MADD Antibody – Rabbit

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]

MADD: a guanine nucleotide exchange factor (GEF) that activates RAB3A/C/D. A GEF for Rab27A/B in melanocytes and during isoproterenol (IPR)-stimulated amylase release from rat parotid acinar cells. Plays a significant role in regulating cell proliferation, survival and death through alternatively spliced isoforms. 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). Interacts with the death domain of TNFRSF1A through its own death domain. Highly expressed in fetal brain and kidney, adult testis, ovary, brain and heart. 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. Isoform 1 is pro-apoptotic, isoform 5 is anti-apoptotic and isoform 3 and isoform 4 have no effect. Isoform 5 is constitutively expressed in all tissues. Isoform 7 is expressed in fetal liver and in several cancer cell lines. Isoform 5 is associated with increased cell proliferation and isoform 2 with decreased proliferation. Belongs to the MADD family. Seven isoforms of the human protein are produced by alternative splicing.

Protein type: Adaptor/scaffold; GEFs; GEFs, Rab; Membrane protein, integral

Chromosomal Location of Human Ortholog: 11p11.2

Cellular Component: cytoplasm; integral to membrane; plasma membrane

Molecular Function: protein binding; death receptor binding; Rab guanyl-nucleotide exchange factor activity; protein kinase activator activity

Biological Process: regulation of apoptosis; regulation of Rab protein signal transduction; cell surface receptor linked signal transduction; regulation of cell cycle; activation of MAPK activity