Rat TIM-1/KIM-1/HAVCR Antibody

TIM-1, also known as KIM-1 (Kidney-injury molecule-1) and HAVCR, is a 50-80 kDa, variably glycosylated, type I transmembrane glycoprotein that is a member of the TIM family of immunoglobulin superfamily molecules (1‑5). This gene family is involved in the regulation of Th1 and Th2-cell-mediated immunity. In mouse, there are eight known TIM/KIM genes (# 1‑8) vs. only three genes in human (# 1, 3, 4) (1, 2, 5). It is unknown if the rat genome exactly parallels that of mouse. Rat TIM-1 is synthesized as a 307 amino acid (aa) precursor that contains a 21 aa signal sequence, a 214 aa extracellular domain (ECD), a 21 aa transmembrane segment and a 51 aa cytoplasmic domain (4). The ECD contains one V-type Ig-like domain and a mucin region characterized by multiple Thr-Ser-Pro motifs. The mucin region may undergo extensive O-linked glycosylation. The mouse TIM-1 gene is highly polymorphic and this may be reflected in rat (4, 6). In human, TIM-1 is known to circulate as a soluble form. It undergoes constitutive cleavage by an undefined MMP, releasing an 85 kDa soluble molecule (7). A similar process has now been described in rat (8). The ECD of rat TIM-1 is 50% and 81% aa identical to human and mouse TIM-1 ECD, respectively. The only two reported ligands for TIM-1 are TIM-4 and the hepatitis A virus (9, 10). However, others are believed to exist, and based on the ligand for TIM-3, one might be an S-type lectin (11). TIM-1 is found on CD4⁺ T cells and proximal renal tubular cells (4, 12). TIM-1 ligation induces T cell proliferation and promotes cytokine production (1, 11). In particular, it induces IL-4 production, and requires the TIM-1 cytoplasmic tyrosine phosphorylation motif (12). Alternatively, TIM-1 activation of TIM-4 induces cell cycle arrest (13).