SIRT1 Recombinant Rabbit Monoclonal Antibody [JE11-04]

功能

The silent information regulator (SIR2) family of genes are highly-conserved from prokaryotes to eukaryotes and are involved in diverse processes, including transcriptional regulation, cell cycle progression, DNA-damage repair and aging. In S. cerevisiae, Sir2p deacetylates histones in an NAD-dependent manner, which regulates silencing at the telomeric, rDNA and silent mating-type loci. Sir2p is the founding member of a large family, designated sirtuins, which contain a conserved catalytic domain. The human homologs, which include SIRT1-7, are divided into four main branches: SIRT1-3 are class I, SIRT4 is class II, SIRT5 is class III and SIRT6-7 are class IV. SIRT1 has the closest homology to the yeast Sir2p and is widely expressed in fetal and adult tissues. SIRT1 is highly expressed in heart, brain and skeletal muscle, with low expression in lung and placenta. SIRT1 regulates the p53-dependent DNA damage response pathway by binding to and deacetylating p53, specifically at Lys 382.

背景文献

1. Luo J. et. al. SIRT1 is required for the neuroprotection of resveratrol on retinal ganglion cells after retinal ischemia-reperfusion injury in mice. Graefes Arch Clin Exp Ophthalmol. 2020 Jan 3.

2. Imperatore F. et. al. SIRT1 regulates macrophage self-renewal. EMBO J. 2017 Aug 15;36(16):2353-2372.

序列相似性

Belongs to the sirtuin family. Class I subfamily.

组织特异性

Widely expressed.

翻译后修饰

Methylated on multiple lysine residues; methylation is enhanced after DNA damage and is dispensable for deacetylase activity toward p53/TP53.; Phosphorylated. Phosphorylated by STK4/MST1, resulting in inhibition of SIRT1-mediated p53/TP53 deacetylation. Phosphorylation by MAPK8/JNK1 at Ser-27, Ser-47, and Thr-530 leads to increased nuclear localization and enzymatic activity. Phosphorylation at Thr-530 by DYRK1A and DYRK3 activates deacetylase activity and promotes cell survival. Phosphorylation by mammalian target of rapamycin complex 1 (mTORC1) at Ser-47 inhibits deacetylation activity. Phosphorylated by CaMK2, leading to increased p53/TP53 and NF-kappa-B p65/RELA deacetylation activity (By similarity). Phosphorylation at Ser-27 implicating MAPK9 is linked to protein stability. There is some ambiguity for some phosphosites: Ser-159/Ser-162 and Thr-544/Ser-545.; Proteolytically cleaved by cathepsin B upon TNF-alpha treatment to yield catalytic inactive but stable SirtT1 75 kDa fragment (75SirT1).; S-nitrosylated by GAPDH, leading to inhibit the NAD-dependent protein deacetylase activity.; Acetylated at various Lys residues. Deacetylated via an autocatalytic mechanism. Autodeacetylation at Lys-238 promotes its protein deacetylase activity.

亚细胞定位

Cytoplasm, Mitochondrion, Nucleus.

UNIPROT #

SwissProt: Q96EB6 Human

别名