Serine protease HTRA1 explained

Serine protease HTRA1 is an enzyme that in humans is encoded by the HTRA1 gene.^{[1] [2]} The HTRA1 protein is composed of four distinct protein domains. They are from amino-terminus to carboxyl-terminus an Insulin-like growth factor binding domain, a kazal domain, a trypsin-like peptidase domain and a PDZ domain.

This gene encodes a member of the trypsin family of serine proteases. This protein is a secreted enzyme that is proposed to regulate the availability of insulin-like growth factors (IGFs) by cleaving IGF-binding proteins. It has also been suggested to be a regulator of cell growth.^[2]

Mutations of this gene are responsible for the development of CARASIL, a genetic form of cerebral vasculopathy.

External links

• GeneReviews/NCBI/NIH/UW entry on CARASIL Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, Maeda Syndrome
• OMIM entries on CARASIL

Further reading

• 10.1038/eye.2011.37 . Complement in age-related macular degeneration: a focus on function . 2011 . Bradley . D T . Zipfel . P F . Hughes . A E . Eye . 25 . 6 . 683–693 . 21394116 . 3178140.
• Zurawa-Janicka D, Narkiewicz J, Lipińska B . [Characterization of the HtrA family of proteins] . Postepy Biochem. . 53 . 1 . 27–36 . 2007 . 17718385 .
• Andersson B, Wentland MA, Ricafrente JY, etal . A "double adaptor" method for improved shotgun library construction . Anal. Biochem. . 236 . 1 . 107–13 . 1996 . 8619474 . 10.1006/abio.1996.0138 .
• Yu W, Andersson B, Worley KC, etal . Large-scale concatenation cDNA sequencing . Genome Res. . 7 . 4 . 353–8 . 1997 . 9110174 . 10.1101/gr.7.4.353. 139146 .
• Zumbrunn J, Trueb B . Localization of the gene for a serine protease with IGF-binding domain (PRSS11) to human chromosome 10q25.3-q26.2 . Genomics . 45 . 2 . 461–2 . 1998 . 9344681 . 10.1006/geno.1997.4953 .
• Hu SI, Carozza M, Klein M, etal . Human HtrA, an evolutionarily conserved serine protease identified as a differentially expressed gene product in osteoarthritic cartilage . J. Biol. Chem. . 273 . 51 . 34406–12 . 1999 . 9852107 . 10.1074/jbc.273.51.34406 . free .
• Baldi A, De Luca A, Morini M, etal . The HtrA1 serine protease is down-regulated during human melanoma progression and represses growth of metastatic melanoma cells . Oncogene . 21 . 43 . 6684–8 . 2002 . 12242667 . 10.1038/sj.onc.1205911 . 9021435 . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Nie GY, Hampton A, Li Y, etal . 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 . Pt 1 . 39–48 . 2003 . 12513693 . 10.1042/BJ20021569 . 1223265 .
• De Luca A, De Falco M, Severino A, etal . Distribution of the serine protease HtrA1 in normal human tissues . J. Histochem. Cytochem. . 51 . 10 . 1279–84 . 2003 . 14500695 . 10.1177/002215540305101004. 19726897 .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Chien J, Staub J, Hu SI, etal . A candidate tumor suppressor HtrA1 is downregulated in ovarian cancer . Oncogene . 23 . 8 . 1636–44 . 2004 . 14716297 . 10.1038/sj.onc.1207271 . free .
• Oka C, Tsujimoto R, Kajikawa M, etal . HtrA1 serine protease inhibits signaling mediated by Tgfbeta family proteins . Development . 131 . 5 . 1041–53 . 2004 . 14973287 . 10.1242/dev.00999 . 27495047 .
• Colland F, Jacq X, Trouplin V, etal . Functional proteomics mapping of a human signaling pathway . Genome Res. . 14 . 7 . 1324–32 . 2004 . 15231748 . 10.1101/gr.2334104 . 442148 .
• Grau S, Baldi A, Bussani R, etal . Implications of the serine protease HtrA1 in amyloid precursor protein processing . Proc. Natl. Acad. Sci. U.S.A. . 102 . 17 . 6021–6 . 2005 . 15855271 . 10.1073/pnas.0501823102 . 1087941 . free .
• Ozturk A, Desai PP, Minster RL, etal . Three SNPs in the GSTO1, GSTO2 and PRSS11 genes on chromosome 10 are not associated with age-at-onset of Alzheimer's disease . Neurobiol. Aging . 26 . 8 . 1161–5 . 2005 . 15917099 . 10.1016/j.neurobiolaging.2004.11.001 . 10878355 .
• Grau S, Richards PJ, Kerr B, etal . The role of human HtrA1 in arthritic disease . J. Biol. Chem. . 281 . 10 . 6124–9 . 2006 . 16377621 . 10.1074/jbc.M500361200 . free .
• Bowden MA, Di Nezza-Cossens LA, Jobling T, etal . Serine proteases HTRA1 and HTRA3 are down-regulated with increasing grades of human endometrial cancer . Gynecol. Oncol. . 103 . 1 . 253–60 . 2006 . 16650464 . 10.1016/j.ygyno.2006.03.006 .
• Chien J, Aletti G, Baldi A, etal . Serine protease HtrA1 modulates chemotherapy-induced cytotoxicity . J. Clin. Invest. . 116 . 7 . 1994–2004 . 2006 . 16767218 . 10.1172/JCI27698 . 1474818 .
• Dewan A, Liu M, Hartman S, etal . HTRA1 promoter polymorphism in wet age-related macular degeneration . Science . 314 . 5801 . 989–92 . 2006 . 17053108 . 10.1126/science.1133807 . 85725181 .

Notes and References

1. Zumbrunn J, Trueb B . Primary structure of a putative serine protease specific for IGF-binding proteins . FEBS Lett . 398 . 2–3 . 187–92 . Jan 1997 . 8977104 . 10.1016/S0014-5793(96)01229-X . 39934612 .
2. Web site: Entrez Gene: HTRA1 HtrA serine peptidase 1.