Serine protease HTRA1 is an enzyme that in humans is encoded by the HTRA1gene.[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.
References
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Zumbrunn J, Trueb B (1998). "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. doi:10.1006/geno.1997.4953. PMID9344681.
Hu SI, Carozza M, Klein M, et al. (1999). "Human HtrA, an evolutionarily conserved serine protease identified as a differentially expressed gene product in osteoarthritic cartilage". J. Biol. Chem. 273 (51): 34406–12. doi:10.1074/jbc.273.51.34406. PMID9852107.
Baldi A, De Luca A, Morini M, et al. (2002). "The HtrA1 serine protease is down-regulated during human melanoma progression and represses growth of metastatic melanoma cells". Oncogene. 21 (43): 6684–8. doi:10.1038/sj.onc.1205911. PMID12242667.
De Luca A, De Falco M, Severino A, et al. (2003). "Distribution of the serine protease HtrA1 in normal human tissues". J. Histochem. Cytochem. 51 (10): 1279–84. doi:10.1177/002215540305101004. PMID14500695.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID14702039.
Chien J, Staub J, Hu SI, et al. (2004). "A candidate tumor suppressor HtrA1 is downregulated in ovarian cancer". Oncogene. 23 (8): 1636–44. doi:10.1038/sj.onc.1207271. PMID14716297.
Oka C, Tsujimoto R, Kajikawa M, et al. (2004). "HtrA1 serine protease inhibits signaling mediated by Tgfbeta family proteins". Development. 131 (5): 1041–53. doi:10.1242/dev.00999. PMID14973287.
Ozturk A, Desai PP, Minster RL, et al. (2005). "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. doi:10.1016/j.neurobiolaging.2004.11.001. PMID15917099.
Grau S, Richards PJ, Kerr B, et al. (2006). "The role of human HtrA1 in arthritic disease". J. Biol. Chem. 281 (10): 6124–9. doi:10.1074/jbc.M500361200. PMID16377621.
Bowden MA, Di Nezza-Cossens LA, Jobling T, et al. (2006). "Serine proteases HTRA1 and HTRA3 are down-regulated with increasing grades of human endometrial cancer". Gynecol. Oncol. 103 (1): 253–60. doi:10.1016/j.ygyno.2006.03.006. PMID16650464.
Dewan A, Liu M, Hartman S, et al. (2006). "HTRA1 promoter polymorphism in wet age-related macular degeneration". Science. 314 (5801): 989–92. doi:10.1126/science.1133807. PMID17053108.