ADAM17 - Disintegrin and metalloproteinase domain-containing protein 17 - human protein (Function)
 
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ADAM17 »  Disintegrin and metalloproteinase domain-containing protein 17   [ EC 3.4.24.86 ]  (ADAM 17)
 
Protein also known as:  TNF-alpha-converting enzyme; CD antigen CD156b.
Gene name:  ADAM17
Entry whose protein(s) existence is based on evidence at protein level
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1 239 2
GENE REF ISO

Function

 show evidences
Overview 
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).  
3
  • CuratedUniProtKB
GO molecular function 
Integrin bindingdefinition[GO:0005178]  
1
  • IPIBHF-UCL
Interleukin-6 receptor bindingdefinition[GO:0005138]  
1
  • IPIBHF-UCL
Metalloendopeptidase activitydefinition[GO:0004222]  
4
  • IDAUniProtKB
  • IDABHF-UCL
Metallopeptidase activitydefinition[GO:0008237]  
2
  • IDABHF-UCL
Notch bindingdefinition[GO:0005112]  
1
  • IDAUniProtKB
PDZ domain bindingdefinition[GO:0030165]  
1
  • IPIBHF-UCL
Protein bindingdefinition[GO:0005515]  
6
  • IPIBHF-UCL
  • IPIIntAct
SH3 domain bindingdefinition[GO:0017124]  
  • IEAUniProtKB KW
Zinc ion bindingdefinition[GO:0008270] silver  
  • IEAInterPro 2 GO
GO biological process 
B cell differentiationdefinition[GO:0030183]  
1
  • ISSBHF-UCL
Cell adhesiondefinition[GO:0007155]  
1
  • IDABHF-UCL
Cell adhesion mediated by integrindefinition[GO:0033627]  
1
  • IDABHF-UCL
Cell motilitydefinition[GO:0048870]  
1
  • ISSBHF-UCL
Epidermal growth factor receptor signaling pathwaydefinition[GO:0007173]  
1
  • IDABHF-UCL
Epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathwaydefinition[GO:0035625]  
1
  • IMPBHF-UCL
Germinal center formationdefinition[GO:0002467]  
1
  • ISSBHF-UCL
Membrane protein ectodomain proteolysisdefinition[GO:0006509]  
8
  • IDABHF-UCL
Negative regulation of interleukin-8 productiondefinition[GO:0032717]  
1
  • IMPBHF-UCL
Neutrophil mediated immunitydefinition[GO:0002446]  
1
  • ICBHF-UCL
Notch receptor processingdefinition[GO:0007220]  
1
  • IDAUniProtKB
Notch signaling pathwaydefinition[GO:0007219]  
  • IEAUniProtKB KW
PMA-inducible membrane protein ectodomain proteolysisdefinition[GO:0051088]  
4
  • IMPBHF-UCL
Positive regulation of cell growthdefinition[GO:0030307]  
1
  • IMPBHF-UCL
Positive regulation of cell migrationdefinition[GO:0030335]  
1
  • IMPBHF-UCL
Positive regulation of cell proliferationdefinition[GO:0008284]  
1
  • IMPBHF-UCL
Positive regulation of cellular component movementdefinition[GO:0051272]  
1
  • ISSBHF-UCL
Positive regulation of chemokine productiondefinition[GO:0032722]  
1
  • IMPBHF-UCL
Positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycledefinition[GO:0031659]  
1
  • IDABHF-UCL
Positive regulation of epidermal growth factor-activated receptor activitydefinition[GO:0045741]  
2
  • IDABHF-UCL
Positive regulation of leukocyte chemotaxisdefinition[GO:0002690]  
1
  • ICBHF-UCL
Positive regulation of protein phosphorylationdefinition[GO:0001934]  
1
  • IMPBHF-UCL
Positive regulation of T cell chemotaxisdefinition[GO:0010820]  
1
  • IMPBHF-UCL
Positive regulation of transforming growth factor beta receptor signaling pathwaydefinition[GO:0030511]  
1
  • ISSBHF-UCL
Regulation of mast cell apoptotic processdefinition[GO:0033025]  
1
  • ISSBHF-UCL
Response to drugdefinition[GO:0042493]  
1
  • ISSBHF-UCL
Response to high density lipoprotein particledefinition[GO:0055099]  
1
  • IDABHF-UCL
Response to hypoxiadefinition[GO:0001666]  
1
  • IDABHF-UCL
Response to lipopolysaccharidedefinition[GO:0032496]  
1
  • IDABHF-UCL
Spleen developmentdefinition[GO:0048536]  
1
  • ISSBHF-UCL
T cell differentiation in thymusdefinition[GO:0033077]  
1
  • ISSBHF-UCL
Wound healing, spreading of epidermal cellsdefinition[GO:0035313]  
1
  • IEPBHF-UCL
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 3.4.24.86: Narrow endopeptidase specificity. Cleaves Pro-Leu-Ala-Gln-Ala-|-Val-Arg-Ser-Ser-Ser in the membrane-bound, 26-kDa form of tumor necrosis factor alpha (TNF-alpha). Similarly cleaves other membrane-anchored, cell-surface proteins to 'shed' the extracellular domains.  
  • CuratedUniProtKB
It requires the following cofactor
Binds 1 zinc ion per subunit.  
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Alzheimer's disease  hsa05010+6868  
Epithelial cell signaling in Helicobacter pylori infection  hsa05120+6868  
Notch signaling pathway  hsa04330+6868  
According to Reactome, this protein belongs to the following pathways:
Apoptosis  REACT_578  
Disease  REACT_116125  
Extracellular matrix organization  REACT_118779  
Immune System  REACT_6900  
Receptor-ligand binding initiates the second proteolytic cleavage of Notch receptor  REACT_2001  
Signal Transduction  REACT_111102  
 

Keywords

Biological process 
Notch signaling pathway  definition   [KW-0914]
Molecular function 
Hydrolase  definition   [KW-0378]
Metalloprotease  definition   [KW-0482]
Protease  definition   [KW-0645]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: ADAM17
GenomeRNAi: 6868
PRO: PR:P78536
Chemistry
GuidetoPHARMACOLOGY: 1662