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Protein

NAD-dependent protein deacetylase sirtuin-7

Gene

SIRT7

Organism
Homo sapiens (Human)
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. Also 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.3 Publications

Catalytic activityi

NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein.PROSITE-ProRule annotation1 Publication

Cofactori

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei187Proton acceptor1
Metal bindingi195ZincPROSITE-ProRule annotation1
Metal bindingi198ZincPROSITE-ProRule annotation1
Metal bindingi225ZincPROSITE-ProRule annotation1
Metal bindingi228ZincPROSITE-ProRule annotation1
Binding sitei315NAD; via amide nitrogenBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi107 – 126NADBy similarityAdd BLAST20
Nucleotide bindingi167 – 170NADBy similarity4
Nucleotide bindingi268 – 270NADBy similarity3
Nucleotide bindingi297 – 299NADBy similarity3

GO - Molecular functioni

  • chromatin binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • NAD+ binding Source: InterPro
  • NAD-dependent histone deacetylase activity (H3-K18 specific) Source: UniProtKB

GO - Biological processi

  • histone H3 deacetylation Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • positive regulation of transcription involved in exit from mitosis Source: UniProtKB
  • rRNA transcription Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Hydrolase, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

Metal-binding, NAD, Zinc

Enzyme and pathway databases

SIGNORiQ9NRC8.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:14935. SIRT7.

Subcellular locationi

  • Cytoplasm
  • Nucleusnucleolus

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

GO - Cellular componenti

  • cytoplasm Source: UniProtKB-SubCell
  • nucleolus Source: UniProtKB
  • nucleolus organizer region Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi111S → A: Abolishes activation of pre-rRNA synthesis. 2 Publications1
Mutagenesisi187H → Y: Abolishes deacetylase activity and activation of pre-rRNA synthesis. 2 Publications1

Organism-specific databases

DisGeNETi51547.
OpenTargetsiENSG00000187531.
PharmGKBiPA37940.

Chemistry databases

ChEMBLiCHEMBL2163184.

Polymorphism and mutation databases

BioMutaiSIRT7.
DMDMi38258650.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001102711 – 400NAD-dependent protein deacetylase sirtuin-7Add BLAST400

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei388Omega-N-methylarginineCombined sources1

Post-translational modificationi

Phosphorylated during mitosis.1 Publication

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

EPDiQ9NRC8.
MaxQBiQ9NRC8.
PaxDbiQ9NRC8.
PeptideAtlasiQ9NRC8.
PRIDEiQ9NRC8.

PTM databases

iPTMnetiQ9NRC8.
PhosphoSitePlusiQ9NRC8.

Expressioni

Gene expression databases

BgeeiENSG00000187531.
CleanExiHS_SIRT7.
ExpressionAtlasiQ9NRC8. baseline and differential.
GenevisibleiQ9NRC8. HS.

Organism-specific databases

HPAiCAB037261.
HPA053669.

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.4 Publications

Protein-protein interaction databases

BioGridi119602. 664 interactors.
DIPiDIP-59906N.
IntActiQ9NRC8. 7 interactors.
MINTiMINT-1424083.
STRINGi9606.ENSP00000329466.

Structurei

3D structure databases

ProteinModelPortaliQ9NRC8.
SMRiQ9NRC8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini90 – 331Deacetylase sirtuin-typePROSITE-ProRule annotationAdd BLAST242

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi8 – 74Arg-richAdd BLAST67

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.
InParanoidiQ9NRC8.
KOiK11417.
OMAiEVCTACT.
OrthoDBiEOG091G00MI.
PhylomeDBiQ9NRC8.
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]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NRC8-1) [UniParc]FASTAAdd to basket

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
MAAGGLSRSE RKAAERVRRL REEQQRERLR QVSRILRKAA AERSAEEGRL
60 70 80 90 100
LAESADLVTE LQGRSRRREG LKRRQEEVCD DPEELRGKVR ELASAVRNAK
110 120 130 140 150
YLVVYTGAGI STAASIPDYR GPNGVWTLLQ KGRSVSAADL SEAEPTLTHM
160 170 180 190 200
SITRLHEQKL VQHVVSQNCD GLHLRSGLPR TAISELHGNM YIEVCTSCVP
210 220 230 240 250
NREYVRVFDV TERTALHRHQ TGRTCHKCGT QLRDTIVHFG ERGTLGQPLN
260 270 280 290 300
WEAATEAASR ADTILCLGSS LKVLKKYPRL WCMTKPPSRR PKLYIVNLQW
310 320 330 340 350
TPKDDWAALK LHGKCDDVMR LLMAELGLEI PAYSRWQDPI FSLATPLRAG
360 370 380 390 400
EEGSHSRKSL CRSREEAPPG DRGAPLSSAP ILGGWFGRGC TKRTKRKKVT
Length:400
Mass (Da):44,898
Last modified:October 1, 2000 - v1
Checksum:i55D7736A864AFE6F
GO
Isoform 2 (identifier: Q9NRC8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     162-183: QHVVSQNCDGLHLRSGLPRTAI → RALGGWYTCQGPGRAPWCPVGN
     184-400: Missing.

Note: No experimental confirmation available.
Show »
Length:183
Mass (Da):20,404
Checksum:iEC211D79031585C2
GO
Isoform 3 (identifier: Q9NRC8-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-30: MAAGGLSRSERKAAERVRRLREEQQRERLR → MPGPRRRSPSACP
     336-400: WQDPIFSLATPLRAGEEGSHSRKSLCRSREEAPPGDRGAPLSSAPILGGWFGRGCTKRTKRKKVT → VL

Note: No experimental confirmation available.
Show »
Length:320
Mass (Da):35,851
Checksum:iC0E80615256EEA7A
GO

Sequence cautioni

The sequence CAB70848 differs from that shown.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti71L → Q in BAG52860 (PubMed:14702039).Curated1
Sequence conflicti384G → S in BAF82954 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0443961 – 30MAAGG…RERLR → MPGPRRRSPSACP in isoform 3. 1 PublicationAdd BLAST30
Alternative sequenceiVSP_008736162 – 183QHVVS…PRTAI → RALGGWYTCQGPGRAPWCPV GN in isoform 2. 1 PublicationAdd BLAST22
Alternative sequenceiVSP_008737184 – 400Missing in isoform 2. 1 PublicationAdd BLAST217
Alternative sequenceiVSP_044397336 – 400WQDPI…RKKVT → VL in isoform 3. 1 PublicationAdd BLAST65

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF233395 mRNA. Translation: AAF43431.1.
AK002027 mRNA. Translation: BAA92044.1.
AK094326 mRNA. Translation: BAG52860.1.
AK290265 mRNA. Translation: BAF82954.1.
AC145207 Genomic DNA. No translation available.
BC017305 mRNA. Translation: AAH17305.1.
BC101791 mRNA. Translation: AAI01792.1.
BC101793 mRNA. Translation: AAI01794.1.
AL137626 mRNA. Translation: CAB70848.2. Sequence problems.
CCDSiCCDS11792.1. [Q9NRC8-1]
PIRiT46324.
RefSeqiNP_057622.1. NM_016538.2. [Q9NRC8-1]
UniGeneiHs.514636.

Genome annotation databases

EnsembliENST00000328666; ENSP00000329466; ENSG00000187531. [Q9NRC8-1]
GeneIDi51547.
KEGGihsa:51547.
UCSCiuc002kcj.3. human. [Q9NRC8-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF233395 mRNA. Translation: AAF43431.1.
AK002027 mRNA. Translation: BAA92044.1.
AK094326 mRNA. Translation: BAG52860.1.
AK290265 mRNA. Translation: BAF82954.1.
AC145207 Genomic DNA. No translation available.
BC017305 mRNA. Translation: AAH17305.1.
BC101791 mRNA. Translation: AAI01792.1.
BC101793 mRNA. Translation: AAI01794.1.
AL137626 mRNA. Translation: CAB70848.2. Sequence problems.
CCDSiCCDS11792.1. [Q9NRC8-1]
PIRiT46324.
RefSeqiNP_057622.1. NM_016538.2. [Q9NRC8-1]
UniGeneiHs.514636.

3D structure databases

ProteinModelPortaliQ9NRC8.
SMRiQ9NRC8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119602. 664 interactors.
DIPiDIP-59906N.
IntActiQ9NRC8. 7 interactors.
MINTiMINT-1424083.
STRINGi9606.ENSP00000329466.

Chemistry databases

ChEMBLiCHEMBL2163184.

PTM databases

iPTMnetiQ9NRC8.
PhosphoSitePlusiQ9NRC8.

Polymorphism and mutation databases

BioMutaiSIRT7.
DMDMi38258650.

Proteomic databases

EPDiQ9NRC8.
MaxQBiQ9NRC8.
PaxDbiQ9NRC8.
PeptideAtlasiQ9NRC8.
PRIDEiQ9NRC8.

Protocols and materials databases

DNASUi51547.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000328666; ENSP00000329466; ENSG00000187531. [Q9NRC8-1]
GeneIDi51547.
KEGGihsa:51547.
UCSCiuc002kcj.3. human. [Q9NRC8-1]

Organism-specific databases

CTDi51547.
DisGeNETi51547.
GeneCardsiSIRT7.
HGNCiHGNC:14935. SIRT7.
HPAiCAB037261.
HPA053669.
MIMi606212. gene.
neXtProtiNX_Q9NRC8.
OpenTargetsiENSG00000187531.
PharmGKBiPA37940.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1905. Eukaryota.
COG0846. LUCA.
GeneTreeiENSGT00530000063706.
HOGENOMiHOG000231240.
HOVERGENiHBG060028.
InParanoidiQ9NRC8.
KOiK11417.
OMAiEVCTACT.
OrthoDBiEOG091G00MI.
PhylomeDBiQ9NRC8.
TreeFamiTF106184.

Enzyme and pathway databases

SIGNORiQ9NRC8.

Miscellaneous databases

ChiTaRSiSIRT7. human.
GeneWikiiSIRT7.
GenomeRNAii51547.
PROiQ9NRC8.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000187531.
CleanExiHS_SIRT7.
ExpressionAtlasiQ9NRC8. baseline and differential.
GenevisibleiQ9NRC8. HS.

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...

Entry informationi

Entry nameiSIR7_HUMAN
AccessioniPrimary (citable) accession number: Q9NRC8
Secondary accession number(s): A8K2K0
, B3KSU8, Q3MIK4, Q9NSZ6, Q9NUS6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: October 1, 2000
Last modified: November 2, 2016
This is version 142 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

Overexpressed in human thyroid carcinoma cell lines and tissues, but not in adenomas.

Caution

Was originally (PubMed:11953824) termed SIR-T8/SIRT8. This was later retracted (PubMed:12454780). See also PubMed:12454781.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. 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.