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Gene Review

HTRA3  -  HtrA serine peptidase 3

Homo sapiens

Synonyms: High-temperature requirement factor A3, PRSP, Pregnancy-related serine protease, Prsp, Serine protease HTRA3, ...
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Disease relevance of HTRA3

  • As part of an ongoing surveillance program of antibiotic-resistant Streptococcus pneumoniae in Sofia, Bulgaria, 120 penicillin-resistant strains (PRSP) (most of them recovered from children hospitalized with pneumococcal disease) were analyzed by microbiological and molecular methods [1].

High impact information on HTRA3

  • Comparison of all members of human HtrA proteins, including their isoforms, suggests that both isoforms of HtrA3 represent active serine proteases, that they may have different substrate specificities and that HtrA3 may have similar functions to HtrA1 [2].
  • We cloned the full-length sequences of two forms (long and short) of human HtrA3 mRNA, located the gene on chromosome 4p16.1, determined its genomic structure and revealed how the two mRNA variants are produced through alternative splicing [2].
  • HTRA3 is a newly identified serine peptidase of the mammalian HTRA (high-temperature requirement factor A) family, that is upregulated dramatically during mouse placental development [3].
  • This study established crucial groundwork for future investigations toward establishing the physiological roles of HTRA3 in human placentation [3].
  • During the first trimester of pregnancy, both glandular and decidual HTRA3 expression increased further with the decidual upregulation being highly significant [3].

Biological context of HTRA3

  • Upregulation of HTRA3 expression in association with placental development was revealed by a significant elevation of this protein in the maternal serum during the first trimester [3].
  • During the menstrual cycle, HTRA3 was expressed primarily in the endometrial glands, being significantly upregulated toward the mid- to late secretory phases; prominent expression in the stroma detected only in the decidual cells in the late secretory phase [3].

Anatomical context of HTRA3

  • Thus, overall endometrial HTRA3 expression was highest in the late secretory phase, when the endometrium is prepared for maternal-trophoblast interaction [3].
  • The strong link between HTRA3 expression and endometrial stromal cell decidualization was further established in an in vitro model using primary endometrial stromal cells [3].

Associations of HTRA3 with chemical compounds


  1. Molecular characterization of penicillin-resistant Streptococcus pneumoniae isolates from Bulgaria. Setchanova, L., Tomasz, A. J. Clin. Microbiol. (1999) [Pubmed]
  2. 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. Nie, G.Y., Hampton, A., Li, Y., Findlay, J.K., Salamonsen, L.A. Biochem. J. (2003) [Pubmed]
  3. Serine peptidase HTRA3 is closely associated with human placental development and is elevated in pregnancy serum. Nie, G., Li, Y., Hale, K., Okada, H., Manuelpillai, U., Wallace, E.M., Salamonsen, L.A. Biol. Reprod. (2006) [Pubmed]
  4. Efficacy of a new pharmacokinetically enhanced formulation of amoxicillin/clavulanate (2000/125 mg) in adults with community-acquired pneumonia caused by Streptococcus pneumoniae, including penicillin-resistant strains. File, T.M., Garau, J., Jacobs, M.R., Wynne, B., Twynholm, M., Berkowitz, E. Int. J. Antimicrob. Agents (2005) [Pubmed]
  5. Penicillin susceptibility and molecular characteristics of clinical isolates of Streptococcus pneumoniae at the University of Malaya Medical Center, Kuala Lumpur, Malaysia. Desa, M.N., Lin, T.K., Yasin, R.M., Parasakthi, N. Int. J. Infect. Dis. (2003) [Pubmed]
  6. Nasopharyngeal carriage of penicillin-resistant Streptococcus pneumoniae in children with sickle cell disease. Daw, N.C., Wilimas, J.A., Wang, W.C., Presbury, G.J., Joyner, R.E., Harris, S.C., Davis, Y., Chen, G., Chesney, P.J. Pediatrics (1997) [Pubmed]
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