Activity |
Catalytic type | Serine |
Peplist | Included in the Peplist with identifier PL00270 |
NC-IUBMB | Subclass 3.4 (Peptidases) >> Sub-subclass 3.4.21 (Serine endopeptidases) >> Peptidase 3.4.21.37
|
Enzymology | BRENDA database |
Proteolytic events | CutDB database (76 cleavages) |
Activity status | human: active (Bieth, 2004) mouse: active (Lane & Ley, 2003)
|
Physiology | Digestion of ingested bacteria, extracellular matrix components and necrotic tissue elements by polymorphonuclear leukocytes. Cyclic and congenital neutropenia are caused by mutations in the human neutrophil elastase gene (Thusberg, J. & Vihinen, M. 2006). |
Knockout | Work with transgenic mice shows that the enzyme has a role in intracellular killing of Gram negative bacteria and fungi in neutrophil leukocytes (Belaaouaj et al., 1998; Tkalcevic et al., 2000; Belaaouaj, 2002). Mutations in the human gene lead to cyclic neutropenia (MIM 162800), with lowered resistance to infection (Horwitz et al., 1999; Dale et al., 2000; Aprikyan & Dale, 2001), and to severe congenital neutropenia (Horwitz et al., 2004; Massullo et al., 2005). |
Pharmaceutical relevance | Drug target for emphysema, cystic fibrosis (Martin et al., 2006), adult respiratory distress syndrome, rheumatoid arthritis and other diseases. Induces proliferation in mouse keratinocytes in concentrations that can be found on the skin surface of psoriatic lesions, so may contribute to the epidermal hyperproliferation observed in psoriasis (Rogalski et al., 2002). An inhibitor reduces myocardial infarct size following ischemia-reperfusion injury in rabbit (Bidouard et al., 2003). Reportedly important for the development of acute promyelocytic leukemia in mice through cleavage of PML-RARalpha (Lane & Ley, 2003). |
Pathways |
KEGG | Systemic lupus erythematosus |
|
KEGG | Transcriptional misregulation in cancer |
Other databases
| TREEFAM | http://www.treefam.org/family/TF335284 |
Cleavage site specificity |
Explanations of how to interpret the
following cleavage site sequence logo and specificity matrix can be found here. |
Cleavage pattern | -/-/-/viat-/-/-/- (based on 488 cleavages) |