TIM-1 (Tcell-immunoglobulin-mucin; also KIM-1 and HAVcr-1) is a 100 kDa, type I transmembrane glycoprotein member of the TIM family of immunoglobulin superfamily molecules (1-3). This gene family is involved in the regulation of Th1 and Th2-cell-mediated immunity. Human TIM-1 is synthesized as a 359 amino acid (aa) precursor that contains a 20 aa signal sequence, a 270 aa extracellular domain (ECD), a 21 aa transmembrane segment and a 48 aa cytoplasmic domain (4-6). The ECD contains oneV-type Ig-like domain and a mucin region characterized by multiple PTTTTL motifs. The mucin region undergoes extensive O-linked glycosylation. The TIM-1 gene is highly polymorphic and undergoes alternate splicing (1). For instance, the presence of a six aa sequence (MTTTVP) at position #137 of the mature molecule is associated with protection from atopy in people with a history of hepatitis A (7, 8). There are two cytoplasmic alternate splice forms of
TIM‑1. One is a long (359 aa) kidney form termed TIM-1b, and one is a short (334 aa) liver form termed TIM-1a. Both are identical through the first 323 aa of their precursors. TIM-1b contains a tyrosine phosphorylation motif that is not present in 1a (6). TIM-1 is also known to circulate as a soluble form. Constitutive cleavage by an undefined MMP (possibly ADAM33) releases an 85 - 90 kDa soluble molecule (6). The ECD of human TIM-1 is 50% and 43% aa identical to mouse and canine TIM-1 ECD, respectively. The only two reported ligands for TIM-1 are TIM-4 and the hepatitis A virus (4, 9). However, others are believed to exist, and based on the ligand for TIM-3, one may well be an S-type lectin (10). TIM-1 ligation induces T cell proliferation and promotes cytokine production (1, 10).

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