EzCatDB: T00411
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DB codeT00411
RLCP classification1.13.30000.10 : Hydrolysis
CATH domainDomain 12.40.10.10 : Thrombin, subunit HCatalytic domain
Domain 22.40.10.10 : Thrombin, subunit HCatalytic domain
Domain 32.30.42.10 : Pdz3 Domain
E.C.3.4.21.108

CATH domainRelated DB codes (homologues)
2.30.42.10 : Pdz3 DomainM00169
2.40.10.10 : Thrombin, subunit HM00139,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

Enzyme Name
UniProtKBKEGG

O43464
Protein nameSerine protease HTRA2, mitochondrialHtrA2 peptidase
High temperature requirement protein A2
HtrA2
Omi stress-regulated endoprotease
Serine proteinase OMI
HtrA2 protease
OMI/HtrA2 protease
HtrA2/Omi
Omi/HtrA2
SynonymsEC 3.4.21.108
High temperature requirement protein A2
HtrA2
Omi stress-regulated endoprotease
Serine protease 25
Serine proteinase OMI
RefSeqNP_037379.1 (Protein)
NM_013247.4 (DNA/RNA sequence)
NP_659540.1 (Protein)
NM_145074.2 (DNA/RNA sequence)
MEROPSS01.278 (Serine)
PfamPF13180 (PDZ_2)
[Graphical view]


UniProtKB:Accession NumberO43464
Entry nameHTRA2_HUMAN
ActivityCleavage 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.
SubunitHomotrimer. Interacts with MXI2. Interacts with THAP5 under apoptotic conditions. The mature protein, but not the precursor, binds to BIRC2, BIRC3 and XIAP.
Subcellular locationMitochondrion 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.
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC00017C00001C00017C00012I00087I00085I00086
CompoundProteinWaterProteinPeptidePeptidyl-Ser-tetrahedral-intermediate (with previous peptide)Acyl-enzyme(Peptidyl-Ser-acyl group)Peptidyl-Ser-tetrahedral-intermediate
Typepeptide/proteinH2Opeptide/proteinpeptide/protein


ChEBI
15377





PubChem
962
22247451





               
1lcyA01Unbound UnboundUnboundUnboundUnboundUnbound
1lcyA02Unbound UnboundUnboundUnboundUnboundUnbound
1lcyA03Unbound UnboundUnboundUnboundUnboundUnbound
2pzdAUnbound UnboundUnboundUnboundUnboundUnbound
2pzdBUnbound UnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Literature [4] & Swiss-prot;O43464
pdbCatalytic residuesMain-chain involved in catalysiscomment
           
1lcyA01HIS 65;ASP 95
 
 
1lcyA02       
GLY 171;       
mutant S173A
1lcyA03 
 
 
2pzdA 
 
 
2pzdB 
 
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]Figure 5, p.4505-4508

references
[1]
PubMed ID12058274
JournalCell Death Differ
Year2002
Volume9
Pages699-701
AuthorsMartins LM
TitleThe serine protease Omi/HtrA2: a second mammalian protein with a Reaper-like function.
[2]
PubMed ID12475199
JournalChem Rev
Year2002
Volume102
Pages4501-24
AuthorsHedstrom L
TitleSerine protease mechanism and specificity.
[3]
PubMed ID12408815
JournalMol Cell
Year2002
Volume10
Pages443-55
AuthorsClausen T, Southan C, Ehrmann M
TitleThe HtrA family of proteases: implications for protein composition and cell fate.
[4]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 134-458, SUBUNIT.
PubMed ID11967569
JournalNat Struct Biol
Year2002
Volume9
Pages436-41
AuthorsLi W, Srinivasula SM, Chai J, Li P, Wu JW, Zhang Z, Alnemri ES, Shi Y
TitleStructural insights into the pro-apoptotic function of mitochondrial serine protease HtrA2/Omi.
Related PDB1lcy
Related UniProtKBO43464
[5]
PubMed ID14512424
JournalJ Biol Chem
Year2003
Volume278
Pages49417-27
AuthorsMartins LM, Turk BE, Cowling V, Borg A, Jarrell ET, Cantley LC, Downward J
TitleBinding specificity and regulation of the serine protease and PDZ domains of HtrA2/Omi.
[6]
PubMed ID15201285
JournalJ Biol Chem
Year2004
Volume279
Pages37588-96
AuthorsSeong YM, Choi JY, Park HJ, Kim KJ, Ahn SG, Seong GH, Kim IK, Kang S, Rhim H
TitleAutocatalytic processing of HtrA2/Omi is essential for induction of caspase-dependent cell death through antagonizing XIAP.
[7]
PubMed ID17266347
JournalJ Proteome Res
Year2007
Volume6
Pages1006-15
AuthorsVande Walle L, Van Damme P, Lamkanfi M, Saelens X, Vandekerckhove J, Gevaert K, Vandenabeele P
TitleProteome-wide Identification of HtrA2/Omi Substrates.
[8]
PubMed ID17656586
JournalProtein Sci
Year2007
Volume16
Pages1738-50
AuthorsZhang Y, Appleton BA, Wu P, Wiesmann C, Sidhu SS
TitleStructural and functional analysis of the ligand specificity of the HtrA2/Omi PDZ domain.
Related PDB2pzd
Related UniProtKBO43464
[9]
PubMed ID21326199
JournalNat Rev Mol Cell Biol
Year2011
Volume12
Pages152-62
AuthorsClausen T, Kaiser M, Huber R, Ehrmann M
TitleHTRA proteases: regulated proteolysis in protein quality control.

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.

createdupdated
2011-05-102012-08-01


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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