3.4.21.108 (35S) Met-labeled proteolytically inactive S306 form of full length HtrA2 + H2O - ? - ? 383441 3.4.21.108 (7-methoxycoumarin-4-yl)acetyl-IRRVSYSF(Dnp)KK + H2O best substrate ? - ? 366272 3.4.21.108 (7-methoxycoumarin-4-yl)acetyl-VTLCAVPS(Dnp)KK + H2O cleavage occurs between cysteine and alanine ? - ? 366271 3.4.21.108 (7-methoxycoumarin-4-yl)AIRRVSYSF-(5-amino-2-nitro)benzamide + H2O - ? - ? 431572 3.4.21.108 2-aminobenzoic acid-Ile-Met-Thr-Abu-Tyr-Met-His-Tyr(3-NO2)-NH2 + H2O - 2-aminobenzoic acid-Ile-Met-Thr + Abu-Tyr-Met-His-Tyr(3-NO2)-NH2 - ? 431303 3.4.21.108 2-aminobenzoic acid-Ile-Met-Thr-Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2 + H2O - 2-aminobenzoic acid-Ile-Met-Thr + Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2 - ? 431304 3.4.21.108 2-aminobenzoic acid-Ile-Met-Thr-Abu-Tyr-Met-Trp-Tyr(3-NO2)-NH2 + H2O - 2-aminobenzoic acid-Ile-Met-Thr + Abu-Tyr-Met-Trp-Tyr(3-NO2)-NH2 - ? 431305 3.4.21.108 2-aminobenzoic acid-Ile-Met-Thr-Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2 + H2O - 2-aminobenzoic acid-Ile-Met-Thr + Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2 - ? 431306 3.4.21.108 2-aminobenzoic acid-Ile-Met-Val-Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2 + H2O - 2-aminobenzoic acid-Ile-Met-Val + Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2 - ? 431307 3.4.21.108 2-aminobenzoic acid-Ile-Met-Val-Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2 + H2O - 2-aminobenzoic acid-Ile-Met-Val + Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2 - ? 431308 3.4.21.108 35S-beta-casein + H2O C-terminus of presenilin-1 interacts the PDZ domain of with Omi/HtrA2, increasing its activity ? - ? 383861 3.4.21.108 A beta 40 HtrA2/Omi binds preferentially to the short form of A beta peptides, the enzyme does not perform degradation by direct hydrolysis ? - ? 384022 3.4.21.108 A beta 42 HtrA2/Omi binds poorly to A beta 42, the enzyme does not perform degradation by direct hydrolysis ? - ? 384023 3.4.21.108 Ala(7-methoxycoumarin-4-acetic acid)-IRRVSYSF-(5-amido-2-nitrobenzamide) + H2O - ? - ? 449529 3.4.21.108 alpha-casein + H2O - ? - ? 366244 3.4.21.108 alpha-secretase peptide HtrA2/Omi does not perform degradation by direct hydrolysis ? - ? 384166 3.4.21.108 amyloid precursor protein + H2O - ? - ? 355643 3.4.21.108 amyloid precursor protein + H2O efficient cleavage by HtrA2 in the normal physiological condition. HtrA2-mediated cleavage product is the C161 fragment encompassing amino acids 535–695 of amyloid precursor protein 695. Mature HtrA2 and full-length HtrA2 can process amyloid precursor protein into C161 ? - ? 355643 3.4.21.108 amyloid precursor protein + H2O APP ? - ? 355643 3.4.21.108 amyloid precursor protein-like protein 1 + H2O processed into two major fragments of 65 and 67 kDa ? - ? 396412 3.4.21.108 amyloid precursor protein-like protein 2 + H2O processed into cleaved fragments of 103 and 109 kDa ? - ? 396413 3.4.21.108 Apollon + H2O HtrA2 cleaves Apollon, a huge inhibitor of apoptosis protein, with its serine protease activity, conversely, Apollon ubiquitylates and facilitates proteasomal degradation of HtrA2, thus both downregulate each other ? - ? 384208 3.4.21.108 Apollon + H2O BRUCE-apollon ? - ? 384208 3.4.21.108 beta-casein protease activity is activated by the binding of the PDZ domain of the mature form of Omi to the C-terminal region of the reduced form of Pag ? - ? 384321 3.4.21.108 beta-casein + H2O - ? - ? 36618 3.4.21.108 beta-casein + H2O preferred substrate ? - ? 36618 3.4.21.108 beta-casein + H2O main selectivity at position P1 is for non-polar aliphatic amino acids, in particular valine, isoleucine and methionine. At the P2 and P3 positions arginine is selected most strongly with a secondary selection for other hydrophilic residues ? - ? 36618 3.4.21.108 beta-casein + H2O cleaved to approximately 50% by GST-HtrA2 after a cleavage reaction for 1 h ? - ? 36618 3.4.21.108 beta-secretase peptide HtrA2/Omi does not perform degradation by direct hydrolysis ? - ? 384333 3.4.21.108 Bir1p - ? - ? 383087 3.4.21.108 Bir1p + H2O inhibitor of apoptosis proteins (IAP) Bir1p is a substrate for Nma11p, which is the yeast homologue of the human OMI/HtrA2, Bir1p physically interacts with the N-terminal HtrA-like repeat of Nma11p ? - ? 384338 3.4.21.108 c-inhibitor of apoptosis protein1 + H2O C-terminus of presenilin-1 interacts with the PDZ domain of Omi/HtrA2, increasing its activity ? - ? 384399 3.4.21.108 c-inhibitor of apoptosis protein2 + H2O C-terminus of presenilin-1 interacts with the PDZ domain of Omi/HtrA2, increasing its activity ? - ? 384400 3.4.21.108 casein + H2O - ? - ? 15445 3.4.21.108 casein + H2O strong hydrolytic activity ? - ? 15445 3.4.21.108 cFLIP + H2O cellular FLICE like inhibitory protein ? - ? 384424 3.4.21.108 dephosphorylated casein + H2O - ? - ? 366261 3.4.21.108 Fas-Fas L + H2O - ? - ? 405119 3.4.21.108 FLIP + H2O Fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein ? - ? 405158 3.4.21.108 gamma-secretase peptide HtrA2/Omi binds less strongly to gamma-secretase substrate peptide as compared to alpha-secretase substrate peptide and beta-secretase substrate peptide, the enzyme does not perform degradation by direct hydrolysis ? - ? 384756 3.4.21.108 glycoprotein alpha1 + H2O - ? - ? 405329 3.4.21.108 glycprotein alpha1 acid + H2O - ? - ? 366263 3.4.21.108 GRIM-19 + H2O - ? - ? 465164 3.4.21.108 GRIM-19 + H2O gene associated with retinoic and interferon-induced mortality 19, also known as NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 (NDUFA13). The cleavage sites are found between 19I-20D, 40I-41G, 49S-50I, 68R-69I, K97-100D and 108E-109S residues ? - ? 465164 3.4.21.108 HAX-1 + H2O - ? - ? 465174 3.4.21.108 HS1-associated protein X-1 + H2O HtrA2/Omi-mediated degradation of HS1-associated protein X-1 correlates with extensive cell death in response to etoposide, cisplatin and H2O2 ? - ? 397441 3.4.21.108 HS1-associated protein X1 + H2O HAX-1 ? - ? 405436 3.4.21.108 hyaluronidase + H2O - ? - ? 366262 3.4.21.108 inhibitor of apoptosis + H2O enzyme cleaves various IAPs ? - ? 366264 3.4.21.108 inhibitor of apoptosis + H2O IAP ? - ? 366264 3.4.21.108 Livin alpha + H2O - ? - ? 366269 3.4.21.108 Livin beta - ? - ? 366270 3.4.21.108 additional information Omi can degrade inhibitor of apoptosis proteins ? - ? 89 3.4.21.108 additional information can promote caspase activation and cell death apoptosis ? - ? 89 3.4.21.108 additional information induces atypical cell death. Inhibits the caspase-inhibitory activity of XIAP by direct binding to it. Only mature form but not its precursor binds to IAPs ? - ? 89 3.4.21.108 additional information induces cell death in a caspase-dependent manner ? - ? 89 3.4.21.108 additional information loss of enzyme activity causes neuromuscular disorder ? - ? 89 3.4.21.108 additional information promotes apoptosis ? - ? 89 3.4.21.108 additional information role in apoptosis ? - ? 89 3.4.21.108 additional information role in apoptosis, amino-terminal IAP interaction motif displaces IAPs from caspases, leading to enhanced caspase activity ? - ? 89 3.4.21.108 additional information role in apoptosis, binds to XIAP-binding protein ? - ? 89 3.4.21.108 additional information role in apoptosis, degradation of aberrantly folded proteins during conditions of cellular stress ? - ? 89 3.4.21.108 additional information role in apoptosis, enzyme can induce apoptosis in a caspase-independent manner through its protease activity and in a caspase-dependent manner via its ability to disrupt caspase-IAP interaction ? - ? 89 3.4.21.108 additional information role in apoptosis, mice with mutant HtrA2/Omi suffer from neurodegenerative disease due to progressive mitochondrial damage, mutant enzyme is proteolytically inactive but can bind to IAPs ? - ? 89 3.4.21.108 additional information does not bind the reversed control peptide A beta 41-1 and peptide H2-Opt ? - ? 89 3.4.21.108 additional information beta-synuclein is not cleaved by HtrA2 ? - ? 89 3.4.21.108 additional information no cleavage of STDGGV-para-nitroaniline and SKAKGGEEPLPEGV-para-nitroaniline ? - ? 89 3.4.21.108 additional information cleavage of DIAP1 between the BIR1 and BIR2 domain and further degradation of BIR1 ? - ? 89 3.4.21.108 additional information HtrA2 cleaves p73alpha in the C-terminal portion ? - ? 89 3.4.21.108 additional information degradation of inhibitor of apoptosis proteins, IAPs ? - ? 89 3.4.21.108 additional information co-immunoprecipitation show direct interaction of Omi/HtrA2 with optic atrophy protein 1 (OPA1) ? - ? 89 3.4.21.108 additional information HtrA2 fails to cleave the Wilms' tumor suppressor 1 cofactors Par-4 and BASP1 ? - ? 89 3.4.21.108 additional information allostery does regulate HtrA2 activity using a non-canonical selective binding pocket in HtrA2 which initiates signal propagation to the distal active site through a complex allosteric mechanism ? - ? 89 3.4.21.108 additional information the enzyme does not affect monomeric alpha-synuclein ? - - 89 3.4.21.108 oligomeric alpha-synuclein + H2O - ? - ? 465392 3.4.21.108 parkin + H2O using cleavage and binding assays, it is demonstrated that HtrA2 specifically binds to and directly cleaves the E3 ubiquitin ligase Parkin ? - ? 361975 3.4.21.108 parkin + H2O HtrA2/Omi cleaves E3 ubiquitin ligase Parkin ? - ? 361975 3.4.21.108 PDZ-interacting peptides + H2O - ? - ? 385510 3.4.21.108 PED-PEA 15 + H2O death effector domain-containing protein ? - ? 406338 3.4.21.108 ped/pea-15 HtrA2 is a specific interactor of the ped/pea-15 death effector domain and leads to its degradation ? - ? 385512 3.4.21.108 protein cIAP1 + H2O best substrate, preferred cleavage sites are after Thr4, Asn133 and Leu161 ? - ? 366265 3.4.21.108 protein cIAP2 + H2O - ? - ? 366266 3.4.21.108 protein DIAP1 + H2O - ? - ? 366268 3.4.21.108 protein XIAP + H2O - ? - ? 366267 3.4.21.108 receptor-interacting protein 1 + H2O the HtrA2/Omi cleavage site receptor-interacting protein 1 is mapped to the intermediate domain and the corresponding N- and C-terminal fragments are impaired in their ability to activate nuclear factor-kappaB, c-Jun N-terminal kinase and p38 mitogen-activated protein kinase ? - ? 419028 3.4.21.108 reduced bovine serum albumin HtrA2-Opt peptides stimulate the delta N-HtrA1 protease activity more than 3fold ? - ? 385670 3.4.21.108 SPMFKGV-p-nitroanilide + H2O - ? - ? 398335 3.4.21.108 thanatos-associated protein 5 (THAP5) + H2O in a yeast two-hybrid assay it is shown that Omi/HtrA2 protease interacts with thanatos-associated protein 5. Degradation assays show that thanatos-associated protein 5 is cleaved by Omi/HtrA2 ? - ? 411030 3.4.21.108 ubiquitin carboxyl-terminal hydrolase L1 + H2O natural substrate for HtrA2 in the apoptotic pathway. HtrA2 directly cleaves UCH-L1 and inhibits its hydrolase activity ? - ? 418112 3.4.21.108 uncoupling protein 2 + H2O - ? - ? 465660 3.4.21.108 unidentified substrate + H2O its cleavage by Omi/HtrA2 leads to permeabilization of the mitochondria outer membrane and release of chytochrome c followed by enhanced caspase activation ? - ? 385891 3.4.21.108 vimentin + H2O - ? - ? 393820 3.4.21.108 WARTS kinase + H2O WARTS, WTS, large tumor-suppressor 1 mitotic kinase ? - ? 406880 3.4.21.108 Wilms' tumor suppressor 1 + H2O bona fide substrate for HtrA2-mediated proteolysis, cleavage sites are in the C terminus at Val286 and Leu320, resulting in fragments of 20000 and 35000 Da, respectively, while another cleavage site is in the N terminus at Leu91 adjacent to suppression domain ? - ? 413659 3.4.21.108 Wilms' tumor suppressor 1 + H2O HtrA2 cleaves at, at least, two specific sites. Wilms' tumor suppressor 1 degradation by HtrA2 reveals two major proteolytic products of 20000 Da and 15000 Da, but the same samples immunoblotted with N-Ter antibody reveals major fragment sizes of 35000 Da and 30000 Da. The potential cleavage site that produces the 20000 Da fragment is at Val286, and the potential cleavage site producing the 15000 Da fragment is at Leu320 ? - ? 413659 3.4.21.108 Wilms' tumor suppressor protein WT1 + H2O using a yeat two-hybrid assay WT1 is identified as a binding partner of HtrA2/Omi. HtrA2/Omi cleaves WT1 at multiple binding sites following the treatment of cells with cytotoxic drugs ? - ? 411061 3.4.21.108 Wilms' tumor suppressor protein WT1 + H2O - ? - ? 411061 3.4.21.108 WTS + H2O is a non-apoptotic substrate of Omi ? - ? 398574 3.4.21.108 WTS + H2O - ? - ? 398574 3.4.21.108 X-linked inhibitor of apoptosis protein HtrA2 promotes degradation of the X-linked inhibitor of apoptosis protein followed by subsequent caspase activation ? - ? 385927 3.4.21.108 X-linked inhibitor of apoptosis protein + H2O - ? - ? 385926 3.4.21.108 X-linked inhibitor of apoptosis protein + H2O BIR2 ? - ? 385926 3.4.21.108 X-linked inhibitor of apoptosis protein + H2O autocatalytically processing of HtrA2 to the 36-kDa protein fragment, which is required for the cytochrome c-dependent caspase activation, promoting apoptotic cell death ? - ? 385926 3.4.21.108 X-linked inhibitor of apoptosis protein + H2O C-terminus of presenilin-1 interacts with the PDZ domain of Omi/HtrA2, increasing its activity ? - ? 385926 3.4.21.108 X-linked inhibitor of apoptosis protein + H2O homotrimeric structure of enzyme is required for executing its activity ? - ? 385926 3.4.21.108 X-linked inhibitor of apoptosis protein + H2O Omi/HtrA2 cleaves as well as directly binds and inactivates X-linked inhibitor of apoptosis protein to promote caspase activation ? - ? 385926