T-cell immunoglobulin and mucin-domain-containing family (TIM family)

The T-cell immunoglobulin and mucin-domain-containing (TIM) family of phosphatidylserine receptors consists of three human members—TIM-1, TIM-3, and TIM-4—that play pivotal roles in regulating immune homeostasis and responses [1.1.1, 1.3.1]. These type I transmembrane glycoproteins are characterized by an N-terminal immunoglobulin-like domain that specifically binds to phosphatidylserine (PS) exposed on apoptotic cells, a process essential for efferocytosis and immune tolerance [1.3.2, 1.3.3]. TIM-1 (HAVCR1) is primarily expressed on Th2 cells and serves as a costimulatory molecule and a receptor for various enveloped viruses, such as Hepatitis A and Ebola [1.1.3, 1.4.2]. TIM-3 (HAVCR2) is a key inhibitory checkpoint receptor on Th1, Tc1, and NK cells, often overexpressed in the tumor microenvironment to facilitate immune evasion, making it a major target for cancer immunotherapy [1.2.1, 1.2.3]. TIM-4 (TIMD4) is expressed on antigen-presenting cells and is critical for the clearance of apoptotic debris to prevent autoimmunity [1.3.5, 1.4.1]. Therapeutic development focuses heavily on TIM-3 inhibitors like sabatolimab to restore anti-tumor immunity, while TIM-1 is explored as a target for antibody-drug conjugates in renal cancers and as a biomarker for kidney injury (KIM-1) [1.4.3, 1.4.4].

Other names

TIM proteinsHAVCR familyT-cell immunoglobulin and mucin domain proteinsPhosphatidylserine receptors

Immune checkpoint inhibition (TIM-3), antibody-drug conjugate mediated cytotoxicity (TIM-1), and blockade of viral entry.