InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Tnfrsf21

Summary

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}.

Comments

Interactions

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]
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

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