HtrA serine peptidase 2

Serine protease HTRA2, mitochondrial is an is_associated_with::enzyme that in humans is encoded by the HTRA2 is_associated_with::gene.

Gene
The gene HTRA2 encodes a serine protease. The human gene has 8 exons and locates at chromosome band 2p12.

Protein
Protein HtrA2, also known as Omi, is a mitochondrially-located serine protease. The human protein Serine protease HTRA2, mitochondrial is 49kDa in size and composed of 458 amino acids. The peptide fragment of 1-31 amino acid is the mitochondrial transition sequence, fragment 32-133 amino acid is propertied, and 134-458 is the mature protein Serine protease HTRA2, mitochondrial, and its theoretical pI of this protein is 6.12. 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 a is_associated_with::carboxy-terminal PDZ domain.

Function
The high-temperature requirement (HtrA) family are conserved evolutionarily and these oligomeric serine proteases has been classified in family S1B of the PA protease clan in the is_associated_with::MEROPS protease database. As one member of HtrA family, serine protease HTRA2, mitochondrial contains a trypsin-like protease domain and one C-terminal is_associated_with::PDZ domain. The PDZ domain preferentially binds C-terminus of the protein substrate and modulate the proteolytic activity of the trypsin-like protease domain. The protease activity of the HtrA member HtrA2/Omi is required for mitochondrial homeostasis in mice and humans and inactivating mutations associated with neurodegenerative disorders such as is_associated_with::Parkinson's disease. Moreover, HtrA2/Omi is released in the cytosol from the is_associated_with::mitochondria during is_associated_with::apoptosis and uses its four most is_associated_with::N-terminal amino acids to mimic a is_associated_with::caspase and be recruited by IAP caspase inhibitors such as is_associated_with::XIAP and CIAP1/2. Once bound, the is_associated_with::serine protease cleaves the IAP, reducing the cell's inhibition to caspase activation. In summary, HTRA2/Omi contributes to apoptosis through both caspase-dependent and -independent pathways.

Clinical significance
The members of the HtrA family of proteases have been shown playing critical roles in cell physiology and being involved in several pathological processes including cancer and neurodegenerative disease. Strong evidences supported of HtrA2's involvement in oncogenesis. This protein is widely expressed in a variety of cancer cell lines,   Analysis of biopsy samples showed changes in expression of HtrA2 in cancer tissues compared with normal tissues.

Function
HtrA2 has recently been identified as a gene related to is_associated_with::Parkinson's disease. Mutations in Htra2 have been found in patients suffering from Parkinson's disease. Additionally, mice lacking HtrA2 have a parkinsonian is_associated_with::phenotype. This suggests that HtrA2 is linked to Parkinson's disease progression in humans and mice.

Interactions
HtrA serine peptidase 2 has been shown to interact with is_associated_with::MAPK14, is_associated_with::XIAP and is_associated_with::BIRC2.