Summary for peptidase S01.278: HtrA2 peptidase

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

 

Names
MEROPS NameHtrA2 peptidase
Other nameshigh temperature requirement A2 peptidase, HTRA2 g.p. (Homo sapiens), OMI g.p. (Homo sapiens), OMI/HtrA2 protease, PARK13 protein, PRSS25 g.p. (Homo sapiens)
Domain architecture
MEROPS Classification
Classification Clan PA >> Subclan PA(S) >> Family S1 >> Subfamily C >> S01.278
HolotypeHtrA2 peptidase (Homo sapiens), Uniprot accession O43464 (peptidase unit: 182-334), MERNUM MER0004093
History Identifier created: MEROPS 3.30 (20 July 1999)
Activity
Catalytic typeSerine
PeplistIncluded in the Peplist with identifier PL00334
NC-IUBMBNot yet included in IUBMB recommendations.
Proteolytic eventsCutDB database (6 cleavages)
Activity statushuman: active (Dingwall & Holbrook, 2004)
mouse: active (Jones et al., 2003)
PhysiologyContributes to apoptosis in some systems (Cilenti et al., 2004).
KnockoutThe mouse mutant mnd2 (motor neuron degeneration 2) carries a missense mutation Ser276Cys in the protease domain of the HtrA2 protease (Jones et al., 2003). Mice lacking expression of HtrA2 as a result of deletion of the gene showed loss of a population of neurons in the striatum, resulting in a neurodegenerative disorder with a parkinsonian phenotype that led to death of the mice around 30 days after birth (Martins etal, 2004). The nature of links between the HTRA2 peptidase and Parkinson"s disease was further investigated by Strauss et al. (2005).
Pathways KEGGParkinson's disease
Other databases TREEFAMhttp://www.treefam.org/family/TF323480
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage patterng/-/l/lvtScissile bond-/f/g/- (based on 233 cleavages)
weblogo
Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 38 10 7 0 22 23 49 22
Pro 32 12 12 0 0 0 33 22
Ala 20 7 4 4 36 40 32 10
Val 23 16 4 61 5 23 3 7
Leu 27 24 61 71 3 15 3 30
Ile 7 8 0 14 7 7 3 6
Met 1 2 13 8 0 0 8 28
Phe 24 31 3 0 8 44 9 21
Tyr 0 1 9 0 18 3 1 8
Trp 1 0 0 12 0 1 0 0
Ser 10 13 12 0 15 6 13 1
Thr 34 24 0 41 28 12 14 25
Cys 0 5 8 16 0 0 0 6
Asn 8 7 8 1 7 17 18 0
Gln 0 7 16 2 1 0 9 0
Asp 0 10 15 3 18 1 17 4
Glu 0 14 12 0 30 20 20 19
Lys 0 5 26 0 13 8 0 13
Arg 0 15 15 0 11 0 1 1
His 8 22 8 0 11 13 0 10
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
HTRA2 2p12 ENSG00000115317 27429 PRSS25 606441
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Prss25 6 ENSMUSG00000035023 64704 MGI:1928676