[1]
|
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND MUTAGENESIS OF SER-306.
DOI=10.1074/jbc.275.4.2581; PubMed=10644717 [NCBI, ExPASy, EBI, Israel, Japan]
Faccio L.,
Fusco C.,
Chen A.,
Martinotti S.,
Bonventre J.V.,
Zervos A.S.;
"Characterization of a novel human serine protease that has extensive homology to bacterial heat shock endoprotease HtrA and is regulated by kidney ischemia.";
J. Biol. Chem. 275:2581-2588(2000).
|
[2]
|
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3 AND 4), AND CHARACTERIZATION.
TISSUE=Brain;
DOI=10.1046/j.1432-1327.2000.01589.x; PubMed=10971580 [NCBI, ExPASy, EBI, Israel, Japan]
Gray C.W.,
Ward R.V.,
Karran E.H.,
Turconi S.,
Rowles A.,
Viglienghi D.,
Southan C.,
Barton A.,
Fantom K.G.,
West A.,
Savopoulos J.W.,
Hassan N.J.,
Clinkenbeard H.,
Hanning C.,
Amegadzie B.,
Davis J.B.,
Dingwall C.,
Livi G.P.,
Creasy C.L.;
"Characterization of human HtrA2, a novel serine protease involved in the mammalian cellular stress response.";
Eur. J. Biochem. 267:5699-5710(2000).
|
[3]
|
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
TISSUE=Kidney;
DOI=10.1006/geno.2000.6263; PubMed=10995577 [NCBI, ExPASy, EBI, Israel, Japan]
Faccio L.,
Fusco C.,
Viel A.,
Zervos A.S.;
"Tissue-specific splicing of Omi stress-regulated endoprotease leads to an inactive protease with a modified PDZ motif.";
Genomics 68:343-347(2000).
|
[4]
|
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature03466; PubMed=15815621 [NCBI, ExPASy, EBI, Israel, Japan]
Hillier L.W.,
Graves T.A.,
Fulton R.S.,
Fulton L.A.,
Pepin K.H.,
Minx P.,
Wagner-McPherson C.,
Layman D.,
Wylie K.,
Sekhon M.,
Becker M.C.,
Fewell G.A.,
Delehaunty K.D.,
Miner T.L.,
Nash W.E.,
Kremitzki C.,
Oddy L.,
Du H.,
Sun H., ![]()
Bradshaw-Cordum H.,
Ali J.,
Carter J.,
Cordes M.,
Harris A.,
Isak A.,
van Brunt A.,
Nguyen C.,
Du F.,
Courtney L.,
Kalicki J.,
Ozersky P.,
Abbott S.,
Armstrong J.,
Belter E.A.,
Caruso L.,
Cedroni M.,
Cotton M.,
Davidson T.,
Desai A.,
Elliott G.,
Erb T.,
Fronick C.,
Gaige T.,
Haakenson W.,
Haglund K.,
Holmes A.,
Harkins R.,
Kim K.,
Kruchowski S.S.,
Strong C.M.,
Grewal N.,
Goyea E.,
Hou S.,
Levy A.,
Martinka S.,
Mead K.,
McLellan M.D.,
Meyer R.,
Randall-Maher J.,
Tomlinson C.,
Dauphin-Kohlberg S.,
Kozlowicz-Reilly A.,
Shah N.,
Swearengen-Shahid S.,
Snider J.,
Strong J.T.,
Thompson J.,
Yoakum M.,
Leonard S.,
Pearman C.,
Trani L.,
Radionenko M.,
Waligorski J.E.,
Wang C.,
Rock S.M.,
Tin-Wollam A.-M.,
Maupin R.,
Latreille P.,
Wendl M.C.,
Yang S.-P.,
Pohl C.,
Wallis J.W.,
Spieth J.,
Bieri T.A.,
Berkowicz N.,
Nelson J.O.,
Osborne J.,
Ding L.,
Meyer R.,
Sabo A.,
Shotland Y.,
Sinha P.,
Wohldmann P.E.,
Cook L.L.,
Hickenbotham M.T.,
Eldred J.,
Williams D.,
Jones T.A.,
She X.,
Ciccarelli F.D.,
Izaurralde E.,
Taylor J.,
Schmutz J.,
Myers R.M.,
Cox D.R.,
Huang X.,
McPherson J.D.,
Mardis E.R.,
Clifton S.W.,
Warren W.C.,
Chinwalla A.T.,
Eddy S.R.,
Marra M.A.,
Ovcharenko I.,
Furey T.S.,
Miller W.,
Eichler E.E.,
Bork P.,
Suyama M.,
Torrents D.,
Waterston R.H.,
Wilson R.K.;
"Generation and annotation of the DNA sequences of human chromosomes 2 and 4.";
Nature 434:724-731(2005).
|
[5]
|
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Brain;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
|
[6]
|
PROTEIN SEQUENCE OF 134-458, INTERACTION WITH XIAP, AND MUTAGENESIS OF ALA-134.
DOI=10.1016/S1097-2765(01)00341-0; PubMed=11583623 [NCBI, ExPASy, EBI, Israel, Japan]
Suzuki Y.,
Imai Y.,
Nakayama H.,
Takahashi K.,
Takio K.,
Takahashi R.;
"A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death.";
Mol. Cell 8:613-621(2001).
|
[7]
|
CHARACTERIZATION.
DOI=10.1006/prep.2000.1240; PubMed=10873535 [NCBI, ExPASy, EBI, Israel, Japan]
Savopoulos J.W.,
Carter P.S.,
Turconi S.,
Pettman G.R.,
Karran E.H.,
Gray C.W.,
Ward R.V.,
Jenkins O.,
Creasy C.L.;
"Expression, purification, and functional analysis of the human serine protease HtrA2.";
Protein Expr. Purif. 19:227-234(2000).
|
[8]
|
IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
Colinge J.,
Superti-Furga G.,
Bennett K.L.;
Submitted (OCT-2008) to UniProtKB.
|
[9]
|
X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 134-458, AND SUBUNIT.
DOI=10.1038/nsb795; PubMed=11967569 [NCBI, ExPASy, EBI, Israel, Japan]
Li W.,
Srinivasula S.M.,
Chai J.,
Li P.,
Wu J.W.,
Zhang Z.,
Alnemri E.S.,
Shi Y.;
"Structural insights into the pro-apoptotic function of mitochondrial serine protease HtrA2/Omi.";
Nat. Struct. Biol. 9:436-441(2002).
|
[10]
|
VARIANT PARK13 SER-399, VARIANT SER-141, AND CHARACTERIZATION OF VARIANTS SER-141 AND SER-399.
DOI=10.1093/hmg/ddi215; PubMed=15961413 [NCBI, ExPASy, EBI, Israel, Japan]
Strauss K.M.,
Martins L.M.,
Plun-Favreau H.,
Marx F.P.,
Kautzmann S.,
Berg D.,
Gasser T.,
Wszolek Z.,
Mueller T.,
Bornemann A.,
Wolburg H.,
Downward J.,
Riess O.,
Schulz J.B.,
Krueger R.;
"Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease.";
Hum. Mol. Genet. 14:2099-2111(2005).
|
[11]
|
VARIANTS PRO-72; SER-141 AND TRP-404, AND ASSOCIATION WITH INCREASED RISK OF PARKINSON DISEASE.
DOI=10.1002/humu.20713; PubMed=18401856 [NCBI, ExPASy, EBI, Israel, Japan]
Bogaerts V.,
Nuytemans K.,
Reumers J.,
Pals P.,
Engelborghs S.,
Pickut B.,
Corsmit E.,
Peeters K.,
Schymkowitz J.,
De Deyn P.P.,
Cras P.,
Rousseau F.,
Theuns J.,
Van Broeckhoven C.;
"Genetic variability in the mitochondrial serine protease HTRA2 contributes to risk for Parkinson disease.";
Hum. Mutat. 29:832-840(2008).
|
|
- FUNCTION: Serine protease that shows proteolytic activity against a non-specific substrate beta-casein. Promotes or induces cell death either by direct binding to and inhibition of BIRC proteins (also called inhibitor of apoptosis proteins, IAPs), leading to an increase in caspase activity, or by a BIRC inhibition-independent, caspase-independent and serine protease activity-dependent mechanism. Isoform 2 seems to be proteolytically inactive.
- CATALYTIC ACTIVITY: 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.
- SUBUNIT: Homotrimer. Interacts with MXI2. The mature protein, but not the precursor, binds to BIRC2, BIRC3 and XIAP.
- INTERACTION:
Q96CA5:BIRC7; NbExp=2; IntAct=EBI-517086, EBI-517623;
Q9P0J0:NDUFA13; NbExp=4; IntAct=EBI-517086, EBI-372742;
P98170:XIAP; NbExp=3; IntAct=EBI-517086, EBI-517127;
- SUBCELLULAR LOCATION: 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.
- ALTERNATIVE PRODUCTS:
4 named isoforms [FASTA] produced by alternative splicing.
| | |
| Name | 4 |
| Synonyms | p4 |
| Isoform ID | O43464-4 |
| Features which should be applied to build the isoform sequence: VSP_005362. |
|
|
- TISSUE SPECIFICITY: Isoform 1 is ubiquitous; isoform 2 is expressed predominantly in the kidney, colon and thyroid.
- DOMAIN: The mature N-terminus is involved in the interaction with XIAP.
- DOMAIN: The PDZ domain mediates interaction with MXI2.
- PTM: Autoproteolytically activated.
- DISEASE: Defects in HTRA2 are the cause of Parkinson disease type 13 (PARK13) [MIM:610297, 168600]. Parkinson disease (PD) is a complex, multifactorial disorder that typically manifests after the age of 50 years, although early-onset cases (before 50 years) are known. PD generally arises as a sporadic condition but is occasionally inherited as a simple mendelian trait. Although sporadic and familial PD are very similar, inherited forms of the disease usually begin at earlier ages and are associated with atypical clinical features. PD is characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain.
- SIMILARITY: Belongs to the peptidase S1B family [view classification].
- SIMILARITY: Contains 1 PDZ (DHR) domain.
|
ExPASy Home page
SIB Switzerland
