HTRA2
Domain
The mature N-terminus is involved in the interaction with XIAP.
The PDZ domain mediates interaction with MXI2.
Function
Isoform 1
Serine protease that shows proteolytic activity against a non-specific substrate beta-casein (PubMed:10873535). Promotes apoptosis by either relieving the inhibition of BIRC proteins on caspases, leading to an increase in caspase activity; or by a BIRC inhibition-independent, caspase-independent and serine protease activity-dependent mechanism (PubMed:15200957). Cleaves BIRC6 and relieves its inhibition on CASP3, CASP7 and CASP9, but it is also prone to inhibition by BIRC6 (PubMed:36758104, PubMed:36758105). Cleaves THAP5 and promotes its degradation during apoptosis (PubMed:19502560).
Isoform 2
Seems to be proteolytically inactive.
Involvement in disease
3-methylglutaconic aciduria 8
MGCA8
An autosomal recessive inborn error of metabolism resulting in early death. Clinical features include extreme hypertonia observed at birth, alternating with hypotonia, subsequent appearance of extrapyramidal symptoms, lack of psychomotor development, microcephaly, and intractable seizures. Patients show lactic acidemia, 3-methylglutaconic aciduria, intermittent neutropenia, and progressive brain atrophy.
None
The disease is caused by variants affecting the gene represented in this entry.
Parkinson disease 13
PARK13
A complex neurodegenerative disorder 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.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Post-translational modifications
Ubiquitinated by BIRC6; this activity is inhibited by DIABLO/SMAC.
Autoproteolytically activated.
Sequence Similarities
Belongs to the peptidase S1C family.
Tissue Specificity
Isoform 1
Ubiquitously expressed.
Cellular localization
- Mitochondrion intermembrane space
- Mitochondrion membrane
- Single-pass membrane protein
- 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.
- Isoform 1
- Endoplasmic reticulum
Alternative names
OMI, PRSS25, HTRA2, High temperature requirement protein A2, Omi stress-regulated endoprotease, Serine protease 25, Serine proteinase OMI, HtrA2