UniProtKB/Swiss-Prot Q8N6T7: Variant p.Glu36Val

NAD-dependent protein deacylase sirtuin-6
Gene: SIRT6
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Variant information Variant position:

36 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Glutamate (E) to Valine (V) at position 36 (E36V, p.Glu36Val). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties:

Change from medium size and acidic (E) to medium size and hydrophobic (V) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-2 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

Lowest score: -4 (low probability of substitution).
Highest score: 11 (high probability of substitution).

More information can be found on the following page
Variant description:

Found in kidney cancer; somatic mutation; reduced histone deacetylase activity; does not affect the protein-lysine demyristoylase activity. Any additional useful information about the variant.

Sequence information Variant position:

36 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:

GKCGLPEIFDPPEELERKVW E LARLVWQSSSVVFHTGAGIS 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                         GKCGLPEIFDPPEELERKVWELARLVWQSSSVVFHTGAGIS

Mouse                         GKCGLPEIFDPPEELERKVWELARLMWQSSSVVFHTGAGIS

Drosophila                    GILGAPESFDSDEVVAEKCQELAELIKKSGHVVLHTGAGIS

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	27 – 272	Deacetylase sirtuin-type
Binding site	53 – 53
Site	18 – 18	Formation of an covalent adduct with nitro-fatty acid activators
Modified residue	33 – 33	N6-acetyllysine
Mutagenesis	17 – 17	K -> R. Does not affect acetylation level.
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.
Helix	27 – 43

Literature citations
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.