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Q9NRC8 (SIR7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
NAD-dependent protein deacetylase sirtuin-7

EC=3.5.1.-
Alternative name(s):
Regulatory protein SIR2 homolog 7
SIR2-like protein 7
Gene names
Name:SIRT7
Synonyms:SIR2L7
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length400 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.10 Ref.11 Ref.13

Catalytic activity

NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein. Ref.13

Cofactor

Binds 1 zinc ion per subunit By similarity.

Subunit structure

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. Ref.10 Ref.11 Ref.12 Ref.13

Subcellular location

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. Ref.6 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13

Post-translational modification

Phosphorylated during mitosis Probable. Ref.11

Miscellaneous

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

Sequence similarities

Belongs to the sirtuin family. Class IV subfamily.

Contains 1 deacetylase sirtuin-type domain.

Caution

Was originally (Ref.6) termed SIR-T8/SIRT8. This was later retracted (Ref.7). See also Ref.8.

Sequence caution

The sequence CAB70848.2 differs from that shown. Reason:

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NRC8-1)

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.
Isoform 2 (identifier: Q9NRC8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     162-183: QHVVSQNCDGLHLRSGLPRTAI → RALGGWYTCQGPGRAPWCPVGN
     184-400: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q9NRC8-3)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 400400NAD-dependent protein deacetylase sirtuin-7
PRO_0000110271

Regions

Domain90 – 331242Deacetylase sirtuin-type
Nucleotide binding107 – 12620NAD By similarity
Nucleotide binding167 – 1704NAD By similarity
Nucleotide binding268 – 2703NAD By similarity
Nucleotide binding297 – 2993NAD By similarity
Compositional bias8 – 7467Arg-rich

Sites

Active site1871Proton acceptor
Metal binding1951Zinc By similarity
Metal binding1981Zinc By similarity
Metal binding2251Zinc By similarity
Metal binding2281Zinc By similarity
Binding site3151NAD; via amide nitrogen By similarity

Natural variations

Alternative sequence1 – 3030MAAGG…RERLR → MPGPRRRSPSACP in isoform 3.
VSP_044396
Alternative sequence162 – 18322QHVVS…PRTAI → RALGGWYTCQGPGRAPWCPV GN in isoform 2.
VSP_008736
Alternative sequence184 – 400217Missing in isoform 2.
VSP_008737
Alternative sequence336 – 40065WQDPI…RKKVT → VL in isoform 3.
VSP_044397

Experimental info

Mutagenesis1111S → A: Abolishes activation of pre-rRNA synthesis. Ref.10 Ref.12
Mutagenesis1871H → Y: Abolishes deacetylase activity and activation of pre-rRNA synthesis. Ref.10 Ref.13
Sequence conflict711L → Q in BAG52860. Ref.2
Sequence conflict3841G → S in BAF82954. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: 55D7736A864AFE6F

FASTA40044,898
        10         20         30         40         50         60 
MAAGGLSRSE RKAAERVRRL REEQQRERLR QVSRILRKAA AERSAEEGRL LAESADLVTE 

        70         80         90        100        110        120 
LQGRSRRREG LKRRQEEVCD DPEELRGKVR ELASAVRNAK YLVVYTGAGI STAASIPDYR 

       130        140        150        160        170        180 
GPNGVWTLLQ KGRSVSAADL SEAEPTLTHM SITRLHEQKL VQHVVSQNCD GLHLRSGLPR 

       190        200        210        220        230        240 
TAISELHGNM YIEVCTSCVP NREYVRVFDV TERTALHRHQ TGRTCHKCGT QLRDTIVHFG 

       250        260        270        280        290        300 
ERGTLGQPLN WEAATEAASR ADTILCLGSS LKVLKKYPRL WCMTKPPSRR PKLYIVNLQW 

       310        320        330        340        350        360 
TPKDDWAALK LHGKCDDVMR LLMAELGLEI PAYSRWQDPI FSLATPLRAG EEGSHSRKSL 

       370        380        390        400 
CRSREEAPPG DRGAPLSSAP ILGGWFGRGC TKRTKRKKVT 

« Hide

Isoform 2 [UniParc].

Checksum: EC211D79031585C2
Show »

FASTA18320,404
Isoform 3 [UniParc].

Checksum: C0E80615256EEA7A
Show »

FASTA32035,851

References

« Hide 'large scale' references
[1]"Phylogenetic classification of prokaryotic and eukaryotic Sir-2 like proteins."
Frye R.A.
Biochem. Biophys. Res. Commun. 273:793-798(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Spleen.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
Tissue: Cerebellum, Colon and Placenta.
[3]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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] (ISOFORM 1).
Tissue: Liver and Lymph.
[5]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 128-400 (ISOFORM 1).
Tissue: Testis.
[6]"Isolation of a SIR-like gene, SIR-T8, that is overexpressed in thyroid carcinoma cell lines and tissues."
de Nigris F., Cerutti J., Morelli C., Califano D., Chiariotti L., Viglietto G., Santelli G., Fusco A.
Br. J. Cancer 86:917-923(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[7]Erratum
De Nigris F., Cerutti J., Morelli C., Califano D., Chiariotti L., Viglietto G., Santelli G., Fusco A.
Br. J. Cancer 87:1479-1479(2002) [PubMed] [Europe PMC] [Abstract]
[8]"'SIRT8' expressed in thyroid cancer is actually SIRT7."
Frye R.A.
Br. J. Cancer 87:1479-1479(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SHOWS THAT SIR-T8 IS SIRT7.
[9]"Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins."
Michishita E., Park J.Y., Burneskis J.M., Barrett J.C., Horikawa I.
Mol. Biol. Cell 16:4623-4635(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[10]"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, IDENTIFICATION IN A RNA POLYMERASE I COMPLEX, INTERACTION WITH HISTONE H2A AND/OR HISTONE H2B, MUTAGENESIS OF SER-111 AND HIS-187, SUBCELLULAR LOCATION.
[11]"Involvement of SIRT7 in resumption of rDNA transcription at the exit from mitosis."
Grob A., Roussel P., Wright J.E., McStay B., Hernandez-Verdun D., Sirri V.
J. Cell Sci. 122:489-498(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH UBTF, PHOSPHORYLATION, SUBCELLULAR LOCATION.
[12]"Functional proteomics establishes the interaction of SIRT7 with chromatin remodeling complexes and expands its role in regulation of RNA polymerase I transcription."
Tsai Y.C., Greco T.M., Boonmee A., Miteva Y., Cristea I.M.
Mol. Cell. Proteomics 11:M111.015156.01-M111.015156.17(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH MYBBP1A; SMARCA5 AND BAZ1B, MUTAGENESIS OF SER-111.
[13]"SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation."
Barber M.F., Michishita-Kioi E., Xi Y., Tasselli L., Kioi M., Moqtaderi Z., Tennen R.I., Paredes S., Young N.L., Chen K., Struhl K., Garcia B.A., Gozani O., Li W., Chua K.F.
Nature 487:114-118(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH ELK4, MUTAGENESIS OF HIS-187.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRT46324.
RefSeqNP_057622.1. NM_016538.2.
UniGeneHs.514636.

3D structure databases

ProteinModelPortalQ9NRC8.
SMRQ9NRC8. Positions 77-339.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119602. 660 interactions.
DIPDIP-59906N.
IntActQ9NRC8. 2 interactions.
MINTMINT-1424083.
STRING9606.ENSP00000329466.

Chemistry

ChEMBLCHEMBL2163184.

Polymorphism databases

DMDM38258650.

Proteomic databases

PaxDbQ9NRC8.
PRIDEQ9NRC8.

Protocols and materials databases

DNASU51547.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000328666; ENSP00000329466; ENSG00000187531. [Q9NRC8-1]
GeneID51547.
KEGGhsa:51547.
UCSCuc002kcj.2. human. [Q9NRC8-1]

Organism-specific databases

CTD51547.
GeneCardsGC17M079869.
HGNCHGNC:14935. SIRT7.
HPACAB037261.
MIM606212. gene.
neXtProtNX_Q9NRC8.
PharmGKBPA37940.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0846.
HOGENOMHOG000231240.
HOVERGENHBG060028.
InParanoidQ9NRC8.
KOK11417.
OMAWFGRGCA.
OrthoDBEOG7M98GV.
PhylomeDBQ9NRC8.
TreeFamTF106184.

Gene expression databases

ArrayExpressQ9NRC8.
BgeeQ9NRC8.
CleanExHS_SIRT7.
GenevestigatorQ9NRC8.

Family and domain databases

InterProIPR003000. Sirtuin.
IPR026590. Ssirtuin_cat_dom.
[Graphical view]
PANTHERPTHR11085. PTHR11085. 1 hit.
PfamPF02146. SIR2. 1 hit.
[Graphical view]
PROSITEPS50305. SIRTUIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSIRT7. human.
GeneWikiSIRT7.
GenomeRNAi51547.
NextBio35463912.
PROQ9NRC8.
SOURCESearch...

Entry information

Entry nameSIR7_HUMAN
AccessionPrimary (citable) accession number: Q9NRC8
Secondary accession number(s): A8K2K0 expand/collapse secondary AC list , B3KSU8, Q3MIK4, Q9NSZ6, Q9NUS6
Entry history
Integrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: October 1, 2000
Last modified: April 16, 2014
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM