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Tumor necrosis factor alpha (TNF-alpha) is a signaling molecule that interacts with one of two receptors on cells targeted for apoptosis. The apoptotic signal is transduced inside these cells by cytoplasmic adaptor proteins. The protein encoded by this gene is a death domain-containing adaptor protein that interacts with the death domain of TNF-alpha receptor 1 to activate mitogen-activated protein kinase (MAPK) and propagate the apoptotic signal. It is membrane-bound and expressed at a higher level in neoplastic cells than in normal cells. Several transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008],caution:The sequence shown here is derived from an Ensembl automatic analysis pipeline and should be considered as preliminary data.,function:Plays a significant role in regulating cell proliferation, survival and death through alternative mRNA splicing. Isoform 5 shows increased cell proliferation and isoform 2 shows decreased. Converts GDP-bound inactive form of RAB3A, RAB3C and RAB3D to the GTP-bound active forms. Component of the TNFRSF1A signaling complex: MADD links TNFRSF1A with MAP kinase activation. Plays an important regulatory role in physiological cell death (TNF-alpha-induced, caspase-mediated apoptosis); isoform 1 is susceptible to inducing apoptosis, isoform 5 is resistant and isoform 3 and isoform 4 have no effect.,miscellaneous:Overexpression of MADD activates the mitogen-activated protein (MAP) kinase extracellular signal-regulated kinase (ERK). Expression of the MADD death domain stimulates both the ERK and c-JUN N-terminal kinase MAP kinases and induces the phosphorylation of cytosolic phospholipase A2.,similarity:Belongs to the MADD family.,similarity:Contains 1 dDENN domain.,similarity:Contains 1 death domain.,similarity:Contains 1 DENN domain.,similarity:Contains 1 uDENN domain.,subunit:Interacts with the death domain of TNFRSF1A through its own death domain.,tissue specificity:Highly expressed in fetal brain and kidney; adult testis, ovary, brain and heart. Isoform 5 is constitutively expressed in all tissues. Isoform 7 is expressed in fetal liver and in several cancer cell lines.,

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