TIMD4
Description
The TIMD4 (T cell immunoglobulin and mucin domain containing 4) is a protein-coding gene located on chromosome 5.
TIMD4, also known as TIM-4, is a protein encoded by the TIMD4 gene in humans. It is located on chromosome 5q33.2. TIM-4 contains an IgV domain with an integrin-binding site and a unique metal-ion-dependent ligand-binding site for phosphatidylserine. It also contains a mucin domain with high levels of O-glycosylation. Unlike other TIM proteins, it lacks a tyrosine-phosphorylation motif in its intracellular tail domain. TIM-4 is expressed on antigen-presenting cells (APCs) such as dendritic cells and macrophages. It acts as a ligand for TIM-1 and a receptor for phosphatidylserine. Its phosphatidylserine binding is not involved in signaling, but rather acts as a tethering receptor. This phosphatidylserine binding plays a vital role in the removal of apoptotic cells. Additionally, recognizing phosphatidylserine contributes to controlling the adaptive immune system by clearing phosphatidylserine-expressing apoptotic T cells.
Phosphatidylserine receptor that plays various roles in immune responses, including the removal of apoptotic cells (efferocytosis) and T cell regulation. It controls T cell activation in a bimodal manner, decreasing naive T cell activation by inducing cell cycle arrest, while increasing the proliferation of activated T cells by activating AKT1 and ERK1/2 phosphorylations and subsequent signaling pathways. TIMD4 also promotes the engulfment of apoptotic cells or exogenous particles by binding to phosphatidylserine on apoptotic cells, thereby securing them to phagocytes. This process works in conjunction with other engulfment receptors, such as MERTK, which efficiently recognize and ingest apoptotic cells. Additionally, TIMD4 promotes autophagy by suppressing NLRP3 inflammasome activity through activation of the LKB1/PRKAA1 pathway in a phosphatidylserine-dependent manner.
TIMD4 is also known as SMUCKLER, TIM4.
