MADD (gene)

MADD
Identifiers
Aliases	MADD, DENN, IG20, RAB3GEP, MAP kinase activating death domain
External IDs	MGI: 2444672 HomoloGene: 14249 GeneCards: MADD
Gene ontology Molecular function • death receptor binding • guanyl-nucleotide exchange factor activity • Rab guanyl-nucleotide exchange factor activity • protein kinase activator activity • protein binding Cellular component • cytoplasm • integral component of membrane • cytosol • membrane • plasma membrane Biological process • regulation of apoptotic process • regulation of extrinsic apoptotic signaling pathway • execution phase of apoptosis • regulation of tumor necrosis factor-mediated signaling pathway • regulation of Rab protein signal transduction • regulation of cell cycle • cell surface receptor signaling pathway • activation of MAPK activity • regulation of extrinsic apoptotic signaling pathway via death domain receptors • apoptotic process • positive regulation of GTPase activity Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8567	228355
Ensembl	ENSG00000110514	ENSMUSG00000040687
UniProt	Q8WXG6	Q80U28
RefSeq (mRNA)	NM_001135943 NM_001135944 NM_003682 NM_130470 NM_130471 NM_130472 NM_130473 NM_130474 NM_130475 NM_130476	NM_001177719 NM_001177720 NM_001177721 NM_001177722 NM_001177723 NM_001177724 NM_001177725 NM_001177726 NM_001177727 NM_001177728 NM_001177729 NM_145527
RefSeq (protein)	NP_001129415.1 NP_001129416.1 NP_003673.3 NP_569826.2 NP_569827.2 NP_569828.2 NP_569829.2 NP_569830.2 NP_569831.1 NP_569832.2	NP_001171190.1 NP_001171191.1 NP_663502.3
Location (UCSC)	Chr 11: 47.27 – 47.33 Mb	Chr 2: 91.14 – 91.18 Mb
PubMed search	[1]	[2]
Wikidata

View/Edit Human

View/Edit Mouse

MAP kinase-activating death domain protein is an enzyme that in humans is encoded by the MADD gene.^[3][4][5]

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.^[5]

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. Schievella AR, Chen JH, Graham JR, Lin LL (Jun 1997). "MADD, a novel death domain protein that interacts with the type 1 tumor necrosis factor receptor and activates mitogen-activated protein kinase". J Biol Chem. 272 (18): 12069–75. doi:10.1074/jbc.272.18.12069. PMID 9115275.
4. Chow VT, Lim KM, Lim D (Nov 1998). "The human DENN gene: genomic organization, alternative splicing, and localization to chromosome 11p11.21-p11.22". Genome. 41 (4): 543–52. doi:10.1139/gen-41-4-543. PMID 9796103.
5. "Entrez Gene: MADD MAP-kinase activating death domain".

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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.