Names & Taxonomy

Uniprot ID:
P78536
Entry Name:
ADA17_HUMAN
Status:
reviewed
Protein Names:
Disintegrin and metalloproteinase domain-containing protein 17 (ADAM 17) (EC 3.4.24.86) (Snake venom-like protease) (TNF-alpha convertase) (TNF-alpha-converting enzyme) (CD antigen CD156b)
Gene Names:
ADAM17 CSVP TACE
Gene Names Primary:
ADAM17
Organism:
Homo sapiens (Human)

Structure

Length:
824
Sequence:
MRQSLLFLTSVVPFVLAPRPPDDPGFGPHQRLEKLDSLLSDYDILSLSNIQQHSVRKRDLQTSTHVETLLTFSALKRHFKLYLTSSTERFSQNFKVVVVDGKNESEYTVKWQDFFTGHVVGEPDSRVLAHIRDDDVIIRINTDGAEYNIEPLWRFVNDTKDKRMLVYKSEDIKNVSRLQSPKVCGYLKVDNEELLPKGLVDREPPEELVHRVKRRADPDPMKNTCKLLVVADHRFYRYMGRGEESTTTNYLIELIDRVDDIYRNTSWDNAGFKGYGIQIEQIRILKSPQEVKPGEKHYNMAKSYPNEEKDAWDVKMLLEQFSFDIAEEASKVCLAHLFTYQDFDMGTLGLAYVGSPRANSHGGVCPKAYYSPVGKKNIYLNSGLTSTKNYGKTILTKEADLVTTHELGHNFGAEHDPDGLAECAPNEDQGGKYVMYPIAVSGDHENNKMFSNCSKQSIYKTIESKAQECFQERSNKVCGNSRVDEGEECDPGIMYLNNDTCCNSDCTLKEGVQCSDRNSPCCKNCQFETAQKKCQEAINATCKGVSYCTGNSSECPPPGNAEDDTVCLDLGKCKDGKCIPFCEREQQLESCACNETDNSCKVCCRDLSGRCVPYVDAEQKNLFLRKGKPCTVGFCDMNGKCEKRVQDVIERFWDFIDQLSINTFGKFLADNIVGSVLVFSLIFWIPFSILVHCVDKKLDKQYESLSLFHPSNVEMLSSMDSASVRIIKPFPAPQTPGRLQPAPVIPSAPAAPKLDHQRMDTIQEDPSTDSHMDEDGFEKDPFPNSSTAAKSFEDLTDHPVTRSEKAASFKLQRQNRVDSKETEC
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Membrane; Single-pass type I membrane protein.

Function

Function:
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.
Catalytic Activity:
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.
Cofactor:
COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
Active Site:
ACT_SITE 406 406
Gene Ontology Go:
actin cytoskeleton
apical plasma membrane
cell surface
cytoplasm
integral component of plasma membrane
membrane
membrane raft
plasma membrane
integrin binding
interleukin-6 receptor binding
metalloendopeptidase activity
metallopeptidase activity
Notch binding
PDZ domain binding
zinc ion binding
B cell differentiation
cell adhesion
cell adhesion mediated by integrin
cell motility
cell surface receptor signaling pathway
collagen catabolic process
defense response to Gram-positive bacterium
epidermal growth factor receptor signaling pathway
epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathway
extracellular matrix disassembly
extracellular matrix organization
germinal center formation
JAK-STAT cascade involved in growth hormone signaling pathway
membrane protein ectodomain proteolysis
membrane protein intracellular domain proteolysis
negative regulation of transforming growth factor beta receptor signaling pathway
neurotrophin TRK receptor signaling pathway
neutrophil mediated immunity
Notch receptor processing
Notch signaling pathway
PMA-inducible membrane protein ectodomain proteolysis
positive regulation of cell growth
positive regulation of cell migration
positive regulation of cell proliferation
positive regulation of cellular component movement
positive regulation of chemokine production
positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle
positive regulation of epidermal growth factor-activated receptor activity
positive regulation of leukocyte chemotaxis
positive regulation of protein phosphorylation
positive regulation of T cell chemotaxis
positive regulation of transforming growth factor beta receptor signaling pathway
proteolysis
regulation of mast cell apoptotic process
response to drug
response to high density lipoprotein particle
response to hypoxia
response to lipopolysaccharide
spleen development
T cell differentiation in thymus
tumor necrosis factor-mediated signaling pathway
wound healing, spreading of epidermal cells
Gene Ontology Biological Process:
B cell differentiation
cell adhesion
cell adhesion mediated by integrin
cell motility
cell surface receptor signaling pathway
collagen catabolic process
defense response to Gram-positive bacterium
epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathway
epidermal growth factor receptor signaling pathway
extracellular matrix disassembly
extracellular matrix organization
germinal center formation
JAK-STAT cascade involved in growth hormone signaling pathway
membrane protein ectodomain proteolysis
membrane protein intracellular domain proteolysis
negative regulation of transforming growth factor beta receptor signaling pathway
neurotrophin TRK receptor signaling pathway
neutrophil mediated immunity
Notch receptor processing
Notch signaling pathway
PMA-inducible membrane protein ectodomain proteolysis
positive regulation of cell growth
positive regulation of cell migration
positive regulation of cell proliferation
positive regulation of cellular component movement
positive regulation of chemokine production
positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle
positive regulation of epidermal growth factor-activated receptor activity
positive regulation of leukocyte chemotaxis
positive regulation of protein phosphorylation
positive regulation of T cell chemotaxis
positive regulation of transforming growth factor beta receptor signaling pathway
proteolysis
regulation of mast cell apoptotic process
response to drug
response to high density lipoprotein particle
response to hypoxia
response to lipopolysaccharide
spleen development
T cell differentiation in thymus
tumor necrosis factor-mediated signaling pathway
wound healing, spreading of epidermal cells
Gene Ontology Molecular Function:
integrin binding
interleukin-6 receptor binding
metalloendopeptidase activity
metallopeptidase activity
Notch binding
PDZ domain binding
zinc ion binding
Gene Ontology Cellular Component:
actin cytoskeleton
apical plasma membrane
cell surface
cytoplasm
integral component of plasma membrane
membrane
membrane raft
plasma membrane
Keywords:
3D-structure
Alternative splicing
Cleavage on pair of basic residues
Complete proteome
Direct protein sequencing
Disulfide bond
Glycoprotein
Hydrolase
Membrane
Metal-binding
Metalloprotease
Notch signaling pathway
Phosphoprotein
Polymorphism
Protease
Reference proteome
SH3-binding
Signal
Transmembrane
Transmembrane helix
Zinc
Zymogen
Interacts With:
Q12959; Q13257

Publication

PubMed ID:
9034191 9034190 9574564 12058067 12441351 12621058 17081983 18669648 20592283 20188673 20068231 22010916 21406692 24226769 24275569 24227843 9520379