Summary for peptidase M12.217: ADAM17 peptidase

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Structure Literature Human EST Mouse EST Substrates Inhibitors Pharma

 

Names
MEROPS NameADAM17 peptidase
Other namesTACE, TNF-alpha converting enzyme, tumor-necrosis factor alpha converting enzyme
Domain architecture
MEROPS Classification
Classification Clan MA >> Subclan MA(M) >> Family M12 >> Subfamily B >> M12.217
HolotypeADAM17 peptidase (Homo sapiens), Uniprot accession P78536 (peptidase unit: 205-474), MERNUM MER0003094
History Identifier created: Handbook of Proteolytic Enzymes (1998) Academic Press, London.
Activity
Catalytic typeMetallo
PeplistIncluded in the Peplist with identifier PL00195
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.24 (Metalloendopeptidases) >> Peptidase 3.4.24.86
EnzymologyBRENDA database
Proteolytic eventsCutDB database (30 cleavages)
Activity statushuman: active (Black, 2004)
mouse: active (Zhao et al., 2001)
PhysiologyThe cleavage of the precursor of tumor necrosis factor alpha releases the soluble, 17-kDa factor, which is a mediator of inflammation. The enzyme also causes shedding of many external membrane proteins including receptors by cleavage at sites near the membrane.
KnockoutGene knockout in mice showed that the enzyme plays a central role in regulated alpha-cleavage of Alzheimer"s amyloid protein precursor (APP). The data suggest that it may be the alpha-secretase responsible for the majority of regulated alpha-cleavage in cultured cells, and that inhibiting this enzyme affects both APP secretion and A beta formation in cultured cells (Buxbaum et al., 1998).
Pharmaceutical relevancePotential drug target for control of formation of tumor necrosis factor alpha (TNF alpha).
Pathways KEGGAlzheimer's disease
KEGGEpithelial cell signaling in Helicobacter pylori infection
KEGGNotch signaling pathway
Other databases WIKIPEDIAhttp://en.wikipedia.org/wiki/ADAM17
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage pattern-/-/-/-Scissile bondvls/-/-/- (based on 60 cleavages)
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Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 2 2 2 2 1 2 6 2
Pro 3 4 1 4 0 2 1 5
Ala 0 12 10 15 2 5 6 4
Val 4 10 5 1 20 14 1 7
Leu 10 8 8 3 9 4 5 1
Ile 0 2 2 3 2 4 5 3
Met 0 2 4 0 2 0 1 2
Phe 0 1 3 2 3 1 2 2
Tyr 0 2 0 3 0 0 0 1
Trp 1 0 0 0 0 0 0 1
Ser 4 6 3 0 8 5 15 10
Thr 4 5 0 4 5 5 3 3
Cys 0 0 1 0 0 0 3 0
Asn 4 0 2 1 0 0 3 1
Gln 2 0 9 4 1 2 3 4
Asp 5 1 2 1 3 0 1 3
Glu 2 0 3 0 1 4 0 4
Lys 5 1 1 5 0 2 2 0
Arg 6 1 2 7 1 7 0 4
His 7 3 1 5 0 3 2 1
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
ADAM17 2p25 ENSG00000151694 6868 ADAM17 603639
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Adam17 12 ENSMUSG00000054627 11491 MGI:1096335