CD156b, A disintegrin & metalloproteinase domain 17; TNF-alpha-converting enzyme; TNF-alpha convertase; snake venom-like protease; CD156b (ADAM17, CSVP, TACE)
Jump to navigation
Jump to search
Function
- endopeptidase with narrow specificity
- cleaves membrane-bound precursor of TNF-alpha to its mature soluble form
- cleaves Pro-Leu-Ala-Gln-Ala-|-Val-Arg-Ser-Ser-Ser in the membrane-bound, 26-kD form of TNF-alpha
- responsible for proteolytic release of several other cell-surface proteins, including:
- Notch1 protein (involved in activation pathway)
- APP (alpha secretase activity)
- p75 TNF-receptor
- p55 TNF-receptor,
- IL1R2,
- TGF-alpha
- L-selectin
- growth hormone receptor
- MUC1 & APP also (putative)
- interacts with MAD2L1 & MUC1
- precursor is cleaved by a furin endopeptidase
- phosphorylated
- stimulation by growth factor or phorbol ester induces phosphorylation of Ser-819 but decreases phosphorylation of Ser-791
- inhibited by TIMP-3, not TIMP-1
Cofactor: binds 1 Zn+2 per subunit
Structure
- must be membrane anchored to cleave substrates
- cytoplasmic domain is not required for activity
- only the catalytic domain is essential to shed TNF & p75 TNFR (putative)
- conserved Cys present in the cysteine-switch motif binds the catalytic Zn+2, thus inhibiting the enzyme
- dissociation of the Cys from the Zn+2 upon activation- peptide release activates the enzyme
- contains 1 disintegrin domain
- contains 1 peptidase M12B domain
Compartment
membrane
Alternative splicing
named isoforms=2; A,B
Expression
- ubiquitously expressed
- expressed at highest levels in adult heart, placenta, skeletal muscle, pancreas, spleen, thymus, prostate, testes, ovary & small intestine, & in fetal brain, lung, liver & kidney
Pathology
- expressed in osteoarthritis-affected cartilage
- high levels of ADAM17 expressed in the psoriasis, thus may olay a role in pathogenesis of psoriasis[4]
More general terms
Additional terms
- notch-1 (Drosophila) homolog protein; translocation-associated notch homolog (NOTCH1, TAN1)
- tumor necrosis factor [TNF]-alpha; tumor necrosis factor ligand superfamily member 2; cachectin (TNF, TNFA, TNFSF2)
References
- ↑ UniProt http://www.uniprot.org/uniprot/P78536.html
- ↑ Yong VW et al Metalloproteinases in biology and pathology of the nervous system. Nat Rev Neurosci. 2001 Jul;2(7):502-11. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11433375
- ↑ Wikipedia; tumor necrosis factor alpha-converting enzyme entry http://en.wikipedia.org/wiki/tumor_necrosis_factor_alpha_converting_Enzyme
- ↑ 4.0 4.1 Gul C, Kilic S, Sehitoglu MH. The importance of ADAM10 and ADAM17 metalloproteinases in the pathogenesis of psoriasis. Clin Exp Dermatol. 2022. April 26 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35474465