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Aliases for MADD Gene

Aliases for MADD Gene

  • MAP Kinase Activating Death Domain 2 3 5
  • 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
  • MAP Kinase-Activating Death Domain Protein 3
  • MAP-Kinase Activating Death Domain 2
  • 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. Among its related pathways are TRAF Pathway and Apoptosis and survival Caspase cascade. GO annotations related to this gene include Rab guanyl-nucleotide exchange factor activity and death receptor binding. An important paralog of this gene is DENND4A.

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 CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MADD Gene

Genomics for MADD Gene

Regulatory Elements for MADD Gene

Enhancers for MADD Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH11G047996 2 FANTOM5 Ensembl ENCODE dbSUPER 12.5 +739.7 739733 24.6 HNRNPUL1 PKNOX1 ZFP64 ARID4B SIN3A DMAP1 YY1 FOS JUNB REST NUP160 ENSG00000200090 FNBP4 PTPRJ SLC39A13 MADD ENSG00000270060 DDB2 MYBPC3 CELF1
GH11G047985 1.8 FANTOM5 Ensembl ENCODE dbSUPER 9.3 +718.2 718240 2.9 HDAC1 PKNOX1 ATF1 RAD21 EGR1 FOS RELB ETV6 CREM IKZF2 PTPRJ-AS1 CELF1 MADD PTPRJ FNBP4
GH11G047537 1.4 Ensembl ENCODE dbSUPER 11.1 +270.2 270232 4.4 PKNOX1 INSM2 KLF17 SIN3A FEZF1 RAD21 ZNF2 GATA2 ZNF366 SCRT2 C1QTNF4 PTPMT1 NDUFS3 CELF1 KBTBD4 RNU5E-10P ENSG00000231880 MADD MTCH2 FNBP4
GH11G047232 1.2 Ensembl ENCODE 12.1 -34.9 -34863 2.9 ELF3 SREBF2 SIN3A ARID4B DMAP1 THRB RAD21 YY1 RARA ZNF335 ACP2 RPS20P26 PACSIN3 MADD LOC101928943 ARFGAP2 MYBPC3 NR1H3 ENSG00000256897
GH11G047252 1.6 FANTOM5 ENCODE dbSUPER 8.1 -14.5 -14537 4.1 PKNOX1 ARNT MLX ARID4B DMAP1 YY1 TCF12 ZNF121 ELK1 ZNF143 ACP2 ENSG00000256897 DDB2 PACSIN3 ARFGAP2 MADD MYBPC3 SPI1 CELF1
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around MADD on UCSC Golden Path with GeneCards custom track

Promoters for MADD Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000039662 839 1601 HDGF PKNOX1 FOXA2 CREB3L1 ARNT AGO1 ZFP64 ARID4B SIN3A FEZF1

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

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

Genes around MADD on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MADD Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
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

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 & Families for MADD Gene

Gene Families for MADD Gene

Protein Domains for MADD Gene

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 :
  • Belongs to the MADD family.
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:0005085 guanyl-nucleotide exchange factor activity IEA --
GO:0005123 death receptor binding TAS 9115275
GO:0005515 protein binding IPI 9115275
GO:0017112 Rab guanyl-nucleotide exchange factor activity TAS --
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

CRISPR Products

miRNA for MADD Gene

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , 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
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for MADD gene
Compartment Confidence
plasma membrane 5
cytosol 5
extracellular 1
mitochondrion 1
peroxisome 1
nucleus 1
lysosome 1
endosome 1

Gene Ontology (GO) - Cellular Components for MADD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm TAS 8988362
GO:0005829 cytosol IDA,TAS --
GO:0005886 plasma membrane IDA --
GO:0016020 membrane IEA --
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

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:0006915 apoptotic process IEA --
GO:0007166 cell surface receptor signaling pathway TAS 9115275
GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway TAS --
GO:0032483 regulation of Rab protein signal transduction IDA 20937701
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
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
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:

CRISPR Products

Clone 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 from GTEx, Illumina, BioGPS, and CGAP SAGE 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, MaxQB, and MOPED for MADD Gene



Protein tissue co-expression partners for MADD Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of MADD Gene:

MADD

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.

Evidence on tissue expression from TISSUES for MADD Gene

  • Nervous system(4.6)
genes like me logo Genes that share expression patterns with MADD: view

Primer Products

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer 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
chimpanzee
(Pan troglodytes)
Mammalia MADD 34 35
  • 99.66 (n)
dog
(Canis familiaris)
Mammalia MADD 34 35
  • 93.1 (n)
mouse
(Mus musculus)
Mammalia Madd 34 16 35
  • 89.74 (n)
cow
(Bos Taurus)
Mammalia MADD 34 35
  • 89.41 (n)
rat
(Rattus norvegicus)
Mammalia Madd 34
  • 89.35 (n)
oppossum
(Monodelphis domestica)
Mammalia MADD 35
  • 89 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 35
  • 88 (a)
OneToMany
-- 35
  • 78 (a)
OneToMany
-- 35
  • 72 (a)
OneToMany
chicken
(Gallus gallus)
Aves MADD 34 35
  • 76.59 (n)
lizard
(Anolis carolinensis)
Reptilia MADD 35
  • 82 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia madd 34
  • 73.26 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.1613 34
zebrafish
(Danio rerio)
Actinopterygii madd 34 35
  • 70.17 (n)
fruit fly
(Drosophila melanogaster)
Insecta rab3-GEF 36 34 35
  • 56.87 (n)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000630 34
  • 56.03 (n)
worm
(Caenorhabditis elegans)
Secernentea aex-3 36 34 35
  • 53.74 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 39 (a)
OneToOne
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.11493 34
Species where no ortholog for MADD was found in the sources mined by GeneCards:
  • 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

Variants for MADD Gene

Sequence variations from dbSNP and Humsavar for MADD Gene

SNP ID Clin Chr 11 pos Sequence Context AA Info Type
rs61731956 Pathogenic 47,268,596(+) CCTCC(A/G)GACCC downstream-variant-500B, upstream-variant-2KB, reference, missense
rs386352327 Uncertain significance 47,292,581(+) AAAAA(A/G)CTTTG intron-variant, reference, missense
rs1000000184 -- 47,322,780(+) AAAGG(A/G)TAGAC intron-variant
rs1000008260 -- 47,298,486(+) CTTTT(-/GA)GAGAG intron-variant
rs1000057628 -- 47,316,132(+) CGCCC(A/G)GCCCC intron-variant

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

Variant ID Type Subtype PubMed ID
nsv1145519 CNV deletion 24896259
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

Human Gene Mutation Database (HGMD)
MADD
SNPedia medical, phenotypic, and genealogical associations of SNPs for
MADD

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

Disorders for MADD Gene

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

No disorders were found for MADD Gene.

No data available for MalaCards , 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 3 4 22 64
  2. 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 22 64
  3. 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 22 64
  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 64
  5. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes. (PMID: 21873549) Strawbridge R.J. … Florez J.C. (Diabetes 2011) 3 46 64

Products for MADD Gene

Sources for MADD Gene

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