TNFAIP8L2
Description
The TNFAIP8L2 (TNF alpha induced protein 8 like 2) is a protein-coding gene located on chromosome 1.
TNF alpha induced protein 8 like 2 (TNFAIP8L2), also known as TIPE2, is a protein that in humans is encoded by the TNFAIP8L2 gene. It is preferentially expressed in human myeloid cell types and serves as an immune checkpoint regulator of inflammation and metabolism.
== Function == TNFAIP8L2 is a member of the TNFAIP8 (tumor necrosis factor-Ξ±-induced protein 8, or TIPE) family that function as transfer proteins for the second messenger lipids PIP2 and PIP3. The other three family members are TNFAIP8, TNFAIP8L1 and TNFAIP8L3.
== Structure == The crystal structure of TIPE2 reveals that it contains a large, hydrophobic central cavity that is poised for cofactor binding.
== Clinical significance == TIPE2 acts as a negative regulator of the immune system. It is down-regulated in patients with infectious and autoimmune diseases and also acts as a tumor suppressor in several types of cancer. Its knockout leads to leukocytosis and systemic inflammatory disorders in mice.
TNFAIP8L2 acts as a negative regulator of both innate and adaptive immunity, maintaining immune homeostasis (PubMed:27043859). It plays a regulatory role in the Toll-like signaling pathway by controlling the strength of LPS-induced signaling and gene expression (PubMed:32188758). TNFAIP8L2 also inhibits TCR-mediated T-cell activation, negatively regulates T-cell function to prevent hyperresponsiveness (By similarity), and inhibits autolysosome formation by negatively modulating MTOR activation through interaction with RAC1 and promoting the disassociation of the RAC1-MTOR complex (PubMed:32460619). This protein is essential for NK-cell biology, serving as a checkpoint with an expression pattern linked to NK-cell maturation. It negatively regulates NK-cell maturation and antitumor immunity (By similarity). Mechanistically, it suppresses IL-15-triggered mTOR activity in NK-cells (By similarity). {ECO:0000250|UniProtKB:Q9D8Y7, ECO:0000269|PubMed:27043859, ECO:0000269|PubMed:32188758, ECO:0000269|PubMed:32460619}
TNFAIP8L2 is also known as TIPE2.
Associated Diseases
- type 2 diabetes mellitus
- gastrointestinal stromal tumor
- laryngotracheoesophageal cleft
- common variable immunodeficiency
- isolated agammaglobulinemia
- T-B+ severe combined immunodeficiency due to JAK3 deficiency
