MADD [The Human Chemical-Genetic Interaction Map Project]

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======= MADD =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: MADD
  * **<color #00a2e8>Official Name</color>**: MAP kinase activating death domain
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=8567|8567]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q8WXG6|Q8WXG6]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=MADD&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20MADD|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/603584|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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. {ECO:0000269|PubMed:11577081, ECO:0000269|PubMed:14716293, ECO:0000269|PubMed:14735464, ECO:0000269|PubMed:15007167, ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:9115275}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|DENN|
|uDENN|
|dDENN|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|regulation of Rab protein signal transduction|
|death receptor binding|
|protein kinase activator activity|
|Rab guanyl-nucleotide exchange factor activity|
|execution phase of apoptosis|
|regulation of extrinsic apoptotic signaling pathway via death domain receptors|
|regulation of tumor necrosis factor-mediated signaling pathway|
|regulation of extrinsic apoptotic signaling pathway|
|activation of MAPK activity|
|regulation of cytokine-mediated signaling pathway|
|regulation of response to cytokine stimulus|
|regulation of Ras protein signal transduction|
|positive regulation of MAP kinase activity|
|activation of protein kinase activity|
|positive regulation of protein serine/threonine kinase activity|
|regulation of MAP kinase activity|
|regulation of small GTPase mediated signal transduction|
|regulation of apoptotic signaling pathway|
|regulation of protein serine/threonine kinase activity|
|positive regulation of protein kinase activity|
|positive regulation of MAPK cascade|
|positive regulation of kinase activity|
|positive regulation of transferase activity|
|regulation of MAPK cascade|
|regulation of protein kinase activity|
|regulation of kinase activity|
|apoptotic process|
|regulation of transferase activity|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|programmed cell death|
|positive regulation of phosphorylation|
|cell death|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|regulation of cell cycle|
|positive regulation of protein modification process|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|regulation of apoptotic process|
|regulation of programmed cell death|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|positive regulation of signal transduction|
|regulation of cell death|
|positive regulation of protein metabolic process|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp415|Trichostatin-A 0.06μM R07 exp415]]|-1.7|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:h:hgc6.3|HGC6.3]]|0.415|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 4756
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.23 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='MADD Expression in NALM6 Cells: 6.23'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>