MAP kinase-activating death domain protein is an enzyme that in humans is encoded by the MADD gene.[5][6][7] MADD is one out of four of the splice variants of the human IG20 (insulinoma-glucagonoma clone 20) gene[8] which is located on human chromosome 11. [9]

MADD
Identifiers
AliasesMADD, DENN, IG20, RAB3GEP, MAP kinase activating death domain
External IDsOMIM: 603584; MGI: 2444672; HomoloGene: 14249; GeneCards: MADD; OMA:MADD - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)

NP_001171190
NP_001171191
NP_663502

Location (UCSC)Chr 11: 47.27 – 47.33 MbChr 2: 91.14 – 91.18 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[7] MADD is mostly expressed in the cell membrane with some cytoplasmic expression in human cells.[10]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000110514Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000040687Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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.
  6. ^ 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/g98-050. PMID 9796103.
  7. ^ a b "Entrez Gene: MADD MAP-kinase activating death domain".
  8. ^ Al-Zoubi, A. M., Efimova, E. V., Kaithamana, S., Martinez, O., El-Idrissi, M.el-A., Dogan, R. E., & Prabhakar, B. S. (2001). 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. The Journal of biological chemistry, 276(50), 47202–47211. https://doi.org/10.1074/jbc.M104835200
  9. ^ Efimova, E. V., Al-Zoubi, A. M., Martinez, O., Kaithamana, S., Lu, S., Arima, T., & Prabhakar, B. S. (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), 1076–1087. https://doi.org/10.1038/sj.onc.1207210
  10. ^ Chow, V. T., & Lee, S. S. (1996). DENN, a novel human gene differentially expressed in normal and neoplastic cells. DNA sequence : the journal of DNA sequencing and mapping, 6(5), 263–273. https://doi.org/10.3109/10425179609020873

Further reading

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