MGP Database

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MGP004945

UniProt Annotations

Entry Information
Gene Nametumor necrosis factor receptor superfamily, member 21
Protein EntryTNR21_HUMAN
UniProt IDO75509
SpeciesHuman
Comments
Comment typeDescription
CautionIt is uncertain whether Met-1 or Met-25 is the initiator. {ECO:0000305}.
FunctionPromotes 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:0000269|PubMed:21725297, ECO:0000269|PubMed:22761420, ECO:0000269|PubMed:9714541}.
InductionUp-regulated by TNF. {ECO:0000269|PubMed:19654028, ECO:0000269|PubMed:23559013}.
InteractionP05067:APP; NbExp=3; IntAct=EBI-2313231, EBI-77613;
Sequence CautionSequence=AAH10241.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
SimilarityContains 1 death domain. {ECO:0000255|PROSITE- ProRule:PRU00064}.
SimilarityContains 4 TNFR-Cys repeats. {ECO:0000255|PROSITE- ProRule:PRU00206}.
Subcellular LocationCell membrane {ECO:0000269|PubMed:19654028}; Single-pass type I membrane protein {ECO:0000269|PubMed:19654028}.
SubunitInteracts with N-APP (By similarity). Associates with TRADD. Interacts with NGFR. {ECO:0000250, ECO:0000269|PubMed:23559013, ECO:0000269|PubMed:9714541}.
Tissue SpecificityDetected in fetal spinal cord and in brain neurons, with higher levels in brain from Alzheimer disease patients (at protein level). Highly expressed in heart, brain, placenta, pancreas, lymph node, thymus and prostate. Detected at lower levels in lung, skeletal muscle, kidney, testis, uterus, small intestine, colon, spleen, bone marrow and fetal liver. Very low levels were found in adult liver and peripheral blood leukocytes. {ECO:0000269|PubMed:21725297, ECO:0000269|PubMed:23559013, ECO:0000269|PubMed:9714541}.
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