TIM recognition of phosphatidylserine regulates innate and adaptive immunity

TIM 识别磷脂酰丝氨酸调节先天性和适应性免疫

• 批准号: 8306825
• 负责人: Gordon James Freeman
• 金额: $ 28.82万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8306825
• 关键词: 5q33.2; Affect; Apoptosis; Apoptotic; Asthma; Attention; Binding; Cell Surface Proteins; Cells; Chromosomes; Congenic Mice; Disease; Event; Family; Food Hypersensitivity; Gene Duplication; Gene Family; Genes; Genetic Polymorphism; Goals; Homologous Gene; Human; Human Chromosomes; Hypersensitivity; Immunity; Inflammatory; Link; Membrane Proteins; Monkeys; Mucins; Mus; N-terminal; Natural Immunity; Orthologous Gene; Pathogenesis; Pathway interactions; Phenotype; Phosphatidylserines; Play; Research; Research Personnel; Role; Signal Transduction; Single Nucleotide Polymorphism; Site; T-Cell Activation; T-Lymphocyte; Tail; Transmembrane Domain; Tyrosine Phosphorylation; Variant; adaptive immunity; gene discovery; glycosylation; insertion/deletion mutation; member; mouse model; phosphatidylserine receptor; positional cloning; programs

The TIM family of genes consists of eight members {TIM-1-8) on mouse chromosome 11B1.1, and three members {Tlf\/I1, TIMS, and TIM4) on human chromosome 5q33.2 (5). All ofthe mouse and human TIM genes encode type 1 membrane proteins, consisting of an N-terminal Cys-rich IgV-like domain, a mucin-like domain, a transmembrane domain, and an intracellular tail (Figure 1). The intracellular tails of TIM-1, TIM-2, and TIM-3, but not TIM-4, contain predicted tyrosine phosphorylation motifs, suggesting that these TIMs are involved in transmembrane signaling. Whereas TIM-3 has only three predicted glycosylation sites, human TIM-1 has 60, which are primarily 0-linked glycosylation motifs located within the mucin-like domain. The N-terminal Cys-rich regions ofthe TIM homologs have a sequence identity of about 40%, whereas sequence identity between the mouse and human orthologs is around 60% (6). The structural similarities between all the TIMs suggest that they arose from an ancestral gene by successive gene duplication events. TIM-1 polymorphisms and protection against asthma and allergy. Human TIM-1 (HUGO designation HAVCR1) is highly polymorphic in humans and monkeys, as it is in mice, with single nucleotide polymorphisms (SNPs) as well as insertion/deletion variants occurring primarily in the mucin-like domain in both mice and humans (as defined in the previous Project 1). We have also performed association analysis ofthe insertion/deletion variants of TIM-1 in

TIM 基因家族由小鼠染色体 11B1.1 上的八个成员 (TIM-1-8) 和人染色体 5q33.2 上的三个成员 (Tlf1/I1、TIMS 和 TIM4) 组成 (5)。所有的鼠标和 人类 TIM 基因编码 1 型膜蛋白，由富含 Cys 的 N 端组成 IgV 样结构域、粘蛋白样结构域、跨膜结构域和细胞内结构域 尾巴（图1）。 TIM-1、TIM-2 和 TIM-3（但 TIM-4 除外）的细胞内尾部包含预测的酪氨酸磷酸化基序，表明这些 TIM 参与跨膜信号传导。 TIM-3 仅具有 3 个预测糖基化位点，而人类 TIM-1 有 60 个，这些位点主要是位于粘蛋白样结构域内的 0 连接糖基化基序。 TIM 同源物的 N 端富含 Cys 的区域具有约 40% 的序列同一性，而小鼠和人类直向同源物之间的序列同一性约为 60% (6)。所有 TIM 之间的结构相似性表明它们是由祖先基因通过连续的基因复制事件产生的。 TIM-1 多态性和预防哮喘和过敏的作用。 人类 TIM-1（HUGO 命名为 HAVCR1）在人类和猴子中具有高度多态性，如 它存在于小鼠体内，具有单核苷酸多态性 (SNP) 以及插入/缺失变异 主要发生在小鼠和人类的粘蛋白样结构域中（如前面的定义） 项目1）。我们还对 TIM-1 的插入/缺失变体进行了关联分析