Sequence information
Variant position: 46 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 355 The length of the canonical sequence.
Location on the sequence:
PPEELERKVWELARLVWQSS
S VVFHTGAGISTASGIPDFRG
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human PPEELERKVWELARLVWQSSS VVFHTGAGISTASGIPDFRG
Mouse PPEELERKVWELARLMWQSSS VVFHTGAGISTASGIPDFRG
Drosophila SDEVVAEKCQELAELIKKSGH VVLHTGAGISTSAGIPDFRG
Sequence annotation in neighborhood: The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:Type: the type of sequence feature. Positions: endpoints of the sequence feature. Description: contains additional information about the feature.
Type Positions Description
Chain
2 – 355
NAD-dependent protein deacylase sirtuin-6
Domain
35 – 274
Deacetylase sirtuin-type
Binding site
53 – 53
Binding site
57 – 57
Binding site
64 – 64
Binding site
65 – 65
Modified residue
33 – 33
N6-acetyllysine
Mutagenesis
33 – 33
K -> Q. Mimics acetylation, leading to impaired ability to recognize and bind double-strand breaks (DSBs) sites.
Mutagenesis
33 – 33
K -> R. Decreased acetylation level.
Mutagenesis
45 – 45
S -> A. In AAA mutant; strongly decreased nucleosome-binding; when associated with 206-A--A-208.
Mutagenesis
56 – 56
S -> Y. Abolished NAD-dependent protein deacetylase, defatty-acylase and mono-ADP-ribosyltransferase activities.
Mutagenesis
60 – 60
G -> A. Does not affect the NAD-dependent protein defatty-acylase activity. Abolished NAD-dependent protein deacetylase and mono-ADP-ribosyltransferase activities.
Mutagenesis
65 – 65
R -> A. Does not affect the mono-ADP-ribosyltransferase activity. Abolished NAD-dependent protein deacetylase and defatty-acylase activities.
Beta strand
45 – 51
Literature citations
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.; 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)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1); VARIANT ASN-46;
Submission
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.; 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.;
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]; VARIANT ASN-46;
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)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2); VARIANT ASN-46;
Identification of and molecular basis for SIRT6 loss-of-function point mutations in cancer.
Kugel S.; Feldman J.L.; Klein M.A.; Silberman D.M.; Sebastian C.; Mermel C.; Dobersch S.; Clark A.R.; Getz G.; Denu J.M.; Mostoslavsky R.;
Cell Rep. 13:479-488(2015)
Cited for: VARIANTS ASN-25; VAL-36; ASN-46; TYR-63; SER-89; ASN-116; 260-GLU--SER-355 DEL; PRO-263 AND LEU-274; FUNCTION; CATALYTIC ACTIVITY; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS ASN-25; VAL-36; ASN-46; TYR-63; SER-89; ASN-116; 260-GLU--SER-355 DEL; PRO-263 AND LEU-274;
Disclaimer:
Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.