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TREM2 Q9NZC2

髓系细胞表达触发受体2 (TREM-2) (单核细胞表达触发受体2)

蛋白质信息 (UniProt)

髓系细胞表达触发受体2 (TREM-2) (单核细胞表达触发受体2)

Q9NZC2

功能描述

与TYROBP形成受体信号复合物,介导配体结合后的信号传导和细胞活化 (PubMed:10799849)。作为淀粉样-beta蛋白42(amyloid-beta protein 42,淀粉样-beta前体蛋白APP的剪切产物)的受体,介导小胶质细胞对其的摄取和降解 (PubMed:27477018, PubMed:29518356)。与淀粉样-beta 42结合介导小胶质细胞活化、增殖、迁移、凋亡以及促炎细胞因子(如IL6R和CCL3)和抗炎细胞因子ARG1的表达 (By similarity)。作为脂蛋白颗粒(如LDL、VLDL和HDL)和载脂蛋白(如APOA1、APOA2、APOB、APOE、APOE2、APOE3、APOE4和CLU)的受体,增强它们在小胶质细胞中的摄取 (PubMed:27477018)。结合磷脂(优先结合阴离子脂质),如磷脂酰丝氨酸、磷脂酰乙醇胺、磷脂酰甘油和鞘磷脂 (PubMed:29794134)。通过作为Wnt/beta-catenin信号级联反应的上游调节因子来调节小胶质细胞增殖 (By similarity)。小胶质细胞吞噬凋亡神经元所必需 (PubMed:24990881)。也是神经元损伤后小胶质细胞活化和吞噬髓鞘碎片以及发育大脑突触消除期间吞噬神经元突触所必需的 (By similarity)。调节小胶质细胞趋化性和突起生长,以及小胶质细胞对氧化应激和脂多糖的反应 (By similarity)。它抑制响应脂多糖的PI3K和NF-kappa-B信号传导;从而促进吞噬作用,抑制促炎细胞因子和一氧化氮的产生,抑制细胞凋亡并增加IL10和TGFB的表达 (By similarity)。在氧化应激期间,它促进抗凋亡的NF-kappa-B信号传导和ERK信号传导 (By similarity)。在小胶质细胞MTOR活化和代谢中起作用 (By similarity)。调节小胶质细胞数量的年龄相关变化 (PubMed:29752066)。触发巨噬细胞和树突状细胞免疫反应的活化 (PubMed:10799849)。介导细胞因子诱导的多核巨细胞形成,该细胞由巨噬细胞融合而成 (By similarity)。在树突状细胞中,作为SEMA6D的受体(以PLEXNA1为共受体),介导趋化因子受体CCR7的上调以及树突状细胞的成熟和存活 (PubMed:11602640)。参与破骨细胞分化的正调节 (PubMed:12925681)。 {ECO:0000250|UniProtKB:Q99NH8, ECO:0000269|PubMed:10799849, ECO:0000269|PubMed:11602640, ECO:0000269|PubMed:12925681, ECO:0000269|PubMed:24990881, ECO:0000269|PubMed:27477018, ECO:0000269|PubMed:29518356, ECO:0000269|PubMed:29752066, ECO:0000269|PubMed:29794134}。

组织特异性

Expressed in the brain, specifically in microglia and in the fusiform gyrus (at protein level) (PubMed:27477018, PubMed:28802038, PubMed:28855300, PubMed:29752066). Expressed on macrophages and dendritic cells but not on granulocytes or monocytes (PubMed:10799849, PubMed:28855301). In the CNS strongest expression seen in the basal ganglia, corpus callosum, medulla oblongata and spinal cord (PubMed:12080485).

亚细胞定位

[Isoform 1]: Cell membrane

关键词

3D-structure Alternative splicing Alzheimer disease Amyloidosis Cell membrane Disease variant Disulfide bond Glycoprotein Immunoglobulin domain Lipid-binding