Hmdb loader
Identification
HMDB Protein ID HMDBP08478
Secondary Accession Numbers
  • 14190
Name MAP kinase-activating death domain protein
Synonyms
  1. Differentially expressed in normal and neoplastic cells
  2. Insulinoma glucagonoma clone 20
  3. Rab3 GDP/GTP exchange factor
Gene Name MADD
Protein Type Unknown
Biological Properties
General Function Involved in death receptor binding
Specific 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
Pathways Not Available
Reactions Not Available
GO Classification Not Available
Cellular Location
  1. Membrane
  2. Multi-pass membrane protein
Gene Properties
Chromosome Location Chromosome:1
Locus 11p11.2
SNPs MADD
Gene Sequence
>4944 bp
ATGGTGCAAAAGAAGAAGTTCTGTCCTCGGTTACTTGACTATCTAGTGATCGTAGGGGCC
AGGCACCCGAGCAGTGATAGCGTGGCCCAGACTCCTGAATTGCTACGGCGATACCCCTTG
GAGGATCACACTGAGTTTCCCCTGCCCCCAGATGTAGTGTTCTTCTGCCAGCCCGAGGGC
TGCCTGAGCGTGCGGCAGCGGCGCATGAGCCTTCGGGATGATACCTCTTTTGTCTTCACC
CTCACTGACAAGGACACTGGAGTCACGCGATATGGCATCTGTGTTAACTTCTACCGCTCC
TTCCAAAAGCGAATCTCTAAGGAGAAGGGGGAAGGTGGGGCAGGGTCCCGTGGGAAGGAA
GGAACCCATGCCACCTGTGCCTCAGAAGAGGGTGGCACTGAGAGCTCAGAGAGTGGCTCA
TCCCTGCAGCCTCTCAGTGCTGACTCTACCCCTGATGTGAACCAGTCTCCTCGGGGCAAA
CGCCGGGCCAAGGCGGGGAGCCGCTCCCGCAACAGTACTCTCACGTCCCTGTGCGTGCTC
AGCCACTACCCTTTCTTCTCCACCTTCCGAGAGTGTTTGTATACTCTCAAGCGCCTGGTG
GACTGCTGTAGTGAGCGCCTTCTGGGCAAGAAACTGGGCATCCCTCGAGGCGTACAAAGG
GACACCATGTGGCGGATCTTTACTGGATCGCTGCTGGTAGAGGAGAAGTCAAGTGCCCTT
CTGCATGACCTTCGAGAGATTGAGGCCTGGATCTATCGATTGCTGCGCTCCCCAGTACCC
GTCTCTGGGCAGAAGCGAGTAGACATCGAGGTCCTACCCCAAGAGCTCCAGCCAGCTCTG
ACCTTTGCTCTTCCAGACCCATCTCGATTCACCCTAGTGGATTTCCCACTGCACCTTCCC
TTGGAACTTCTAGGTGTGGACGCCTGTCTCCAGGTGCTAACCTGCATTCTGTTAGAGCAC
AAGGTGGTGCTACAGTCCCGAGACTACAATGCACTCTCCATGTCTGTGATGGCATTCGTG
GCAATGATCTACCCACTGGAGTATATGTTTCCTGTCATCCCGCTGCTACCCACCTGCATG
GCATCAGCAGAGCAGCTGCTGTTGGCTCCAACCCCGTACATCATTGGGGTTCCTGCCAGC
TTCTTCCTCTACAAACTGGACTTCAAAATGCCTGATGATGTATGGCTAGTGGATCTGGAC
AGCAATAGGGTGATTGCCCCCACCAATGCAGAAGTGCTGCCTATCCTGCCAGAACCAGAA
TCACTAGAGCTGAAAAAGCATTTAAAGCAGGCCTTGGCCAGCATGAGTCTCAACACCCAG
CCCATCCTCAATCTGGAGAAATTTCATGAGGGCCAGGAGATCCCCCTTCTCTTGGGAAGG
CCTTCTAATGACCTGCAGTCCACACCGTCCACTGAATTCAACCCACTCATCTATGGCAAT
GATGTGGATTCTGTGGATGTTGCAACCAGGGTTGCCATGGTACGGTTCTTCAATTCCGCC
AACGTGCTGCAGGGATTTCAGATGCACACGCGTACCCTGCGCCTCTTTCCTCGGCCTGTG
GTAGCTTTTCAAGCTGGCTCCTTTCTAGCCTCACGTCCCCGGCAGACTCCTTTTGCCGAG
AAATTGGCCAGGACTCAGGCTGTGGAGTACTTTGGGGAATGGATCCTTAACCCCACCAAC
TATGCCTTTCAGCGAATTCACAACAATATGTTTGATCCAGCCCTGATTGGTGACAAGCCA
AAGTGGTATGCTCATCAGCTGCAGCCTATCCACTATCGCGTCTATGACAGCAATTCCCAG
CTGGCTGAGGCCCTGAGTGTACCACCAGAGCGGGACTCTGACTCCGAACCTACTGATGAT
AGTGGCAGTGATAGTATGGATTATGACGATTCAAGCTCTTCTTACTCCTCCCTTGGTGAC
TTTGTCAGTGAAATGATGAAATGTGACATTAATGGTGATACTCCCAATGTGGACCCTCTG
ACACATGCAGCACTGGGGGATGCCAGCGAGGTGGAGATTGACGAGCTGCAGAATCAGAAG
GAAGCAGAAGAGCCTGGCCCAGACAGTGAGAACTCTCAGGAAAACCCCCCACTGCGCTCC
AGCTCTAGCACCACAGCCAGCAGCAGCCCCAGCACTGTCATCCACGGAGCCAACTCTGAA
CCTGCTGACTCTACGGAGATGGATGATAAGGCAGCAGTAGGCGTCTCCAAGCCCCTCCCT
TCCGTGCCTCCCAGCATTGGCAAATCGAACGTGGACAGACGTCAGGCAGAAATTGGAGAG
GGGTCAGTGCGCCGGCGAATCTATGACAATCCATACTTCGAGCCCCAATATGGCTTTCCC
CCTGAGGAAGATGAGGATGAGCAGGGGGAAAGTTACACTCCCCGATTCAGCCAACATGTC
AGTGGCAATCGGGCTCAAAAGCTGCTGCGGCCCAACAGCTTGAGACTGGCAAGTGACTCA
GATGCAGAGTCAGACTCTCGGGCAAGCTCTCCCAACTCCACCGTCTCCAACACCAGCACC
GAGGGCTTCGGGGGCATCATGTCTTTTGCCAGCAGCCTCTATCGGAACCACAGTACCAGC
TTCAGTCTTTCAAACCTCACACTGCCCACCAAAGGTGCCCGAGAGAAGGCCACGCCCTTC
CCCAGTCTGAAAGTATTTGGGCTAAATACTCTAATGGAGATTGTTACTGAAGCCGGCCCC
GGGAGTGGTGAAGGAAACAGGAGGGCGTTAGTGGATCAGAAGTCATCTGTCATTAAACAC
AGCCCAACAGTGAAAAGAGAACCTCCATCACCCCAGGGTCGATCCAGCAATTCTAGTGAG
AACCAGCAGTTCCTGAAGGAGGTGGTGCACAGCGTGCTGGACGGCCAGGGAGTTGGCTGG
CTCAACATGAAAAAGGTGCGCCGGCTGCTGGAGAGCGAGCAGCTGCGAGTCTTTGTCCTG
AGCAAGCTGAACCGCATGGTGCAGTCAGAGGACGATGCCCGGCAGGACATCATCCCGGAT
GTGGAGATCAGTCGGAAGGTGTACAAGGGAATGTTAGACCTCCTCAAGTGTACAGTCCTC
AGCTTGGAGCAGTCCTATGCCCACGCGGGTCTGGGTGGCATGGCCAGCATCTTTGGGCTT
TTGGAGATTGCCCAGACCCACTACTATAGTAAAGAACCAGACAAGCGGAAGAGAAGTCCA
ACAGAAAGTGTAAATACCCCAGTTGGCAAGGATCCTGGCCTAGCTGGGCGGGGGGACCCA
AAGGCTATGGCACAACTGAGAGTTCCACAACTGGGACCTCGGGCACCAAGTGCCACAGGA
AAGGGTCCTAAGGAACTGGACACCAGAAGTTTAAAGGAAGAAAATTTTATAGCATCTATT
GAATTGTGGAACAAGCACCAGGAAGTGAAAAAGCAAAAAGCTTTGGAAAAACAGAGGCCT
GAAGTAATCAAACCTGTCTTTGACCTTGGTGAGACAGAGGAGAAAAAGTCCCAGATCAGC
GCAGACAGTGGTGTGAGCCTGACGTCTAGTTCCCAGAGGACTGATCAAGACTCTGTCATC
GGCGTGAGTCCAGCTGTTATGATCCGCAGCTCAAGTCAGGATTCTGAAGTTAGCACCGTG
GTGAGTAATAGCTCTGGAGAGACCCTTGGAGCTGACAGTGACTTGAGCAGCAATGCAGGT
GATGGACCAGGTGGCGAGGGCAGTGTTCACCTGGCAAGCTCTCGGGGCACTTTGTCTGAT
AGTGAAATTGAGACCAACTCTGCCACAAGCACCATCTTTGGTAAAGCCCACAGCTTGAAG
CCAAGCATAAAGGAGAAGCTGGCAGGCAGCCCCATTCGTACTTCTGAAGATGTGAGCCAG
CGAGTCTATCTCTATGAGGGACTCCTAGGAAGGGACAAAGGATCCATGTGGGACCAGTTA
GAGGATGCAGCTATGGAGACCTTTTCTATAAGCAAAGAGCGTTCTACTTTATGGGACCAA
ATGCAATTCTGGGAAGATGCCTTCTTAGATGCTGTGATGTTGGAGAGAGAAGGGATGGGT
ATGGACCAGGGTCCCCAGGAAATGATCGACAGGTACCTGTCCCTTGGAGAACATGACCGG
AAGCGCCTGGAAGATGATGAAGATCGCTTGCTGGCCACACTTCTGCACAACCTCATCTCC
TACATGCTGCTGATGAAGGTAAATAAGAATGACATCCGCAAGAAGGTGAGGCGCCTAATG
GGAAAGTCGCACATTGGGCTTGTGTACAGCCAGCAAATCAATGAGGTGCTTGATCAGCTG
GCGAACCTGAATGGACGCGATCTCTCTATCTGGTCCAGTGGCAGCCGGCACATGAAGAAG
CAGACATTTGTGGTACATGCAGGGACAGATACAAACGGAGATATCTTTTTCATGGAGGTG
TGCGATGACTGTGTGGTGTTGCGTAGTAACATCGGAACAGTGTATGAGCGCTGGTGGTAC
GAGAAGCTCATCAACATGACCTACTGTCCCAAGACGAAGGTGTTGTGCTTGTGGCGTAGA
AATGGCTCTGAGACCCAGCTCAACAAGTTCTATACTAAAAAGTGTCGGGAGCTGTACTAC
TGTGTGAAGGACAGCATGGAGCGCGCTGCCGCCCGACAGCAAAGCATCAAACCCGGACCT
GAATTGGGTGGCGAGTTCCCTGTGCAGGACCTGAAGACTGGTGAGGGTGGCCTGCTGCAG
GTGACCCTGGAAGGGATCAACCTCAAATTCATGCACAATCAGGTTTTCATAGAGCTGAAT
CACATTAAAAAGTGCAATACAGTTCGAGGCGTCTTTGTCCTGGAGGAATTTGTTCCTGAA
ATTAAAGAAGTGGTGAGCCACAAGTACAAGACACCAATGGCCCACGAAATCTGCTACTCC
GTATTATGTCTCTTCTCGTACGTGGCTGCAGTTCATAGCAGTGAGGAAGATCTCAGAACC
CCGCCCCGGCCTGTCTCTAGCTGA
Protein Properties
Number of Residues 1647
Molecular Weight 183301.5
Theoretical pI 5.9
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • 336-356
  • 366-386
Protein Sequence
>MAP kinase-activating death domain protein
MVQKKKFCPRLLDYLVIVGARHPSSDSVAQTPELLRRYPLEDHTEFPLPPDVVFFCQPEG
CLSVRQRRMSLRDDTSFVFTLTDKDTGVTRYGICVNFYRSFQKRISKEKGEGGAGSRGKE
GTHATCASEEGGTESSESGSSLQPLSADSTPDVNQSPRGKRRAKAGSRSRNSTLTSLCVL
SHYPFFSTFRECLYTLKRLVDCCSERLLGKKLGIPRGVQRDTMWRIFTGSLLVEEKSSAL
LHDLREIEAWIYRLLRSPVPVSGQKRVDIEVLPQELQPALTFALPDPSRFTLVDFPLHLP
LELLGVDACLQVLTCILLEHKVVLQSRDYNALSMSVMAFVAMIYPLEYMFPVIPLLPTCM
ASAEQLLLAPTPYIIGVPASFFLYKLDFKMPDDVWLVDLDSNRVIAPTNAEVLPILPEPE
SLELKKHLKQALASMSLNTQPILNLEKFHEGQEIPLLLGRPSNDLQSTPSTEFNPLIYGN
DVDSVDVATRVAMVRFFNSANVLQGFQMHTRTLRLFPRPVVAFQAGSFLASRPRQTPFAE
KLARTQAVEYFGEWILNPTNYAFQRIHNNMFDPALIGDKPKWYAHQLQPIHYRVYDSNSQ
LAEALSVPPERDSDSEPTDDSGSDSMDYDDSSSSYSSLGDFVSEMMKCDINGDTPNVDPL
THAALGDASEVEIDELQNQKEAEEPGPDSENSQENPPLRSSSSTTASSSPSTVIHGANSE
PADSTEMDDKAAVGVSKPLPSVPPSIGKSNVDRRQAEIGEGSVRRRIYDNPYFEPQYGFP
PEEDEDEQGESYTPRFSQHVSGNRAQKLLRPNSLRLASDSDAESDSRASSPNSTVSNTST
EGFGGIMSFASSLYRNHSTSFSLSNLTLPTKGAREKATPFPSLKVFGLNTLMEIVTEAGP
GSGEGNRRALVDQKSSVIKHSPTVKREPPSPQGRSSNSSENQQFLKEVVHSVLDGQGVGW
LNMKKVRRLLESEQLRVFVLSKLNRMVQSEDDARQDIIPDVEISRKVYKGMLDLLKCTVL
SLEQSYAHAGLGGMASIFGLLEIAQTHYYSKEPDKRKRSPTESVNTPVGKDPGLAGRGDP
KAMAQLRVPQLGPRAPSATGKGPKELDTRSLKEENFIASIELWNKHQEVKKQKALEKQRP
EVIKPVFDLGETEEKKSQISADSGVSLTSSSQRTDQDSVIGVSPAVMIRSSSQDSEVSTV
VSNSSGETLGADSDLSSNAGDGPGGEGSVHLASSRGTLSDSEIETNSATSTIFGKAHSLK
PSIKEKLAGSPIRTSEDVSQRVYLYEGLLGRDKGSMWDQLEDAAMETFSISKERSTLWDQ
MQFWEDAFLDAVMLEREGMGMDQGPQEMIDRYLSLGEHDRKRLEDDEDRLLATLLHNLIS
YMLLMKVNKNDIRKKVRRLMGKSHIGLVYSQQINEVLDQLANLNGRDLSIWSSGSRHMKK
QTFVVHAGTDTNGDIFFMEVCDDCVVLRSNIGTVYERWWYEKLINMTYCPKTKVLCLWRR
NGSETQLNKFYTKKCRELYYCVKDSMERAAARQQSIKPGPELGGEFPVQDLKTGEGGLLQ
VTLEGINLKFMHNQVFIELNHIKKCNTVRGVFVLEEFVPEIKEVVSHKYKTPMAHEICYS
VLCLFSYVAAVHSSEEDLRTPPRPVSS
GenBank ID Protein 209862994
UniProtKB/Swiss-Prot ID Q8WXG6
UniProtKB/Swiss-Prot Entry Name MADD_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_003682.3
GeneCard ID MADD
GenAtlas ID MADD
HGNC ID HGNC:6766
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  3. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332 ]
  4. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [PubMed:19369195 ]
  5. Nagase T, Ishikawa K, Nakajima D, Ohira M, Seki N, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O: 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. 1997 Apr 28;4(2):141-50. [PubMed:9205841 ]
  6. Chow VT, Lee SS: DENN, a novel human gene differentially expressed in normal and neoplastic cells. DNA Seq. 1996;6(5):263-73. [PubMed:8988362 ]
  7. Schievella AR, Chen JH, Graham JR, Lin LL: 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. 1997 May 2;272(18):12069-75. [PubMed:9115275 ]
  8. Chow VT, Lim KM, Lim D: The human DENN gene: genomic organization, alternative splicing, and localization to chromosome 11p11.21-p11.22. Genome. 1998 Aug;41(4):543-52. [PubMed:9796103 ]
  9. Al-Zoubi AM, Efimova EV, Kaithamana S, Martinez O, El-Idrissi Mel-A, Dogan RE, Prabhakar BS: 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. 2001 Dec 14;276(50):47202-11. Epub 2001 Sep 27. [PubMed:11577081 ]
  10. Lim KM, Yeo WS, Chow VT: 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. 2004 Mar;109(1):24-37. [PubMed:14735464 ]
  11. Efimova EV, Al-Zoubi AM, Martinez O, Kaithamana S, Lu S, Arima T, Prabhakar BS: IG20, in contrast to DENN-SV, (MADD splice variants) suppresses tumor cell survival, and enhances their susceptibility to apoptosis and cancer drugs. Oncogene. 2004 Feb 5;23(5):1076-87. [PubMed:14716293 ]
  12. Del Villar K, Miller CA: 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. 2004 Mar 23;101(12):4210-5. Epub 2004 Mar 8. [PubMed:15007167 ]