APOE P02649

载脂蛋白E (Apo-E)

功能描述

APOE是一种载脂蛋白，一种与脂质颗粒结合的蛋白质，主要通过血浆和组织间液在器官之间进行脂蛋白介导的脂质运输 (PubMed:14754908, PubMed:1911868, PubMed:6860692)。APOE是血浆脂蛋白的核心成分，参与其生成、转化和清除 (PubMed:14754908, PubMed:1911868, PubMed:1917954, PubMed:23620513, PubMed:2762297, PubMed:6860692, PubMed:9395455)。载脂蛋白是两亲性分子，既与脂蛋白颗粒核心的脂质相互作用，又与血浆的水环境相互作用 (PubMed:2762297, PubMed:6860692, PubMed:9395455)。因此，APOE与乳糜微粒、乳糜微粒残余物、极低密度脂蛋白 (VLDL) 和中密度脂蛋白 (IDL) 结合，但显示出对高密度脂蛋白 (HDL) 的优先结合 (PubMed:1911868, PubMed:6860692)。它还结合多种细胞受体，包括LDL受体/LDLR、LDL受体相关蛋白LRP1、LRP2和LRP8以及极低密度脂蛋白受体/VLDLR，这些受体介导含APOE脂蛋白颗粒的细胞摄取 (PubMed:12950167, PubMed:1530612, PubMed:1917954, PubMed:20030366, PubMed:20303980, PubMed:2063194, PubMed:2762297, PubMed:7635945, PubMed:7768901, PubMed:8756331, PubMed:8939961)。最后，APOE还具有肝素结合活性，并结合细胞表面的硫酸乙酰肝素蛋白聚糖，这一特性支持细胞对含APOE脂蛋白的捕获和受体介导的摄取 (PubMed:23676495, PubMed:7635945, PubMed:9395455, PubMed:9488694)。APOE的一个主要功能是通过肝细胞摄取乳糜微粒、VLDL和HDL来介导脂蛋白清除 (PubMed:1911868, PubMed:1917954, PubMed:23676495, PubMed:29516132, PubMed:9395455)。APOE还参与肝脏VLDL的生物合成及其被外周组织的摄取，确保甘油三酯的输送和能量在肌肉、心脏和脂肪组织中的储存 (PubMed:2762297, PubMed:29516132)。通过参与组织间脂蛋白介导的脂质分布，APOE在血浆和组织脂质稳态中发挥关键作用 (PubMed:1917954, PubMed:2762297, PubMed:29516132)。APOE还参与逆向胆固醇转运的两个步骤，即HDL介导的胆固醇从外周组织运输到肝脏，从而在胆固醇稳态中发挥重要作用 (PubMed:14754908, PubMed:23620513, PubMed:9395455)。首先，它在组织中HDL的生物合成过程中与ABCA1功能相关 (PubMed:14754908, PubMed:23620513)。其次，它在循环HDL中富集并介导其被肝细胞摄取 (PubMed:9395455)。APOE在中枢神经系统的脂质运输中也发挥重要作用，调节神经元存活和发芽 (PubMed:25173806, PubMed:8939961)。APOE还参与先天性和适应性免疫反应，例如控制髓源性抑制细胞的存活 (By similarity)。结合免疫细胞受体LILRB4 (PubMed:30333625)。APOE可能还通过受体依赖且不依赖胆固醇的机制在转录调节中发挥作用，该机制激活MAP3K12和非经典MAPK信号转导通路，导致AP-1介导的APP转录增强 (PubMed:28111074)。 {ECO:0000250|UniProtKB:P08226, ECO:0000269|PubMed:12950167, ECO:0000269|PubMed:14754908, ECO:0000269|PubMed:1530612, ECO:0000269|PubMed:1911868, ECO:0000269|PubMed:1917954, ECO:0000269|PubMed:20030366, ECO:0000269|PubMed:20303980, ECO:0000269|PubMed:2063194, ECO:0000269|PubMed:23620513, ECO:0000269|PubMed:23676495, ECO:0000269|PubMed:2762297, ECO:0000269|PubMed:28111074, ECO:0000269|PubMed:30333625, ECO:0000269|PubMed:6860692, ECO:0000269|PubMed:7635945, ECO:0000269|PubMed:7768901, ECO:0000269|PubMed:8756331, ECO:0000269|PubMed:8939961, ECO:0000269|PubMed:9395455, ECO:0000269|PubMed:9488694, ECO:0000303|PubMed:25173806, ECO:0000303|PubMed:29516132}.; FUNCTION: (Microbial infection) 通过与HCV包膜糖蛋白E2的相互作用，参与HCV与细胞表面HSPGs及其他受体 (LDLr, VLDLr, 和 SR-B1) 的附着，以及HCV病毒颗粒的组装、成熟和感染 (PubMed:25122793, PubMed:29695434)。这种相互作用可能是通过病毒上调细胞自噬来促进的 (PubMed:29695434)。 {ECO:0000269|PubMed:25122793, ECO:0000269|PubMed:29695434}.

组织特异性

Produced by several tissues and cell types and mainly found associated with lipid particles in the plasma, the interstitial fluid and lymph (PubMed:25173806). Mainly synthesized by liver hepatocytes (PubMed:25173806). Significant quantities are also produced in brain, mainly by astrocytes and glial cells in the cerebral cortex, but also by neurons in frontal cortex and hippocampus (PubMed:10027417, PubMed:3115992). It is also expressed by cells of the peripheral nervous system (PubMed:10027417, PubMed:25173806). Also expressed by adrenal gland, testis, ovary, skin, kidney, spleen and adipose tissue and macrophages in various tissues (PubMed:25173806).

亚细胞定位

Secreted