[cite web | title = Entrez Gene: HTRA2 HtrA serine peptidase 2| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27429| accessdate = ] PBB_Summary]
section_title =
summary_text = This gene encodes a serine protease. HtrA2, also known as Omi, is a mitochondrially-located serine protease. HtrA2 can be released from the mitochondria during apoptosis and uses its four most N-terminal amino acids to mimic a caspase and be recruited by IAP caspase inhibitors such as XIAP and CIAP1/2. Once bound, the serine protease cleaves the IAP, reducing the cell's inhibition to caspase activation. Additionally, HtrA2 has a PDZ domain, though little is known about it's ability to bind PDZ binding motif peptides. HtrA2 has recently been identified as a gene related to Parkinson's disease. Mutations in Htra2 have been found in patients suffering from Parkinson's disease. Additionally, mice lacking HtrA2 have a parkinsonian phenotype. This suggests that HtrA2 is linked to Parkinson's disease progression in humans and mice.HtrA2 shows similarities with DegS, a bacterial protease present in the periplasm of gram-negative bacteria. Structurally, HtrA2 is a trimeric molecule with central protease domains and carboxy-terminal PDZ domains.
References
Further reading
PBB_Further_reading
citations =
*cite journal | author=Zurawa-Janicka D, Narkiewicz J, Lipińska B |title= [Characterization of the HtrA family of proteins] |journal=Postepy Biochem. |volume=53 |issue= 1 |pages= 27–36 |year= 2007 |pmid= 17718385 |doi=
*cite journal | author=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171–4 |year= 1994 |pmid= 8125298 |doi=
*cite journal | author=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, "et al." |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1-2 |pages= 149–56 |year= 1997 |pmid= 9373149 |doi=
*cite journal | author=Faccio L, Fusco C, Chen A, "et al." |title=Characterization of a novel human serine protease that has extensive homology to bacterial heat shock endoprotease HtrA and is regulated by kidney ischemia. |journal=J. Biol. Chem. |volume=275 |issue= 4 |pages= 2581–8 |year= 2000 |pmid= 10644717 |doi=
*cite journal | author=Savopoulos JW, Carter PS, Turconi S, "et al." |title=Expression, purification, and functional analysis of the human serine protease HtrA2. |journal=Protein Expr. Purif. |volume=19 |issue= 2 |pages= 227–34 |year= 2000 |pmid= 10873535 |doi= 10.1006/prep.2000.1240
*cite journal | author=Gray CW, Ward RV, Karran E, "et al." |title=Characterization of human HtrA2, a novel serine protease involved in the mammalian cellular stress response. |journal=Eur. J. Biochem. |volume=267 |issue= 18 |pages= 5699–710 |year= 2000 |pmid= 10971580 |doi=
*cite journal | author=Faccio L, Fusco C, Viel A, Zervos AS |title=Tissue-specific splicing of Omi stress-regulated endoprotease leads to an inactive protease with a modified PDZ motif. |journal=Genomics |volume=68 |issue= 3 |pages= 343–7 |year= 2000 |pmid= 10995577 |doi= 10.1006/geno.2000.6263
*cite journal | author=Suzuki Y, Imai Y, Nakayama H, "et al." |title=A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death. |journal=Mol. Cell |volume=8 |issue= 3 |pages= 613–21 |year= 2001 |pmid= 11583623 |doi=
*cite journal | author=Verhagen AM, Silke J, Ekert PG, "et al." |title=HtrA2 promotes cell death through its serine protease activity and its ability to antagonize inhibitor of apoptosis proteins. |journal=J. Biol. Chem. |volume=277 |issue= 1 |pages= 445–54 |year= 2002 |pmid= 11604410 |doi= 10.1074/jbc.M109891200
*cite journal | author=Hegde R, Srinivasula SM, Zhang Z, "et al." |title=Identification of Omi/HtrA2 as a mitochondrial apoptotic serine protease that disrupts inhibitor of apoptosis protein-caspase interaction. |journal=J. Biol. Chem. |volume=277 |issue= 1 |pages= 432–8 |year= 2002 |pmid= 11606597 |doi= 10.1074/jbc.M109721200
*cite journal | author=Vucic D, Deshayes K, Ackerly H, "et al." |title=SMAC negatively regulates the anti-apoptotic activity of melanoma inhibitor of apoptosis (ML-IAP). |journal=J. Biol. Chem. |volume=277 |issue= 14 |pages= 12275–9 |year= 2002 |pmid= 11801603 |doi= 10.1074/jbc.M112045200
*cite journal | author=van Loo G, van Gurp M, Depuydt B, "et al." |title=The serine protease Omi/HtrA2 is released from mitochondria during apoptosis. Omi interacts with caspase-inhibitor XIAP and induces enhanced caspase activity. |journal=Cell Death Differ. |volume=9 |issue= 1 |pages= 20–6 |year= 2002 |pmid= 11803371 |doi= 10.1038/sj/cdd/4400970
*cite journal | author=Li W, Srinivasula SM, Chai J, "et al." |title=Structural insights into the pro-apoptotic function of mitochondrial serine protease HtrA2/Omi. |journal=Nat. Struct. Biol. |volume=9 |issue= 6 |pages= 436–41 |year= 2002 |pmid= 11967569 |doi= 10.1038/nsb795
*cite journal | author=Strausberg RL, Feingold EA, Grouse LH, "et al." |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899
*cite journal | author=Yang QH, Church-Hajduk R, Ren J, "et al." |title=Omi/HtrA2 catalytic cleavage of inhibitor of apoptosis (IAP) irreversibly inactivates IAPs and facilitates caspase activity in apoptosis. |journal=Genes Dev. |volume=17 |issue= 12 |pages= 1487–96 |year= 2003 |pmid= 12815069 |doi= 10.1101/gad.1097903
*cite journal | author=Srinivasula SM, Gupta S, Datta P, "et al." |title=Inhibitor of apoptosis proteins are substrates for the mitochondrial serine protease Omi/HtrA2. |journal=J. Biol. Chem. |volume=278 |issue= 34 |pages= 31469–72 |year= 2003 |pmid= 12835328 |doi= 10.1074/jbc.C300240200
*cite journal | author=Suzuki Y, Takahashi-Niki K, Akagi T, "et al." |title=Mitochondrial protease Omi/HtrA2 enhances caspase activation through multiple pathways. |journal=Cell Death Differ. |volume=11 |issue= 2 |pages= 208–16 |year= 2004 |pmid= 14605674 |doi= 10.1038/sj.cdd.4401343
*cite journal | author=Okada M, Adachi S, Imai T, "et al." |title=A novel mechanism for imatinib mesylate-induced cell death of BCR-ABL-positive human leukemic cells: caspase-independent, necrosis-like programmed cell death mediated by serine protease activity. |journal=Blood |volume=103 |issue= 6 |pages= 2299–307 |year= 2004 |pmid= 14645012 |doi= 10.1182/blood-2003-05-1605
*cite journal | author=Park HJ, Seong YM, Choi JY, "et al." |title=Alzheimer's disease-associated amyloid beta interacts with the human serine protease HtrA2/Omi. |journal=Neurosci. Lett. |volume=357 |issue= 1 |pages= 63–7 |year= 2004 |pmid= 15036614 |doi= 10.1016/j.neulet.2003.11.068
*cite journal | author=Guo Y, Cheong N, Zhang Z, "et al." |title=Tim50, a component of the mitochondrial translocator, regulates mitochondrial integrity and cell death. |journal=J. Biol. Chem. |volume=279 |issue= 23 |pages= 24813–25 |year= 2004 |pmid= 15044455 |doi= 10.1074/jbc.M402049200
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