TNFRSF21

Description

The TNFRSF21 (TNF receptor superfamily member 21) is a protein-coding gene located on chromosome 6.

TNFRSF21, also known as Death receptor 6 (DR6), is a cell surface receptor belonging to the tumor necrosis factor receptor superfamily. It activates the JNK and NF-κB pathways. TNFRSF21 is mainly expressed in the thymus, spleen, and white blood cells. The gene encoding TNFRSF21 is 78,450 bases long and located on chromosome 6. It is transcribed into a 655 amino acid chain weighing 71.8 kDa. Post-transcriptional modifications include glycosylation on asparagines at amino acid positions 82, 141, 252, 257, 278, and 289. TNFRSF21 is a member of the TNF-receptor superfamily. This receptor activates NF-κB and MAPK8/JNK, and induces cell apoptosis. Through its death domain, TNFRSF21 interacts with the TRADD protein, which serves as an adaptor mediating signal transduction of TNF-receptors. Knockout studies in mice suggest that TNFRSF21 plays a role in T helper cell activation, and may be involved in inflammation and immune regulation. TNFRSF21 is an alpha-helical integral membrane receptor protein that shows evidence of involvement in inhibiting blood vessel formation on tumors, potentially allowing them to grow larger.

TNFRSF21 promotes apoptosis, possibly via a pathway that involves the activation of NF-kappa-B. It can also promote apoptosis mediated by BAX and by the release of cytochrome c from the mitochondria into the cytoplasm. TNFRSF21 plays a role in neuronal apoptosis, including apoptosis in response to amyloid peptides derived from APP, and is required for both normal cell body death and axonal pruning. Trophic-factor deprivation triggers the cleavage of surface APP by beta-secretase to release sAPP-beta, which is further cleaved to release an N-terminal fragment of APP (N-APP). N-APP binds TNFRSF21; this triggers caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6). TNFRSF21 negatively regulates oligodendrocyte survival, maturation, and myelination. It plays a role in signaling cascades triggered by stimulation of T-cell receptors, in the adaptive immune response and in the regulation of T-cell differentiation and proliferation. TNFRSF21 negatively regulates T-cell responses and the release of cytokines such as IL4, IL5, IL10, IL13, and IFNG by Th2 cells. It negatively regulates the production of IgG, IgM, and IgM in response to antigens. TNFRSF21 may inhibit the activation of JNK in response to T-cell stimulation. It also acts as a regulator of pyroptosis: it recruits CASP8 in response to reactive oxygen species (ROS) and subsequent oxidation, leading to activation of GSDMC (PubMed:34012073).

TNFRSF21 is also known as BM-018, CD358, DR6.

Associated Diseases

WES Whole Exome Sequencing