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Protein

NAD-dependent protein deacetylase sirtuin-7

Gene

Sirt7

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

NAD-dependent protein deacetylase that specifically mediates deacetylation of histone H3 at 'Lys-18' (H3K18Ac). In contrast to other histone deacetylases, displays selectivity for a single histone mark, H3K18Ac, directly linked to control of gene expression. H3K18Ac is mainly present around the transcription start site of genes and has been linked to activation of nuclear hormone receptors. SIRT7 thereby acts as a transcription repressor. Moreover, H3K18 hypoacetylation has been reported as a marker of malignancy in various cancers and seems to maintain the transformed phenotype of cancer cells. These data suggest that SIRT7 may play a key role in oncogenic transformation by suppresses expression of tumor suppressor genes by locus-specific deacetylation of H3K18Ac at promoter regions (By similarity). Required to restore the transcription of ribosomal RNA (rRNA) at the exit from mitosis. Promotes the association of RNA polymerase I with the rDNA promoter region and coding region. Stimulates transcription activity of the RNA polymerase I complex. May also deacetylate p53/TP53 and promotes cell survival, however such data need additional confirmation.By similarity2 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)LengthDescriptionGraphical viewFeature identifierActions
Active sitei188 – 1881Proton acceptor
Metal bindingi196 – 1961ZincPROSITE-ProRule annotation
Metal bindingi199 – 1991ZincPROSITE-ProRule annotation
Metal bindingi226 – 2261ZincPROSITE-ProRule annotation
Metal bindingi229 – 2291ZincPROSITE-ProRule annotation
Binding sitei316 – 3161NAD; via amide nitrogenBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi108 – 12720NADBy similarityAdd
BLAST
Nucleotide bindingi168 – 1714NADBy similarity
Nucleotide bindingi269 – 2713NADBy similarity
Nucleotide bindingi298 – 3003NADBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Hydrolase, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

Metal-binding, NAD, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
NAD-dependent protein deacetylase sirtuin-7 (EC:3.5.1.-)
Alternative name(s):
Regulatory protein SIR2 homolog 7
SIR2-like protein 7
Gene namesi
Name:Sirt7
Synonyms:Sir2l7
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:2385849. Sirt7.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleusnucleolus 1 Publication

  • Note: Located close to the nuclear membrane when in the cytoplasm (By similarity). Associated with chromatin. Associated with rDNA promoter and transcribed region. Associated with nucleolar organizer regions during mitosis (By similarity).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice show a reduction in lifespan and develop heart hypertrophy. The mean and maximum lifespan is reduced by 59% and 55%. Mice develop kyphosis and lose subcutaneous fat early in life; they also show a general decrease in stress-resistance mechanisms. Mice suffer from degenerative heart hypertrophy and inflammatory cardiomyopathy. Hearts are also characterized by an extensive fibrosis.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi188 – 1881H → Y: Abolishes deacetylase activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 402402NAD-dependent protein deacetylase sirtuin-7PRO_0000110272Add
BLAST

Post-translational modificationi

Phosphorylated during mitosis.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ8BKJ9.
MaxQBiQ8BKJ9.
PaxDbiQ8BKJ9.
PRIDEiQ8BKJ9.

Expressioni

Tissue specificityi

Detected in liver, spleen and testis. Detected in embryos.1 Publication

Gene expression databases

BgeeiQ8BKJ9.
ExpressionAtlasiQ8BKJ9. baseline and differential.
GenevisibleiQ8BKJ9. MM.

Interactioni

Subunit structurei

Interacts with UBTF and the RNA polymerase I complex. Interacts with components of the B-WICH complex, such as MYBBP1A, SMARCA5/SNF2H and BAZ1B/WSTF. Interacts with ELK4, leading to stabilization at target promoters for H3K18Ac deacetylation. Interacts with histone H2A and/or histone H2B (By similarity).By similarity

Protein-protein interaction databases

BioGridi229037. 1 interaction.
IntActiQ8BKJ9. 1 interaction.
MINTiMINT-4997649.
STRINGi10090.ENSMUSP00000079093.

Structurei

3D structure databases

ProteinModelPortaliQ8BKJ9.
SMRiQ8BKJ9. Positions 78-335.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini91 – 332242Deacetylase sirtuin-typePROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi9 – 10193Arg-richAdd
BLAST

Sequence similaritiesi

Belongs to the sirtuin family. Class IV subfamily.Curated
Contains 1 deacetylase sirtuin-type domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1905. Eukaryota.
COG0846. LUCA.
GeneTreeiENSGT00530000063706.
HOGENOMiHOG000231240.
HOVERGENiHBG060028.
InParanoidiQ8BKJ9.
KOiK11417.
OMAiEVCTACT.
OrthoDBiEOG7M98GV.
PhylomeDBiQ8BKJ9.
TreeFamiTF106184.

Family and domain databases

Gene3Di3.40.50.1220. 2 hits.
InterProiIPR029035. DHS-like_NAD/FAD-binding_dom.
IPR003000. Sirtuin.
IPR026590. Ssirtuin_cat_dom.
[Graphical view]
PANTHERiPTHR11085. PTHR11085. 1 hit.
PfamiPF02146. SIR2. 1 hit.
[Graphical view]
SUPFAMiSSF52467. SSF52467. 1 hit.
PROSITEiPS50305. SIRTUIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8BKJ9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAGGGLSRS ERKAAERVRR LREEQQRERL RQVSRILRKA AAERSAEEGR
60 70 80 90 100
LLAESEDLVT ELQGRSRRRE GLKRRQEEVC DDPEELRRKV RELAGAVRSA
110 120 130 140 150
RHLVVYTGAG ISTAASIPDY RGPNGVWTLL QKGRPVSAAD LSEAEPTLTH
160 170 180 190 200
MSITRLHEQK LVQHVVSQNC DGLHLRSGLP RTAISELHGN MYIEVCTSCI
210 220 230 240 250
PNREYVRVFD VTERTALHRH LTGRTCHKCG TQLRDTIVHF GERGTLGQPL
260 270 280 290 300
NWEAATEAAS KADTILCLGS SLKVLKKYPR LWCMTKPPSR RPKLYIVNLQ
310 320 330 340 350
WTPKDDWAAL KLHGKCDDVM QLLMNELGLE IPVYNRWQDP IFSLATPLRA
360 370 380 390 400
GEEGSHSRKS LCRSREEAPP GDQSDPLASA PPILGGWFGR GCAKRAKRKK

VA
Length:402
Mass (Da):45,146
Last modified:October 31, 2003 - v2
Checksum:iAE43102816173958
GO

Sequence cautioni

The sequence AAH26403.1 differs from that shown. Reason: Erroneous initiation. Curated
The sequence AAH26650.1 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti95 – 951G → R in AAP83960 (Ref. 1) Curated
Sequence conflicti320 – 3201M → I in AAP83960 (Ref. 1) Curated
Sequence conflicti335 – 3351N → S in AAP83960 (Ref. 1) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY251540 mRNA. Translation: AAP83960.1.
AL663030 Genomic DNA. Translation: CAM27095.1.
BC026403 mRNA. Translation: AAH26403.1. Different initiation.
BC026650 mRNA. Translation: AAH26650.1. Different initiation.
CCDSiCCDS49006.1.
RefSeqiNP_694696.2. NM_153056.2.
UniGeneiMm.292957.

Genome annotation databases

EnsembliENSMUST00000080202; ENSMUSP00000079093; ENSMUSG00000025138.
GeneIDi209011.
KEGGimmu:209011.
UCSCiuc011yjf.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY251540 mRNA. Translation: AAP83960.1.
AL663030 Genomic DNA. Translation: CAM27095.1.
BC026403 mRNA. Translation: AAH26403.1. Different initiation.
BC026650 mRNA. Translation: AAH26650.1. Different initiation.
CCDSiCCDS49006.1.
RefSeqiNP_694696.2. NM_153056.2.
UniGeneiMm.292957.

3D structure databases

ProteinModelPortaliQ8BKJ9.
SMRiQ8BKJ9. Positions 78-335.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi229037. 1 interaction.
IntActiQ8BKJ9. 1 interaction.
MINTiMINT-4997649.
STRINGi10090.ENSMUSP00000079093.

Proteomic databases

EPDiQ8BKJ9.
MaxQBiQ8BKJ9.
PaxDbiQ8BKJ9.
PRIDEiQ8BKJ9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000080202; ENSMUSP00000079093; ENSMUSG00000025138.
GeneIDi209011.
KEGGimmu:209011.
UCSCiuc011yjf.1. mouse.

Organism-specific databases

CTDi51547.
MGIiMGI:2385849. Sirt7.

Phylogenomic databases

eggNOGiKOG1905. Eukaryota.
COG0846. LUCA.
GeneTreeiENSGT00530000063706.
HOGENOMiHOG000231240.
HOVERGENiHBG060028.
InParanoidiQ8BKJ9.
KOiK11417.
OMAiEVCTACT.
OrthoDBiEOG7M98GV.
PhylomeDBiQ8BKJ9.
TreeFamiTF106184.

Miscellaneous databases

PROiQ8BKJ9.
SOURCEiSearch...

Gene expression databases

BgeeiQ8BKJ9.
ExpressionAtlasiQ8BKJ9. baseline and differential.
GenevisibleiQ8BKJ9. MM.

Family and domain databases

Gene3Di3.40.50.1220. 2 hits.
InterProiIPR029035. DHS-like_NAD/FAD-binding_dom.
IPR003000. Sirtuin.
IPR026590. Ssirtuin_cat_dom.
[Graphical view]
PANTHERiPTHR11085. PTHR11085. 1 hit.
PfamiPF02146. SIR2. 1 hit.
[Graphical view]
SUPFAMiSSF52467. SSF52467. 1 hit.
PROSITEiPS50305. SIRTUIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Mus musculus sirtuin 7 (silent mating type information regulation 2, homolog 7) mRNA."
    Poloumienko A., Bakovic M.
    Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C57BL/6J.
    Tissue: Embryonic carcinoma.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-402.
    Strain: FVB/N.
    Tissue: Colon.
  4. "Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription."
    Ford E., Voit R., Liszt G., Magin C., Grummt I., Guarente L.
    Genes Dev. 20:1075-1080(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  5. "Sirt7 increases stress resistance of cardiomyocytes and prevents apoptosis and inflammatory cardiomyopathy in mice."
    Vakhrusheva O., Smolka C., Gajawada P., Kostin S., Boettger T., Kubin T., Braun T., Bober E.
    Circ. Res. 102:703-710(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE, MUTAGENESIS OF HIS-188.

Entry informationi

Entry nameiSIR7_MOUSE
AccessioniPrimary (citable) accession number: Q8BKJ9
Secondary accession number(s): A2ABY7, Q6X7B7, Q8QZZ5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: October 31, 2003
Last modified: June 8, 2016
This is version 114 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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.