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Reviewed, UniProtKB/Swiss-Prot Q8N6T7 (SIRT6_HUMAN)

Last modified November 3, 2009. Version 72. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    NAD-dependent deacetylase sirtuin-6
    EC=3.5.1.-
Alternative name(s):
    SIR2-like protein 6
Gene names
Name: SIRT6
Synonyms: SIR2L6
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length355 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

NAD-dependent protein deacetylase. Has deacetylase activity towards 'Lys-9' and 'Lys-56' of histone H3. Modulates acetylation of histone H3 in telomeric chromatin during the S-phase of the cell cycle. Deacetylates 'Lys-9' of histone H3 at NF-kappa-B target promoters and may down-regulate the expression of a subset of NF-kappa-B target genes. Deacetylation of nucleosomes interferes with RELA binding to target DNA. May be required for the association of WRN with telomeres during S-phase and for normal telomere maintenance. Required for genomic stability. Required for normal IGF1 serum levels and normal glucose homeostasis. Modulates cellular senescence and apoptosis. Regulates the production of TNF protein By similarity.

Catalytic activity

NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein. Ref.8

Cofactor

Binds 1 zinc ion per subunit By similarity.

Subunit structure

Interacts with RELA. Ref.10

Subcellular location

Nucleusnucleoplasm. Note: Predominantly nuclear. Associated with telomeric heterochromatin regions. Ref.8 Ref.10 Ref.7

Sequence similarities

Belongs to the sirtuin family.

Contains 1 deacetylase sirtuin-type domain.

Sequence caution

The sequence AAC34468.1 differs from that shown. Reason: Erroneous gene model prediction.

The sequence AAD15478.1 differs from that shown. Reason: Erroneous gene model prediction.

The sequence AAH04218.1 differs from that shown. Reason: Frameshift at position 23.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

RELAQ042063EBI-712415,EBI-73886

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8N6T7-1)

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: Q8N6T7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     179-205: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q8N6T7-3)

The sequence of this isoform differs from the canonical sequence as follows:
     65-125: Missing.
     206-248: NADLSITLGT...VNLQPTKHDR → SGPAGTCRWL...SASMATLTRS
     249-355: Missing.
Note: No experimental confirmation available.
Isoform 4 (identifier: Q8N6T7-4)

The sequence of this isoform differs from the canonical sequence as follows:
     23-64: Missing.
     179-205: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 355355NAD-dependent deacetylase sirtuin-6
PRO_0000110269

Regions

Domain35 – 274240Deacetylase sirtuin-type
Nucleotide binding52 – 7120NAD By similarity
Nucleotide binding113 – 1175NAD By similarity
Compositional bias287 – 34559Pro-rich

Sites

Active site1331Proton acceptor
Metal binding1411Zinc By similarity
Metal binding1441Zinc By similarity
Metal binding1661Zinc By similarity
Metal binding1771Zinc By similarity

Amino acid modifications

Modified residue2941Phosphothreonine Ref.9
Modified residue3031Phosphoserine Ref.9

Natural variations

Alternative sequence23 – 6442Missing in isoform 4.
VSP_013659
Alternative sequence65 – 12561Missing in isoform 3.
VSP_008732
Alternative sequence179 – 20527Missing in isoform 2 and isoform 4.
VSP_008733
Alternative sequence206 – 24843NADLS…TKHDR → SGPAGTCRWLPSAGEAAWSS STCSPPSTTAMLTSASMATL TRS in isoform 3.
VSP_008734
Alternative sequence249 – 355107Missing in isoform 3.
VSP_008735
Natural variant461S → N: dbSNP rs352493. Ref.2 Ref.5 Ref.6
VAR_017154

Experimental info

Mutagenesis1331H → Y: Loss of enzyme activity. Ref.8
Sequence conflict421W → R in CAG33481. Ref.3
Sequence conflict2491H → Y in AAH04218. Ref.6
Sequence conflict2671K → E in AAF43432. Ref.1

Sequences

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

Last modified October 31, 2003. Version 2.
Checksum: 0C86AAC497130BBF

FASTA35539,119
        10         20         30         40         50         60 
MSVNYAAGLS PYADKGKCGL PEIFDPPEEL ERKVWELARL VWQSSSVVFH TGAGISTASG 

        70         80         90        100        110        120 
IPDFRGPHGV WTMEERGLAP KFDTTFESAR PTQTHMALVQ LERVGLLRFL VSQNVDGLHV 

       130        140        150        160        170        180 
RSGFPRDKLA ELHGNMFVEE CAKCKTQYVR DTVVGTMGLK ATGRLCTVAK ARGLRACRGE 

       190        200        210        220        230        240 
LRDTILDWED SLPDRDLALA DEASRNADLS ITLGTSLQIR PSGNLPLATK RRGGRLVIVN 

       250        260        270        280        290        300 
LQPTKHDRHA DLRIHGYVDE VMTRLMKHLG LEIPAWDGPR VLERALPPLP RPPTPKLEPK 

       310        320        330        340        350 
EESPTRINGS IPAGPKQEPC AQHNGSEPAS PKRERPTSPA PHRPPKRVKA KAVPS 

« Hide

Isoform 2.

Checksum: 503805C898FD7769
Show »

FASTA32836,065
Isoform 3.

Checksum: 7410BAB73DB086B2
Show »

FASTA18720,078
Isoform 4.

Checksum: 792F5F783F4B9F83
Show »

FASTA28631,409

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: 10873683] [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: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ASN-46.
Tissue: Heart and Teratocarcinoma.
[3]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed: 15057824] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ASN-46.
[6]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2; 3 AND 4), VARIANT ASN-46.
Tissue: Blood, Eye, Lung and Placenta.
[7]"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: 16079181] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[8]"SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin."
Michishita E., McCord R.A., Berber E., Kioi M., Padilla-Nash H., Damian M., Cheung P., Kusumoto R., Kawahara T.L.A., Barrett J.C., Chang H.Y., Bohr V.A., Ried T., Gozani O., Chua K.F.
Nature 452:492-496(2008) [PubMed: 18337721] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-133, SUBCELLULAR LOCATION.
[9]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-294 AND SER-303, MASS SPECTROMETRY.
[10]"SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span."
Kawahara T.L.A., Michishita E., Adler A.S., Damian M., Berber E., Lin M., McCord R.A., Ongaigui K.C.L., Boxer L.D., Chang H.Y., Chua K.F.
Cell 136:62-74(2009) [PubMed: 19135889] [Abstract]
Cited for: FUNCTION, INTERACTION WITH RELA, SUBCELLULAR LOCATION.
[11]"Cell cycle-dependent deacetylation of telomeric histone H3 lysine K56 by human SIRT6."
Michishita E., McCord R.A., Boxer L.D., Barber M.F., Hong T., Gozani O., Chua K.F.
Cell Cycle 8:2664-2666(2009) [PubMed: 19625767] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

AF233396 mRNA. Translation: AAF43432.1.
AK074810 mRNA. Translation: BAC11222.1.
AK315048 mRNA. Translation: BAG37527.1.
CR457200 mRNA. Translation: CAG33481.1.
AC005620 Genomic DNA. Translation: AAC34468.1. Sequence problems.
AC006930 Genomic DNA. Translation: AAD15478.1. Sequence problems.
CH471139 Genomic DNA. Translation: EAW69252.1.
BC000090 mRNA. Translation: AAH00090.1. Different initiation.
BC004218 mRNA. Translation: AAH04218.1. Frameshift.
BC005026 mRNA. Translation: AAH05026.1.
BC028220 mRNA. Translation: AAH28220.1.
IPIIPI00332636.
IPI00383640.
IPI00396170.
IPI00556638.
RefSeqNP_057623.1.
UniGeneHs.423756

3D structure databases

HSSPHSSP built from PDB template 1ICI based on UniProtKB O28597.
ModBaseSearch...

Protein-protein interaction databases

IntActQ8N6T7. 6 interactions.
STRINGQ8N6T7.

PTM databases

PhosphoSiteQ8N6T7.

Genome annotation databases

EnsemblENST00000269860; ENSP00000269860; ENSG00000077463; Homo sapiens. [Genome view]
ENST00000305232; ENSP00000305310; ENSG00000077463; Homo sapiens. [Genome view]
ENST00000337491; ENSP00000337332; ENSG00000077463; Homo sapiens. [Genome view]
ENST00000381935; ENSP00000371360; ENSG00000077463; Homo sapiens. [Genome view]
GeneID51548.
KEGGhsa:51548.
UCSCuc002lzn.1. human.
uc002lzo.1. human.
uc002lzq.1. human.

Organism-specific databases

CTD51548.
GeneCardsGC19M004125.
H-InvDBHIX0014654.
HGNCHGNC:14934. SIRT6.
MIM606211. gene.
PharmGKBPA37939.
GenAtlasSearch...

Phylogenomic databases

HOVERGENQ8N6T7.
OMAIPAWDGP.

Enzyme and pathway databases

BRENDA2.4.2.31. 247.
Pathway_Interaction_DBhdac_classi_pathway. Signaling events mediated by HDAC Class I.

Gene expression databases

ArrayExpressQ8N6T7.
BgeeQ8N6T7.
GenevestigatorQ8N6T7.
GermOnlineENSG00000077463. Homo sapiens.

Family and domain databases

InterProIPR003000. NAD-dep_histone_deAcase_SIR2.
[Graphical view]
PANTHERPTHR11085. SIR2. 1 hit.
PfamPF02146. SIR2. 1 hit.
[Graphical view]
PROSITEPS50305. SIRTUIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio55327.
SOURCESearch...

Entry information

Entry nameSIRT6_HUMAN
AccessionPrimary (citable) accession number: Q8N6T7
Secondary accession number(s): B2RCD0 expand/collapse secondary AC list , O75291, Q6IAF5, Q6PK99, Q8NCD2, Q9BSI5, Q9BWP3, Q9NRC7, Q9UQD1
Entry history
Integrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: October 31, 2003
Last modified: November 3, 2009
This is version 72 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents