|Detection of TIM‑4 in HEK Human Cell Line Transfected with Human TIM-4 and eGFP by Flow Cytometry. HEK293 human embryonic kidney cell line transfected with human TIM-4 and eGFP was stained with and either (A) Mouse Anti-Human TIM‑4 Alexa Fluor® 647‑conjugated Monoclonal Antibody (Catalog # FAB2929R) or (B) Mouse IgG1 Alexa Fluor 647 Isotype Control (Catalog # IC002R). View our protocol for Staining Membrane-associated Proteins.|
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 - 3). The human TIM-4 cDNA encodes a 378 amino acid (aa) precursor that includes a 24 aa signal sequence, a 290 aa extracellular domain (ECD), a 21 aa transmembrane segment, and a 43 aa cytoplasmic tail (4). 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. The mucin domain in TIM-4 is larger than in TIM-1 or TIM-3. Within the ECD, human TIM-4 shares 35% and 23% aa sequence identity with TIM-1 and TIM-3, respectively. A TIM-2 ortholog has not been identified in human. The ECD of human TIM-4 shares 45% aa sequence identity with that of mouse and rat TIM-4. TIM-4 is expressed by macrophages and mature dendritic cells but not by lymphocytes (4, 5). TIM-4 binds specifically to TIM-1 which is also the cellular receptor for the hepatitis A virus, and has been implicated in the development of asthma (5 - 7). Among hematopoietic cells, TIM-1 is expressed on activated B and T cells, preferentially in the Th2 subset of CD4+ T cells (5, 8). The interaction of TIM-4 with TIM-1 induces costimulatory and hyperproliferative signals in T cells (5).
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