TOLLIP
Description
The TOLLIP (toll interacting protein) is a protein-coding gene located on chromosome 11.
TOLLIP (Toll interacting protein) is an inhibitory adaptor protein that in humans is encoded by the TOLLIP gene. It is a key component of the Toll-like receptor (TLR) pathway, which is part of the innate immune system. TLRs recognize molecular patterns of microbial pathogens, triggering an inflammatory immune response. TOLLIP interacts with cellular compartments like endosomes and lysosomes through its C2 domain, which binds to phosphoinositides. This interaction enables TOLLIP to coordinate communication between organelles, contributing to the fusion of endosomes, lysosomes, and autophagosomes. Mice lacking TOLLIP show increased susceptibility to inflammatory diseases, such as atherosclerosis and neurodegeneration. Variations in the TOLLIP gene have been linked to diseases such as tuberculosis and idiopathic pulmonary fibrosis.
TOLLIP is involved in the signaling pathways of IL-1 and Toll-like receptors, inhibiting cell activation by microbial products. It recruits IRAK1 to the IL-1 receptor complex and inhibits IRAK1 phosphorylation and kinase activity. TOLLIP connects the ubiquitin pathway to autophagy by acting as a ubiquitin-ATG8 family adapter, facilitating the autophagic clearance of ubiquitin conjugates. The TOLLIP-dependent selective autophagy pathway plays a crucial role in the clearance of cytotoxic polyQ protein aggregates. In a complex with TOM1, TOLLIP recruits ubiquitin-conjugated proteins to early endosomes and binds to phosphatidylinositol 3-phosphate (PtdIns(3)P).
TOLLIP is also known as IL-1RAcPIP.
Associated Diseases
- combined pulmonary fibrosis-emphysema syndrome
- acute kidney failure
- hyperinsulinemic hypoglycemia, familial, 4
- tuberculosis
