SIR2_RAT
ID SIR2_RAT Reviewed; 350 AA.
AC Q5RJQ4;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=NAD-dependent protein deacetylase sirtuin-2;
DE EC=2.3.1.286 {ECO:0000305|PubMed:17344398};
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;
GN Name=Sirt2; Synonyms=Sir2l2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [2]
RP PROTEIN SEQUENCE OF 6-18; 21-32; 41-116; 176-183; 187-216; 239-245; 302-308
RP AND 310-332, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain, Hippocampus, and Spinal cord;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Kang S.U.;
RL Submitted (JUL-2007) to UniProtKB.
RN [3]
RP INDUCTION.
RX PubMed=12065666; DOI=10.1046/j.1471-4159.2002.00847.x;
RA De Smet C., Nishimori H., Furnari F.B., Boegler O., Huang H.-J.S.,
RA Cavenee W.K.;
RT "A novel seven transmembrane receptor induced during the early steps of
RT astrocyte differentiation identified by differential expression.";
RL J. Neurochem. 81:575-588(2002).
RN [4]
RP FUNCTION IN DEACETYLATION OF ALPHA TUBULIN, FUNCTION AS REGULATOR OF
RP OLIGODENDROCYTE DIFFERENTIATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND MUTAGENESIS OF ASN-131; ASP-133 AND HIS-150.
RX PubMed=17344398; DOI=10.1523/jneurosci.4181-06.2007;
RA Li W., Zhang B., Tang J., Cao Q., Wu Y., Wu C., Guo J., Ling E.A.,
RA Liang F.;
RT "Sirtuin 2, a mammalian homolog of yeast silent information regulator-2
RT longevity regulator, is an oligodendroglial protein that decelerates cell
RT differentiation through deacetylating alpha-tubulin.";
RL J. Neurosci. 27:2606-2616(2007).
RN [5]
RP FUNCTION IN REGULATION OF PERIPHERAL MYELINATION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16; SER-63; SER-170 AND
RP SER-330, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [7]
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).
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:17344398).
CC Participates in the modulation of multiple and diverse biological
CC processes such as cell cycle control, genomic integrity, microtubule
CC dynamics, cell differentiation, metabolic networks, and autophagy.
CC Plays a major role in the control of cell cycle progression and genomic
CC stability. Functions in the antephase checkpoint preventing precocious
CC mitotic entry in response to microtubule stress agents, and hence
CC allowing proper inheritance of chromosomes. Positively regulates the
CC anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex
CC activity by deacetylating CDC20 and FZR1, then allowing progression
CC through mitosis. Associates both with chromatin at transcriptional
CC start sites (TSSs) and enhancers of active genes. Plays a role in cell
CC cycle and chromatin compaction through epigenetic modulation of the
CC regulation of histone H4 'Lys-20' methylation (H4K20me1) during early
CC mitosis. Specifically deacetylates histone H4 at 'Lys-16' (H4K16ac)
CC between the G2/M transition and metaphase enabling H4K20me1 deposition
CC by KMT5A 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. Phosphorylation at Ser-368 by a
CC G1/S-specific cyclin E-CDK2 complex inactivates SIRT2-mediated alpha-
CC tubulin deacetylation, negatively regulating cell adhesion, cell
CC migration and neurite outgrowth during neuronal differentiation.
CC Deacetylates PARD3 and participates in the regulation of Schwann cell
CC peripheral myelination formation during early postnatal development and
CC during postinjury remyelination. Involved in several cellular metabolic
CC pathways. Plays a role in the regulation of blood glucose homeostasis
CC by deacetylating and stabilizing phosphoenolpyruvate carboxykinase PCK1
CC activity in response to low nutrient availability. Acts as a key
CC regulator in the pentose phosphate pathway (PPP) by deacetylating and
CC activating the glucose-6-phosphate G6PD enzyme, and therefore,
CC stimulates the production of cytosolic NADPH to counteract oxidative
CC damage. Maintains energy homeostasis in response to nutrient
CC deprivation as well as energy expenditure by inhibiting adipogenesis
CC and promoting lipolysis. Attenuates adipocyte differentiation by
CC deacetylating and promoting FOXO1 interaction to PPARG and subsequent
CC repression of PPARG-dependent transcriptional activity. Plays a role in
CC the regulation of lysosome-mediated degradation of protein aggregates
CC by autophagy in neuronal cells. Deacetylates FOXO1 in response to
CC oxidative stress or serum deprivation, thereby negatively regulating
CC FOXO1-mediated autophagy (By similarity). Deacetylates a broad range of
CC transcription factors and co-regulators regulating target gene
CC expression. Deacetylates transcriptional factor FOXO3 stimulating the
CC ubiquitin ligase SCF(SKP2)-mediated FOXO3 ubiquitination and
CC degradation (By similarity). Deacetylates HIF1A and therefore promotes
CC HIF1A degradation and inhibition of HIF1A transcriptional activity in
CC tumor cells in response to hypoxia. Deacetylates RELA in the cytoplasm
CC inhibiting NF-kappaB-dependent transcription activation upon TNF-alpha
CC stimulation. Inhibits transcriptional activation by deacetylating
CC p53/TP53 and EP300. Deacetylates also EIF5A. Functions as a negative
CC regulator on oxidative stress-tolerance in response to anoxia-
CC reoxygenation conditions. Plays a role as tumor suppressor
CC (PubMed:22943040). In addition to protein deacetylase activity, also
CC has activity toward long-chain fatty acyl groups and mediates protein-
CC lysine demyristoylation and depalmitoylation of target proteins, such
CC as ARF6 and KRAS, thereby regulating their association with membranes
CC (By similarity). {ECO:0000250|UniProtKB:Q8IXJ6,
CC ECO:0000250|UniProtKB:Q8VDQ8, ECO:0000269|PubMed:17344398,
CC ECO:0000269|PubMed:21949390, ECO:0000269|PubMed:22943040}.
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:0000305|PubMed:17344398};
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 (By similarity).
CC Associates with microtubules in primary cortical mature neurons (By
CC similarity). Homotrimer. Interacts (via both phosphorylated,
CC unphosphorylated, active or inactive forms) with HDAC6; the interaction
CC is necessary for the complex to interact with alpha-tubulin, suggesting
CC that these proteins belong to a large complex that deacetylates the
CC cytoskeleton. Interacts with FOXO1; the interaction is disrupted upon
CC serum-starvation or oxidative stress, leading to increased level of
CC acetylated FOXO1 and induction of autophagy (By similarity). Interacts
CC with RELA; the interaction occurs in the cytoplasm and is increased in
CC a TNF-alpha-dependent manner. Interacts with HOXA10; the interaction is
CC direct. Interacts with YWHAB and YWHAG; the interactions occur in a
CC AKT-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). Interacts with BEX4;
CC negatively regulates alpha-tubulin deacetylation by SIRT2 (By
CC similarity). {ECO:0000250|UniProtKB:Q8IXJ6,
CC ECO:0000250|UniProtKB:Q8VDQ8}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8IXJ6}.
CC Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q8VDQ8}. Cytoplasm
CC {ECO:0000269|PubMed:17344398}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q8IXJ6}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250|UniProtKB:Q8IXJ6}.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome,
CC centriole {ECO:0000250|UniProtKB:Q8IXJ6}. Cytoplasm, cytoskeleton,
CC spindle {ECO:0000250|UniProtKB:Q8IXJ6}. Midbody
CC {ECO:0000250|UniProtKB:Q8IXJ6}. Chromosome
CC {ECO:0000250|UniProtKB:Q8IXJ6}. Perikaryon
CC {ECO:0000269|PubMed:17344398}. Cell projection
CC {ECO:0000250|UniProtKB:Q8VDQ8}. Cell projection, growth cone
CC {ECO:0000250|UniProtKB:Q8VDQ8}. Myelin membrane
CC {ECO:0000269|PubMed:17344398}. 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). Detected in perinuclear foci that
CC may be aggresomes containing misfolded, ubiquitinated proteins (By
CC similarity). Shuttles between the cytoplasm and the nucleus through the
CC CRM1 export pathway. Colocalizes with EP300 in the nucleus.
CC Translocates to the nucleus and chromatin upon bacterium Listeria
CC monocytogenes infection in interphase cells (By similarity).
CC Deacetylates FOXO3 in the cytoplasm. Colocalizes with PLP1 in
CC internodal regions, at paranodal axoglial junction and Schmidt-
CC Lanterman incisures of myelin sheat. Colocalizes with CDK5R1 in the
CC perikaryon, neurites and growth cone of hippocampal neurons.
CC Colocalizes with alpha-tubulin in neuronal growth cone. Localizes in
CC the cytoplasm and nucleus of germinal vesicle (GV) stage oocytes.
CC Colocalizes with alpha-tubulin on the meiotic spindle as the oocytes
CC enter into metaphase, and also during meiotic anaphase and telophase,
CC especially with the midbody. Colocalizes with PARD3 in internodal
CC region of axons (By similarity). Colocalizes with acetylated alpha-
CC tubulin in cell projection processes during primary oligodendrocyte
CC precursor (OLP) differentiation (By similarity).
CC {ECO:0000250|UniProtKB:Q8IXJ6, ECO:0000250|UniProtKB:Q8VDQ8}.
CC -!- TISSUE SPECIFICITY: Expressed in the cerebellum, cerebral cortex and
CC cervival spinal cord. Expressed in Purkinje cells, oligodendrocytes and
CC Schwann cells (at protein level). Expressed in the central nervous
CC system (CNS). {ECO:0000269|PubMed:17344398,
CC ECO:0000269|PubMed:21949390}.
CC -!- INDUCTION: In oligodendrocytes during differentiation of CG-4 cells.
CC {ECO:0000269|PubMed:12065666}.
CC -!- PTM: Phosphorylated at phosphoserine and phosphothreonine.
CC Phosphorylated at Ser-330 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-330 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-330 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 -!- MISCELLANEOUS: Has some ability to deacetylate histones in vitro, but
CC seeing its subcellular location, this is unlikely in vivo.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class I subfamily.
CC {ECO:0000305}.
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DR EMBL; BC086545; AAH86545.1; -; mRNA.
DR RefSeq; NP_001008369.1; NM_001008368.1.
DR AlphaFoldDB; Q5RJQ4; -.
DR SMR; Q5RJQ4; -.
DR BioGRID; 262752; 2.
DR IntAct; Q5RJQ4; 1.
DR MINT; Q5RJQ4; -.
DR STRING; 10116.ENSRNOP00000059450; -.
DR ChEMBL; CHEMBL3232690; -.
DR iPTMnet; Q5RJQ4; -.
DR PhosphoSitePlus; Q5RJQ4; -.
DR SwissPalm; Q5RJQ4; -.
DR jPOST; Q5RJQ4; -.
DR PaxDb; Q5RJQ4; -.
DR PRIDE; Q5RJQ4; -.
DR GeneID; 361532; -.
DR KEGG; rno:361532; -.
DR UCSC; RGD:621481; rat.
DR CTD; 22933; -.
DR RGD; 621481; Sirt2.
DR VEuPathDB; HostDB:ENSRNOG00000020102; -.
DR eggNOG; KOG2682; Eukaryota.
DR HOGENOM; CLU_023643_7_4_1; -.
DR InParanoid; Q5RJQ4; -.
DR OrthoDB; 973532at2759; -.
DR Reactome; R-RNO-2995383; Initiation of Nuclear Envelope (NE) Reformation.
DR PRO; PR:Q5RJQ4; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000020102; Expressed in testis and 19 other tissues.
DR ExpressionAtlas; Q5RJQ4; baseline and differential.
DR Genevisible; Q5RJQ4; RN.
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:RGD.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0097386; C:glial cell projection; IDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0030426; C:growth cone; IEA:UniProtKB-SubCell.
DR GO; GO:0000792; C:heterochromatin; IDA:UniProtKB.
DR GO; GO:0044224; C:juxtaparanode region of axon; IDA:UniProtKB.
DR GO; GO:0043219; C:lateral loop; IDA:UniProtKB.
DR GO; GO:0072687; C:meiotic spindle; ISS:UniProtKB.
DR GO; GO:0005874; C:microtubule; ISO:RGD.
DR GO; GO:0030496; C:midbody; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
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; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0033010; C:paranodal junction; IDA:UniProtKB.
DR GO; GO:0033270; C:paranode region of axon; IDA:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-KW.
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; IDA:RGD.
DR GO; GO:0048487; F:beta-tubulin binding; ISO:RGD.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0035035; F:histone acetyltransferase binding; ISO:RGD.
DR GO; GO:0004407; F:histone deacetylase activity; ISS:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:RGD.
DR GO; GO:0003950; F:NAD+ ADP-ribosyltransferase activity; ISO:RGD.
DR GO; GO:0070403; F:NAD+ binding; ISO:RGD.
DR GO; GO:0017136; F:NAD-dependent histone deacetylase activity; ISO:RGD.
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; IDA: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; ISS:UniProtKB.
DR GO; GO:0042903; F:tubulin deacetylase activity; IDA:UniProtKB.
DR GO; GO:0043130; F:ubiquitin binding; ISO:RGD.
DR GO; GO:0008270; F:zinc ion binding; ISO:RGD.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0044242; P:cellular lipid catabolic process; ISS:UniProtKB.
DR GO; GO:0061433; P:cellular response to caloric restriction; ISS:UniProtKB.
DR GO; GO:0071872; P:cellular response to epinephrine stimulus; ISS:UniProtKB.
DR GO; GO:0035729; P:cellular response to hepatocyte growth factor stimulus; 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; ISS:UniProtKB.
DR GO; GO:0007417; P:central nervous system development; IEP:RGD.
DR GO; GO:0048012; P:hepatocyte growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0016575; P:histone deacetylation; ISO:RGD.
DR GO; GO:0070932; P:histone H3 deacetylation; ISS:UniProtKB.
DR GO; GO:0070933; P:histone H4 deacetylation; ISS: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; IMP:RGD.
DR GO; GO:0010507; P:negative regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:1900425; P:negative regulation of defense response to bacterium; ISS:UniProtKB.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; ISS:UniProtKB.
DR GO; GO:1900226; P:negative regulation of NLRP3 inflammasome complex assembly; ISO:RGD.
DR GO; GO:0048715; P:negative regulation of oligodendrocyte differentiation; IMP:RGD.
DR GO; GO:0070446; P:negative regulation of oligodendrocyte progenitor proliferation; IMP:UniProtKB.
DR GO; GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; ISS:UniProtKB.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; ISS:UniProtKB.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; ISS:UniProtKB.
DR GO; GO:0045843; P:negative regulation of striated muscle tissue development; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS: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; ISO:RGD.
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; ISS:UniProtKB.
DR GO; GO:0051781; P:positive regulation of cell division; ISS:UniProtKB.
DR GO; GO:0043388; P:positive regulation of DNA binding; ISS:UniProtKB.
DR GO; GO:1900119; P:positive regulation of execution phase of apoptosis; ISS:UniProtKB.
DR GO; GO:0045836; P:positive regulation of meiotic nuclear division; ISS:UniProtKB.
DR GO; GO:1900195; P:positive regulation of oocyte maturation; ISS:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:2000777; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process involved in cellular response to hypoxia; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0006471; P:protein ADP-ribosylation; ISO:RGD.
DR GO; GO:0006476; P:protein deacetylation; IMP: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; ISO:RGD.
DR GO; GO:0031641; P:regulation of myelination; IMP:UniProtKB.
DR GO; GO:0099149; P:regulation of postsynaptic neurotransmitter receptor internalization; IDA:SynGO.
DR GO; GO:0090042; P:tubulin deacetylation; IDA:UniProtKB.
DR Gene3D; 3.30.1600.10; -; 1.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR InterPro; IPR003000; Sirtuin.
DR InterPro; IPR026591; Sirtuin_cat_small_dom_sf.
DR InterPro; IPR017328; Sirtuin_class_I.
DR InterPro; IPR026590; Ssirtuin_cat_dom.
DR Pfam; PF02146; SIR2; 1.
DR PIRSF; PIRSF037938; SIR2_euk; 1.
DR SUPFAM; SSF52467; SSF52467; 1.
DR PROSITE; PS50305; SIRTUIN; 1.
PE 1: Evidence at protein level;
KW Autophagy; Cell cycle; Cell division; Cell membrane; Cell projection;
KW Chromosome; Cytoplasm; Cytoskeleton; Differentiation;
KW Direct protein sequencing; Meiosis; Membrane; Metal-binding; Microtubule;
KW Mitosis; NAD; Neurogenesis; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Transferase; Ubl conjugation;
KW Zinc.
FT CHAIN 1..350
FT /note="NAD-dependent protein deacetylase sirtuin-2"
FT /id="PRO_0000244536"
FT DOMAIN 28..303
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT REGION 312..350
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 4..14
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 314..329
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 150
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 48..52
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 58..60
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 130..133
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 158
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 163
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 184
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 187
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 225..226
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 249..251
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 287
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT MOD_RES 16
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 63
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 170
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 330
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 334
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT MUTAGEN 131
FT /note="N->A: Reduced deacetylase activity on alpha-tubulin
FT and stimulates oligodendrocyte precursor (OLP)
FT differentiation."
FT /evidence="ECO:0000269|PubMed:17344398"
FT MUTAGEN 133
FT /note="D->A: Reduced deacetylase activity on alpha-
FT tubulin."
FT /evidence="ECO:0000269|PubMed:17344398"
FT MUTAGEN 150
FT /note="H->A: Reduced deacetylase activity on alpha-tubulin
FT and stimulates oligodendrocyte precursor (OLP)
FT differentiation."
FT /evidence="ECO:0000269|PubMed:17344398"
SQ SEQUENCE 350 AA; 39319 MW; EA3621A7CCE695FB CRC64;
MDFLRNLFTQ TLGLGSQKER LLDELTLEGV TRYMQSERCR RVICLVGAGI STSAGIPDFR
SPSTGLYANL EKYHLPYPEA IFEISYFKKH PEPFFALAKE LYPGQFKPTI CHYFIRLLKE
KGLLLRCYTQ NIDTLERVAG LEPQDLVEAH GTFYTSHCVN TSCGKEYTMS WMKEKIFSEA
TPKCEKCQNV VKPDIVFFGE NLPPRFFSCM QSDFSKVDLL IIMGTSLQVQ PFASLISKAP
LATPRLLINK EKTGQTDPFL GMMMGLGGGM DFDSKKAYRD VAWLGDCDQG CLALADLLGW
KELEDLVRRE HANIDAQSGS QASNPSATVS PRKSPPPAKE AARTKEKEEH
