Protein: O43464

UniprotKB AC UniprotKB ID Gene name Full name Species Curated set
O43464 (Uniprot) HTRA2_HUMAN HTRA2 Serine protease HTRA2, mitochondrial human No
Uniprot: 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. Cleaves THAP5 and promotes its degradation during apoptosis. Isoform 2 seems to be proteolytically inactive. more..
GO ID 1 Function 1 Module ID 1 GO ID 2 Function 2 Module ID 2 Association Probability (PrOnto) Interaction Probability (PrOnto)
GO:0009056 catabolic process 125 GO:0009059 macromolecule biosynthetic process 270 6.37e-04 1.88e-40
Module ID (MoonGO) GO ID (BP) GO Name
125 GO:0044248 cellular catabolic process
125 GO:0016567 protein ubiquitination
125 GO:0060255 regulation of macromolecule metabolic process
270 GO:0034645 cellular macromolecule biosynthetic process
270 GO:0010467 gene expression
270 GO:0090304 nucleic acid metabolic process
270 GO:0032446 protein modification by small protein conjugation
270 GO:0060255 regulation of macromolecule metabolic process
270 GO:0007165 signal transduction
Module ID (MoonGO) GO ID (CC) GO Name
125 GO:0005829 cytosol
125 GO:0005634 nucleus
270 GO:0005829 cytosol
270 GO:0070013 intracellular organelle lumen
270 GO:0005634 nucleus
GO ID (BP) GO Name Evidence Code (GO EC)
GO:0006508 proteolysis IDA
GO:0006672 ceramide metabolic process IEA
GO:0007005 mitochondrion organization IEA
GO:0007568 aging IEA
GO:0007628 adult walking behavior IEA
GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage IMP
GO:0009635 response to herbicide IEA
GO:0010822 positive regulation of mitochondrion organization IMP
GO:0010942 positive regulation of cell death IDA
GO:0016540 protein autoprocessing TAS
GO:0019742 pentacyclic triterpenoid metabolic process IEA
GO:0030900 forebrain development IEA
GO:0034599 cellular response to oxidative stress IMP
GO:0034605 cellular response to heat IDA
GO:0035458 cellular response to interferon-beta IDA
GO:0040014 regulation of multicellular organism growth IEA
GO:0043065 positive regulation of apoptotic process IMP
GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process IDA
GO:0044257 cellular protein catabolic process IDA
GO:0045786 negative regulation of cell cycle TAS
GO:0048666 neuron development IEA
GO:0070207 protein homotrimerization IMP
GO:0071300 cellular response to retinoic acid IDA
GO:0071363 cellular response to growth factor stimulus IMP
GO:0097194 execution phase of apoptosis TAS
GO:1901215 negative regulation of neuron death TAS
GO:1902176 negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway NAS
GO:1903146 regulation of autophagy of mitochondrion TAS
GO:1903955 positive regulation of protein targeting to mitochondrion IMP
GO:1904924 negative regulation of mitophagy in response to mitochondrial depolarization IEA
GO:2001241 positive regulation of extrinsic apoptotic signaling pathway in absence of ligand IMP
GO:2001269 positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway IMP
GO ID (CC) GO Name Evidence Code (GO EC)
GO:0000785 chromatin IDA
GO:0005634 nucleus IDA
GO:0005739 mitochondrion TAS
GO:0005758 mitochondrial intermembrane space IDA
GO:0005783 endoplasmic reticulum NAS
GO:0005789 endoplasmic reticulum membrane TAS
GO:0005829 cytosol IDA
GO:0005856 cytoskeleton IDA
GO:0009898 cytoplasmic side of plasma membrane ISS
GO:0016020 membrane IDA
GO:0031966 mitochondrial membrane IEA
GO:0035631 CD40 receptor complex ISS
GO:1905370 serine-type endopeptidase complex IMP
GO ID 1 Component 1 GO ID 2 Component 2 Association Probability (PrOnto) Interaction Probability (PrOnto)
GO:0000785 chromatin GO:0005783 endoplasmic reticulum 8.02e-10 1.28e-67
GO:0000785 chromatin GO:0005789 endoplasmic reticulum membrane 2.50e-06 4.03e-103
GO:0000785 chromatin GO:0016020 membrane 1.14e-59 2.58e-148
GO:0005634 nucleus GO:0005783 endoplasmic reticulum 8.26e-33 3.22e-89
GO:0005634 nucleus GO:0005789 endoplasmic reticulum membrane 1.61e-25 3.10e-56
GO:0005634 nucleus GO:0016020 membrane 0.00e+00 4.39e-236
GO:0005634 nucleus GO:0031966 mitochondrial membrane 7.12e-06 7.29e-05
GO:0005783 endoplasmic reticulum GO:0005856 cytoskeleton 1.80e-20 2.15e-98
GO:0005789 endoplasmic reticulum membrane GO:0005829 cytosol 4.27e-12 7.53e-04
GO:0005789 endoplasmic reticulum membrane GO:0005856 cytoskeleton 1.07e-13 1.06e-67
GO:0005856 cytoskeleton GO:0031966 mitochondrial membrane 1.97e-06 3.02e-27
PMID Article Title
10644717 Characterization of a novel human serine protease that has extensive homology to bacterial heat shock endoprotease HtrA and is regulated by kidney ischemia.
10873535 Expression, purification, and functional analysis of the human serine protease HtrA2.
10971580 Characterization of human HtrA2, a novel serine protease involved in the mammalian cellular stress response.
10995577 Tissue-specific splicing of Omi stress-regulated endoprotease leads to an inactive protease with a modified PDZ motif.
11583623 A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death.
11967569 Structural insights into the pro-apoptotic function of mitochondrial serine protease HtrA2/Omi.
15200957 Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2/E3 ubiquitin ligase.
15489334 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15815621 Generation and annotation of the DNA sequences of human chromosomes 2 and 4.
15961413 Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease.
18364387 Sequencing analysis of OMI/HTRA2 shows previously reported pathogenic mutations in neurologically normal controls.
18401856 Genetic variability in the mitochondrial serine protease HTRA2 contributes to risk for Parkinson disease.
19502560 THAP5 is a human cardiac-specific inhibitor of cell cycle that is cleaved by the proapoptotic Omi/HtrA2 protease during cell death.
21269460 Initial characterization of the human central proteome.
24275569 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
25422467 Mitochondrial serine protease HTRA2 p.G399S in a kindred with essential tremor and Parkinson disease.
25944712 N-terminome analysis of the human mitochondrial proteome.
27208207 Deficiency of HTRA2/Omi is associated with infantile neurodegeneration and 3-methylglutaconic aciduria.
27535533 Analysis of protein-coding genetic variation in 60,706 humans.
27696117 Pathogenic variants in HTRA2 cause an early-onset mitochondrial syndrome associated with 3-methylglutaconic aciduria.
OMIM ID Disease Name
610297 Parkinson disease 13
617248 3-methylglutaconic aciduria 8
Domain Name Domain ID Source
PDZ IPR001478 InterPro
Peptidase_S1C IPR001940 InterPro
Peptidase_S1_PA IPR009003 InterPro
PDZ_sf IPR036034 InterPro
PDZ_2 PF13180 Pfam
SSF50156 SSF50156 SUPFAM
SSF50494 SSF50494 SUPFAM