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CD156b, A disintegrin & metalloproteinase domain 17; TNF-alpha-converting enzyme; TNF-alpha convertase; snake venom-like protease; CD156b (ADAM17, CSVP, TACE)

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: a) Notch1 protein (involved in activation pathway) b) APP (alpha secretase activity) c) p75 TNF-receptor d) p55 TNF-receptor, e) IL1R2, f) TGF-alpha g) L-selectin h) growth hormone receptor i) 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]

Interactions

molecular events

Related

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)

General

ADAM (A disintegrin & metalloproteinase domain); MDC (metalloproteinase, disintegrin, cysteine-rich) protein APP alpha-secretase cluster-of-differentiation antigen; cluster designation antigen; CD antigen glycoprotein phosphoprotein

Properties

SIZE: MW = 93 kD entity length = 824 aa COMPARTMENT: plasma membrane MOTIF: N-glycosylation site {N103} N-glycosylation site {N157} N-glycosylation site {N174} metalloprotease domain {215-474} MOTIF: cysteine residue {C225} MODIFICATION: cysteine residue {C333} N-glycosylation site {N264} cysteine residue {C333} MODIFICATION: cysteine residue {C225} cysteine residue {C365} MODIFICATION: cysteine residue {C469} active site SITE: E406 cysteine residue {C423} MODIFICATION: cysteine residue {C453} N-glycosylation site {N452} cysteine residue {C453} MODIFICATION: cysteine residue {C423} cysteine residue {C469} MODIFICATION: cysteine residue {C365} disintegrin domain {475-563} MOTIF: cysteine residue {C478} MODIFICATION: cysteine residue {C501} N-glycosylation site {N498} cysteine residue {C501} MODIFICATION: cysteine residue {C478} N-glycosylation site {N539} N-glycosylation site {N551} EGF domain {569-601} MOTIF: cysteine residue {C573} MODIFICATION: cysteine residue {C582} cysteine residue {C578} MODIFICATION: cysteine residue {C591} cysteine residue {C582} MODIFICATION: cysteine residue {C573} cysteine residue {C591} MODIFICATION: cysteine residue {C578} cysteine residue {C593} MODIFICATION: cysteine residue {C600} N-glycosylation site {N594} cysteine residue {C600} MODIFICATION: cysteine residue {C593} transmembrane domain {672-692} src homology 3 [SH3] domain SITE: 731-738

Database Correlations

OMIM 603639 UniProt P78536 PFAM correlations Entrez Gene 6868 Kegg hsa:6868 ENZYME 3.4.24.86

References

  1. UniProt :accession P78536
  2. Yong VW et al Metalloproteinases in biology and pathology of the nervous system. Nat Rev Neurosci. 2001 Jul;2(7):502-11. Review. PMID: 11433375
  3. Wikipedia; tumor necrosis factor alpha-converting enzyme entry http://en.wikipedia.org/wiki/tumor_necrosis_factor_alpha_converting_Enzyme
  4. 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: 35474465