GENERAL INFORMATIONi
Gene namei SIRT2
Synonyms SIR2L
Gene descriptioni Sirtuin 2
Protein classi Cancer-related genes
Enzymes
Metabolic proteins
Predicted locationi Intracellular
Protein evidence Evidence at protein level (all genes)
GENE INFORMATIONi
Chromosome 19
Cytoband q13.2
Chromosome location (bp) 38878555 - 38899862
Number of transcriptsi 8
Ensembl ENSG00000068903 (version 109)
Entrez gene 22933
HGNC HGNC:10886
UniProt Q8IXJ6 (UniProt - Evidence at protein level)
neXtProt NX_Q8IXJ6
GeneCards SIRT2
Antibodypedia SIRT2 antibodies


PROTEIN FUNCTION
Protein function (UniProt)i NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and alpha-tubulin as well as many other proteins such as key transcription factors 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18. Participates in the modulation of multiple and diverse biological processes such as cell cycle control, genomic integrity, microtubule dynamics, cell differentiation, metabolic networks, and autophagy 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36. Plays a major role in the control of cell cycle progression and genomic stability 37, 38, 39, 40, 41, 42. Functions in the antephase checkpoint preventing precocious mitotic entry in response to microtubule stress agents, and hence allowing proper inheritance of chromosomes 43, 44, 45, 46, 47, 48. Positively regulates the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex activity by deacetylating CDC20 and FZR1, then allowing progression through mitosis 49. Associates both with chromatin at transcriptional start sites (TSSs) and enhancers of active genes 50. Plays a role in cell cycle and chromatin compaction through epigenetic modulation of the regulation of histone H4 'Lys-20' methylation (H4K20me1) during early mitosis 51. Specifically deacetylates histone H4 at 'Lys-16' (H4K16ac) between the G2/M transition and metaphase enabling H4K20me1 deposition by KMT5A leading to ulterior levels of H4K20me2 and H4K20me3 deposition throughout cell cycle, and mitotic S-phase progression 52. Deacetylates KMT5A modulating KMT5A chromatin localization during the mitotic stress response 53. Deacetylates also histone H3 at 'Lys-57' (H3K56ac) during the mitotic G2/M transition 54. Upon bacterium Listeria monocytogenes infection, deacetylates 'Lys-18' of histone H3 in a receptor tyrosine kinase MET- and PI3K/Akt-dependent manner, thereby inhibiting transcriptional activity and promoting late stages of listeria infection 55. During oocyte meiosis progression, may deacetylate histone H4 at 'Lys-16' (H4K16ac) and alpha-tubulin, regulating spindle assembly and chromosome alignment by influencing microtubule dynamics and kinetochore function 56. Deacetylates histone H4 at 'Lys-16' (H4K16ac) at the VEGFA promoter and thereby contributes to regulate expression of VEGFA, a key regulator of angiogenesis 57. Deacetylates alpha-tubulin at 'Lys-40' and hence controls neuronal motility, oligodendroglial cell arbor projection processes and proliferation of non-neuronal cells 58, 59. Phosphorylation at Ser-368 by a G1/S-specific cyclin E-CDK2 complex inactivates SIRT2-mediated alpha-tubulin deacetylation, negatively regulating cell adhesion, cell migration and neurite outgrowth during neuronal differentiation 60. Deacetylates PARD3 and participates in the regulation of Schwann cell peripheral myelination formation during early postnatal development and during postinjury remyelination 61. Involved in several cellular metabolic pathways 62, 63, 64. Plays a role in the regulation of blood glucose homeostasis by deacetylating and stabilizing phosphoenolpyruvate carboxykinase PCK1 activity in response to low nutrient availability 65. Acts as a key regulator in the pentose phosphate pathway (PPP) by deacetylating and activating the glucose-6-phosphate G6PD enzyme, and therefore, stimulates the production of cytosolic NADPH to counteract oxidative damage 66. Maintains energy homeostasis in response to nutrient deprivation as well as energy expenditure by inhibiting adipogenesis and promoting lipolysis 67. Attenuates adipocyte differentiation by deacetylating and promoting FOXO1 interaction to PPARG and subsequent repression of PPARG-dependent transcriptional activity 68. Plays a role in the regulation of lysosome-mediated degradation of protein aggregates by autophagy in neuronal cells 69. Deacetylates FOXO1 in response to oxidative stress or serum deprivation, thereby negatively regulating FOXO1-mediated autophagy 70. Deacetylates a broad range of transcription factors and co-regulators regulating target gene expression. Deacetylates transcriptional factor FOXO3 stimulating the ubiquitin ligase SCF(SKP2)-mediated FOXO3 ubiquitination and degradation (By similarity). Deacetylates HIF1A and therefore promotes HIF1A degradation and inhibition of HIF1A transcriptional activity in tumor cells in response to hypoxia 71. Deacetylates RELA in the cytoplasm inhibiting NF-kappaB-dependent transcription activation upon TNF-alpha stimulation 72. Inhibits transcriptional activation by deacetylating p53/TP53 and EP300 73, 74. Deacetylates also EIF5A 75. Functions as a negative regulator on oxidative stress-tolerance in response to anoxia-reoxygenation conditions 76. Plays a role as tumor suppressor 77. In addition to protein deacetylase activity, also has activity toward long-chain fatty acyl groups and mediates protein-lysine demyristoylation and depalmitoylation of target proteins, such as ARF6 and KRAS, thereby regulating their association with membranes 78, 79, 80. show less
Molecular function (UniProt)i Transferase
Biological process (UniProt)i Autophagy, Cell cycle, Cell division, Differentiation, Immunity, Innate immunity, Meiosis, Mitosis, Neurogenesis, Transcription, Transcription regulation
Ligand (UniProt)i Metal-binding, NAD, Zinc
Gene summary (Entrez)i This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class I of the sirtuin family. Several transcript variants are resulted from alternative splicing of this gene. [provided by RefSeq, Jul 2010] show less
PROTEIN INFORMATIONi
Splice variant SwissProt TrEMBL Protein class Gene ontology Length & mass Signal peptide
(predicted)		 Transmembrane regions
(predicted)
SIRT2-201
ENSP00000249396
ENST00000249396
Q8IXJ6
[Direct mapping] NAD-dependent protein deacetylase sirtuin-2
Show all
Enzymes
   ENZYME proteins
   Transferases
Metabolic proteins
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Cancer-related genes
   Candidate cancer biomarkers
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Kim et al 2014)
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000122 [negative regulation of transcription by RNA polymerase II]
GO:0000183 [rDNA heterochromatin formation]
GO:0000781 [chromosome, telomeric region]
GO:0000792 [heterochromatin]
GO:0002376 [immune system process]
GO:0003682 [chromatin binding]
GO:0003950 [NAD+ ADP-ribosyltransferase activity]
GO:0004407 [histone deacetylase activity]
GO:0005515 [protein binding]
GO:0005634 [nucleus]
GO:0005677 [chromatin silencing complex]
GO:0005694 [chromosome]
GO:0005730 [nucleolus]
GO:0005737 [cytoplasm]
GO:0005739 [mitochondrion]
GO:0005813 [centrosome]
GO:0005814 [centriole]
GO:0005815 [microtubule organizing center]
GO:0005819 [spindle]
GO:0005829 [cytosol]
GO:0005856 [cytoskeleton]
GO:0005874 [microtubule]
GO:0005886 [plasma membrane]
GO:0006476 [protein deacetylation]
GO:0006914 [autophagy]
GO:0007049 [cell cycle]
GO:0007084 [mitotic nuclear membrane reassembly]
GO:0007096 [regulation of exit from mitosis]
GO:0007399 [nervous system development]
GO:0008270 [zinc ion binding]
GO:0008285 [negative regulation of cell population proliferation]
GO:0010507 [negative regulation of autophagy]
GO:0010801 [negative regulation of peptidyl-threonine phosphorylation]
GO:0014065 [phosphatidylinositol 3-kinase signaling]
GO:0016020 [membrane]
GO:0016575 [histone deacetylation]
GO:0016740 [transferase activity]
GO:0017136 [NAD-dependent histone deacetylase activity]
GO:0021762 [substantia nigra development]
GO:0022011 [myelination in peripheral nervous system]
GO:0030154 [cell differentiation]
GO:0030426 [growth cone]
GO:0030496 [midbody]
GO:0031507 [heterochromatin formation]
GO:0031509 [subtelomeric heterochromatin formation]
GO:0031641 [regulation of myelination]
GO:0032436 [positive regulation of proteasomal ubiquitin-dependent protein catabolic process]
GO:0033010 [paranodal junction]
GO:0033270 [paranode region of axon]
GO:0033558 [protein lysine deacetylase activity]
GO:0034599 [cellular response to oxidative stress]
GO:0034979 [NAD-dependent protein deacetylase activity]
GO:0034983 [peptidyl-lysine deacetylation]
GO:0035035 [histone acetyltransferase binding]
GO:0035729 [cellular response to hepatocyte growth factor stimulus]
GO:0042177 [negative regulation of protein catabolic process]
GO:0042325 [regulation of phosphorylation]
GO:0042826 [histone deacetylase binding]
GO:0042903 [tubulin deacetylase activity]
GO:0042995 [cell projection]
GO:0043130 [ubiquitin binding]
GO:0043161 [proteasome-mediated ubiquitin-dependent protein catabolic process]
GO:0043204 [perikaryon]
GO:0043209 [myelin sheath]
GO:0043219 [lateral loop]
GO:0043220 [Schmidt-Lanterman incisure]
GO:0043388 [positive regulation of DNA binding]
GO:0043491 [protein kinase B signaling]
GO:0043687 [post-translational protein modification]
GO:0044224 [juxtaparanode region of axon]
GO:0044242 [cellular lipid catabolic process]
GO:0044546 [NLRP3 inflammasome complex assembly]
GO:0045087 [innate immune response]
GO:0045598 [regulation of fat cell differentiation]
GO:0045599 [negative regulation of fat cell differentiation]
GO:0045836 [positive regulation of meiotic nuclear division]
GO:0045843 [negative regulation of striated muscle tissue development]
GO:0045892 [negative regulation of DNA-templated transcription]
GO:0045944 [positive regulation of transcription by RNA polymerase II]
GO:0046872 [metal ion binding]
GO:0046970 [NAD-dependent histone deacetylase activity (H4-K16 specific)]
GO:0048012 [hepatocyte growth factor receptor signaling pathway]
GO:0048471 [perinuclear region of cytoplasm]
GO:0051287 [NAD binding]
GO:0051301 [cell division]
GO:0051321 [meiotic cell cycle]
GO:0051726 [regulation of cell cycle]
GO:0051775 [response to redox state]
GO:0051781 [positive regulation of cell division]
GO:0051987 [positive regulation of attachment of spindle microtubules to kinetochore]
GO:0061428 [negative regulation of transcription from RNA polymerase II promoter in response to hypoxia]
GO:0061433 [cellular response to caloric restriction]
GO:0070403 [NAD+ binding]
GO:0070446 [negative regulation of oligodendrocyte progenitor proliferation]
GO:0070932 [histone H3 deacetylation]
GO:0070933 [histone H4 deacetylation]
GO:0071219 [cellular response to molecule of bacterial origin]
GO:0071456 [cellular response to hypoxia]
GO:0071872 [cellular response to epinephrine stimulus]
GO:0072686 [mitotic spindle]
GO:0072687 [meiotic spindle]
GO:0090042 [tubulin deacetylation]
GO:0097386 [glial cell projection]
GO:0140297 [DNA-binding transcription factor binding]
GO:0140773 [NAD-dependent protein demyristoylase activity]
GO:0140774 [NAD-dependent protein depalmitoylase activity]
GO:1900119 [positive regulation of execution phase of apoptosis]
GO:1900195 [positive regulation of oocyte maturation]
GO:1900226 [negative regulation of NLRP3 inflammasome complex assembly]
GO:1900425 [negative regulation of defense response to bacterium]
GO:2000378 [negative regulation of reactive oxygen species metabolic process]
GO:2000777 [positive regulation of proteasomal ubiquitin-dependent protein catabolic process involved in cellular response to hypoxia]
Show all
 389 aa
43.2 kDa 		No 0
SIRT2-202
ENSP00000351809
ENST00000358931
A0A0A0MRF5
[Direct mapping] NAD-dependent protein deacetylase sirtuin-2
Show all
Metabolic proteins
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Protein evidence (Kim et al 2014)
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0005730 [nucleolus]
GO:0005829 [cytosol]
GO:0005886 [plasma membrane]
GO:0016740 [transferase activity]
GO:0070403 [NAD+ binding]
Show all
 234 aa
26.7 kDa 		No 0
SIRT2-203
ENSP00000401203
ENST00000381766
C9JZQ0
[Direct mapping] NAD-dependent protein deacetylase sirtuin-2
Show all
Metabolic proteins
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0016740 [transferase activity]
GO:0070403 [NAD+ binding]
Show all
 130 aa
15.1 kDa 		No 0
SIRT2-204
ENSP00000375931
ENST00000392081
Q8IXJ6
[Direct mapping] NAD-dependent protein deacetylase sirtuin-2
Show all
A0A024R0G8
[Target identity:100%; Query identity:100%] NAD-dependent protein deacetylase
Show all
Enzymes
   ENZYME proteins
   Transferases
Metabolic proteins
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Cancer-related genes
   Candidate cancer biomarkers
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Kim et al 2014)
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000122 [negative regulation of transcription by RNA polymerase II]
GO:0000183 [rDNA heterochromatin formation]
GO:0000781 [chromosome, telomeric region]
GO:0000792 [heterochromatin]
GO:0002376 [immune system process]
GO:0003682 [chromatin binding]
GO:0003950 [NAD+ ADP-ribosyltransferase activity]
GO:0004407 [histone deacetylase activity]
GO:0005515 [protein binding]
GO:0005634 [nucleus]
GO:0005677 [chromatin silencing complex]
GO:0005694 [chromosome]
GO:0005730 [nucleolus]
GO:0005737 [cytoplasm]
GO:0005813 [centrosome]
GO:0005814 [centriole]
GO:0005815 [microtubule organizing center]
GO:0005819 [spindle]
GO:0005829 [cytosol]
GO:0005856 [cytoskeleton]
GO:0005874 [microtubule]
GO:0005886 [plasma membrane]
GO:0006476 [protein deacetylation]
GO:0006914 [autophagy]
GO:0007049 [cell cycle]
GO:0007084 [mitotic nuclear membrane reassembly]
GO:0007096 [regulation of exit from mitosis]
GO:0007399 [nervous system development]
GO:0008270 [zinc ion binding]
GO:0008285 [negative regulation of cell population proliferation]
GO:0010507 [negative regulation of autophagy]
GO:0010801 [negative regulation of peptidyl-threonine phosphorylation]
GO:0014065 [phosphatidylinositol 3-kinase signaling]
GO:0016020 [membrane]
GO:0016570 [histone modification]
GO:0016575 [histone deacetylation]
GO:0016740 [transferase activity]
GO:0017136 [NAD-dependent histone deacetylase activity]
GO:0021762 [substantia nigra development]
GO:0022011 [myelination in peripheral nervous system]
GO:0030154 [cell differentiation]
GO:0030426 [growth cone]
GO:0030496 [midbody]
GO:0031507 [heterochromatin formation]
GO:0031509 [subtelomeric heterochromatin formation]
GO:0031641 [regulation of myelination]
GO:0032436 [positive regulation of proteasomal ubiquitin-dependent protein catabolic process]
GO:0033010 [paranodal junction]
GO:0033270 [paranode region of axon]
GO:0033558 [protein lysine deacetylase activity]
GO:0034599 [cellular response to oxidative stress]
GO:0034979 [NAD-dependent protein deacetylase activity]
GO:0034983 [peptidyl-lysine deacetylation]
GO:0035035 [histone acetyltransferase binding]
GO:0035729 [cellular response to hepatocyte growth factor stimulus]
GO:0042177 [negative regulation of protein catabolic process]
GO:0042325 [regulation of phosphorylation]
GO:0042826 [histone deacetylase binding]
GO:0042903 [tubulin deacetylase activity]
GO:0042995 [cell projection]
GO:0043130 [ubiquitin binding]
GO:0043161 [proteasome-mediated ubiquitin-dependent protein catabolic process]
GO:0043204 [perikaryon]
GO:0043209 [myelin sheath]
GO:0043219 [lateral loop]
GO:0043220 [Schmidt-Lanterman incisure]
GO:0043388 [positive regulation of DNA binding]
GO:0043491 [protein kinase B signaling]
GO:0043687 [post-translational protein modification]
GO:0044224 [juxtaparanode region of axon]
GO:0044242 [cellular lipid catabolic process]
GO:0045087 [innate immune response]
GO:0045599 [negative regulation of fat cell differentiation]
GO:0045836 [positive regulation of meiotic nuclear division]
GO:0045843 [negative regulation of striated muscle tissue development]
GO:0045892 [negative regulation of DNA-templated transcription]
GO:0045944 [positive regulation of transcription by RNA polymerase II]
GO:0046872 [metal ion binding]
GO:0046970 [NAD-dependent histone deacetylase activity (H4-K16 specific)]
GO:0048012 [hepatocyte growth factor receptor signaling pathway]
GO:0048471 [perinuclear region of cytoplasm]
GO:0051287 [NAD binding]
GO:0051301 [cell division]
GO:0051321 [meiotic cell cycle]
GO:0051726 [regulation of cell cycle]
GO:0051775 [response to redox state]
GO:0051781 [positive regulation of cell division]
GO:0051987 [positive regulation of attachment of spindle microtubules to kinetochore]
GO:0061428 [negative regulation of transcription from RNA polymerase II promoter in response to hypoxia]
GO:0061433 [cellular response to caloric restriction]
GO:0070403 [NAD+ binding]
GO:0070446 [negative regulation of oligodendrocyte progenitor proliferation]
GO:0070932 [histone H3 deacetylation]
GO:0070933 [histone H4 deacetylation]
GO:0071219 [cellular response to molecule of bacterial origin]
GO:0071456 [cellular response to hypoxia]
GO:0071872 [cellular response to epinephrine stimulus]
GO:0072686 [mitotic spindle]
GO:0072687 [meiotic spindle]
GO:0090042 [tubulin deacetylation]
GO:0097386 [glial cell projection]
GO:0140297 [DNA-binding transcription factor binding]
GO:0140773 [NAD-dependent protein demyristoylase activity]
GO:0140774 [NAD-dependent protein depalmitoylase activity]
GO:1900119 [positive regulation of execution phase of apoptosis]
GO:1900195 [positive regulation of oocyte maturation]
GO:1900425 [negative regulation of defense response to bacterium]
GO:2000378 [negative regulation of reactive oxygen species metabolic process]
GO:2000777 [positive regulation of proteasomal ubiquitin-dependent protein catabolic process involved in cellular response to hypoxia]
Show all
 352 aa
39.5 kDa 		No 0
SIRT2-205
ENSP00000385146
ENST00000407552
B5MCS1
[Direct mapping] NAD-dependent protein deacetylase sirtuin-2
Show all
Metabolic proteins
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0016740 [transferase activity]
GO:0070403 [NAD+ binding]
Show all
 169 aa
19.5 kDa 		No 0
SIRT2-206
ENSP00000404309
ENST00000414941
E7EWX6
[Direct mapping] NAD-dependent protein deacetylase sirtuin-2
Show all
Metabolic proteins
   SPOCTOPUS predicted membrane proteins
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0005730 [nucleolus]
GO:0005829 [cytosol]
GO:0005886 [plasma membrane]
GO:0016740 [transferase activity]
GO:0070403 [NAD+ binding]
Show all
 237 aa
27.1 kDa 		No 0
SIRT2-209
ENSP00000397022
ENST00000437828
C9J3U7
[Direct mapping] NAD-dependent protein deacetylase sirtuin-2
Show all
Metabolic proteins
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0016740 [transferase activity]
GO:0070403 [NAD+ binding]
Show all
 78 aa
8.8 kDa 		No 0
SIRT2-211
ENSP00000408023
ENST00000447739
C9JR33
[Direct mapping] NAD-dependent protein deacetylase sirtuin-2
Show all
Metabolic proteins
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0016740 [transferase activity]
GO:0070403 [NAD+ binding]
Show all
 73 aa
8.2 kDa 		No 0

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