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Protein

NAD-dependent protein deacetylase sirtuin-3

Gene

Sirt3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

NAD-dependent protein deacetylase. Activates or deactivates mitochondrial target proteins by deacetylating key lysine residues. Known targets include ACSS1, IDH, GDH, PDHA1, SOD2, LCAD, SDHA and the ATP synthase subunit ATP5O. Contributes to the regulation of the cellular energy metabolism. Important for regulating tissue-specific ATP levels.7 Publications

Miscellaneous

Has some ability to deacetylate histones in vitro, but seeing its subcellular location, this is unlikely in vivo.By similarity

Catalytic activityi

NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein.PROSITE-ProRule annotation

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei183Proton acceptorPROSITE-ProRule annotation1
Metal bindingi191ZincPROSITE-ProRule annotation1
Metal bindingi194ZincPROSITE-ProRule annotation1
Metal bindingi215ZincPROSITE-ProRule annotation1
Metal bindingi218ZincPROSITE-ProRule annotation1
Binding sitei301NAD; via amide nitrogenBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi80 – 100NADBy similarityAdd BLAST21
Nucleotide bindingi163 – 166NADBy similarity4
Nucleotide bindingi254 – 256NADBy similarity3
Nucleotide bindingi279 – 281NADBy similarity3

GO - Molecular functioni

  • NAD+ binding Source: InterPro
  • NAD-dependent histone deacetylase activity (H3-K14 specific) Source: MGI
  • sequence-specific DNA binding Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • aerobic respiration Source: UniProtKB
  • negative regulation of peptidyl-lysine acetylation Source: MGI
  • peptidyl-lysine deacetylation Source: UniProtKB
  • positive regulation of mitochondrial transcription Source: UniProtKB
  • protein deacetylation Source: MGI

Keywordsi

Molecular functionHydrolase
LigandMetal-binding, NAD, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-2151201 Transcriptional activation of mitochondrial biogenesis

Names & Taxonomyi

Protein namesi
Recommended name:
NAD-dependent protein deacetylase sirtuin-3 (EC:3.5.1.-)
Alternative name(s):
Regulatory protein SIR2 homolog 3
SIR2-like protein 3
Short name:
mSIR2L3
Gene namesi
Name:Sirt3
Synonyms:Sir2l3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1927665 Sirt3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Mitochondrion

Pathology & Biotechi

Disruption phenotypei

Decreased muscle endurance under energetically demanding conditions. Decreased Mn-SOD activity in liver, increased mitochondrial superoxide levels and genomic instability upon exposure to ionizing radiations. In vivo ATP levels are reduced by 50 % in organs that normally express high levels of this protein. ATP levels are unchanged in organs that normally express low levels of this protein. Leads to increased mitochondrial protein acetylation.3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000110263? – 334NAD-dependent protein deacetylase sirtuin-3
Transit peptidei1 – ?Mitochondrion

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei57N6-succinyllysineCombined sources1

Proteomic databases

PaxDbiQ8R104
PeptideAtlasiQ8R104
PRIDEiQ8R104

PTM databases

PhosphoSitePlusiQ8R104

Expressioni

Tissue specificityi

Strongly expressed in liver and kidney. Weakly expressed in lung.1 Publication

Inductioni

Sirt3 expression decreases by 50% in skeletal muscle upon fasting.1 Publication

Gene expression databases

BgeeiENSMUSG00000025486
ExpressionAtlasiQ8R104 baseline and differential
GenevisibleiQ8R104 MM

Interactioni

Subunit structurei

Interacts with NDUFA9, ACSS1, IDH2 and GDH (By similarity). Interacts with PCCA (PubMed:23438705).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Aldh2P477382EBI-6999888,EBI-2308120

Protein-protein interaction databases

BioGridi2110713 interactors.
IntActiQ8R104 2 interactors.
MINTiQ8R104
STRINGi10090.ENSMUSP00000026559

Structurei

3D structure databases

ProteinModelPortaliQ8R104
SMRiQ8R104
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini78 – 334Deacetylase sirtuin-typePROSITE-ProRule annotationAdd BLAST257

Sequence similaritiesi

Belongs to the sirtuin family. Class I subfamily.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG2682 Eukaryota
COG0846 LUCA
GeneTreeiENSGT00870000136486
HOGENOMiHOG000085952
HOVERGENiHBG057095
InParanoidiQ8R104
KOiK11413
TreeFamiTF106181

Family and domain databases

Gene3Di3.30.1600.102 hits
InterProiView 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
PfamiView protein in Pfam
PF02146 SIR2, 1 hit
PIRSFiPIRSF037938 SIR2_euk, 1 hit
SUPFAMiSSF52467 SSF52467, 1 hit
PROSITEiView protein in PROSITE
PS50305 SIRTUIN, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform L (identifier: Q8R104-1) [UniParc]FASTAAdd to basket
Also known as: M1

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MALDPLGAVV LQSIMALSGR LALAALRLWG PGGGRRPISL CVGASGGFGG
60 70 80 90 100
GGSSEKKFSL QDVAELLRTR ACSRVVVMVG AGISTPSGIP DFRSPGSGLY
110 120 130 140 150
SNLQQYDIPY PEAIFELGFF FHNPKPFFML AKELYPGHYR PNVTHYFLRL
160 170 180 190 200
LHDKELLLRL YTQNIDGLER ASGIPASKLV EAHGTFVTAT CTVCRRSFPG
210 220 230 240 250
EDIWADVMAD RVPRCPVCTG VVKPDIVFFG EQLPARFLLH MADFALADLL
260 270 280 290 300
LILGTSLEVE PFASLSEAVQ KSVPRLLINR DLVGPFVLSP RRKDVVQLGD
310 320 330
VVHGVERLVD LLGWTQELLD LMQRERGKLD GQDR
Length:334
Mass (Da):36,615
Last modified:March 19, 2014 - v2
Checksum:iD8C936A83C4A8AF7
GO
Isoform S (identifier: Q8R104-2) [UniParc]FASTAAdd to basket
Also known as: M3

The sequence of this isoform differs from the canonical sequence as follows:
     1-77: Missing.

Show »
Length:257
Mass (Da):28,822
Checksum:iF756041FBC9B985E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti216P → A in AAG39258 (PubMed:11056054).Curated1
Sequence conflicti216P → A in AAG33227 (PubMed:11056054).Curated1
Sequence conflicti216P → A in AAG39257 (PubMed:11056054).Curated1
Sequence conflicti216P → A in ACJ70655 (PubMed:19241369).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0537601 – 77Missing in isoform S. 3 PublicationsAdd BLAST77

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF299339 mRNA Translation: AAG39258.1
FJ621493 mRNA Translation: ACM68947.1
EU886466 mRNA Translation: ACJ70655.1
AF302278
, AF302274, AF302275, AF302276, AF302277 Genomic DNA Translation: AAG33227.1
AF299338 mRNA Translation: AAG39257.1
AK075861 mRNA Translation: BAC36012.1
BC025878 mRNA Translation: AAH25878.1
CCDSiCCDS21989.1 [Q8R104-2]
RefSeqiNP_001120823.1, NM_001127351.1 [Q8R104-2]
NP_001171275.1, NM_001177804.1 [Q8R104-1]
NP_071878.2, NM_022433.2 [Q8R104-2]
UniGeneiMm.244216
Mm.29760

Genome annotation databases

EnsembliENSMUST00000026559; ENSMUSP00000026559; ENSMUSG00000025486 [Q8R104-2]
ENSMUST00000106048; ENSMUSP00000101663; ENSMUSG00000025486 [Q8R104-2]
GeneIDi64384
KEGGimmu:64384
UCSCiuc009kik.2 mouse [Q8R104-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiSIR3_MOUSE
AccessioniPrimary (citable) accession number: Q8R104
Secondary accession number(s): B9W0A9, C6ZII7, Q9EPA8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: March 19, 2014
Last modified: April 25, 2018
This is version 138 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome