• Purity

  >90%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie? Blue Staining.

• Endotoxin Level

  <0.10 EU per 1 μg of the protein by the LAL method.  

• Activity

  Measured by its ability to inhibit anti-CD3-induced proliferation of stimulated human T cells. Human T lymphocytes cultured for 72 hours with PHA were incubated for an additional 3 days in 96 well plates coated with 500 ng/mL    
  anti-CD3 and Recombinant Human TIM?1/KIM?1/HAVCR.    
  The ED    ₅₀ for this effect is 0.2-0.8 μg/mL.    
     Optimal dilutions should be determined by each laboratory for each application.  

• Source

  Mouse myeloma cell line, NS0-derived Ser21-Thr288, with a C-terminal 6-His tag

• Accession #

• N-terminal Sequence    
  Analysis

  Ser21

• Predicted Molecular Mass

  29.6 kDa

• SDS-PAGE

  85-105 kDa, reducing conditions

Background: TIM-1/KIM-1/HAVCR

TIM-1 (T cell-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 one V-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).

• References:

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.

• Long Name:

  T Cell Immunoglobulin Mucin-1

• Entrez Gene IDs:

  26762 (Human); 171283 (Mouse); 286934 (Rat); 102141332 (Cynomolgus Monkey)

• Alternate Names:

  CD365; HAVCR1; HAVCR-1; HAVCRT cell immunoglobin domain and mucin domain protein 1; hepatitis A virus cellular receptor 1; Kidney injury molecule 1; KIM1; KIM-1; T-cell immunoglobulin and mucin domain-containing protein 1; TIM1; TIM-1; TIM-1TIM; TIM1TIMD-1; TIMD1T-cell membrane protein 1