; CCDS21055.1; -. [Q8VDQ8-1]
DR CCDS; CCDS52165.1; -. [Q8VDQ8-4]
DR CCDS; CCDS85253.1; -. [Q8VDQ8-2]
DR RefSeq; NP_001116237.1; NM_001122765.1. [Q8VDQ8-2]
DR RefSeq; NP_001116238.1; NM_001122766.1. [Q8VDQ8-4]
DR RefSeq; NP_071877.3; NM_022432.4. [Q8VDQ8-1]
DR AlphaFoldDB; Q8VDQ8; -.
DR SMR; Q8VDQ8; -.
DR BioGRID; 211070; 26.
DR IntAct; Q8VDQ8; 19.
DR STRING; 10090.ENSMUSP00000072732; -.
DR ChEMBL; CHEMBL3232691; -.
DR iPTMnet; Q8VDQ8; -.
DR PhosphoSitePlus; Q8VDQ8; -.
DR SwissPalm; Q8VDQ8; -.
DR EPD; Q8VDQ8; -.
DR jPOST; Q8VDQ8; -.
DR MaxQB; Q8VDQ8; -.
DR PaxDb; Q8VDQ8; -.
DR PeptideAtlas; Q8VDQ8; -.
DR PRIDE; Q8VDQ8; -.
DR ProteomicsDB; 257014; -. [Q8VDQ8-1]
DR ProteomicsDB; 257015; -. [Q8VDQ8-2]
DR ProteomicsDB; 257016; -. [Q8VDQ8-3]
DR ProteomicsDB; 257017; -. [Q8VDQ8-4]
DR Antibodypedia; 2167; 593 antibodies from 47 providers.
DR DNASU; 64383; -.
DR Ensembl; ENSMUST00000072965; ENSMUSP00000072732; ENSMUSG00000015149. [Q8VDQ8-1]
DR Ensembl; ENSMUST00000122915; ENSMUSP00000147217; ENSMUSG00000015149. [Q8VDQ8-2]
DR Ensembl; ENSMUST00000170068; ENSMUSP00000132783; ENSMUSG00000015149. [Q8VDQ8-4]
DR GeneID; 64383; -.
DR KEGG; mmu:64383; -.
DR UCSC; uc009fzt.2; mouse. [Q8VDQ8-1]
DR UCSC; uc012fgx.1; mouse. [Q8VDQ8-4]
DR CTD; 22933; -.
DR MGI; MGI:1927664; Sirt2.
DR VEuPathDB; HostDB:ENSMUSG00000015149; -.
DR eggNOG; KOG2682; Eukaryota.
DR GeneTree; ENSGT00940000157514; -.
DR HOGENOM; CLU_023643_7_4_1; -.
DR InParanoid; Q8VDQ8; -.
DR OMA; FNMEKVG; -.
DR OrthoDB; 973532at2759; -.
DR PhylomeDB; Q8VDQ8; -.
DR TreeFam; TF106181; -.
DR Reactome; R-MMU-2995383; Initiation of Nuclear Envelope (NE) Reformation.
DR BioGRID-ORCS; 64383; 4 hits in 75 CRISPR screens.
DR ChiTaRS; Sirt2; mouse.
DR PRO; PR:Q8VDQ8; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q8VDQ8; protein.
DR Bgee; ENSMUSG00000015149; Expressed in cranial nerve II and 262 other tissues.
DR ExpressionAtlas; Q8VDQ8; baseline and differential.
DR Genevisible; Q8VDQ8; MM.
DR GO; GO:0005814; C:centriole; ISS:UniProtKB.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005694; C:chromosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0097386; C:glial cell projection; ISS:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
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; IDA:UniProtKB.
DR GO; GO:0005874; C:microtubule; ISS:UniProtKB.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0072686; C:mitotic spindle; ISS:UniProtKB.
DR GO; GO:0043209; C:myelin sheath; IDA:UniProtKB.
DR GO; GO:0035748; C:myelin sheath abaxonal region; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0033010; C:paranodal junction; IDA:UniProtKB.
DR GO; GO:0033270; C:paranode region of axon; ISS:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0043220; C:Schmidt-Lanterman incisure; IDA:UniProtKB.
DR GO; GO:0005819; C:spindle; ISS:UniProtKB.
DR GO; GO:0097456; C:terminal loop; ISO:MGI.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISS:UniProtKB.
DR GO; GO:0035035; F:histone acetyltransferase binding; ISS:UniProtKB.
DR GO; GO:0004407; F:histone deacetylase activity; IMP:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; ISS:UniProtKB.
DR GO; GO:0003950; F:NAD+ ADP-ribosyltransferase activity; IEA:Ensembl.
DR GO; GO:0070403; F:NAD+ binding; ISO:MGI.
DR GO; GO:0017136; F:NAD-dependent histone deacetylase activity; ISS:UniProtKB.
DR GO; GO:0046970; F:NAD-dependent histone deacetylase activity (H4-K16 specific); ISS:UniProtKB.
DR GO; GO:0034979; F:NAD-dependent protein deacetylase activity; ISS:UniProtKB.
DR GO; GO:0140773; F:NAD-dependent protein demyristoylase activity; ISS:UniProtKB.
DR GO; GO:0140774; F:NAD-dependent protein depalmitoylase activity; ISS:UniProtKB.
DR GO; GO:0033558; F:protein lysine deacetylase activity; IDA:UniProtKB.
DR GO; GO:0042903; F:tubulin deacetylase activity; IMP:UniProtKB.
DR GO; GO:0043130; F:ubiquitin binding; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISO:MGI.
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; IMP:UniProtKB.
DR GO; GO:0061433; P:cellular response to caloric restriction; IDA:UniProtKB.
DR GO; GO:0071872; P:cellular response to epinephrine stimulus; IDA:UniProtKB.
DR GO; GO:0035729; P:cellular response to hepatocyte growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0071456; P:cellular response to hypoxia; ISS:UniProtKB.
DR GO; GO:0071219; P:cellular response to molecule of bacterial origin; ISS:UniProtKB.
DR GO; GO:0034599; P:cellular response to oxidative stress; IDA:UniProtKB.
DR GO; GO:0048012; P:hepatocyte growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0016575; P:histone deacetylation; IGI:MGI.
DR GO; GO:0070932; P:histone H3 deacetylation; IMP:UniProtKB.
DR GO; GO:0070933; P:histone H4 deacetylation; IMP:UniProtKB.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0022011; P:myelination in peripheral nervous system; IMP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0010507; P:negative regulation of autophagy; ISS: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; IMP:UniProtKB.
DR GO; GO:1900226; P:negative regulation of NLRP3 inflammasome complex assembly; IMP:MGI.
DR GO; GO:0048715; P:negative regulation of oligodendrocyte differentiation; ISO:MGI.
DR GO; GO:0070446; P:negative regulation of oligodendrocyte progenitor proliferation; ISS:UniProtKB.
DR GO; GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; IMP:UniProtKB.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; ISS:UniProtKB.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IMP:UniProtKB.
DR GO; GO:0045843; P:negative regulation of striated muscle tissue development; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0061428; P:negative regulation of transcription from RNA polymerase II promoter in response to hypoxia; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0044546; P:NLRP3 inflammasome complex assembly; IMP:MGI.
DR GO; GO:0034983; P:peptidyl-lysine deacetylation; ISS:UniProtKB.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR GO; GO:0051987; P:positive regulation of attachment of spindle microtubules to kinetochore; IMP:UniProtKB.
DR GO; GO:0051781; P:positive regulation of cell division; IMP:UniProtKB.
DR GO; GO:0043388; P:positive regulation of DNA binding; IDA:UniProtKB.
DR GO; GO:1900119; P:positive regulation of execution phase of apoptosis; IMP:UniProtKB.
DR GO; GO:0045836; P:positive regulation of meiotic nuclear division; IMP:UniProtKB.
DR GO; GO:1900195; P:positive regulation of oocyte maturation; IMP:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:2000777; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process involved in cellular response to hypoxia; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0006471; P:protein ADP-ribosylation; IEA:Ensembl.
DR GO; GO:0006476; P:protein deacetylation; IDA:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0045598; P:regulation of fat cell differentiation; IMP:MGI.
DR GO; GO:0031641; P:regulation of myelination; IMP:UniProtKB.
DR GO; GO:0099149; P:regulation of postsynaptic neurotransmitter receptor internalization; ISO:MGI.
DR GO; GO:0090042; P:tubulin deacetylation; IMP: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 Acetylation; Alternative splicing; Autophagy; Cell cycle; Cell division;
KW Cell membrane; Cell projection; Chromosome; Cytoplasm; Cytoskeleton;
KW Differentiation; Direct protein sequencing; Meiosis; Membrane;
KW Metal-binding; Microtubule; Mitosis; NAD; Neurogenesis; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Transferase; Ubl conjugation; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT CHAIN 2..389
FT /note="NAD-dependent protein deacetylase sirtuin-2"
FT /id="PRO_0000110259"
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 350..389
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 41..51
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 14..28
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 352..366
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 187
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 85..89
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 95..97
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 167..170
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 195
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 200
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 221
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 224
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 262..263
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 286..288
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 324
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT MOD_RES 23
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 27
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
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 368
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 372
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..37
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_008729"
FT VAR_SEQ 6..76
FT /note="PSDPLETQAGKVQEAQDSDSDTEGGATGGEAEMDFLRNLFTQTLGLGSQKER
FT LLDELTLEGVTRYMQSERC -> R (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_055329"
FT VAR_SEQ 236..389
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:24177535"
FT /id="VSP_055330"
FT MUTAGEN 187
FT /note="H->A: Abolishes deacetylation of FOXO3. Does not
FT inhibit interaction with FOXO3."
FT /evidence="ECO:0000269|PubMed:17521387,
FT ECO:0000269|PubMed:21841822"
FT CONFLICT 230
FT /note="P -> L (in Ref. 1; AAG32038)"
FT /evidence="ECO:0000305"
FT CONFLICT 241
FT /note="S -> P (in Ref. 5; AAH21439)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 389 AA; 43256 MW; 15F96635445A1BC0 CRC64;
MAEPDPSDPL ETQAGKVQEA QDSDSDTEGG ATGGEAEMDF LRNLFTQTLG LGSQKERLLD
ELTLEGVTRY MQSERCRKVI CLVGAGISTS AGIPDFRSPS TGLYANLEKY HLPYPEAIFE
ISYFKKHPEP FFALAKELYP GQFKPTICHY FIRLLKEKGL LLRCYTQNID TLERVAGLEP
QDLVEAHGTF YTSHCVNTSC RKEYTMGWMK EKIFSEATPR CEQCQSVVKP DIVFFGENLP
SRFFSCMQSD FSKVDLLIIM GTSLQVQPFA SLISKAPLAT PRLLINKEKT GQTDPFLGMM
MGLGGGMDFD SKKAYRDVAW LGDCDQGCLA LADLLGWKKE LEDLVRREHA NIDAQSGSQA
PNPSTTISPG KSPPPAKEAA RTKEKEEQQ
