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: 8831796
• 负责人: Gordon James Freeman
• 金额: $ 4.34万
• 依托单位: DANA-FARBER CANCER INST
• 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
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8831796
• 关键词: TIM; recognition; phosphatidylserine; regulates; innate

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（TIM-1、TIM和TIM 4）组成（5）。所有的老鼠和 人TIM基因编码1型膜蛋白，由N-末端富含Cys的 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（图1）TIM-1、TIM-2和TIM-3的胞内尾区含有预测的酪氨酸磷酸化基序，但TIM-4没有，这表明这些TIM参与跨膜信号传导。尽管TIM-3仅具有三个预测的糖基化位点，但人TIM-1具有60个，其主要是位于粘蛋白样结构域内的0-连接的糖基化基序。TIM同源物的N-末端富含Cys的区域具有约40%的序列同一性，而小鼠和人直系同源物之间的序列同一性约为60%（6）。所有的TIM之间的结构相似性表明，他们从一个祖先的基因连续的基因复制事件。 TIM-1多态性与哮喘和过敏的保护作用 人TIM-1（HUGO命名为HAVCR 1）在人和猴中高度多态， 在小鼠中，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的粘蛋白样结构域中（如前所述 项目1）。我们还进行了TIM-1插入/缺失变异体在