Nanoparticle Detection of Urinary Markers for Point-of-Care Diagnosis of Kidney Injury.
Authors: Chung H, Pellegrini K, Chung J, Wanigasuriya K, Jayawardene I, Lee K, Lee H, Vaidya V, Weissleder R
PLoS ONE, 2015;10(7):e0133417.
Species: Human
Sample Type: Urine
Application: ELISA Development
Characterizing functional domains for TIM-mediated enveloped virus entry.
Authors: Moller-Tank S, Albritton L, Rennert P, Maury W
J Virol, 2014;88(12):6702-13.
Species: Human
Sample Type: Whole Cells
Application: Flow

TIM-1 (T cell-immunoglobulin-mucin; also known as KIM-1 and HAVCR) 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).

1. Meyers, J.H. et al. (2005) Trends Mol. Med. 11:1471.
2. Kuchroo, V.K. et al. (2003) Nat. Rev. Immunol. 3:454.
3. Mariat, C. et al. (2005) Phil. Trans. R. Soc. B 360:1681.
4. Feigelstock, D. et al. (1998) J. Virol. 72:6621.
5. Ichimura, T. et al. (1998) J. Biol. Chem. 273:4135.
6. Bailly, V. et al. (2002) J. Biol. Chem. 277:39739.
7. Umetsu, D.T. et al. (2005) J. Pediatr. Gastroenterol. Nutr. 40:S43.
8. Gao, P-S. et al. (2005) J. Allergy Clin. Immunol. 115:982.
9. Zhu, C. et al. (2005) Nat. Immunol. 6:1245.
10. Meyers, J.H. et al. (2005) Nat. Immunol. 6:455.