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FLASH GENE
Symbol SIRT2 contributors: mct - updated : 17-10-2019
HGNC name sirtuin 2
HGNC id 10886
Location 19q13.2      Physical location : 39.369.194 - 39.390.502
Synonym name
  • sirtuin (silent mating type information regulation 2 homolog) 2 (S. cerevisiae)
  • sir2-related protein type 2
  • silencing information regulator 2-like
  • SIR2-like protein 2
  • NAD-dependent deacetylase sirtuin-2
  • Synonym symbol(s) SIR2L, SIR2L2, SIR2, FLJ35621, FLJ37491
    EC.number 3.5.1.-
    DNA
    TYPE functioning gene
    STRUCTURE 21.16 kb     16 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence cytosine-phosphate-guanine/HTF
    Binding site   transcription factor
    text structure
  • a 0.67-kb CpG island
  • a number of NFkappaB and GATA transcription factor binding sites
  • MAPPING cloned Y linked N status provisional
    Physical map
    PSMD8 19q13.13 proteasome (prosome, macropain) 26S subunit, non-ATPase, 8 GGN 19q13.13 gametogenetin LOC388538 19 similar to SPRED-3 LOC147965 19q13.2 hypothetical protein LOC147965 RASGRP4 19q13.1 RAS guanyl releasing protein 4 RYR1 19q13.1 ryanodine receptor 1 (skeletal) MAP4K1 19q13.2 mitogen-activated protein kinase kinase kinase kinase 1 eIF3k 19q13.2 mitogen-activated protein kinase kinase kinase kinase 1 ACTN4 19q13 actinin, alpha 4 CAPN12 19q13.2 calpain 12 LGALS7 19q13.2 lectin, galactoside-binding, soluble, 7 (galectin 7) LGALS4 19q13.2 lectin, galactoside-binding, soluble, 4 (galectin 4) ECH1 19q13.1 enoyl Coenzyme A hydratase 1, peroxisomal HNRPL 19q13.2 heterogeneous nuclear ribonucleoprotein L FLJ45909 19q13.2 FLJ45909 protein SIRT2 19q13 sirtuin (silent mating type information regulation 2 homolog) 2 (S. cerevisiae) NFKBIB 19q13.1 nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, beta LOC388539 19 LOC388539 SARS2 19q13.2 seryl-tRNA synthetase 2 MRPS12 19q13.11 mitochondrial ribosomal protein S12 FBXO26 19q13.2 F-box only protein 26 FBXO27 19q13.2 F-box only protein 27 LOC390928 19 similar to RIKEN cDNA C330005M16 LOC284321 19q13.2 hypothetical LOC284321 PAK4 19q13.2 p21(CDKN1A)-activated kinase 4 LOC342897 19q13.2 similar to F-box only protein 2 SYCN 19q13.2 syncollin IL28B 19q13.13 interleukin 28B (interferon, lambda 3) LOC390929 19 similar to Methionine-R-sulfoxide reductase (Selenoprotein X 1) (HSPC270)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    16 splicing 2086 43.05 389 . predominate in non-neural tissues and in immortalized cells in culture 2011 21791548
  • SIRT2.1 isoform
  • containing an additional 47 nt which introduces an earlier in-frame start codon compared to transcript variant 2
  • 13 splicing 1926 26.6 234 - 2003 12697818
  • lacking the additional 47 nt present in the 5' end of the coding region in transcript variant 1
  • translation is thought to initiate at a downstream in-frame ATG
  • 15 - 2078 39.4 352 strikingly abundant and preferential expression in the brain and spinal cord 2011 21791548
  • SIRT2.2
  • - - - - - - 2011 21791548
  • accumulation of SIRT2.3 is an age-dependent marker in the CNS
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   predominantly
    Digestivestomach   moderately
    Nervousbrainforebraincerebral cortex highly Homo sapiens
     brainbasal nucleistriatum highly Homo sapiens
     spinal cord   highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadiposewhite   Homo sapiens
    Connectiveadiposebrown   Homo sapiens
    Connectivebone   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    cell cycle     cell cycle, M
    Text
  • tissues
  • expressed at very low levels in the developing CNS
  • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a deacetylase sirtuin-type conserved core domain
  • HOMOLOGY
    interspecies homolog to yeast S.cerevisiae SIR.2 homolog-like
    ortholog to rattus Sirt2
    ortholog to murine Sirt2
    Homologene
    FAMILY
  • sirtuin family, class I, class III histone deacetylase family
  • silent information regulator 2 (Sir2) family of sirtuin histone deacetylases (HDACs)
  • CATEGORY enzyme , regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus
    text
  • nucleo-cytoplasmic shuttling regulates the SIRT2 function
  • SIRT2 and RIPK1 are identified in the cytotrophoblast cytoplasm
  • is the only sirtuin protein which is predominantly found in the cytoplasm but is also found in the mitochondria and in the nucleus
  • basic FUNCTION
  • conserved NAD+-dependent deacetylases and ADP-ribosyltransferases involved in the regulation of cell division, apoptosis, DNA damage repair, genomic silencing, and longevity
  • deacetylating the Lys-40 of alpha-tubulin (role in the cell cycle regulation)
  • involved in the control of mitotic exit in the cell cycle, probably via its role in the regulation of cytoskeleton
  • involved in chromatin structure
  • involved in control of cellular life span
  • involved in mitotic progression in the normal cell cycle
  • mitotic checkpoint protein that functions in the early metaphase to prevent chromosomal instability
  • acts as an important regulator of adipocyte differentiation through modulation of FOXO1 acetylation/phosphorylation and activity and may play a role in controlling adipose tissue mass and function
  • responds to nutrient deprivation and energy expenditure to maintain energy homeostasis by promoting lipolysis and inhibiting adipocyte differentiation
  • deacetylase for tubulin and histone H4
  • function of SIRT2 for centrosome maintenance upon exposure to mitotic stress caused by microtubule inhibitors, but also the existence of a centrosome-mediated signaling pathway to sustain the spindle checkpoint
  • by participating in the stress response to genomic insults, sirtuins are thought to protect against cancer, but they are also emerging as direct participants in the growth of some cancers
  • tubulin deacetylase and an important regulator of cell division and myelinogenesis
  • having an unique role in the control of neuronal metabolism
  • in non-neuronal cells, function as a tubulin deacetylase and a key regulator of cell division and differentiation
  • role in regulating microtubule acetylation patterns in neurons, suggesting a novel mechanism by which neuronal function might become impaired in the aging brain
  • NAD-dependent deacetylase that is an important regulator of programmed necrosis and inhibitors of this deacetylase may constitute a novel approach to protect against necrotic injuries, including ischaemic stroke and myocardial infarction
  • regulation of protein acetylation by SIRT2 plays a central role in platelet function
  • SIRT1 and SIRT2 are NAD(+)-dependent histone deacetylases that operate as post-translational regulators for the deacetylation of acetyllysine
  • function of SIRT2 extends beyond the regulation of microtubules to include the regulation of nuclear envelope dynamics
  • cytoplasmic sirtuin that plays a role in various cellular processes, including tumorigenesis, metabolism, and inflammation
  • link between SIRT2 and physiological aging impacting the axonal compartment of the central nervous system, while supporting a major role for SIRT2 in orchestrating its metabolic regulation
  • inhibits cell motility by suppressing actin polymerization
  • SIRT2 plays a critical role in mediating the radiation-induced DNA damage response, thus regulating radiation-induced cell death and survival
  • plays an important role in the response to stress, thereby modulating depression-like behaviors
  • NAD-dependent sirtuin deacetylase that regulates microtubule and chromatin dynamics, gene expression, cell cycle progression as well as nuclear envelope reassembly
  • SIRT2 may also play a role in Golgi structure formation
  • CELLULAR PROCESS cell cycle, division, mitosis
    nucleotide, chromatin organization
    nucleotide, repair
    nucleotide, transcription, regulation
    protein, post translation
    protein, translation regulation
    PHYSIOLOGICAL PROCESS development
    text
  • protein ADP ribosylation chromatin silencing
  • mammalian development
  • negative regulation of striated muscle development
  • negative regulation of transcription
  • PATHWAY
    metabolism
    signaling
    a component
  • phosphorylated at the G2/M transition of the cell cycle
  • chromatin silencing complex
  • INTERACTION
    DNA binding
    RNA
    small molecule metal binding, cofactor,
  • Zn2+
  • protein
  • HOXA10
  • HDAC6
  • target for the mitotic kinase CDC2, and its phosphorylation by CDC2 is required to mediate a delay in cell-cycle progression
  • direct interaction between SIRT2 and FOXO1, enhancing insulin-stimulated phosphorylation of FOXO1, which in turn regulates FOXO1 nuclear and cytosolic localization
  • interacting with EP300 (triggers the acetylation and subsequent down-regulation of the deacetylation activity of SIRT2, and acetylation of SIRT2 by EP300 relieves the inhibitory effect of SIRT2 on the transcriptional activity of TP53)
  • NKX2.2 binds to the SIRT2 promoter via histone deacetylase 1 (HDAC1), the binding site for NKX2.2 maps close to the start codon of the SIRT2 gene
  • SIRT2 enhanced MYCN and MYC protein stability and promoted cancer cell proliferation
  • RIPK1 is a critical target of SIRT2-dependent deacetylation
  • FRY binds to the tubulin deacetylase SIRT2, preferentially in mitotic cells
  • SIRT2, inhibits the Wnt signaling pathway in nonmalignant cells by binding to CTNNB1 and SIRT2 plays a critical role in the response to oxidative stress from radiation
  • CBLB and CBL increased the protein level and stability of SIRT2 and CBLB and CBL interact with SIRT2
  • effects of SIRT2 are mediated in part by the acetylation and inhibition of AKT1
  • PLA2G4A acts as a bridge in the formation of a multiprotein complex at the G2-to-M transition to promote binding of SIRT2 to CCNA2-CDK2
  • ANKLE2 acetylation at K302 and phosphorylation at S662 are dynamically regulated throughout the cell cycle by SIRT2 and are essential for normal nuclear envelope reassembly
  • novel regulation of SIRT2 by SPOP mediated degradation, which is important for the growth of lung tumor cells
  • maintains cellular iron levels by binding to and deacetylating nuclear factor erythroid-derived 2-related factor 2 (NFE2L2) on lysines 506 and 508, leading to a reduction in total and nuclear NFE2L2 levels
  • SIRT2 promotes AMPK activation by deacetylating the kinase STK11
  • SIRT2-dependent GCKR deacetylation improves impaired hepatic glucose uptake (HGU)
  • the deacetylase activity of SIRT2 is required for the regulation of actin polymerization and the ubiquitin-mediated proteasomal degradation of HSP90 induced by SIRT2
  • NQO1 interacts with and activates SIRT2 in an NAD-dependent manner
  • cell & other
    REGULATION
    inhibited by sirtinol
    A3 small molecules
    M15 small molecules
    nicotinamide
    Other nucleo-cytoplasmic shuttling regulates the SIRT2 function
    regulated by SREBF2 (a crucial mediator of the effects of SIRT2 on metabolism)
    CBL-mediated SIRT2 regulation occurred via ubiquitination of SIRT2 (
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    down-regulated in gliomas and glioma cell lines, which are characterized by aneuploidy
    constitutional     --low  
    in both preeclampsia (PE) and fetal growth restriction (FGR)
    constitutional     --low  
    of SIRT2 protein expression in both Preeclampsia (PE) and fetal growth restriction (FGR) placentas
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologyneurodegenerativehuntington chorea
    SIRT2 inhibition is a promising avenue for HD therapy
    neuromuscularmyopathycongenital
    SIRT2 inhibitors and AMPK inhibitors as potential therapeutics for OPMD and perhaps other muscular dystrophies and polyAla diseases
    cancer  
    utilization of sirtuin activators that specifically target SIRT2 could serve as potential anticancer therapy
    miscelleaneous  
    SIRT2 targeting may be therapeutically beneficial in diseases where aggregation of misfolded proteins is central to disease pathogenesis
    neurologyneurodegenerative 
    viable molecular target for neuroprotective therapy.
    neurologyneurodegenerative 
    therapeutic target in the most prevalent neurodegenerative diseases that undergo with axonal degeneration associated with redox and energetic dyshomeostasis
    cardiovascularaquired 
    potential target for therapeutic interventions in aging- and stress-induced cardiac hypertrophy
    ANIMAL & CELL MODELS