TNFAIP8L2
Domain
The central region was initially thought to constitute a DED (death effector) domain. However, 3D-structure data reveal a previously uncharacterized fold that is different from the predicted fold of a DED (death effector) domain. It consists of a large, hydrophobic central cavity that is poised for cofactor binding.
Function
Acts as a negative regulator of innate and adaptive immunity by maintaining immune homeostasis (PubMed:27043859). Plays a regulatory role in the Toll-like signaling pathway by determining the strength of LPS-induced signaling and gene expression (PubMed:32188758). Inhibits TCR-mediated T-cell activation and negatively regulate T-cell function to prevent hyperresponsiveness (By similarity). Inhibits also autolysosome formation via negatively modulating MTOR activation by interacting with RAC1 and promoting the disassociation of the RAC1-MTOR complex (PubMed:32460619). Plays an essential role in NK-cell biology by acting as a checkpoint and displaying an expression pattern correlating with NK-cell maturation process and by negatively regulating NK-cell maturation and antitumor immunity (By similarity). Mechanistically, suppresses IL-15-triggered mTOR activity in NK-cells (By similarity).
Post-translational modifications
Phosphorylated by TAK1/MAP3K7; this phosphorylation triggers association with BTRC and subsequent ubiquitination and degradation.
Ubiquitinated in a BTRC-depdent manner; leading to degradation mediated through the proteasome pathway.
Sequence Similarities
Belongs to the TNFAIP8 family. TNFAIP8L2 subfamily.
Tissue Specificity
Expressed in T-cells, B-cells, macrophages, neurons in the brain and brainstem, and stratified squamous epithelia of the esophagus, cervix and skin.
Cellular localization
- Cytoplasm
- Nucleus
- Lysosome
Alternative names
Tumor necrosis factor alpha-induced protein 8-like protein 2, TIPE2, TNF alpha-induced protein 8-like protein 2, TNFAIP8-like protein 2, Inflammation factor protein 20, TNFAIP8L2