HTRA1

Summary

Gene Symbol: HTRA1
Description: HtrA serine peptidase 1
Alias: ARMD7, CADASIL2, CARASIL, HtrA, L56, ORF480, PRSS11, serine protease HTRA1, IGFBP5-protease, high-temperature requirement A serine peptidase 1, protease, serine, 11 (IGF binding)
Species: human
Products:     HTRA1

Top Publications

  1. DeAngelis M, Ji F, Adams S, Morrison M, Harring A, Sweeney M, et al. Alleles in the HtrA serine peptidase 1 gene alter the risk of neovascular age-related macular degeneration. Ophthalmology. 2008;115:1209-1215.e7 pubmed publisher
    ..domain-containing protein gene (PLEKHA1), hypothetical LOC387715/ARMS2 gene, and HtrA serine peptidase 1 gene (HTRA1) located on the long arm of chromosome 10 (10q26 region) confer risk for neovascular age-related macular ..
  2. Chu J, Zhou C, Lu N, Zhang X, Dong F. Genetic variants in three genes and smoking show strong associations with susceptibility to exudative age-related macular degeneration in a Chinese population. Chin Med J (Engl). 2008;121:2525-33 pubmed
    ..polymorphisms in three genes (complement factor H (CFH), complement factor B (BF) and HtrA serine peptidase 1 (HTRA1)) with exudative age-related macular degeneration (AMD) in a Han Chinese population, and to test if the modifiable ..
  3. McKay G, Silvestri G, Patterson C, Hogg R, Chakravarthy U, Hughes A. Further assessment of the complement component 2 and factor B region associated with age-related macular degeneration. Invest Ophthalmol Vis Sci. 2009;50:533-9 pubmed publisher
    ..of the complement system has been implicated as a major cause of genetic risk, in addition to the LOC387715/HTRA1 locus and other environmental influences...
  4. Seddon J, Reynolds R, Maller J, Fagerness J, Daly M, Rosner B. Prediction model for prevalence and incidence of advanced age-related macular degeneration based on genetic, demographic, and environmental variables. Invest Ophthalmol Vis Sci. 2009;50:2044-53 pubmed publisher
    ..831 for progression to advanced AMD. Factors reflective of nature and nurture are independently related to prevalence and incidence of advanced AMD, with excellent predictive power. ..
  5. Jones A, Kumar S, Zhang N, Tong Z, Yang J, WATT C, et al. Increased expression of multifunctional serine protease, HTRA1, in retinal pigment epithelium induces polypoidal choroidal vasculopathy in mice. Proc Natl Acad Sci U S A. 2011;108:14578-83 pubmed publisher
    ..Genome-wide association studies have linked a multifunctional serine protease, HTRA1, to AMD. However, the precise role of HTRA1 in AMD remains elusive...
  6. Hu S, Carozza M, Klein M, Nantermet P, Luk D, Crowl R. Human HtrA, an evolutionarily conserved serine protease identified as a differentially expressed gene product in osteoarthritic cartilage. J Biol Chem. 1998;273:34406-12 pubmed
    The human homologue of the Escherichia coli htrA gene product was identified by the differential display analysis of transcripts expressed in osteoarthritic cartilage...
  7. Zurawa Janicka D, Skorko Glonek J, Lipinska B. HtrA proteins as targets in therapy of cancer and other diseases. Expert Opin Ther Targets. 2010;14:665-79 pubmed publisher
    ..We present characteristics of the human HtrA1, HtrA2 and HtrA3 proteins, with the stress on their function in apoptosis and in the diseases...
  8. Park D, Kim I. Association of ARMS2/HTRA1 variants with polypoidal choroidal vasculopathy phenotype in a Korean population. Jpn J Ophthalmol. 2012;56:60-7 pubmed publisher
    To investigate whether ARMS2 (rs10490924)/HTRA1 (rs11200638) variants are associated with polypoidal choroidal vasculopathy (PCV) in a Korean population and with various PCV phenotypes.
  9. Eigenbrot C, Ultsch M, Lipari M, Moran P, Lin S, Ganesan R, et al. Structural and functional analysis of HtrA1 and its subdomains. Structure. 2012;20:1040-50 pubmed publisher
    The homotrimeric human serine protease HtrA1 is homologous to bacterial HtrA proteases regarding the trypsin-like catalytic and PDZ domains but differs by the presence of an N-terminal domain with IGFBP and Kazal homology...
  10. Narkiewicz J, Klasa Mazurkiewicz D, Zurawa Janicka D, Skorko Glonek J, Emerich J, Lipinska B. Changes in mRNA and protein levels of human HtrA1, HtrA2 and HtrA3 in ovarian cancer. Clin Biochem. 2008;41:561-9 pubmed publisher
    Expression of human HtrA1, HtrA2, HtrA3 and TGF-beta1 genes was examined in ovarian tissue specimens including 19 normal ovaries, 20 benign tumors, 7 borderline tumors, 44 cancers and 8 Krukenberg tumors...

Detail Information

Publications62

  1. DeAngelis M, Ji F, Adams S, Morrison M, Harring A, Sweeney M, et al. Alleles in the HtrA serine peptidase 1 gene alter the risk of neovascular age-related macular degeneration. Ophthalmology. 2008;115:1209-1215.e7 pubmed publisher
    ..domain-containing protein gene (PLEKHA1), hypothetical LOC387715/ARMS2 gene, and HtrA serine peptidase 1 gene (HTRA1) located on the long arm of chromosome 10 (10q26 region) confer risk for neovascular age-related macular ..
  2. Chu J, Zhou C, Lu N, Zhang X, Dong F. Genetic variants in three genes and smoking show strong associations with susceptibility to exudative age-related macular degeneration in a Chinese population. Chin Med J (Engl). 2008;121:2525-33 pubmed
    ..polymorphisms in three genes (complement factor H (CFH), complement factor B (BF) and HtrA serine peptidase 1 (HTRA1)) with exudative age-related macular degeneration (AMD) in a Han Chinese population, and to test if the modifiable ..
  3. McKay G, Silvestri G, Patterson C, Hogg R, Chakravarthy U, Hughes A. Further assessment of the complement component 2 and factor B region associated with age-related macular degeneration. Invest Ophthalmol Vis Sci. 2009;50:533-9 pubmed publisher
    ..of the complement system has been implicated as a major cause of genetic risk, in addition to the LOC387715/HTRA1 locus and other environmental influences...
  4. Seddon J, Reynolds R, Maller J, Fagerness J, Daly M, Rosner B. Prediction model for prevalence and incidence of advanced age-related macular degeneration based on genetic, demographic, and environmental variables. Invest Ophthalmol Vis Sci. 2009;50:2044-53 pubmed publisher
    ..831 for progression to advanced AMD. Factors reflective of nature and nurture are independently related to prevalence and incidence of advanced AMD, with excellent predictive power. ..
  5. Jones A, Kumar S, Zhang N, Tong Z, Yang J, WATT C, et al. Increased expression of multifunctional serine protease, HTRA1, in retinal pigment epithelium induces polypoidal choroidal vasculopathy in mice. Proc Natl Acad Sci U S A. 2011;108:14578-83 pubmed publisher
    ..Genome-wide association studies have linked a multifunctional serine protease, HTRA1, to AMD. However, the precise role of HTRA1 in AMD remains elusive...
  6. Hu S, Carozza M, Klein M, Nantermet P, Luk D, Crowl R. Human HtrA, an evolutionarily conserved serine protease identified as a differentially expressed gene product in osteoarthritic cartilage. J Biol Chem. 1998;273:34406-12 pubmed
    The human homologue of the Escherichia coli htrA gene product was identified by the differential display analysis of transcripts expressed in osteoarthritic cartilage...
  7. Zurawa Janicka D, Skorko Glonek J, Lipinska B. HtrA proteins as targets in therapy of cancer and other diseases. Expert Opin Ther Targets. 2010;14:665-79 pubmed publisher
    ..We present characteristics of the human HtrA1, HtrA2 and HtrA3 proteins, with the stress on their function in apoptosis and in the diseases...
  8. Park D, Kim I. Association of ARMS2/HTRA1 variants with polypoidal choroidal vasculopathy phenotype in a Korean population. Jpn J Ophthalmol. 2012;56:60-7 pubmed publisher
    To investigate whether ARMS2 (rs10490924)/HTRA1 (rs11200638) variants are associated with polypoidal choroidal vasculopathy (PCV) in a Korean population and with various PCV phenotypes.
  9. Eigenbrot C, Ultsch M, Lipari M, Moran P, Lin S, Ganesan R, et al. Structural and functional analysis of HtrA1 and its subdomains. Structure. 2012;20:1040-50 pubmed publisher
    The homotrimeric human serine protease HtrA1 is homologous to bacterial HtrA proteases regarding the trypsin-like catalytic and PDZ domains but differs by the presence of an N-terminal domain with IGFBP and Kazal homology...
  10. Narkiewicz J, Klasa Mazurkiewicz D, Zurawa Janicka D, Skorko Glonek J, Emerich J, Lipinska B. Changes in mRNA and protein levels of human HtrA1, HtrA2 and HtrA3 in ovarian cancer. Clin Biochem. 2008;41:561-9 pubmed publisher
    Expression of human HtrA1, HtrA2, HtrA3 and TGF-beta1 genes was examined in ovarian tissue specimens including 19 normal ovaries, 20 benign tumors, 7 borderline tumors, 44 cancers and 8 Krukenberg tumors...
  11. Gibbs D, Yang Z, Constantine R, Ma X, Camp N, Yang X, et al. Further mapping of 10q26 supports strong association of HTRA1 polymorphisms with age-related macular degeneration. Vision Res. 2008;48:685-9 pubmed publisher
    ..A polymorphism (rs11200638) in a transcription factor binding site of the HTRA1 gene has been described, in previous reports, as being most significantly associated with AMD...
  12. Leveziel N, Souied E, Richard F, Barbu V, Zourdani A, Morineau G, et al. PLEKHA1-LOC387715-HTRA1 polymorphisms and exudative age-related macular degeneration in the French population. Mol Vis. 2007;13:2153-9 pubmed
    ..Protein Family A member 1 (PLEKHA1) gene, rs10490924:G>T at LOC387715, and rs11200638:G>A of HTRA1 (HTRA serine peptidase 1) gene were analyzed in AMD cases (n=118, age=72.3+/-3...
  13. Murwantoko -, Yano M, Ueta Y, Murasaki A, Kanda H, Oka C, et al. Binding of proteins to the PDZ domain regulates proteolytic activity of HtrA1 serine protease. Biochem J. 2004;381:895-904 pubmed
    b>HtrA1, a member of the mammalian HtrA (high temperature requirement A) serine protease family, has a highly conserved protease domain followed by a PDZ domain...
  14. Chen W, Stambolian D, Edwards A, Branham K, Othman M, Jakobsdottir J, et al. Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration. Proc Natl Acad Sci U S A. 2010;107:7401-6 pubmed publisher
    ..Our studies extend the catalog of AMD associated loci, help identify individuals at high risk of disease, and provide clues about underlying cellular pathways that should eventually lead to new therapies. ..
  15. Losonczy G, Fekete A, Vokó Z, Takacs L, Káldi I, Ajzner E, et al. Analysis of complement factor H Y402H, LOC387715, HTRA1 polymorphisms and ApoE alleles with susceptibility to age-related macular degeneration in Hungarian patients. Acta Ophthalmol. 2011;89:255-62 pubmed publisher
    ..of the complement factor H (CFH) gene, Ser69Ala polymorphism at LOC387715, rs11200638 polymorphism of the HTRA1 gene and different apolipoprotein E (ApoE) alleles in Hungarian patients with AMD in order to determine the ..
  16. Grau S, Baldi A, Bussani R, Tian X, Stefanescu R, Przybylski M, et al. Implications of the serine protease HtrA1 in amyloid precursor protein processing. Proc Natl Acad Sci U S A. 2005;102:6021-6 pubmed
    ..Our data suggest that HtrA1 is directly involved in the beta-amyloid pathway as it degrades various fragments of amyloid precursor protein ..
  17. Lee K, Vithana E, Mathur R, Yong V, Yeo I, Thalamuthu A, et al. Association analysis of CFH, C2, BF, and HTRA1 gene polymorphisms in Chinese patients with polypoidal choroidal vasculopathy. Invest Ophthalmol Vis Sci. 2008;49:2613-9 pubmed publisher
    ..Variants in the CFH and HTRA1/LOC387715 genes are strongly associated with AMD in Caucasians and Chinese...
  18. Kaur I, Katta S, Hussain A, Hussain N, Mathai A, Narayanan R, et al. Variants in the 10q26 gene cluster (LOC387715 and HTRA1) exhibit enhanced risk of age-related macular degeneration along with CFH in Indian patients. Invest Ophthalmol Vis Sci. 2008;49:1771-6 pubmed publisher
    Single nucleotide polymorphisms (SNPs) in the LOC387715 (rs10490924), HTRA1 (rs11200638), and CFH (rs1061170) genes have been implicated in age-related macular degeneration (AMD)...
  19. Yu Y, Bhangale T, Fagerness J, Ripke S, Thorleifsson G, Tan P, et al. Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration. Hum Mol Genet. 2011;20:3699-709 pubmed publisher
    ..15; P = 8.7 × 10(-9)). In addition to the two novel loci, 10 previously reported loci in ARMS2/HTRA1 (rs10490924), CFH (rs1061170, and rs1410996), CFB (rs641153), C3 (rs2230199), C2 (rs9332739), CFI (rs10033900), ..
  20. Yang Z, Camp N, Sun H, Tong Z, Gibbs D, Cameron D, et al. A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration. Science. 2006;314:992-3 pubmed
    ..We demonstrate that a single-nucleotide polymorphism, rs11200638, in the promoter region of HTRA1 is the most likely causal variant for AMD at 10q26 and is estimated to confer a population attributable risk of 49...
  21. Tsuchihashi T, Mori K, Horie Inoue K, Gehlbach P, Kabasawa S, Takita H, et al. Complement factor H and high-temperature requirement A-1 genotypes and treatment response of age-related macular degeneration. Ophthalmology. 2011;118:93-100 pubmed publisher
    To determine whether there is an association between complement factor H (CFH), high-temperature requirement A-1 (HTRA1), vascular endothelial growth factor (VEGF), and pigment epithelium-derived factor (PEDF) genotypes and response to ..
  22. Kopplin L, Igo R, Wang Y, Sivakumaran T, Hagstrom S, Peachey N, et al. Genome-wide association identifies SKIV2L and MYRIP as protective factors for age-related macular degeneration. Genes Immun. 2010;11:609-21 pubmed publisher
    ..From these efforts, we report the identification of two novel protective factors for AMD and confirm the previously known associations at CFH, ARMS2 and C3. ..
  23. De Luca A, De Falco M, Severino A, Campioni M, Santini D, Baldi F, et al. Distribution of the serine protease HtrA1 in normal human tissues. J Histochem Cytochem. 2003;51:1279-84 pubmed
    The human HtrA family of proteases consists of three members: HtrA1, HtrA2, and HtrA3...
  24. Andreoli M, Morrison M, Kim B, Chen L, Adams S, Miller J, et al. Comprehensive analysis of complement factor H and LOC387715/ARMS2/HTRA1 variants with respect to phenotype in advanced age-related macular degeneration. Am J Ophthalmol. 2009;148:869-74 pubmed publisher
    ..variation of 16 single-nucleotide polymorphisms (SNP) in the complement factor H (CFH) and LOC387715/ARMS2/HTRA1 loci with clinical characteristics of age-related macular degeneration (AMD). Retrospective cohort study...
  25. Chamberland A, Wang E, Jones A, Collins Racie L, LaVallie E, Huang Y, et al. Identification of a novel HtrA1-susceptible cleavage site in human aggrecan: evidence for the involvement of HtrA1 in aggrecan proteolysis in vivo. J Biol Chem. 2009;284:27352-9 pubmed publisher
    Mass spectrometry-based proteomic analyses performed on cartilage tissue extracts identified the serine protease HtrA1/PRSS11 as a major protein component of human articular cartilage, with elevated levels occurring in association with ..
  26. Clawson G, Bui V, Xin P, Wang N, Pan W. Intracellular localization of the tumor suppressor HtrA1/Prss11 and its association with HPV16 E6 and E7 proteins. J Cell Biochem. 2008;105:81-8 pubmed publisher
    ..We recently identified the protease as high temperature requirement factor A 1 (HtrA1), also known as Prss11, which is member of an oxidative stress-response family of proteases...
  27. Zurawa Janicka D, Narkiewicz J, Lipinska B. [Characterization of the HtrA family of proteins]. Postepy Biochem. 2007;53:27-36 pubmed
    The HtrA family of proteins consists of evolutionary conserved serine proteases, which are homologues of the HtrA protein from a model bacterium Escherichia coli...
  28. He X, Ota T, Liu P, Su C, Chien J, Shridhar V. Downregulation of HtrA1 promotes resistance to anoikis and peritoneal dissemination of ovarian cancer cells. Cancer Res. 2010;70:3109-18 pubmed publisher
    We previously identified serine protease HtrA1 as a downregulated gene in epithelial ovarian cancer (EOC), but the functional consequence of loss of HtrA1 in EOC remains largely unclear...
  29. Narkiewicz J, Lapinska Szumczyk S, Zurawa Janicka D, Skorko Glonek J, Emerich J, Lipinska B. Expression of human HtrA1, HtrA2, HtrA3 and TGF-beta1 genes in primary endometrial cancer. Oncol Rep. 2009;21:1529-37 pubmed
    ..Downregulation of human HtrA1 and HtrA3 genes has been reported in some cancers, including endometrial cancer (EC), suggesting a tumor-..
  30. Truebestein L, Tennstaedt A, Mönig T, Krojer T, Canellas F, Kaiser M, et al. Substrate-induced remodeling of the active site regulates human HTRA1 activity. Nat Struct Mol Biol. 2011;18:386-8 pubmed publisher
    Crystal structures of active and inactive conformations of the human serine protease HTRA1 reveal that substrate binding to the active site is sufficient to stimulate proteolytic activity...
  31. Shiga A, Nozaki H, Yokoseki A, Nihonmatsu M, Kawata H, Kato T, et al. Cerebral small-vessel disease protein HTRA1 controls the amount of TGF-β1 via cleavage of proTGF-β1. Hum Mol Genet. 2011;20:1800-10 pubmed publisher
    ..disease, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL)...
  32. Zhang L, Lim S, Du H, Zhang M, Kozak I, Hannum G, et al. High temperature requirement factor A1 (HTRA1) gene regulates angiogenesis through transforming growth factor-β family member growth differentiation factor 6. J Biol Chem. 2012;287:1520-6 pubmed publisher
    ..study (GWAS) has identified genetic variants in the promoter region of the high temperature requirement factor A1 (HTRA1) gene associated with age-related macular degeneration (AMD)...
  33. Xu Y, Guan N, Xu J, Yang X, Ma K, Zhou H, et al. Association of CFH, LOC387715, and HTRA1 polymorphisms with exudative age-related macular degeneration in a northern Chinese population. Mol Vis. 2008;14:1373-81 pubmed
    Variants in complement factor H (CFH), the hypothetical LOC387715, and the high-temperature requirement A-1 (HTRA1) genes have been reported to be associated with age-related macular degeneration (AMD)...