Characterization of a novel human serine protease that has extensive homology to bacterial heat shock endoprotease HtrA and is regulated by kidney ischemia.
We report the isolation and characterization of a cDNA encoding the novel mammalian serine protease Omi. Omi protein consists of 458 amino acids and has homology to bacterial HtrA endoprotease, which acts as a chaperone at low temperatures and as a proteolytic enzyme that removes denatured or damaged substrates at elevated temperatures. The carboxyl terminus of Omi has extensive homology to a mammalian protein called L56 (human HtrA), but unlike L56, which is secreted, Omi is localized in the endoplasmic reticulum. Omi has several novel putative protein-protein interaction motifs, as well as a PDZ domain and a Src homology 3-binding domain. Omi mRNA is expressed ubiquitously, and the gene is localized on human chromosome 2p12. Omi interacts with Mxi2, an alternatively spliced form of the p38 stress-activated kinase. Omi protein, when made in a heterologous system, shows proteolytic activity against a nonspecific substrate beta-casein. The proteolytic activity of Omi is markedly up-regulated in the mouse kidney following ischemia/reperfusion.
Faccio
L
L
Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
Fusco
C
C
Chen
A
A
Martinotti
S
S
Bonventre
J V
JV
Zervos
A S
AS
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics; D001483:Base Sequence; D020134:Catalytic Domain; D018076:DNA, Complementary; D015971:Gene Expression Regulation, Enzymologic; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics; D000074923:High-Temperature Requirement A Serine Peptidase 2; D006801:Humans; D006868:Hydrolysis; D007511:Ischemia / Q000235:genetics*; D007668:Kidney / Q000098:blood supply*; D051379:Mice; D024101:Mitochondrial Proteins; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D033903:Periplasmic Proteins; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D001426:Bacterial Proteins; D018076:DNA, Complementary; D006360:Heat-Shock Proteins; D024101:Mitochondrial Proteins; D033903:Periplasmic Proteins; D011994:Recombinant Proteins; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C061682:DegP protease; D012697:Serine Endopeptidases; C000615914:HTRA2 protein, human; D000074923:High-Temperature Requirement A Serine Peptidase 2; C000615915:Htra2 protein, mouse