MADD (gene)

MAP-kinase activating death domain
Identifiers
Symbols	MADD; DENN; FLJ35600; FLJ36300; IG20; KIAA0358; RAB3GEP
External IDs	OMIM: 603584 MGI: 2444672 HomoloGene: 14249 GeneCards: MADD Gene
Gene Ontology Molecular function • guanyl-nucleotide exchange factor activity • death receptor binding • protein binding • Rab guanyl-nucleotide exchange factor activity • protein kinase activator activity Cellular component • cytoplasm • plasma membrane • integral to membrane Biological process • activation of MAPK activity • positive regulation of protein phosphorylation • cell surface receptor linked signaling pathway • regulation of apoptosis • regulation of cell cycle Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8567	228355
Ensembl	ENSG00000110514	ENSMUSG00000040687
UniProt	Q8WXG6	n/a
RefSeq (mRNA)	NM_001135943.1	NM_145527
RefSeq (protein)	NP_001129415.1	NP_663502
Location (UCSC)	Chr 11: 47.29 – 47.36 Mb	Chr 2: 90.98 – 91.02 Mb
PubMed search	[1]	[2]

MAP kinase-activating death domain protein is an enzyme that in humans is encoded by the MADD gene.

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.

Further reading

• Chow VT, Lee SS (1997). "DENN, a novel human gene differentially expressed in normal and neoplastic cells". DNA Seq. 6 (5): 263–73. doi:10.3109/10425179609020873. PMID 8988362. 
• Nagase T, Ishikawa K, Nakajima D, et al. (1997). "Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro". DNA Res. 4 (2): 141–50. doi:10.1093/dnares/4.2.141. PMID 9205841. 
• Zhang Y, Zhou L, Miller CA (1998). "A splicing variant of a death domain protein that is regulated by a mitogen-activated kinase is a substrate for c-Jun N-terminal kinase in the human central nervous system". Proc. Natl. Acad. Sci. U.S.A. 95 (5): 2586–91. doi:10.1073/pnas.95.5.2586. PMC 19423. PMID 9482930. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=19423. 
• Suzuki Y, Ishihara D, Sasaki M, et al. (2000). "Statistical analysis of the 5' untranslated region of human mRNA using "Oligo-Capped" cDNA libraries". Genomics 64 (3): 286–97. doi:10.1006/geno.2000.6076. PMID 10756096. 
• Telliez JB, Bean KM, Lin LL (2000). "LRDD, a novel leucine rich repeat and death domain containing protein". Biochim. Biophys. Acta 1478 (2): 280–8. doi:10.1016/S0167-4838(00)00029-7. PMID 10825539. 
• Iwasaki K, Toyonaga R (2000). "The Rab3 GDP/GTP exchange factor homolog AEX-3 has a dual function in synaptic transmission". EMBO J. 19 (17): 4806–16. doi:10.1093/emboj/19.17.4806. PMC 302062. PMID 10970871. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=302062. 
• Al-Zoubi AM, Efimova EV, Kaithamana S, et al. (2002). "Contrasting effects of IG20 and its splice isoforms, MADD and DENN-SV, on tumor necrosis factor alpha-induced apoptosis and activation of caspase-8 and -3". J. Biol. Chem. 276 (50): 47202–11. doi:10.1074/jbc.M104835200. PMID 11577081. 
• Lim KM, Chow VT (2002). "Induction of marked apoptosis in mammalian cancer cell lines by antisense DNA treatment to abolish expression of DENN (differentially expressed in normal and neoplastic cells)". Mol. Carcinog. 35 (3): 110–26. doi:10.1002/mc.10082. PMID 12410563. 
• Nakayama M, Kikuno R, Ohara O (2003). "Protein–Protein Interactions Between Large Proteins: Two-Hybrid Screening Using a Functionally Classified Library Composed of Long cDNAs". Genome Res. 12 (11): 1773–84. doi:10.1101/gr.406902. PMC 187542. PMID 12421765. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=187542. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Efimova E, Martinez O, Lokshin A, et al. (2004). "IG20, a MADD splice variant, increases cell susceptibility to gamma-irradiation and induces soluble mediators that suppress tumor cell growth". Cancer Res. 63 (24): 8768–76. PMID 14695193. 
• Efimova EV, Al-Zoubi AM, Martinez O, et al. (2004). "IG20, in contrast to DENN-SV, (MADD splice variants) suppresses tumor cell survival, and enhances their susceptibility to apoptosis and cancer drugs". Oncogene 23 (5): 1076–87. doi:10.1038/sj.onc.1207210. PMID 14716293. 
• Lim KM, Yeo WS, Chow VT (2004). "Antisense abrogation of DENN expression induces apoptosis of leukemia cells in vitro, causes tumor regression in vivo and alters the transcription of genes involved in apoptosis and the cell cycle". Int. J. Cancer 109 (1): 24–37. doi:10.1002/ijc.11660. PMID 14735464. 
• Del Villar K, Miller CA (2004). "Down-regulation of DENN/MADD, a TNF receptor binding protein, correlates with neuronal cell death in Alzheimer's disease brain and hippocampal neurons". Proc. Natl. Acad. Sci. U.S.A. 101 (12): 4210–5. doi:10.1073/pnas.0307349101. PMC 384720. PMID 15007167. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=384720. 
• Xu Y, Kulkosky J, Acheampong E, et al. (2004). "HIV-1-mediated apoptosis of neuronal cells: Proximal molecular mechanisms of HIV-1-induced encephalopathy". Proc. Natl. Acad. Sci. U.S.A. 101 (18): 7070–5. doi:10.1073/pnas.0304859101. PMC 406467. PMID 15103018. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=406467. 
• Ramaswamy M, Efimova EV, Martinez O, et al. (2005). "IG20 (MADD splice variant-5), a proapoptotic protein, interacts with DR4/DR5 and enhances TRAIL-induced apoptosis by increasing recruitment of FADD and caspase-8 to the DISC". Oncogene 23 (36): 6083–94. doi:10.1038/sj.onc.1207804. PMID 15208670. 
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928. 
• Hu YF, Zhang HL, Cai T, et al. (2006). "The IA-2 interactome". Diabetologia 48 (12): 2576–81. doi:10.1007/s00125-005-0037-y. PMID 16273344.