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Protein

NAD-dependent protein deacetylase sirtuin-3

Gene

Sirt3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Metal-binding, NAD, Zinc

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1927665. Sirt3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • membrane Source: MGI
  • mitochondrial inner membrane Source: CACAO
  • mitochondrial matrix Source: MGI
  • mitochondrion Source: UniProtKB
Complete GO annotation...

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

Binary interactionsi

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

Protein-protein interaction databases

BioGridi211071. 2 interactors.
IntActiQ8R104. 2 interactors.
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
Contains 1 deacetylase sirtuin-type domain.PROSITE-ProRule annotation

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG2682. Eukaryota.
COG0846. LUCA.
GeneTreeiENSGT00850000132288.
HOGENOMiHOG000085952.
HOVERGENiHBG057095.
InParanoidiQ8R104.
KOiK11413.
OMAiCTGIVKP.
TreeFamiTF106181.

Family and domain databases

Gene3Di3.30.1600.10. 2 hits.
3.40.50.1220. 3 hits.
InterProiIPR029035. DHS-like_NAD/FAD-binding_dom.
IPR003000. Sirtuin.
IPR026591. Sirtuin_cat_small_dom.
IPR017328. Sirtuin_class_I.
IPR026590. Ssirtuin_cat_dom.
[Graphical view]
PANTHERiPTHR11085. PTHR11085. 1 hit.
PfamiPF02146. SIR2. 1 hit.
[Graphical view]
PIRSFiPIRSF037938. SIR2_euk. 1 hit.
SUPFAMiSSF52467. SSF52467. 1 hit.
PROSITEiPS50305. SIRTUIN. 1 hit.
[Graphical view]

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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ8R104.
SMRiQ8R104.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi211071. 2 interactors.
IntActiQ8R104. 2 interactors.
STRINGi10090.ENSMUSP00000026559.

PTM databases

PhosphoSitePlusiQ8R104.

Proteomic databases

PaxDbiQ8R104.
PeptideAtlasiQ8R104.
PRIDEiQ8R104.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi23410.
MGIiMGI:1927665. Sirt3.

Phylogenomic databases

eggNOGiKOG2682. Eukaryota.
COG0846. LUCA.
GeneTreeiENSGT00850000132288.
HOGENOMiHOG000085952.
HOVERGENiHBG057095.
InParanoidiQ8R104.
KOiK11413.
OMAiCTGIVKP.
TreeFamiTF106181.

Miscellaneous databases

ChiTaRSiSirt3. mouse.
PROiQ8R104.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000025486.
ExpressionAtlasiQ8R104. baseline and differential.
GenevisibleiQ8R104. MM.

Family and domain databases

Gene3Di3.30.1600.10. 2 hits.
3.40.50.1220. 3 hits.
InterProiIPR029035. DHS-like_NAD/FAD-binding_dom.
IPR003000. Sirtuin.
IPR026591. Sirtuin_cat_small_dom.
IPR017328. Sirtuin_class_I.
IPR026590. Ssirtuin_cat_dom.
[Graphical view]
PANTHERiPTHR11085. PTHR11085. 1 hit.
PfamiPF02146. SIR2. 1 hit.
[Graphical view]
PIRSFiPIRSF037938. SIR2_euk. 1 hit.
SUPFAMiSSF52467. SSF52467. 1 hit.
PROSITEiPS50305. SIRTUIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSIR3_MOUSE
AccessioniPrimary (citable) accession number: Q8R104
Secondary accession number(s): B9W0A9, C6ZII7, Q9EPA8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: March 19, 2014
Last modified: November 2, 2016
This is version 129 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.