NAD依赖性蛋白硫辛酰胺酶sirtuin-4，线粒体 (EC 2.3.1.-) (NAD依赖性ADP核糖基转移酶sirtuin-4) (EC 2.4.2.-) (NAD依赖性蛋白生物素化酶sirtuin-4) (EC 2.3.1.-) (NAD依赖性蛋白去乙酰化酶sirtuin-4) (EC 2.3.1.286) (调节蛋白SIR2同源物4) (SIR2样蛋白4)
NAD依赖性蛋白硫辛酰胺酶sirtuin-4，线粒体 (EC 2.3.1.-) (NAD依赖性ADP核糖基转移酶sirtuin-4) (EC 2.4.2.-) (NAD依赖性蛋白生物素化酶sirtuin-4) (EC 2.3.1.-) (NAD依赖性蛋白去乙酰化酶sirtuin-4) (EC 2.3.1.286) (调节蛋白SIR2同源物4) (SIR2样蛋白4)
Q9Y6E7功能描述
作为NAD依赖性protein lipoamidase、biotinylase、deacetylase和ADP-ribosyl transferase发挥作用 (PubMed:16959573, PubMed:17715127, PubMed:24052263, PubMed:25525879)。与acetyl-lysine修饰相比，更高效地催化lipoyl-和biotinyl-修饰的去除 (PubMed:24052263, PubMed:25525879)。以不依赖磷酸化的方式，通过酶解E2组分DLAT上的lipoamide辅因子，抑制pyruvate dehydrogenase complex (PDH)活性 (PubMed:25525879)。催化ADP-ribosyl基团转移至靶蛋白，包括线粒体GLUD1，从而抑制GLUD1 enzyme活性 (PubMed:16959573, PubMed:17715127)。作为线粒体glutamine代谢的负调节因子，通过介导GLUD1的单ADP-ribosylation发挥作用：在DNA损伤反应中表达，并通过抑制GLUD1负向调节anaplerosis，导致glutamine进入tricarboxylic acid cycle的代谢受阻，促进cell cycle arrest (PubMed:16959573, PubMed:17715127)。响应mTORC1信号，SIRT4表达受抑制，从而促进anaplerosis和cell proliferation (PubMed:23663782)。作为tumor suppressor发挥作用 (PubMed:23562301, PubMed:23663782)。也作为NAD依赖性protein deacetylase发挥作用：介导MLYCD的'Lys-471'去乙酰化，抑制其活性，从而作为lipid homeostasis的调节因子 (By similarity)。似乎不使PC去乙酰化 (PubMed:23438705)。通过抑制PPARA转录激活来控制fatty acid oxidation (PubMed:24043310)。可能通过调节NAD(+)水平损害SIRT1-PPARA相互作用 (PubMed:24043310)。下调insulin分泌 (PubMed:17715127)。 {ECO:0000255|HAMAP-Rule:MF_03161, ECO:0000269|PubMed:16959573, ECO:0000269|PubMed:17715127, ECO:0000269|PubMed:23438705, ECO:0000269|PubMed:23562301, ECO:0000269|PubMed:23663782, ECO:0000269|PubMed:24043310, ECO:0000269|PubMed:24052263, ECO:0000269|PubMed:25525879}。
组织特异性
Detected in vascular smooth muscle and striated muscle. Detected in insulin-producing beta-cells in pancreas islets of Langerhans (at protein level). Widely expressed. Weakly expressed in leukocytes and fetal thymus.
亚细胞定位
Mitochondrion matrix
关键词