HtrA serine peptidase 2

From Wikipedia, the free encyclopedia
Jump to: navigation, search
HtrA serine peptidase 2
Protein HTRA2 PDB 1lcy.png
PDB rendering based on 1lcy.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols HTRA2 ; OMI; PARK13; PRSS25
External IDs OMIM606441 MGI1928676 HomoloGene113300 GeneCards: HTRA2 Gene
EC number 3.4.21.108
RNA expression pattern
PBB GE HTRA2 211152 s at tn.png
PBB GE HTRA2 203089 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 27429 64704
Ensembl ENSG00000115317 ENSMUSG00000068329
UniProt O43464 Q9JIY5
RefSeq (mRNA) NM_013247 NM_019752
RefSeq (protein) NP_037379 NP_062726
Location (UCSC) Chr 2:
74.76 – 74.76 Mb
Chr 6:
83.05 – 83.06 Mb
PubMed search [1] [2]

Serine protease HTRA2, mitochondrial is an enzyme that in humans is encoded by the HTRA2 gene.[1][2][3] 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 its 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.

Interactions[edit]

HtrA serine peptidase 2 has been shown to interact with MAPK14,[1] XIAP[4][5] and BIRC2.[4][5]

References[edit]

  1. ^ a b Faccio L, Fusco C, Chen A, Martinotti S, Bonventre JV, Zervos AS (Feb 2000). "Characterization of a novel human serine protease that has extensive homology to bacterial heat shock endoprotease HtrA and is regulated by kidney ischemia". J Biol Chem 275 (4): 2581–8. doi:10.1074/jbc.275.4.2581. PMID 10644717. 
  2. ^ Gray CW, Ward RV, Karran E, Turconi S, Rowles A, Viglienghi D, Southan C, Barton A, Fantom KG, West A, Savopoulos J, Hassan NJ, Clinkenbeard H, Hanning C, Amegadzie B, Davis JB, Dingwall C, Livi GP, Creasy CL (Oct 2000). "Characterization of human HtrA2, a novel serine protease involved in the mammalian cellular stress response". Eur J Biochem 267 (18): 5699–710. doi:10.1046/j.1432-1327.2000.01589.x. PMID 10971580. 
  3. ^ "Entrez Gene: HTRA2 HtrA serine peptidase 2". 
  4. ^ a b Hegde, Ramesh; Srinivasula Srinivasa M, Datta Pinaki, Madesh Muniswamy, Wassell Richard, Zhang ZhiJia, Cheong NaEun, Nejmeh Julie, Fernandes-Alnemri Teresa, Hoshino Shin-ichi, Alnemri Emad S (Oct 2003). "The polypeptide chain-releasing factor GSPT1/eRF3 is proteolytically processed into an IAP-binding protein". J. Biol. Chem. (United States) 278 (40): 38699–706. doi:10.1074/jbc.M303179200. ISSN 0021-9258. PMID 12865429. 
  5. ^ a b Verhagen, Anne M; Silke John, Ekert Paul G, Pakusch Miha, Kaufmann Hitto, Connolly Lisa M, Day Catherine L, Tikoo Anjali, Burke Richard, Wrobel Carolyn, Moritz Robert L, Simpson Richard J, Vaux David L (Jan 2002). "HtrA2 promotes cell death through its serine protease activity and its ability to antagonize inhibitor of apoptosis proteins". J. Biol. Chem. (United States) 277 (1): 445–54. doi:10.1074/jbc.M109891200. ISSN 0021-9258. PMID 11604410. 

Further reading[edit]

External links[edit]

  • The MEROPS online database for peptidases and their inhibitors: S01.278