UniProtKB - Q5RJQ4 (SIR2_RAT)
NAD-dependent protein deacetylase sirtuin-2
Sirt2
Functioni
Miscellaneous
Catalytic activityi
- H2O + N6-acetyl-L-lysyl-[protein] + NAD+ = 2''-O-acetyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamidePROSITE-ProRule annotationEC:2.3.1.286PROSITE-ProRule annotation
Cofactori
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 150 | Proton acceptorPROSITE-ProRule annotation | 1 | |
Metal bindingi | 158 | ZincPROSITE-ProRule annotation | 1 | |
Metal bindingi | 163 | ZincPROSITE-ProRule annotation | 1 | |
Metal bindingi | 184 | ZincPROSITE-ProRule annotation | 1 | |
Metal bindingi | 187 | ZincPROSITE-ProRule annotation | 1 | |
Binding sitei | 287 | NAD; via amide nitrogenBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 48 – 52 | NADBy similarity | 5 | |
Nucleotide bindingi | 58 – 60 | NADBy similarity | 3 | |
Nucleotide bindingi | 130 – 133 | NADBy similarity | 4 | |
Nucleotide bindingi | 225 – 226 | NADBy similarity | 2 | |
Nucleotide bindingi | 249 – 251 | NADBy similarity | 3 |
GO - Molecular functioni
- beta-tubulin binding Source: RGD
- chromatin binding Source: UniProtKB
- histone acetyltransferase binding Source: RGD
- histone deacetylase activity Source: UniProtKB
- histone deacetylase binding Source: RGD
- NAD+ ADP-ribosyltransferase activity Source: RGD
- NAD+ binding Source: RGD
- NAD-dependent histone deacetylase activity Source: RGD
- NAD-dependent histone deacetylase activity (H4-K16 specific) Source: UniProtKB
- NAD-dependent protein deacetylase activity Source: UniProtKB
- protein deacetylase activity Source: UniProtKB
- transcription factor binding Source: RGD
- tubulin deacetylase activity Source: UniProtKB
- ubiquitin binding Source: RGD
- zinc ion binding Source: RGD
GO - Biological processi
- autophagy Source: UniProtKB-KW
- cell division Source: UniProtKB-KW
- cellular lipid catabolic process Source: UniProtKB
- cellular response to caloric restriction Source: UniProtKB
- cellular response to epinephrine stimulus Source: UniProtKB
- cellular response to hepatocyte growth factor stimulus Source: UniProtKB
- cellular response to hypoxia Source: UniProtKB
- cellular response to molecule of bacterial origin Source: UniProtKB
- cellular response to oxidative stress Source: UniProtKB
- central nervous system development Source: RGD
- hepatocyte growth factor receptor signaling pathway Source: UniProtKB
- histone deacetylation Source: RGD
- histone H3 deacetylation Source: UniProtKB
- histone H4 deacetylation Source: UniProtKB
- meiotic cell cycle Source: UniProtKB-KW
- myelination in peripheral nervous system Source: UniProtKB
- negative regulation of apoptotic process Source: RGD
- negative regulation of autophagy Source: UniProtKB
- negative regulation of cell population proliferation Source: UniProtKB
- negative regulation of defense response to bacterium Source: UniProtKB
- negative regulation of fat cell differentiation Source: UniProtKB
- negative regulation of NLRP3 inflammasome complex assembly Source: RGD
- negative regulation of oligodendrocyte differentiation Source: RGD
- negative regulation of oligodendrocyte progenitor proliferation Source: UniProtKB
- negative regulation of peptidyl-threonine phosphorylation Source: UniProtKB
- negative regulation of protein catabolic process Source: UniProtKB
- negative regulation of reactive oxygen species metabolic process Source: UniProtKB
- negative regulation of striated muscle tissue development Source: RGD
- negative regulation of transcription, DNA-templated Source: RGD
- negative regulation of transcription by RNA polymerase II Source: UniProtKB
- negative regulation of transcription from RNA polymerase II promoter in response to hypoxia Source: UniProtKB
- peptidyl-lysine deacetylation Source: UniProtKB
- phosphatidylinositol 3-kinase signaling Source: UniProtKB
- positive regulation of attachment of spindle microtubules to kinetochore Source: UniProtKB
- positive regulation of cell division Source: UniProtKB
- positive regulation of DNA binding Source: UniProtKB
- positive regulation of execution phase of apoptosis Source: UniProtKB
- positive regulation of meiotic nuclear division Source: UniProtKB
- positive regulation of oocyte maturation Source: UniProtKB
- positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
- positive regulation of proteasomal ubiquitin-dependent protein catabolic process involved in cellular response to hypoxia Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
- protein ADP-ribosylation Source: RGD
- protein deacetylation Source: UniProtKB
- protein kinase B signaling Source: UniProtKB
- regulation of cell cycle Source: UniProtKB
- regulation of fat cell differentiation Source: RGD
- regulation of myelination Source: UniProtKB
- regulation of postsynaptic neurotransmitter receptor internalization Source: SynGO
- tubulin deacetylation Source: UniProtKB
Keywordsi
Molecular function | Transferase |
Biological process | Autophagy, Cell cycle, Cell division, Differentiation, Meiosis, Mitosis, Neurogenesis, Transcription, Transcription regulation |
Ligand | Metal-binding, NAD, Zinc |
Enzyme and pathway databases
Reactomei | R-RNO-2995383, Initiation of Nuclear Envelope (NE) Reformation |
Names & Taxonomyi
Protein namesi | Recommended name: NAD-dependent protein deacetylase sirtuin-2 (EC:2.3.1.286)Alternative name(s): Regulatory protein SIR2 homolog 2 SIR2-like protein 2 |
Gene namesi | Name:Sirt2 Synonyms:Sir2l2 |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 621481, Sirt2 |
Subcellular locationi
Cytoskeleton
- cytoskeleton By similarity
- centrosome By similarity
- centriole By similarity
- spindle By similarity
Nucleus
- Nucleus By similarity
Plasma membrane
- Myelin membrane By similarity
Other locations
- perinuclear region By similarity
- Cytoplasm By similarity
- Midbody By similarity
- Chromosome By similarity
- Perikaryon By similarity
- Cell projection By similarity
- growth cone By similarity
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 (By similarity).By similarity
Cytoskeleton
- centriole Source: UniProtKB
- centrosome Source: UniProtKB
- meiotic spindle Source: UniProtKB
- microtubule Source: RGD
- mitotic spindle Source: UniProtKB
- spindle Source: UniProtKB
Cytosol
- cytosol Source: UniProtKB
Mitochondrion
- mitochondrion Source: RGD
Nucleus
- nuclear heterochromatin Source: UniProtKB
- nucleus Source: RGD
Plasma Membrane
- plasma membrane Source: UniProtKB-KW
Other locations
- chromosome Source: UniProtKB
- cytoplasm Source: RGD
- glial cell projection Source: UniProtKB
- glutamatergic synapse Source: SynGO
- growth cone Source: UniProtKB-SubCell
- juxtaparanode region of axon Source: UniProtKB
- lateral loop Source: UniProtKB
- midbody Source: UniProtKB
- myelin sheath Source: UniProtKB
- myelin sheath abaxonal region Source: RGD
- paranodal junction Source: UniProtKB
- paranode region of axon Source: UniProtKB
- perikaryon Source: UniProtKB
- perinuclear region of cytoplasm Source: UniProtKB
- Schmidt-Lanterman incisure Source: UniProtKB
- terminal loop Source: RGD
Keywords - Cellular componenti
Cell membrane, Cell projection, Chromosome, Cytoplasm, Cytoskeleton, Membrane, Microtubule, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 131 | N → A: Reduced deacetylase activity on alpha-tubulin and stimulates oligodendrocyte precursor (OLP) differentiation. 1 Publication | 1 | |
Mutagenesisi | 133 | D → A: Reduced deacetylase activity on alpha-tubulin. 1 Publication | 1 | |
Mutagenesisi | 150 | H → A: Reduced deacetylase activity on alpha-tubulin and stimulates oligodendrocyte precursor (OLP) differentiation. 1 Publication | 1 |
Chemistry databases
ChEMBLi | CHEMBL3232690 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000244536 | 1 – 350 | NAD-dependent protein deacetylase sirtuin-2Add BLAST | 350 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 16 | PhosphoserineCombined sources | 1 | |
Modified residuei | 63 | PhosphoserineCombined sources | 1 | |
Modified residuei | 170 | PhosphoserineCombined sources | 1 | |
Modified residuei | 330 | PhosphoserineCombined sources | 1 | |
Modified residuei | 334 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
jPOSTi | Q5RJQ4 |
PaxDbi | Q5RJQ4 |
PRIDEi | Q5RJQ4 |
PTM databases
iPTMneti | Q5RJQ4 |
PhosphoSitePlusi | Q5RJQ4 |
SwissPalmi | Q5RJQ4 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSRNOG00000020102, Expressed in testis and 21 other tissues |
ExpressionAtlasi | Q5RJQ4, baseline and differential |
Genevisiblei | Q5RJQ4, RN |
Interactioni
Subunit structurei
Interacts with CDC20, FOXO3 and FZR1 (By similarity). Associates with microtubules in primary cortical mature neurons (By similarity). Homotrimer.
Interacts (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 (By similarity).
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 H2O2-induced oxidative stress-dependent manner.
Interacts with G6PD; the interaction is enhanced by H2O2 treatment.
Interacts with a G1/S-specific cyclin E-CDK2 complex.
Interacts with AURKA, CDK5R1 (p35 form) and CDK5 and HIF1A.
Interacts with the tRNA ligase SARS1; recruited to the VEGFA promoter via interaction with SARS1 (By similarity).
Interacts with BEX4; negatively regulates alpha-tubulin deacetylation by SIRT2 (By similarity).
By similarityGO - Molecular functioni
- beta-tubulin binding Source: RGD
- histone acetyltransferase binding Source: RGD
- histone deacetylase binding Source: RGD
- transcription factor binding Source: RGD
- ubiquitin binding Source: RGD
Protein-protein interaction databases
BioGRIDi | 262752, 2 interactors |
STRINGi | 10116.ENSRNOP00000059450 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 28 – 303 | Deacetylase sirtuin-typePROSITE-ProRule annotationAdd BLAST | 276 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 79 – 83 | Peptide inhibitor bindingBy similarity | 5 | |
Regioni | 195 – 264 | Peptide inhibitor bindingBy similarityAdd BLAST | 70 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 4 – 14 | Nuclear export signalBy similarityAdd BLAST | 11 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG2682, Eukaryota |
GeneTreei | ENSGT00940000157514 |
HOGENOMi | CLU_023643_7_4_1 |
InParanoidi | Q5RJQ4 |
OrthoDBi | 973532at2759 |
Family and domain databases
Gene3Di | 3.30.1600.10, 1 hit |
InterProi | View protein in InterPro IPR029035, DHS-like_NAD/FAD-binding_dom IPR003000, Sirtuin IPR026591, Sirtuin_cat_small_dom_sf IPR017328, Sirtuin_class_I IPR026590, Ssirtuin_cat_dom |
Pfami | View protein in Pfam PF02146, SIR2, 1 hit |
PIRSFi | PIRSF037938, SIR2_euk, 1 hit |
SUPFAMi | SSF52467, SSF52467, 1 hit |
PROSITEi | View protein in PROSITE PS50305, SIRTUIN, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
10 20 30 40 50
MDFLRNLFTQ TLGLGSQKER LLDELTLEGV TRYMQSERCR RVICLVGAGI
60 70 80 90 100
STSAGIPDFR SPSTGLYANL EKYHLPYPEA IFEISYFKKH PEPFFALAKE
110 120 130 140 150
LYPGQFKPTI CHYFIRLLKE KGLLLRCYTQ NIDTLERVAG LEPQDLVEAH
160 170 180 190 200
GTFYTSHCVN TSCGKEYTMS WMKEKIFSEA TPKCEKCQNV VKPDIVFFGE
210 220 230 240 250
NLPPRFFSCM QSDFSKVDLL IIMGTSLQVQ PFASLISKAP LATPRLLINK
260 270 280 290 300
EKTGQTDPFL GMMMGLGGGM DFDSKKAYRD VAWLGDCDQG CLALADLLGW
310 320 330 340 350
KELEDLVRRE HANIDAQSGS QASNPSATVS PRKSPPPAKE AARTKEKEEH
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A0G2JWM2 | A0A0G2JWM2_RAT | NAD-dependent protein deacetylase | Sirt2 rCG_53640 | 388 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | BC086545 mRNA Translation: AAH86545.1 |
RefSeqi | NP_001008369.1, NM_001008368.1 |
Genome annotation databases
Ensembli | ENSRNOT00000064153; ENSRNOP00000059450; ENSRNOG00000020102 |
GeneIDi | 361532 |
KEGGi | rno:361532 |
UCSCi | RGD:621481, rat |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | BC086545 mRNA Translation: AAH86545.1 |
RefSeqi | NP_001008369.1, NM_001008368.1 |
3D structure databases
SMRi | Q5RJQ4 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 262752, 2 interactors |
STRINGi | 10116.ENSRNOP00000059450 |
Chemistry databases
ChEMBLi | CHEMBL3232690 |
PTM databases
iPTMneti | Q5RJQ4 |
PhosphoSitePlusi | Q5RJQ4 |
SwissPalmi | Q5RJQ4 |
Proteomic databases
jPOSTi | Q5RJQ4 |
PaxDbi | Q5RJQ4 |
PRIDEi | Q5RJQ4 |
Genome annotation databases
Ensembli | ENSRNOT00000064153; ENSRNOP00000059450; ENSRNOG00000020102 |
GeneIDi | 361532 |
KEGGi | rno:361532 |
UCSCi | RGD:621481, rat |
Organism-specific databases
CTDi | 22933 |
RGDi | 621481, Sirt2 |
Phylogenomic databases
eggNOGi | KOG2682, Eukaryota |
GeneTreei | ENSGT00940000157514 |
HOGENOMi | CLU_023643_7_4_1 |
InParanoidi | Q5RJQ4 |
OrthoDBi | 973532at2759 |
Enzyme and pathway databases
Reactomei | R-RNO-2995383, Initiation of Nuclear Envelope (NE) Reformation |
Miscellaneous databases
PROi | PR:Q5RJQ4 |
Gene expression databases
Bgeei | ENSRNOG00000020102, Expressed in testis and 21 other tissues |
ExpressionAtlasi | Q5RJQ4, baseline and differential |
Genevisiblei | Q5RJQ4, RN |
Family and domain databases
Gene3Di | 3.30.1600.10, 1 hit |
InterProi | View protein in InterPro IPR029035, DHS-like_NAD/FAD-binding_dom IPR003000, Sirtuin IPR026591, Sirtuin_cat_small_dom_sf IPR017328, Sirtuin_class_I IPR026590, Ssirtuin_cat_dom |
Pfami | View protein in Pfam PF02146, SIR2, 1 hit |
PIRSFi | PIRSF037938, SIR2_euk, 1 hit |
SUPFAMi | SSF52467, SSF52467, 1 hit |
PROSITEi | View protein in PROSITE PS50305, SIRTUIN, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | SIR2_RAT | |
Accessioni | Q5RJQ4Primary (citable) accession number: Q5RJQ4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 27, 2006 |
Last sequence update: | December 21, 2004 | |
Last modified: | December 2, 2020 | |
This is version 131 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families