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

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Foks, Amanda C; Engelbertsen, Daniel; Kuperwaser, Felicia et al. (2016) Blockade of Tim-1 and Tim-4 Enhances Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice. Arterioscler Thromb Vasc Biol 36:456-65
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Kroy, Daniela C; Ciuffreda, Donatella; Cooperrider, Jennifer H et al. (2014) Liver environment and HCV replication affect human T-cell phenotype and expression of inhibitory receptors. Gastroenterology 146:550-61
Xiao, Yanping; Yu, Sanhong; Zhu, Baogong et al. (2014) RGMb is a novel binding partner for PD-L2 and its engagement with PD-L2 promotes respiratory tolerance. J Exp Med 211:943-59
Recacha, Rosario; Jiménez, David; Tian, Li et al. (2014) Crystal structures of an ICAM-5 ectodomain fragment show electrostatic-based homophilic adhesions. Acta Crystallogr D Biol Crystallogr 70:1934-43
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