Alternative titles; symbols
HGNC Approved Gene Symbol: HTRA3
Cytogenetic location: 4p16.1 Genomic coordinates (GRCh38) : 4:8,269,754-8,307,098 (from NCBI)
By screening a heart cDNA library with mouse Prsp, Nie et al. (2003) isolated 2 nearly identical variants encoding isoforms of the human Prsp homolog, which they called HTRA3. The long isoform, HTRA3L, contains 453 amino acids and has a predicted molecular mass of 49 kD. It contains an N-terminal signal peptide, followed by an insulin/IGF (see 147440)-binding domain, a Kazal-type S protease inhibitor domain, a trypsin protease domain, and a PDZ domain. The short isoform, HTRA3S, contains 357 amino acids and has a predicted molecular mass of 38 kD. HTRA3S is truncated at the C terminus relative to HTRA3L and contains 7 unique C-terminal residues; it lacks the PDZ domain. HTRA3L and HTRA3S have domain structures similar to that of HTRA1 (PRSS11; 602194), and they share 61% and 66% amino acid identity with HTRA1, respectively. Both HTRA3 isoforms contain active site sequence motifs characteristic of the HTRA serine protease family. Northern blot analysis detected strong expression of 2.8- and 2.2-kb HTRA3 transcripts in heart, placenta, skeletal muscle, and kidney. Weaker expression of the 2.2-kb transcript was detected in brain, and weaker expression of the 2.8-kb transcript was detected in lung and small intestine. Screening of a human RNA dot blot with a probe from mouse Prsp showed widespread expression, with highest levels in fetal and adult heart, as well as in some reproductive organs, including ovary, uterus, and placenta.
Nie et al. (2003) determined that the HTRA3 gene contains at least 10 exons. The HTRA3S isoform is encoded by exons 1 through 7, while the HTRA3L isoform is encoded by exons 1 through 6 plus exons 8 through 10.
By genomic sequence analysis, Nie et al. (2003) mapped the HTRA3 gene to chromosome 4p16.1.
Nie, G.-Y., Hampton, A., Li, Y., Findlay, J. K., Salamonsen, L. A. Identification and cloning of two isoforms of human high-temperature requirement factor A3 (HtrA3), characterization of its genomic structure and comparison of its tissue distribution with HtrA1 and HtrA2. Biochem. J. 371: 39-48, 2003. [PubMed: 12513693] [Full Text: https://doi.org/10.1042/BJ20021569]