DB code: T00411

RLCP classification 1.13.30000.10 : Hydrolysis
CATH domain 2.40.10.10 : Thrombin, subunit H Catalytic domain
2.40.10.10 : Thrombin, subunit H Catalytic domain
2.30.42.10 : Pdz3 Domain
E.C. 3.4.21.108
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
2.30.42.10 : Pdz3 Domain M00169
2.40.10.10 : Thrombin, subunit H M00139 D00214 M00167 D00426 M00133 D00428 D00429 D00430 D00431 D00432 D00433 D00434 D00435 M00227 M00209 D00194 D00197 D00211 D00212 D00216 M00212 D00224 D00497 M00217 M00216 D00528 D00848 D00850 D00851 D00852 D00855 M00152 M00155 M00157 M00181 M00315 M00316 M00317 M00348 M00349 T00074 T00410

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq MEROPS Pfam
O43464 Serine protease HTRA2, mitochondrial
EC 3.4.21.108
High temperature requirement protein A2
HtrA2
Omi stress-regulated endoprotease
Serine protease 25
Serine proteinase OMI
NP_037379.1 (Protein)
NM_013247.4 (DNA/RNA sequence)
NP_659540.1 (Protein)
NM_145074.2 (DNA/RNA sequence)
S01.278 (Serine)
PF13180 (PDZ_2)
[Graphical View]

KEGG enzyme name
HtrA2 peptidase
High temperature requirement protein A2
HtrA2
Omi stress-regulated endoprotease
Serine proteinase OMI
HtrA2 protease
OMI/HtrA2 protease
HtrA2/Omi
Omi/HtrA2

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
O43464 HTRA2_HUMAN Cleavage of non-polar aliphatic amino-acids at the P1 position, with a preference for Val, Ile and Met. At the P2 and P3 positions, Arg is selected most strongly with a secondary preference for other hydrophilic residues. Homotrimer. Interacts with MXI2. Interacts with THAP5 under apoptotic conditions. The mature protein, but not the precursor, binds to BIRC2, BIRC3 and XIAP. Mitochondrion intermembrane space. Mitochondrion membrane, Single-pass membrane protein (Potential). Note: Predominantly present in the intermembrane space. Released into the cytosol following apoptotic stimuli, such as UV treatment, and stimulation of mitochondria with caspase-8 truncated BID/tBID.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00017 C00001 C00017 C00012 I00087 I00085 I00086
E.C.
Compound Protein Water Protein Peptide Peptidyl-Ser-tetrahedral-intermediate (with previous peptide) Acyl-enzyme(Peptidyl-Ser-acyl group) Peptidyl-Ser-tetrahedral-intermediate
Type peptide/protein H2O peptide/protein peptide/protein
ChEBI 15377
 15377
PubChem 22247451
 962
 22247451
 962
1lcyA01 Unbound Unbound Unbound Unbound Unbound Unbound
1lcyA02 Unbound Unbound Unbound Unbound Unbound Unbound
1lcyA03 Unbound Unbound Unbound Unbound Unbound Unbound
2pzdA Unbound Unbound Unbound Unbound Unbound Unbound
2pzdB Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Literature [4] & Swiss-prot;O43464

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1lcyA01 HIS 65;ASP 95
1lcyA02 GLY 171; mutant S173A
1lcyA03
2pzdA
2pzdB

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
Figure 5, p.4505-4508

References
[1]
Resource
Comments
Medline ID
PubMed ID 12058274
Journal Cell Death Differ
Year 2002
Volume 9
Pages 699-701
Authors Martins LM
Title The serine protease Omi/HtrA2: a second mammalian protein with a Reaper-like function.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 12475199
Journal Chem Rev
Year 2002
Volume 102
Pages 4501-24
Authors Hedstrom L
Title Serine protease mechanism and specificity.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 12408815
Journal Mol Cell
Year 2002
Volume 10
Pages 443-55
Authors Clausen T, Southan C, Ehrmann M
Title The HtrA family of proteases: implications for protein composition and cell fate.
Related PDB
Related UniProtKB
[4]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 134-458, SUBUNIT.
Medline ID
PubMed ID 11967569
Journal Nat Struct Biol
Year 2002
Volume 9
Pages 436-41
Authors Li W, Srinivasula SM, Chai J, Li P, Wu JW, Zhang Z, Alnemri ES, Shi Y
Title Structural insights into the pro-apoptotic function of mitochondrial serine protease HtrA2/Omi.
Related PDB 1lcy
Related UniProtKB O43464
[5]
Resource
Comments
Medline ID
PubMed ID 14512424
Journal J Biol Chem
Year 2003
Volume 278
Pages 49417-27
Authors Martins LM, Turk BE, Cowling V, Borg A, Jarrell ET, Cantley LC, Downward J
Title Binding specificity and regulation of the serine protease and PDZ domains of HtrA2/Omi.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 15201285
Journal J Biol Chem
Year 2004
Volume 279
Pages 37588-96
Authors Seong YM, Choi JY, Park HJ, Kim KJ, Ahn SG, Seong GH, Kim IK, Kang S, Rhim H
Title Autocatalytic processing of HtrA2/Omi is essential for induction of caspase-dependent cell death through antagonizing XIAP.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 17266347
Journal J Proteome Res
Year 2007
Volume 6
Pages 1006-15
Authors Vande Walle L, Van Damme P, Lamkanfi M, Saelens X, Vandekerckhove J, Gevaert K, Vandenabeele P
Title Proteome-wide Identification of HtrA2/Omi Substrates.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 17656586
Journal Protein Sci
Year 2007
Volume 16
Pages 1738-50
Authors Zhang Y, Appleton BA, Wu P, Wiesmann C, Sidhu SS
Title Structural and functional analysis of the ligand specificity of the HtrA2/Omi PDZ domain.
Related PDB 2pzd
Related UniProtKB O43464
[9]
Resource
Comments
Medline ID
PubMed ID 21326199
Journal Nat Rev Mol Cell Biol
Year 2011
Volume 12
Pages 152-62
Authors Clausen T, Kaiser M, Huber R, Ehrmann M
Title HTRA proteases: regulated proteolysis in protein quality control.
Related PDB
Related UniProtKB

Comments
This enzyme belongs to peptidase family-S1B.
This enzyme is homologous to the bacterial enzyme HtrA (also called DegP;EC 3.4.21.107)(see [9]). These enzymes are involved in protein quality control (see [9]).
Since this enzyme has got the same catalytic site as trypsin, it must catalyze the trypsin-like reaction.

Created Updated
2011-05-10 2012-08-01