Gene Symbol: Htra1
Description: HtrA serine peptidase 1
Alias: AI429470, HTRA, L56, Prss11, RSPP11, serine protease HTRA1, high-temperature requirement A serine peptidase 1, insulin-like growth factor binding protein 5 protease, protease, serine, 11 (Igf binding), serine protease 11
Species: mouse
Products:     Htra1

Top Publications

  1. Tsuchiya A, Yano M, Tocharus J, Kojima H, Fukumoto M, Kawaichi M, et al. Expression of mouse HtrA1 serine protease in normal bone and cartilage and its upregulation in joint cartilage damaged by experimental arthritis. Bone. 2005;37:323-36 pubmed
    Levels of HtrA1 protein in cartilage have been reported to elevate in joints of human osteoarthritis patients...
  2. Oka C, Tsujimoto R, Kajikawa M, Koshiba Takeuchi K, Ina J, Yano M, et al. HtrA1 serine protease inhibits signaling mediated by Tgfbeta family proteins. Development. 2004;131:1041-53 pubmed
    b>HtrA1, a member of the mammalian HtrA serine protease family, has a highly conserved protease domain followed by a PDZ domain...
  3. Tocharus J, Tsuchiya A, Kajikawa M, Ueta Y, Oka C, Kawaichi M. Developmentally regulated expression of mouse HtrA3 and its role as an inhibitor of TGF-beta signaling. Dev Growth Differ. 2004;46:257-74 pubmed
    The expression of mouse HtrA1 is developmentally regulated and restricted in embryo tissues which depend largely on TGF-beta signaling for their differentiation...
  4. Glanz S, Mirsaidi A, López Fagundo C, Filliat G, Tiaden A, Richards P. Loss-of-Function of HtrA1 Abrogates All-Trans Retinoic Acid-Induced Osteogenic Differentiation of Mouse Adipose-Derived Stromal Cells Through Deficiencies in p70S6K Activation. Stem Cells Dev. 2016;25:687-98 pubmed publisher
    ..High temperature requirement protease A1 (HtrA1) is a newly recognized modulator of human multipotent stromal cell (MSC) osteogenesis and as such, may play a role ..
  5. Filliat G, Mirsaidi A, Tiaden A, Kuhn G, Weber F, Oka C, et al. Role of HTRA1 in bone formation and regeneration: In vitro and in vivo evaluation. PLoS ONE. 2017;12:e0181600 pubmed publisher
    The role of mammalian high temperature requirement protease A1 (HTRA1) in somatic stem cell differentiation and mineralized matrix formation remains controversial, having been demonstrated to impart either anti- or pro-osteogenic effects,..
  6. Nie G, Li Y, Salamonsen L. Serine protease HtrA1 is developmentally regulated in trophoblast and uterine decidual cells during placental formation in the mouse. Dev Dyn. 2005;233:1102-9 pubmed
    ..In this study, we identified that the serine protease HtrA1 (high temperature requirement factor A1) was specifically expressed in differentiated trophoblast cells, ..
  7. Kaji K, Nichols J, Hendrich B. Mbd3, a component of the NuRD co-repressor complex, is required for development of pluripotent cells. Development. 2007;134:1123-32 pubmed
  8. 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...
  9. Launay S, Maubert E, Lebeurrier N, Tennstaedt A, Campioni M, Docagne F, et al. HtrA1-dependent proteolysis of TGF-beta controls both neuronal maturation and developmental survival. Cell Death Differ. 2008;15:1408-16 pubmed publisher
    ..Moreover, we showed that neurons exhibit increasing amounts of the serine protease HtrA1 (high temperature responsive antigen 1) and corresponding cleavage products during both in vitro neuronal ..

More Information


  1. Beaufort N, Scharrer E, Kremmer E, Lux V, Ehrmann M, Huber R, et al. Cerebral small vessel disease-related protease HtrA1 processes latent TGF-β binding protein 1 and facilitates TGF-β signaling. Proc Natl Acad Sci U S A. 2014;111:16496-501 pubmed publisher
    High temperature requirement protein A1 (HtrA1) is a primarily secreted serine protease involved in a variety of cellular processes including transforming growth factor β (TGF-β) signaling...
  2. Gilicze A, Kohalmi B, Pocza P, Keszei M, Jaeger J, Gorbe E, et al. HtrA1 is a novel mast cell serine protease of mice and men. Mol Immunol. 2007;44:2961-8 pubmed
    ..attempt to identify novel genes that are highly upregulated during mucosal mast cell differentiation, we detected HtrA1 protease as a novel protein in mast cells by microarray experiments...
  3. Nakayama M, Iejima D, Akahori M, Kamei J, Goto A, Iwata T. Overexpression of HtrA1 and exposure to mainstream cigarette smoke leads to choroidal neovascularization and subretinal deposits in aged mice. Invest Ophthalmol Vis Sci. 2014;55:6514-23 pubmed publisher
    We determined the function of ARMS2 and HtrA1 in the choroid and retina using transgenic (Tg) mice and evaluated the effects of mainstream cigarette smoke on these mice...
  4. Xu L, Golshirazian I, Asbury B, Li Y. Induction of high temperature requirement A1, a serine protease, by TGF-beta1 in articular chondrocytes of mouse models of OA. Histol Histopathol. 2014;29:609-18 pubmed publisher to determine whether transforming growth factor beta 1 (Tgf-?1) induces the high temperature requirement A1 (HtrA1) in articular chondrocytes of two mouse models of osteoarthritis (OA)...
  5. Gray C, Ward R, Karran E, Turconi S, Rowles A, Viglienghi D, et al. Characterization of human HtrA2, a novel serine protease involved in the mammalian cellular stress response. Eur J Biochem. 2000;267:5699-710 pubmed
    ..HumHtrA2 is also homologous to human HtrA1, also known as L56/HtrA, which is differentially expressed in human osteoarthritic cartilage and after SV40 ..
  6. 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-? family member growth differentiation factor 6. J Biol Chem. 2012;287:1520-6 pubmed publisher (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)...
  7. 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...
  8. Polur I, Lee P, Servais J, Xu L, Li Y. Role of HTRA1, a serine protease, in the progression of articular cartilage degeneration. Histol Histopathol. 2010;25:599-608 pubmed publisher
    This study is to investigate the possible role of high temperature requirement A 1 (HtrA1) in the articular cartilage degeneration...
  9. Supanji -, Shimomachi M, Hasan M, Kawaichi M, Oka C. HtrA1 is induced by oxidative stress and enhances cell senescence through p38 MAPK pathway. Exp Eye Res. 2013;112:79-92 pubmed publisher
    ..Single-nucleotide polymorphisms in HTRA1 are strongly linked to the onset of AMD...
  10. Cao H, Jheon A, Li X, Sun Z, Wang J, Florez S, et al. The Pitx2:miR-200c/141:noggin pathway regulates Bmp signaling and ameloblast differentiation. Development. 2013;140:3348-59 pubmed publisher
    ..Our in vivo and in vitro studies reveal a multistep transcriptional program involving the Pitx2:miR-200c/141:noggin regulatory pathway that is important in epithelial cell differentiation and tooth development. ..
  11. Ciferri C, Lipari M, Liang W, Estevez A, Hang J, Stawicki S, et al. The trimeric serine protease HtrA1 forms a cage-like inhibition complex with an anti-HtrA1 antibody. Biochem J. 2015;472:169-81 pubmed publisher
    High temperature requirement A1 (HtrA1) is a trypsin-fold serine protease implicated in the progression of age-related macular degeneration (AMD)...
  12. Hou Y, Lin H, Zhu L, Liu Z, Hu F, Shi J, et al. Lipopolysaccharide increases the incidence of collagen-induced arthritis in mice through induction of protease HTRA-1 expression. Arthritis Rheum. 2013;65:2835-46 pubmed publisher
    The protease HTRA-1 is closely associated with rheumatoid arthritis (RA). The molecular mechanisms that control HTRA-1 expression are currently unknown...
  13. Graham J, Chamberland A, Lin Q, Li X, Dai D, Zeng W, et al. Serine protease HTRA1 antagonizes transforming growth factor-? signaling by cleaving its receptors and loss of HTRA1 in vivo enhances bone formation. PLoS ONE. 2013;8:e74094 pubmed publisher
    b>HTRA1 is a member of the High Temperature Requirement (HTRA1) family of serine proteases, which play a role in several biological and pathological processes...
  14. Friedrich U, Myers C, Fritsche L, Milenkovich A, Wolf A, Corbo J, et al. Risk- and non-risk-associated variants at the 10q26 AMD locus influence ARMS2 mRNA expression but exclude pathogenic effects due to protein deficiency. Hum Mol Genet. 2011;20:1387-99 pubmed publisher
    ..tag a single-risk haplotype encompassing the genes ARMS2 (age-related maculopathy susceptibility 2) and part of HTRA1 (HtrA serine peptidase 1)...
  15. Ferrer Vaquer A, Maurey P, Werzowa J, Firnberg N, Leibbrandt A, Neubüser A. Expression and regulation of HTRA1 during chick and early mouse development. Dev Dyn. 2008;237:1893-900 pubmed publisher
    b>HTRA1, a member of the high temperature requirement factor A family, is a secreted serine protease that can bind to and inactivate members of the transforming growth factor-beta (TGFbeta) family, modulate insulin-like growth factor ..
  16. Hou Y, Lin H, Zhu L, Liu Z, Hu F, Shi J, et al. The inhibitory effect of IFN-? on protease HTRA1 expression in rheumatoid arthritis. J Immunol. 2014;193:130-8 pubmed publisher
    The high temperature requirement A1 (HTRA1) is a potent protease involved in many diseases, including rheumatoid arthritis (RA). However, the regulatory mechanisms that control HTRA1 expression need to be determined...
  17. Wu X, Chim S, Kuek V, Lim B, Chow S, Zhao J, et al. HtrA1 is upregulated during RANKL-induced osteoclastogenesis, and negatively regulates osteoblast differentiation and BMP2-induced Smad1/5/8, ERK and p38 phosphorylation. FEBS Lett. 2014;588:143-50 pubmed publisher
    ..Here, we show that HtrA1 is produced as a secreted protein during osteoclastogenesis, and negatively regulates osteoblast differentiation...
  18. Wahlberg P, Nylander A, Ahlskog N, Liu K, Ny T. Expression and localization of the serine proteases high-temperature requirement factor A1, serine protease 23, and serine protease 35 in the mouse ovary. Endocrinology. 2008;149:5070-7 pubmed publisher
    ..serine proteases that were relatively highly expressed during ovulation: high-temperature requirement factor A1 (HtrA1), which was not regulated much during ovulation; serine protease 23 (PRSS23), which was down-regulated by ..
  19. Hasan M, Ikawati M, Tocharus J, Kawaichi M, Oka C. Abnormal development of placenta in HtrA1-deficient mice. Dev Biol. 2015;397:89-102 pubmed publisher
    Abnormal levels of High temperature requirement A1 (HtrA1) protein have been repeatedly observed in sera and placentas of preeclampsia patients...
  20. Liu J, Hoh J. Postnatal overexpression of the human ARMS2 gene does not induce abnormalities in retina and choroid in transgenic mouse models. Invest Ophthalmol Vis Sci. 2015;56:1387-8 pubmed publisher
  21. De Luca A, De Falco M, De Luca L, Penta R, Shridhar V, Baldi F, et al. Pattern of expression of HtrA1 during mouse development. J Histochem Cytochem. 2004;52:1609-17 pubmed
    The human HtrA family of proteases consists of four members: HtrA1, HtrA2, HtrA3, and HtrA4...
  22. Marker P, Dahiya R, Cunha G. Spontaneous mutation in mice provides new insight into the genetic mechanisms that pattern the seminal vesicles and prostate gland. Dev Dyn. 2003;226:643-53 pubmed
  23. Muratoglu S, Belgrave S, Hampton B, Migliorini M, Coksaygan T, Chen L, et al. LRP1 protects the vasculature by regulating levels of connective tissue growth factor and HtrA1. Arterioscler Thromb Vasc Biol. 2013;33:2137-46 pubmed publisher
    ..that smLRP1(-/-) vessels contain a 4-fold increase in protein levels of high-temperature requirement factor A1 (HtrA1), which is a secreted serine protease that is known to degrade matrix components and to impair elastogenesis, ..