• Purity

  >95%, 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. The ED    ₅₀ for this effect is 0.15-0.75 μg/mL.

• Source

  Human embryonic kidney cell, HEK293-derived

  Human TIM-4 (Glu25-Gln314) Accession # Q96H15	IEGRMD	Human IgG1 (Pro100-Lys330)
  N-terminus		C-terminus

• Accession #

• N-terminal Sequence    
  Analysis

  Glu25

• Predicted Molecular Mass

  58 kDa

• SDS-PAGE

  95-113 kDa, reducing conditions

Data Images

Background: TIM-4

TIM-4 (T cell; immunoglobulin; mucin-4), also known as SMUCKLER,  is a 60 kDa member of the TIM family of immune regulating proteins. TIMs are type I transmembrane proteins with one Ig-like V domain and one Ser/Thr-rich mucin domain (1). Mature human TIM-4 consists of a 290 aa extracellular domain (ECD), a 21 aa transmembrane segment, and a 43 aa cytoplasmic tail (2). Structurally, TIM-4 is distinguished from other TIMs by the presence of an RGD motif in its Ig domain and the lack of a site for tyrosine phosphorylation in its cytoplasmic tail. Within the ECD human TIM-4 shares 45% aa sequence identity with mouse and rat TIM-4. TIM-4 is expressed by macrophages and mature dendritic cells but not by lymphocytes (2, 3). It binds specifically to TIM-1 which is also the cellular receptor for hepatitis A virus and has been implicated in the development of asthma (3-5). Among hematopoietic cells, TIM-1 is expressed on activated B and T cells, preferentially in the Th2 subset of CD4  ⁺ T cells (3, 6). The interaction of TIM-4 with TIM-1 induces co-stimulatory and hyperproliferative signals in T cells (3). TIM-4 also binds to phosphatidylserine (PS) on the surface of apoptotic cells (7). It enhances the clearance of apoptotic cells including T cells in the contraction phase of immune responses, apoptotic macrophages that accumulate in atherosclerosis, and dying neurons in the brain (7-10). TIM-4 is upregulated on some tumor cells and tumor-associated myeloid cells where it binds Integrin alpha V beta 3, contributes to tumor progression, and inhibits tumor-specific cellular immunity (11, 12).

• References:

1. Fang, X.Y. et al. (2015) Autoimmunity 48:189.

2. Shakhov, A.N. et al. (2004) Eur. J. Immunol. 34:494.

3. Meyers, J.H. et al. (2005) Nat. Immunol. 6:455.

4. Feigelstock, D. et al. (1998) J. Virol. 72:6621.

5. McIntire, J.J. et al. (2001) Nat. Immunol. 2:1109.

6. Khademi, M. et al. (2004) J. Immunol. 172:7169.

7. Kobayashi, N. et al. (2007) Immunity 27:927.

8. Albacker, L.A. et al. (2010) J. Immunol. 185:6839.

9. Mazaheri, F. et al. (2014) Nat. Commun. 5:4046.

10. Foks, A.C. et al. (2016) Arterioscler. Thromb. Vasc. Biol. 36:456.

11. Zhang, Q. et al. (2015) Br. J. Cancer 113:1484.

12. Baghdadi, M. et al. (2013) Immunity 39:1070.

• Long Name:

  T Cell Immunoglobulin Mucin-4

• Entrez Gene IDs:

  91937 (Human); 276891 (Mouse); 102140672 (Cynomolgus Monkey)

• Alternate Names:

  FLJ27515; Smuckler; T-cell immunoglobulin and mucin domain containing 4; T-cell immunoglobulin and mucin domain-containing protein 4; T-cell membrane protein 4; TIM4; TIM-4; TIMD4; TIMD-4