Mus musculus Protein: Tnfrsf21
InnateDB Protein IDBP-184037.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol Tnfrsf21
Protein Name tumor necrosis factor receptor superfamily, member 21
Synonyms AA959878; DR6; R74815; TR7;
Species Mus musculus
Ensembl Protein ENSMUSP00000024708
InnateDB Gene IDBG-184035 (Tnfrsf21)
Protein Structure
UniProt Annotation
Function Promotes apoptosis, possibly via a pathway that involves the activation of NF-kappa-B. Can also promote apoptosis mediated by BAX and by the release of cytochrome c from the mitochondria into the cytoplasm. 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). Negatively regulates oligodendrocyte survival, maturation and myelination. 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. Negatively regulates T-cell responses and the release of cytokines such as IL4, IL5, IL10, IL13 and IFNG by Th2 cells. Negatively regulates the production of IgG, IgM and IgM in response to antigens. May inhibit the activation of JNK in response to T-cell stimulation. {ECO:0000269PubMed:11485735, ECO:0000269PubMed:11714751, ECO:0000269PubMed:12515813, ECO:0000269PubMed:19225519, ECO:0000269PubMed:21725297, ECO:0000269PubMed:23559013}.
Subcellular Localization Cell membrane {ECO:0000269PubMed:12515813}; Single-pass type I membrane protein {ECO:0000269PubMed:12515813}.
Disease Associations
Tissue Specificity Detected in spleen B-cells (at protein level). Ubiquitous. Highly expressed in adult spleen, thymus, testis, prostate, ovary, small intestine, colon, brain, lung and kidney, and in fetal brain, liver and lung. Detected at lower levels in adult peripheral blood leukocytes, lung, and in fetal muscle, heart, kidney, small intestine and skin. Detected in T-cells, B- cells and monocytes. In T-cells expression is highest in Th0 cells, intermediate in Th2 cells and lower in Th1 cells. Expressed at low levels in proliferating progenitors in the spinal cord, but is highly expressed by differentiating neurons within the spinal cord and adjacent dorsal root ganglia. Expressed by developing neurons as they differentiate and enter a pro-apoptotic state. Expressed by both cell bodies and axons. {ECO:0000269PubMed:11485735, ECO:0000269PubMed:11714751, ECO:0000269PubMed:12515813, ECO:0000269PubMed:19225519}.
Number of Interactions This gene and/or its encoded proteins are associated with 3 experimentally validated interaction(s) in this database.
They are also associated with 6 interaction(s) predicted by orthology.
Experimentally validated
Total 3 [view]
Protein-Protein 2 [view]
Protein-DNA 0
Protein-RNA 1 [view]
Predicted by orthology
Total 6 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0005515 protein binding
Biological Process
GO:0001783 B cell apoptotic process
GO:0002250 adaptive immune response
GO:0006915 apoptotic process
GO:0006959 humoral immune response
GO:0007165 signal transduction
GO:0030889 negative regulation of B cell proliferation
GO:0031642 negative regulation of myelination
GO:0042130 negative regulation of T cell proliferation
GO:0042552 myelination
GO:0048713 regulation of oligodendrocyte differentiation
GO:0050852 T cell receptor signaling pathway
GO:0051402 neuron apoptotic process
GO:0071356 cellular response to tumor necrosis factor
GO:0097252 oligodendrocyte apoptotic process
GO:2000663 negative regulation of interleukin-5 secretion
GO:2000666 negative regulation of interleukin-13 secretion
GO:2001180 negative regulation of interleukin-10 secretion
Cellular Component
GO:0005737 cytoplasm
GO:0005887 integral component of plasma membrane
GO:0016021 integral component of membrane
GO:0030424 axon
GO:0031226 intrinsic component of plasma membrane
Protein Structure and Domains
PDB ID MGI:2151075
InterPro IPR000488 Death domain
IPR001368 TNFR/NGFR cysteine-rich region
IPR011029 Death-like domain
IPR022330 Tumour necrosis factor receptor 21
PFAM PF00531
Post-translational Modifications
SwissProt Q9EPU5
PhosphoSite PhosphoSite-Q9EPU5
UniProt Splice Variant
Entrez Gene 94185
UniGene Mm.400930
RefSeq NP_848704
MGI Symbol Tnfrsf21
EMBL AF322069 AK043823 AK134704 AY043489 BC016420
GenPept AAG38115 AAH16420 AAK74193 BAC31664 BAE22249