Descriptions

Sirtuin 2 (SIRT2) is a NAD+ dependent deacetylase that has been associated with neurodegeneration and cancer. The C-terminal region of SIRT2 functions as an autoinhibitory region that regulates the deacetylation activity of SIRT2. Phosphorylation at S331 causes large conformational changes in the CT that enhance the autoinhibitory activity of the CT region. This serine residue islocated within the naturally disordered C-terminal region (CT, residues 320-352 in isoform 2).

Autoinhibitory domains (AIDs)

Target domain

5-284 (Catalytic core domain)

Relief mechanism

Others

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

13 structures for P53686

Entry ID Method Resolution Chain Position Source
1Q14 X-ray 250 A A 1-357 PDB
1Q17 X-ray 270 A A/B/C 1-294 PDB
1Q1A X-ray 150 A A 5-293 PDB
1SZC X-ray 175 A A 1-294 PDB
1SZD X-ray 150 A A 1-294 PDB
2OD2 X-ray 200 A A 1-294 PDB
2OD7 X-ray 200 A A 1-294 PDB
2OD9 X-ray 205 A A 1-294 PDB
2QQF X-ray 200 A A 1-294 PDB
2QQG X-ray 205 A A 1-294 PDB
7F4E X-ray 178 A A 8-294 PDB
7F51 X-ray 198 A A 8-294 PDB
AF-P53686-F1 Predicted AlphaFoldDB

9 variants for P53686

Variant ID(s) Position Change Description Diseaes Association Provenance
s16-526811 24 N>D No SGRP
s16-526389 164 I>M No SGRP
s16-526378 168 V>A No SGRP
s16-526235 216 Q>K No SGRP
s16-526234 216 Q>R No SGRP
s16-526112 257 A>T No SGRP
s16-526091 264 L>V No SGRP
s16-525995 296 G>R No SGRP
s16-525871 337 G>D No SGRP

No associated diseases with P53686

1 regional properties for P53686

Type Name Position InterPro Accession
domain Sirtuin family, catalytic core domain 5 - 284 IPR026590

Functions

Description
EC Number 2.3.1.286 Transferring groups other than amino-acyl groups
Subcellular Localization
  • Cytoplasm
  • Nucleus
  • Shuttles between the nucleus and cytoplasm, but is largely cytoplasmic owing to efficient nuclear export
  • Nuclear exclusion is mediated by the exportin CRM1
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

2 GO annotations of cellular component

Name Definition
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.

5 GO annotations of molecular function

Name Definition
NAD+ binding Binding to the oxidized form, NAD, of nicotinamide adenine dinucleotide, a coenzyme involved in many redox and biosynthetic reactions.
NAD-dependent histone deacetylase activity Catalysis of the reaction: histone N6-acetyl-L-lysine + H2O = histone L-lysine + acetate. This reaction requires the presence of NAD, and represents the removal of an acetyl group from a histone.
NAD-dependent histone deacetylase activity (H4-K16 specific) Catalysis of the reaction: histone H4 N6-acetyl-L-lysine (position 16) + H2O = histone H4 L-lysine (position 16) + acetate. This reaction requires the presence of NAD, and represents the removal of an acetyl group from lysine at position 16 of the histone H4 protein.
transferase activity Catalysis of the transfer of a group, e.g. a methyl group, glycosyl group, acyl group, phosphorus-containing, or other groups, from one compound (generally regarded as the donor) to another compound (generally regarded as the acceptor). Transferase is the systematic name for any enzyme of EC class 2.
zinc ion binding Binding to a zinc ion (Zn).

3 GO annotations of biological process

Name Definition
histone H4 deacetylation The modification of histone H4 by the removal of one or more acetyl groups.
negative regulation of mitotic recombination Any process that inhibits or decreases the rate of DNA recombination during mitosis.
rDNA heterochromatin assembly The formation of heterochromatin at ribosomal DNA, characterized by the modified histone H3K9me3.

4 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q8IXJ6 SIRT2 NAD-dependent protein deacetylase sirtuin-2 Homo sapiens (Human) EV
Q8VDQ8 Sirt2 NAD-dependent protein deacetylase sirtuin-2 Mus musculus (Mouse) SS
Q5RJQ4 Sirt2 NAD-dependent protein deacetylase sirtuin-2 Rattus norvegicus (Rat) PR
Q7ZVK3 sirt2 NAD-dependent protein deacetylase sirtuin-2 Danio rerio (Zebrafish) (Brachydanio rerio) SS
10 20 30 40 50 60
MSVSTASTEM SVRKIAAHMK SNPNAKVIFM VGAGISTSCG IPDFRSPGTG LYHNLARLKL
70 80 90 100 110 120
PYPEAVFDVD FFQSDPLPFY TLAKELYPGN FRPSKFHYLL KLFQDKDVLK RVYTQNIDTL
130 140 150 160 170 180
ERQAGVKDDL IIEAHGSFAH CHCIGCGKVY PPQVFKSKLA EHPIKDFVKC DVCGELVKPA
190 200 210 220 230 240
IVFFGEDLPD SFSETWLNDS EWLREKITTS GKHPQQPLVI VVGTSLAVYP FASLPEEIPR
250 260 270 280 290 300
KVKRVLCNLE TVGDFKANKR PTDLIVHQYS DEFAEQLVEE LGWQEDFEKI LTAQGGMGDN
310 320 330 340 350
SKEQLLEIVH DLENLSLDQS EHESADKKDK KLQRLNGHDS DEDGASNSSS SQKAAKE