======= ADAM17 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: ADAM17
  * **<color #00a2e8>Official Name</color>**: ADAM metallopeptidase domain 17
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=6868|6868]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P78536|P78536]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=ADAM17&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20ADAM17|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/603639|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biologic processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The encoded preproprotein is proteolytically processed to generate the mature protease. The encoded protease functions in the ectodomain shedding of tumor necrosis factor-alpha, in which soluble tumor necrosis factor-alpha is released from the membrane-bound precursor. This protease also functions in the processing of numerous other substrates, including cell adhesion proteins, cytokine and growth factor receptors and epidermal growth factor (EGF) receptor ligands. The encoded protein also plays a prominent role in the activation of the Notch signaling pathway. Elevated expression of this gene has been observed in specific cell types derived from psoriasis, rheumatoid arthritis, multiple sclerosis and Crohn's disease patients, suggesting that the encoded protein may play a role in autoimmune disease. [provided by RefSeq, Feb 2016]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface. Responsible for the proteolytic release of several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF-receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid precursor protein. Acts as an activator of Notch pathway by mediating cleavage of Notch, generating the membrane-associated intermediate fragment called Notch extracellular truncation (NEXT). Plays a role in the proteolytic processing of ACE2. {ECO:0000269|PubMed:12441351, ECO:0000269|PubMed:20592283, ECO:0000269|PubMed:24226769, ECO:0000269|PubMed:24227843}.

<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'>
|Reprolysin|
|Pep M12B propep|
|Disintegrin|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|cellular response to high density lipoprotein particle stimulus|
|regulation of mast cell apoptotic process|
|PMA-inducible membrane protein ectodomain proteolysis|
|receptor transactivation|
|interleukin-6 receptor binding|
|germinal center formation|
|positive regulation of epidermal growth factor-activated receptor activity|
|positive regulation of tumor necrosis factor-mediated signaling pathway|
|wound healing, spreading of epidermal cells|
|Notch receptor processing|
|positive regulation of vascular endothelial cell proliferation|
|positive regulation of T cell chemotaxis|
|regulation of T cell chemotaxis|
|regulation of vascular endothelial cell proliferation|
|membrane protein intracellular domain proteolysis|
|positive regulation of lymphocyte chemotaxis|
|membrane protein ectodomain proteolysis|
|cell adhesion mediated by integrin|
|wound healing, spreading of cells|
|epiboly involved in wound healing|
|epiboly|
|regulation of lymphocyte chemotaxis|
|Notch binding|
|regulation of epidermal growth factor-activated receptor activity|
|regulation of myeloid cell apoptotic process|
|positive regulation of cellular response to transforming growth factor beta stimulus|
|cellular response to lipoprotein particle stimulus|
|positive regulation of transforming growth factor beta receptor signaling pathway|
|positive regulation of cyclin-dependent protein serine/threonine kinase activity|
|positive regulation of T cell migration|
|positive regulation of epidermal growth factor receptor signaling pathway|
|spleen development|
|positive regulation of ERBB signaling pathway|
|positive regulation of signaling receptor activity|
|positive regulation of cyclin-dependent protein kinase activity|
|positive regulation of G1/S transition of mitotic cell cycle|
|membrane protein proteolysis|
|positive regulation of lymphocyte migration|
|regulation of T cell migration|
|T cell differentiation in thymus|
|negative regulation of cold-induced thermogenesis|
|positive regulation of cell cycle G1/S phase transition|
|morphogenesis of an epithelial sheet|
|epidermal growth factor receptor signaling pathway|
|positive regulation of cytokine-mediated signaling pathway|
|positive regulation of protein tyrosine kinase activity|
|positive regulation of blood vessel endothelial cell migration|
|positive regulation of chemokine production|
|positive regulation of response to cytokine stimulus|
|regulation of tumor necrosis factor-mediated signaling pathway|
|regulation of lymphocyte migration|
|metallopeptidase activity|
|ERBB signaling pathway|
|negative regulation of transforming growth factor beta receptor signaling pathway|
|negative regulation of cellular response to transforming growth factor beta stimulus|
|endopeptidase activity|
|positive regulation of mitotic cell cycle phase transition|
|regulation of chemokine production|
|peptidase activity|
|regulation of leukocyte apoptotic process|
|regulation of epidermal growth factor receptor signaling pathway|
|PDZ domain binding|
|positive regulation of leukocyte chemotaxis|
|regulation of protein tyrosine kinase activity|
|regulation of blood vessel endothelial cell migration|
|regulation of ERBB signaling pathway|
|positive regulation of cell cycle phase transition|
|defense response to Gram-positive bacterium|
|positive regulation of endothelial cell proliferation|
|ruffle membrane|
|regulation of cyclin-dependent protein serine/threonine kinase activity|
|positive regulation of endothelial cell migration|
|regulation of cyclin-dependent protein kinase activity|
|positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway|
|metalloendopeptidase activity|
|B cell differentiation|
|regulation of leukocyte chemotaxis|
|regulation of transforming growth factor beta receptor signaling pathway|
|negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway|
|regulation of cellular response to transforming growth factor beta stimulus|
|tumor necrosis factor-mediated signaling pathway|
|Notch signaling pathway|
|positive regulation of leukocyte migration|
|regulation of endothelial cell proliferation|
|SH3 domain binding|
|integrin binding|
|T cell differentiation|
|positive regulation of chemotaxis|
|positive regulation of epithelial cell migration|
|regulation of cold-induced thermogenesis|
|negative regulation of cellular response to growth factor stimulus|
|regulation of G1/S transition of mitotic cell cycle|
|positive regulation of mitotic cell cycle|
|B cell activation|
|regulation of endothelial cell migration|
|regulation of cytokine-mediated signaling pathway|
|positive regulation of cell growth|
|regulation of cell cycle G1/S phase transition|
|cell-cell junction|
|regulation of signaling receptor activity|
|regulation of response to cytokine stimulus|
|positive regulation of epithelial cell proliferation|
|positive regulation of peptidyl-tyrosine phosphorylation|
|regulation of leukocyte migration|
|regulation of chemotaxis|
|actin cytoskeleton|
|regulation of epithelial cell migration|
|membrane raft|
|T cell activation|
|regulation of transmembrane receptor protein serine/threonine kinase signaling pathway|
|lymphocyte differentiation|
|cellular response to tumor necrosis factor|
|regulation of peptidyl-tyrosine phosphorylation|
|positive regulation of growth|
|response to tumor necrosis factor|
|regulation of cellular response to growth factor stimulus|
|adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|positive regulation of cell cycle process|
|response to lipopolysaccharide|
|apical plasma membrane|
|response to molecule of bacterial origin|
|defense response to bacterium|
|leukocyte differentiation|
|regulation of epithelial cell proliferation|
|positive regulation of protein serine/threonine kinase activity|
|response to hypoxia|
|response to decreased oxygen levels|
|positive regulation of cell cycle|
|response to oxygen levels|
|lymphocyte activation|
|regulation of mitotic cell cycle phase transition|
|focal adhesion|
|regulation of cell growth|
|morphogenesis of an epithelium|
|regulation of cell cycle phase transition|
|positive regulation of cytokine production|
|wound healing|
|neutrophil mediated immunity|
|positive regulation of cell migration|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|regulation of protein serine/threonine kinase activity|
|myeloid leukocyte mediated immunity|
|positive regulation of cell motility|
|positive regulation of protein kinase activity|
|positive regulation of cellular component movement|
|positive regulation of locomotion|
|hemopoiesis|
|tissue morphogenesis|
|response to wounding|
|positive regulation of kinase activity|
|positive regulation of response to external stimulus|
|hematopoietic or lymphoid organ development|
|adaptive immune response|
|cell surface|
|regulation of mitotic cell cycle|
|immune system development|
|positive regulation of transferase activity|
|regulation of growth|
|cytokine-mediated signaling pathway|
|response to bacterium|
|regulation of cytokine production|
|enzyme linked receptor protein signaling pathway|
|regulation of cell cycle process|
|leukocyte mediated immunity|
|regulation of protein kinase activity|
|regulation of cell migration|
|response to lipid|
|regulation of kinase activity|
|anatomical structure formation involved in morphogenesis|
|regulation of cell motility|
|positive regulation of cell population proliferation|
|leukocyte activation|
|cell adhesion|
|biological adhesion|
|defense response to other organism|
|cell migration|
|regulation of transferase activity|
|regulation of locomotion|
|regulation of cellular component movement|
|cellular response to cytokine stimulus|
|positive regulation of protein phosphorylation|
|response to drug|
|positive regulation of phosphorylation|
|cell activation|
|cell motility|
|localization of cell|
|immune effector process|
|regulation of response to external stimulus|
|response to cytokine|
|epithelium development|
|positive regulation of phosphorus metabolic process|
|positive regulation of phosphate metabolic process|
|positive regulation of immune system process|
|response to abiotic stimulus|
|regulation of cell cycle|
|negative regulation of multicellular organismal process|
|positive regulation of protein modification process|
|negative regulation of signal transduction|
|proteolysis|
|response to other organism|
|response to external biotic stimulus|
|locomotion|
|response to biotic stimulus|
|defense response|
|negative regulation of cell communication|
|negative regulation of signaling|
|integral component of plasma membrane|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|regulation of apoptotic process|
|movement of cell or subcellular component|
|response to oxygen-containing compound|
|regulation of programmed cell death|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|regulation of immune system process|
|positive regulation of signal transduction|
|regulation of cell death|
|positive regulation of protein metabolic process|
|positive regulation of multicellular organismal process|
|tissue development|
|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 protein modification process|
|immune response|
|membrane|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' 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:exp82|Torin1 0.08μM R02 exp82]]|-2.06|
|[[:results:exp488|Hippuristanol 0.12μM R08 exp488]]|-1.83|
|[[:results:exp280|Daidzin 10μM R06 exp280]]|1.84|
|[[:results:exp289|Hydroxyurea 15μM R06 exp289]]|2.27|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</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>**: 18932
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.32 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='ADAM17 Expression in NALM6 Cells: 6.32'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>