Summary for peptidase S01.131: elastase-2

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

 

Names
MEROPS Nameelastase-2
Other nameslysosomal elastase, medullasin, leukocyte elastase, neutrophil elastase, polymorphonuclear leukocyte elastase, spleen fibrinolytic endopeptidase, ELANE g.p. (Homo sapiens)
Domain architecture
MEROPS Classification
Classification Clan PA >> Subclan PA(S) >> Family S1 >> Subfamily A >> S01.131
Holotypeelastase-2 (Homo sapiens), Uniprot accession P08246 (peptidase unit: 30-249), MERNUM MER0000118
History Identifier created: Handbook of Proteolytic Enzymes (1998) Academic Press, London.
Activity
Catalytic typeSerine
PeplistIncluded in the Peplist with identifier PL00270
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.21 (Serine endopeptidases) >> Peptidase 3.4.21.37
EnzymologyBRENDA database
Proteolytic eventsCutDB database (76 cleavages)
Activity statushuman: active (Bieth, 2004)
mouse: active (Lane & Ley, 2003)
PhysiologyDigestion 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).
KnockoutWork 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 relevanceDrug 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 KEGGSystemic lupus erythematosus
KEGGTranscriptional misregulation in cancer
Other databases TREEFAMhttp://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-/-/-/viatScissile bond-/-/-/- (based on 483 cleavages)
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Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 42 28 51 2 54 60 33 34
Pro 35 3 77 2 3 9 39 64
Ala 38 26 43 61 37 34 28 30
Val 31 27 29 141 23 21 48 23
Leu 33 32 62 32 20 86 58 41
Ile 32 32 24 127 18 31 20 27
Met 10 29 23 2 33 9 10 9
Phe 21 11 19 10 16 39 13 22
Tyr 12 14 5 2 14 18 9 5
Trp 4 1 1 0 2 14 2 5
Ser 13 28 31 17 68 32 37 28
Thr 19 39 31 54 56 19 21 26
Cys 12 10 6 4 6 8 8 7
Asn 16 22 7 18 28 28 30 37
Gln 14 38 17 2 22 11 24 11
Asp 15 21 4 1 18 11 34 36
Glu 27 69 20 1 9 13 23 27
Lys 6 16 10 1 18 9 26 15
Arg 9 12 10 5 14 13 5 6
His 19 14 9 0 18 12 9 23
Specificity from combinatorial peptides
 
Organism comment P4 P3 P2 P1 P1' P2' P3' P4' optimal substrate fluorophore or acceptor-donor pair Reference
Homo sapiens recombinant nd nd nd A/V - - - - A ACC Harris et al., 2000
Homo sapiens wild type - M/F/I A/P I/L - - - - xMAI+xxxx Abz-Anb Wysocka et al., 2008
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
ELANE 19p13.3 ENSG00000115644 1991 ELA2 130130
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
EL2 10:C1 ENSMUSG00000020125 50701 MGI:95316