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Aliases for MADD Gene

Aliases for MADD Gene

  • MAP-Kinase Activating Death Domain 2 3
  • DENN 3 4 6
  • Differentially Expressed In Normal And Neoplastic Cells 3 4
  • Insulinoma Glucagonoma Clone 20 3 4
  • Rab3 GDP/GTP Exchange Factor 3 4
  • IG20 3 4
  • MAP Kinase-Activating Death Domain Protein 3
  • KIAA0358 4
  • RAB3GEP 3

External Ids for MADD Gene

Summaries for MADD Gene

Entrez Gene Summary for 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. [provided by RefSeq, Jul 2008]

GeneCards Summary for MADD Gene

MADD (MAP-Kinase Activating Death Domain) is a Protein Coding gene. Diseases associated with MADD include glucagonoma and insulinoma. Among its related pathways are Apoptosis and survival Caspase cascade and Apoptosis (WikiPathways). GO annotations related to this gene include Rab guanyl-nucleotide exchange factor activity and death receptor binding.

UniProtKB/Swiss-Prot for MADD Gene

  • 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.

Gene Wiki entry for MADD Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MADD Gene

Genomics for MADD Gene

Genomic Location for MADD Gene

Start:
47,269,161 bp from pter
End:
47,330,031 bp from pter
Size:
60,871 bases
Orientation:
Plus strand

Genomic View for MADD Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for MADD Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MADD Gene

Regulatory Elements for MADD Gene

Transcription factor binding sites by QIAGEN in the MADD gene promoter:

Proteins for MADD Gene

  • Protein details for MADD Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8WXG6-MADD_HUMAN
    Recommended name:
    MAP kinase-activating death domain protein
    Protein Accession:
    Q8WXG6
    Secondary Accessions:
    • A8K8S7
    • B5MEE5
    • D3DQR4
    • O15065
    • O15293
    • Q15732
    • Q15741
    • Q8IWD7
    • Q8WXG3
    • Q8WXG4
    • Q8WXG5
    • Q8WZ63

    Protein attributes for MADD Gene

    Size:
    1647 amino acids
    Molecular mass:
    183303 Da
    Quaternary structure:
    • Interacts with the death domain of TNFRSF1A through its own death domain. Interacts with PIDD1.
    Miscellaneous:
    • 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.
    SequenceCaution:
    • Sequence=BAA20814.2; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};

    Alternative splice isoforms for MADD Gene

neXtProt entry for MADD Gene

Proteomics data for MADD Gene at MOPED

Post-translational modifications for MADD Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for MADD Gene

Domains for MADD Gene

Gene Families for MADD Gene

HGNC:
  • DENND :DENN/MADD domain containing

Protein Domains for MADD Gene

InterPro:
ProtoNet:

UniProtKB/Swiss-Prot:

MADD_HUMAN
Domain:
  • Contains 1 dDENN domain.:
    • Q8WXG6
  • Contains 1 death domain.:
    • Q8WXG6
  • Contains 1 DENN domain.:
    • Q8WXG6
  • Contains 1 uDENN domain.:
    • Q8WXG6
Family:
  • Belongs to the MADD family.:
    • Q8WXG6
genes like me logo Genes that share domains with MADD: view

Function for MADD Gene

Molecular function for MADD Gene

GENATLAS Biochemistry: Map kinase-activating death domain protein homolog and similar to C elegans AEX3,differentially expressed in normal and neoplastic cell,linkingTNFR1 with MAP kinase activation and arachidonic acid release and provide further insight into the mechanisms by which TNF exerts its pleiotropic effects
UniProtKB/Swiss-Prot 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.

Gene Ontology (GO) - Molecular Function for MADD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005123 death receptor binding TAS 9115275
GO:0005515 protein binding IPI 16273344
GO:0017112 Rab guanyl-nucleotide exchange factor activity IMP 9115275
GO:0030295 protein kinase activator activity TAS 9115275
genes like me logo Genes that share ontologies with MADD: view
genes like me logo Genes that share phenotypes with MADD: view

Animal Models for MADD Gene

MGI Knock Outs for MADD:

miRNA for MADD Gene

miRTarBase miRNAs that target MADD

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targeting and HOMER Transcription for MADD Gene

Localization for MADD Gene

Subcellular locations from UniProtKB/Swiss-Prot for MADD Gene

Membrane. Cytoplasm.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for MADD Gene COMPARTMENTS Subcellular localization image for MADD gene
Compartment Confidence
plasma membrane 4
cytosol 1
extracellular 1
mitochondrion 1
nucleus 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for MADD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA --
GO:0005886 plasma membrane IDA --
GO:0016021 integral component of membrane IDA 8988362
genes like me logo Genes that share ontologies with MADD: view

Pathways for MADD Gene

genes like me logo Genes that share pathways with MADD: view

Gene Ontology (GO) - Biological Process for MADD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000187 activation of MAPK activity IMP 9115275
GO:0007166 cell surface receptor signaling pathway TAS 9115275
GO:0032483 regulation of Rab protein signal transduction IDA 20937701
GO:0042981 regulation of apoptotic process IMP 11577081
GO:0043547 positive regulation of GTPase activity IMP 9115275
genes like me logo Genes that share ontologies with MADD: view

Compounds for MADD Gene

(2) HMDB Compounds for MADD Gene

Compound Synonyms Cas Number PubMed IDs
Guanosine diphosphate
  • 5'-GDP
146-91-8
Guanosine triphosphate
  • 5'-GTP
86-01-1

(4) Novoseek inferred chemical compound relationships for MADD Gene

Compound -log(P) Hits PubMed IDs
gdp 66.9 4
gtp 56.4 4
vinblastine 46.1 1
etoposide 31.8 1
genes like me logo Genes that share compounds with MADD: view

Transcripts for MADD Gene

Unigene Clusters for MADD Gene

MAP-kinase activating death domain:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for MADD Gene

ExUns: 1 ^ 2 ^ 3 ^ 4a · 4b · 4c ^ 5 ^ 6 ^ 7a · 7b · 7c · 7d ^ 8a · 8b ^ 9a · 9b ^ 10a · 10b ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17a · 17b ^
SP1: - - - - - -
SP2: - -
SP3: - - - - - - -
SP4: - - - - - -
SP5: - - - - - - -
SP6: - - - - - - -
SP7: - - -
SP8: - -
SP9: - - - - - - -
SP10:
SP11:
SP12:
SP13:
SP14: -
SP15:
SP16: - - - - - - - - - - -
SP17:
SP18: - - - -
SP19:
SP20: - -
SP21:

ExUns: 18a · 18b ^ 19 ^ 20 ^ 21 ^ 22a · 22b ^ 23a · 23b · 23c · 23d ^ 24 ^ 25 ^ 26 ^ 27a · 27b ^ 28a · 28b ^ 29 ^ 30 ^ 31 ^ 32 ^ 33 ^ 34 ^ 35 ^ 36 ^
SP1: -
SP2: -
SP3: - - -
SP4: - - -
SP5: - - - -
SP6: - - - -
SP7: - - - -
SP8: - - - -
SP9: - - - -
SP10: - -
SP11: -
SP12:
SP13:
SP14: - - -
SP15: -
SP16:
SP17:
SP18:
SP19:
SP20:
SP21:

ExUns: 37 ^ 38a · 38b ^ 39a · 39b ^ 40a · 40b
SP1: - -
SP2: - - -
SP3: - -
SP4: - -
SP5: - -
SP6: - -
SP7: - -
SP8: - -
SP9: - - -
SP10:
SP11:
SP12:
SP13:
SP14:
SP15:
SP16:
SP17:
SP18:
SP19:
SP20:
SP21:

Relevant External Links for MADD Gene

GeneLoc Exon Structure for
MADD
ECgene alternative splicing isoforms for
MADD

Expression for MADD Gene

mRNA expression in normal human tissues for MADD Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for MADD Gene

SOURCE GeneReport for Unigene cluster for MADD Gene Hs.82548

mRNA Expression by UniProt/SwissProt for MADD Gene

Q8WXG6-MADD_HUMAN
Tissue specificity: Highly expressed in fetal brain and kidney; adult testis, ovary, brain and heart. Isoform 5 is constitutively expressed in all tissues. Isoform 7 is expressed in fetal liver and in several cancer cell lines.
genes like me logo Genes that share expressions with MADD: view

Orthologs for MADD Gene

This gene was present in the common ancestor of animals.

Orthologs for MADD Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia MADD 36
  • 99.66 (n)
  • 99.76 (a)
MADD 37
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia MADD 36
  • 89.41 (n)
  • 93.99 (a)
MADD 37
  • 94 (a)
OneToOne
dog
(Canis familiaris)
Mammalia MADD 36
  • 93.1 (n)
  • 96.93 (a)
MADD 37
  • 97 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Madd 36
  • 89.74 (n)
  • 95.81 (a)
Madd 16
Madd 37
  • 96 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia MADD 37
  • 89 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 37
  • 72 (a)
OneToMany
-- 37
  • 78 (a)
OneToMany
-- 37
  • 88 (a)
OneToMany
rat
(Rattus norvegicus)
Mammalia Madd 36
  • 89.35 (n)
  • 95.63 (a)
chicken
(Gallus gallus)
Aves MADD 36
  • 76.59 (n)
  • 85.18 (a)
MADD 37
  • 84 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia MADD 37
  • 82 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.1613 36
tropical clawed frog
(Silurana tropicalis)
Amphibia madd 36
  • 73.26 (n)
  • 79.75 (a)
zebrafish
(Danio rerio)
Actinopterygii madd 36
  • 70.17 (n)
  • 75.5 (a)
madd 37
  • 74 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000630 36
  • 56.03 (n)
  • 56.42 (a)
fruit fly
(Drosophila melanogaster)
Insecta rab3-GEF 36
  • 56.87 (n)
  • 56.47 (a)
rab3-GEF 37
  • 34 (a)
OneToOne
rab3-GEF 38
  • 41 (a)
worm
(Caenorhabditis elegans)
Secernentea aex-3 36
  • 53.74 (n)
  • 49.85 (a)
aex-3 37
  • 39 (a)
OneToOne
aex-3 38
  • 41 (a)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.11493 36
sea squirt
(Ciona savignyi)
Ascidiacea -- 37
  • 39 (a)
OneToOne
Species with no ortholog for MADD:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for MADD Gene

ENSEMBL:
Gene Tree for MADD (if available)
TreeFam:
Gene Tree for MADD (if available)

Paralogs for MADD Gene

Selected SIMAP similar genes for MADD Gene using alignment to 6 proteins:

genes like me logo Genes that share paralogs with MADD: view

No data available for Paralogs for MADD Gene

Variants for MADD Gene

Sequence variations from dbSNP and Humsavar for MADD Gene

SNP ID Clin Chr 11 pos Sequence Context AA Info Type MAF
rs167824 -- 47,291,176(-) CCAAA(A/G)ATGCA intron-variant
rs182735 -- 47,291,161(-) TAAAC(C/T)TCCTG intron-variant
rs326214 -- 47,276,809(+) CTGGA(A/G)TATAT synonymous-codon, reference, nc-transcript-variant
rs326215 -- 47,269,549(+) TCCTG(A/C)GGCGG upstream-variant-2KB, utr-variant-5-prime
rs326216 -- 47,287,353(-) TTCAA(A/G)TAAGG intron-variant

Structural Variations from Database of Genomic Variants (DGV) for MADD Gene

Variant ID Type Subtype PubMed ID
nsv897323 CNV Loss 21882294
nsv825870 CNV Gain 20364138
nsv832141 CNV Loss 17160897

Relevant External Links for MADD Gene

HapMap Linkage Disequilibrium report
MADD
Human Gene Mutation Database (HGMD)
MADD

Disorders for MADD Gene

(3) Novoseek inferred disease relationships for MADD Gene

Disease -log(P) Hits PubMed IDs
necrosis 41 9
cancer 29.2 11
tumors 25.9 14

Relevant External Links for MADD

Genetic Association Database (GAD)
MADD
Human Genome Epidemiology (HuGE) Navigator
MADD
genes like me logo Genes that share disorders with MADD: view

No data available for UniProtKB/Swiss-Prot for MADD Gene

Publications for MADD Gene

  1. The human DENN gene: genomic organization, alternative splicing, and localization to chromosome 11p11.21-p11.22. (PMID: 9796103) Chow V.T.K. … Lim D. (Genome 1998) 2 3 4 23
  2. 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. (PMID: 11577081) Al-Zoubi A.M. … Prabhakar B.S. (J. Biol. Chem. 2001) 3 4 23
  3. IG20, in contrast to DENN-SV, (MADD splice variants) suppresses tumor cell survival, and enhances their susceptibility to apoptosis and cancer drugs. (PMID: 14716293) Efimova E.V. … Prabhakar B.S. (Oncogene 2004) 3 4 23
  4. MADD, a novel death domain protein that interacts with the type 1 tumor necrosis factor receptor and activates mitogen-activated protein kinase. (PMID: 9115275) Schievella A.R. … Lin L.-L. (J. Biol. Chem. 1997) 2 3 4
  5. 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. (PMID: 9205841) Nagase T. … Ohara O. (DNA Res. 1997) 3 4

Products for MADD Gene

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