Free for academic non-profit institutions. Other users need a Commercial license

Aliases for MADD Gene

Aliases for MADD Gene

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

External Ids for MADD Gene

Previous GeneCards Identifiers for MADD Gene

  • GC11P049230
  • GC11P048168
  • GC11P047322
  • GC11P047255
  • GC11P047247
  • GC11P046990

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 glutaric acidemia iic. Among its related pathways are Signaling by GPCR and Apoptosis and survival Caspase cascade. 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

Regulatory Elements for MADD Gene

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

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for MADD Gene

Chromosome:
11
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

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

Antibody Products

No data available for DME Specific Peptides for MADD Gene

Domains & Families for MADD Gene

Gene Families for MADD Gene

Protein Domains for MADD Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for MADD Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q8WXG6

UniProtKB/Swiss-Prot:

MADD_HUMAN :
  • Contains 1 dDENN domain.
  • Belongs to the MADD family.
Domain:
  • Contains 1 dDENN domain.
  • Contains 1 death domain.
  • Contains 1 DENN domain.
  • Contains 1 uDENN domain.
Family:
  • Belongs to the MADD family.
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 9115275
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:

Animal Model Products

miRNA for MADD Gene

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for MADD

In Situ Assay Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets 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 2
endosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for MADD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA --
GO:0005829 cytosol TAS --
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 & Interactions for MADD Gene

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

PCR Array Products

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 --
GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway TAS --
GO:0032483 regulation of Rab protein signal transduction IDA 20937701
GO:0033209 tumor necrosis factor-mediated signaling pathway TAS --
genes like me logo Genes that share ontologies with MADD: view

No data available for SIGNOR curated interactions for MADD Gene

Drugs & Compounds for MADD Gene

(4) Drugs for MADD Gene - From: HMDB and NovoSeek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Etoposide Approved Pharma Topo II inhibitor, Topoisomerase 2 Inhibitors, Topoisomerase II inhibitor 1127
Vinblastine Approved Pharma 218
Guanosine diphosphate Experimental Pharma 0
Guanosine triphosphate Experimental Pharma 0

(2) Additional Compounds for MADD Gene - From: NovoSeek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
gdp
gtp
Partial agonist, Agonist
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:

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for MADD

Flow Cytometry Products

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

Protein differential expression in normal tissues from HIPED for MADD Gene

This gene is overexpressed in Cervix (15.5), Peripheral blood mononuclear cells (11.8), Plasma (11.0), Frontal cortex (9.8), and Brain (8.1).

Integrated Proteomics: protein expression in normal tissues and cell lines 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 expression patterns with MADD: view

Protein tissue co-expression partners for MADD Gene

- Elite partner

Primer Products

In Situ Assay Products

No data available for mRNA differential expression in normal tissues for MADD Gene

Orthologs for MADD Gene

This gene was present in the common ancestor of animals.

Orthologs for MADD Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia MADD 35
  • 89.41 (n)
  • 93.99 (a)
MADD 36
  • 94 (a)
OneToOne
dog
(Canis familiaris)
Mammalia MADD 35
  • 93.1 (n)
  • 96.93 (a)
MADD 36
  • 97 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Madd 35
  • 89.74 (n)
  • 95.81 (a)
Madd 16
Madd 36
  • 96 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia MADD 35
  • 99.66 (n)
  • 99.76 (a)
MADD 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Madd 35
  • 89.35 (n)
  • 95.63 (a)
oppossum
(Monodelphis domestica)
Mammalia MADD 36
  • 89 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 72 (a)
OneToMany
-- 36
  • 78 (a)
OneToMany
-- 36
  • 88 (a)
OneToMany
chicken
(Gallus gallus)
Aves MADD 35
  • 76.59 (n)
  • 85.18 (a)
MADD 36
  • 84 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia MADD 36
  • 82 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia madd 35
  • 73.26 (n)
  • 79.75 (a)
African clawed frog
(Xenopus laevis)
Amphibia Xl.1613 35
zebrafish
(Danio rerio)
Actinopterygii madd 35
  • 70.17 (n)
  • 75.5 (a)
madd 36
  • 74 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta rab3-GEF 37
  • 41 (a)
rab3-GEF 35
  • 56.87 (n)
  • 56.47 (a)
rab3-GEF 36
  • 34 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000630 35
  • 56.03 (n)
  • 56.42 (a)
worm
(Caenorhabditis elegans)
Secernentea aex-3 37
  • 41 (a)
aex-3 35
  • 53.74 (n)
  • 49.85 (a)
aex-3 36
  • 39 (a)
OneToOne
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.11493 35
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 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

(3) 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

Variation tolerance for MADD Gene

Residual Variation Intolerance Score: 1.72% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 9.53; 88.86% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for MADD Gene

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

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MADD Gene

Disorders for MADD Gene

MalaCards: The human disease database

(1) MalaCards diseases for MADD Gene - From: OMIM

Disorder Aliases PubMed IDs
glutaric acidemia iic
  • glutaric acidemia iia
- elite association
Search MADD in MalaCards View complete list of genes associated with diseases

Relevant External Links for MADD

Genetic Association Database (GAD)
MADD
Human Genome Epidemiology (HuGE) Navigator
MADD
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
MADD
genes like me logo Genes that share disorders with MADD: view

No data available for UniProtKB/Swiss-Prot and Genatlas 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 23 67
  2. Knockdown of IG20 gene expression renders thyroid cancer cells susceptible to apoptosis. (PMID: 19190106) Subramanian M. … Prabhakar B.S. (J. Clin. Endocrinol. Metab. 2009) 23 67
  3. MADD, a splice variant of IG20, is indispensable for MAPK activation and protection against apoptosis upon tumor necrosis factor-alpha treatment. (PMID: 19289468) Kurada B.R. … Prabhakar B.S. (J. Biol. Chem. 2009) 23 67
  4. Role of IG20 splice variants in TRAIL resistance. (PMID: 18223207) Prabhakar B.S. … Prasad K.V. (Clin. Cancer Res. 2008) 23 67
  5. Regulation of apoptosis and caspase-8 expression in neuroblastoma cells by isoforms of the IG20 gene. (PMID: 18794122) Li L.C. … Meriggioli M.N. (Cancer Res. 2008) 23 67

Products for MADD Gene

Sources for MADD Gene

Back to Top

Content