Tissue-specific splicing of Omi stress-regulated endoprotease leads to an inactive protease with a modified PDZ motif.
Omi is a human serine protease whose catalytic domain is homologous to a bacterial heat shock endoprotease (HtrA), a protein indispensable to the survival of bacteria at elevated temperatures. Omi is expressed ubiquitously, and its protein product is predominantly localized in the endoplasmic reticulum of mammalian cells. Here we present the genomic structure of Omi, consisting of eight exons located on human chromosome 2p12-p13. Furthermore, we describe an alternatively splice form of Omi (D-Omi) that is expressed predominantly in the kidney, colon, and thyroid. D-Omi lacks peptide sequence encoded by two exons (exons III and VII). The absence of exon VII leads to a protein with a modified PDZ domain unable to interact with a known partner, the Mxi2 protein. The absence of exon III affects the catalytic domain and leads to a protein with no detectable protease activity. Our studies suggest that D-Omi may have a unique role in the normal function of kidney, colon, and thyroid.
Faccio
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Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Charlestown, Massachusetts 02129, USA.
Fusco
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C
Viel
A
A
Zervos
A S
AS
D000595:Amino Acid Sequence; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D005091:Exons; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics; D000074923:High-Temperature Requirement A Serine Peptidase 2; D006801:Humans; D024101:Mitochondrial Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D033903:Periplasmic Proteins; D017433:Protein Structure, Secondary; D012326:RNA Splicing; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D006360:Heat-Shock Proteins; D024101:Mitochondrial Proteins; D033903:Periplasmic Proteins; C061682:DegP protease; D012697:Serine Endopeptidases; C000615914:HTRA2 protein, human; D000074923:High-Temperature Requirement A Serine Peptidase 2