matriptase 2


Gene Symbol: matriptase 2
Description: transmembrane serine protease 6
Alias: 1300008A22Rik, transmembrane protease serine 6, matriptase 2, transmembrane protease, serine 6, type II transmembrane serine protease 6
Species: mouse
Products:     matriptase 2

Top Publications

  1. Hooper J, Campagnolo L, Goodarzi G, Truong T, Stuhlmann H, Quigley J. Mouse matriptase-2: identification, characterization and comparative mRNA expression analysis with mouse hepsin in adult and embryonic tissues. Biochem J. 2003;373:689-702 pubmed
    ..Mechanistic insight into the potential role of this new transmembrane serine protease is provided by its novel expression profile in embryonic and adult mouse. ..
  2. Velasco G, Cal S, Quesada V, Sanchez L, Lopez Otin C. Matriptase-2, a membrane-bound mosaic serine proteinase predominantly expressed in human liver and showing degrading activity against extracellular matrix proteins. J Biol Chem. 2002;277:37637-46 pubmed
  3. Krijt J, Fujikura Y, Ramsay A, Velasco G, Necas E. Liver hemojuvelin protein levels in mice deficient in matriptase-2 (Tmprss6). Blood Cells Mol Dis. 2011;47:133-7 pubmed publisher
    ..These data do not provide direct support for the concept that matriptase-2 cleaves membrane hemojuvelin and may indicate that, in vivo, the role of matriptase-2 in the regulation of hepcidin gene expression is more complex. ..
  4. Du X, She E, Gelbart T, Truksa J, Lee P, Xia Y, et al. The serine protease TMPRSS6 is required to sense iron deficiency. Science. 2008;320:1088-92 pubmed publisher
    ..TMPRSS6 is an essential component of a pathway that detects iron deficiency and blocks Hamp transcription, permitting enhanced dietary iron absorption. ..
  5. Pagani A, Nai A, Corna G, Bosurgi L, Rovere Querini P, Camaschella C, et al. Low hepcidin accounts for the proinflammatory status associated with iron deficiency. Blood. 2011;118:736-46 pubmed publisher
    ..The proinflammatory status associated with chronic iron deficiency could explain the resistance to infection seen in this condition. ..
  6. Finberg K, Whittlesey R, Fleming M, Andrews N. Down-regulation of Bmp/Smad signaling by Tmprss6 is required for maintenance of systemic iron homeostasis. Blood. 2010;115:3817-26 pubmed publisher
    ..These findings suggest that down-regulation of Bmp/Smad signaling by Tmprss6 is required for regulation of hepcidin expression and maintenance of systemic iron homeostasis. ..
  7. Zhang A, Anderson S, Wang J, Yang F, Demaster K, Ahmed R, et al. Suppression of hepatic hepcidin expression in response to acute iron deprivation is associated with an increase of matriptase-2 protein. Blood. 2011;117:1687-99 pubmed publisher
    ..However, an increase in matriptase-2 protein in the liver from ID rats was detected, suggesting that suppression of hepcidin expression in response to acute iron deprivation is mediated by an increase in matriptase-2 protein levels. ..
  8. Folgueras A, de Lara F, Pendas A, Garabaya C, Rodriguez F, Astudillo A, et al. Membrane-bound serine protease matriptase-2 (Tmprss6) is an essential regulator of iron homeostasis. Blood. 2008;112:2539-45 pubmed publisher
    ..On the basis of these findings, we conclude that matriptase-2 activity represents a novel and relevant step in hepcidin regulation and iron homeostasis. ..
  9. Lenoir A, Deschemin J, Kautz L, Ramsay A, Roth M, Lopez Otin C, et al. Iron-deficiency anemia from matriptase-2 inactivation is dependent on the presence of functional Bmp6. Blood. 2011;117:647-50 pubmed publisher
    ..This finding suggests that elevated hepcidin levels in patients with familial iron-refractory, iron-deficiency anemia are the result of excess signaling through the Bmp6/Hjv pathway. ..

More Information


  1. Finberg K, Whittlesey R, Andrews N. Tmprss6 is a genetic modifier of the Hfe-hemochromatosis phenotype in mice. Blood. 2011;117:4590-9 pubmed publisher
  2. Frýdlová J, Rychtarčíková Z, Gurieva I, Vokurka M, Truksa J, Krijt J. Effect of erythropoietin administration on proteins participating in iron homeostasis in Tmprss6-mutated mask mice. PLoS ONE. 2017;12:e0186844 pubmed publisher
  3. Frýdlová J, Přikryl P, Truksa J, Falke L, Du X, Gurieva I, et al. Effect of Erythropoietin, Iron Deficiency and Iron Overload on Liver Matriptase-2 (TMPRSS6) Protein Content in Mice and Rats. PLoS ONE. 2016;11:e0148540 pubmed publisher
    ..Overall, the results demonstrate posttranscriptional regulation of liver TMPRSS6 protein by iron status and erythropoietin administration, and provide support for the interaction of TMPRSS6 and hemojuvelin proteins in vivo. ..
  4. Gnana Prakasam J, Baldowski R, Ananth S, Martin P, Smith S, Ganapathy V. Retinal expression of the serine protease matriptase-2 (Tmprss6) and its role in retinal iron homeostasis. Mol Vis. 2014;20:561-74 pubmed
    ..We conclude that matriptase-2 is a critical participant in retinal iron homeostasis. ..
  5. Lee P, Hsu M, Welser Alves J, Peng H. Severe microcytic anemia but increased erythropoiesis in mice lacking Hfe or Tfr2 and Tmprss6. Blood Cells Mol Dis. 2012;48:173-8 pubmed publisher
    ..Furthermore, repression of hepcidin expression by hypoxia was unaffected by the loss of functional Hfe, Tfr2 and Tmprss6...
  6. Frýdlová J, Fujikura Y, Vokurka M, Necas E, Krijt J. Decreased hemojuvelin protein levels in mask mice lacking matriptase-2-dependent proteolytic activity. Physiol Res. 2013;62:405-11 pubmed
    ..The regulation of transferrin receptor 2 protein levels by transferrin saturation was not affected in mask mice. How the loss of matriptase-2 proteolytic activity leads to decreased hemojuvelin protein levels is at present unclear. ..
  7. Riba M, Rausa M, Sorosina M, Cittaro D, Garcia Manteiga J, Nai A, et al. A strong anti-inflammatory signature revealed by liver transcription profiling of Tmprss6-/- mice. PLoS ONE. 2013;8:e69694 pubmed publisher
    ..Altogether our results confirm the anti-inflammatory status of Tmprss6 KO mice and identify new potential target pathways/genes of Tmprss6. ..
  8. Meynard D, Sun C, Wu Q, Chen W, Chen S, Nelson C, et al. Inflammation regulates TMPRSS6 expression via STAT5. PLoS ONE. 2013;8:e82127 pubmed publisher
    ..TMPRSS6 inhibition via decreased STAT5 phosphorylation may be an additional mechanism by which inflammation stimulates hepcidin expression to regulate iron homeostasis and immunity. ..
  9. Buzza M, Johnson T, Conway G, Martin E, Mukhopadhyay S, Shea Donohue T, et al. Inflammatory cytokines down-regulate the barrier-protective prostasin-matriptase proteolytic cascade early in experimental colitis. J Biol Chem. 2017;292:10801-10812 pubmed publisher
  10. Kim T, Heinlein C, Hackman R, Nelson P. Phenotypic analysis of mice lacking the Tmprss2-encoded protease. Mol Cell Biol. 2006;26:965-75 pubmed
    ..Alternatively, TMPRSS2 may contribute a specialized but nonvital function that is apparent only in the context of stress, disease, or other systemic perturbation. ..
  11. Rausa M, Pagani A, Nai A, Campanella A, Gilberti M, Apostoli P, et al. Bmp6 expression in murine liver non parenchymal cells: a mechanism to control their high iron exporter activity and protect hepatocytes from iron overload?. PLoS ONE. 2015;10:e0122696 pubmed publisher
    ..This mechanism, that contributes to protect HC from iron loading or deficiency, is lost in disease models of hepcidin production. ..
  12. Nai A, Pagani A, Mandelli G, Lidonnici M, Silvestri L, Ferrari G, et al. Deletion of TMPRSS6 attenuates the phenotype in a mouse model of ?-thalassemia. Blood. 2012;119:5021-9 pubmed publisher
  13. Bartnikas T, Steinbicker A, Campagna D, Blevins S, Woodward L, Herrera C, et al. Identification and characterization of a novel murine allele of Tmprss6. Haematologica. 2013;98:854-61 pubmed publisher
    ..In conclusion, the hem8 mouse model carries a novel allele of Tmprss6. Potential uses for this strain in the study of iron metabolism are discussed. ..
  14. Wahedi M, Wortham A, Kleven M, Zhao N, Jue S, Enns C, et al. Matriptase-2 suppresses hepcidin expression by cleaving multiple components of the hepcidin induction pathway. J Biol Chem. 2017;292:18354-18371 pubmed publisher
    ..Together, these observations indicate that MT2 suppresses hepcidin expression by cleaving multiple components of the hepcidin induction pathway. ..
  15. Schmidt P, Toudjarska I, Sendamarai A, Racie T, Milstein S, Bettencourt B, et al. An RNAi therapeutic targeting Tmprss6 decreases iron overload in Hfe(-/-) mice and ameliorates anemia and iron overload in murine ?-thalassemia intermedia. Blood. 2013;121:1200-8 pubmed publisher
  16. Guo S, Casu C, Gardenghi S, Booten S, Aghajan M, Peralta R, et al. Reducing TMPRSS6 ameliorates hemochromatosis and ?-thalassemia in mice. J Clin Invest. 2013;123:1531-41 pubmed publisher
    ..These data suggest that ASOs targeting Tmprss6 could be beneficial in individuals with hemochromatosis, ?-thalassemia, and related disorders. ..
  17. Aschemeyer S, Gabayan V, Ganz T, Nemeth E, Kautz L. Erythroferrone and matriptase-2 independently regulate hepcidin expression. Am J Hematol. 2017;92:E61-E63 pubmed publisher
  18. Netzel Arnett S, Hooper J, Szabo R, Madison E, Quigley J, Bugge T, et al. Membrane anchored serine proteases: a rapidly expanding group of cell surface proteolytic enzymes with potential roles in cancer. Cancer Metastasis Rev. 2003;22:237-58 pubmed
    ..Diagnostic or therapeutic targeting of the membrane anchored serine proteases has potential as promising new approaches for the treatment of cancer and other diseases. ..
  19. Nai A, Pagani A, Silvestri L, Camaschella C. Increased susceptibility to iron deficiency of Tmprss6-haploinsufficient mice. Blood. 2010;116:851-2 pubmed publisher
  20. Nai A, Rubio A, Campanella A, Gourbeyre O, Artuso I, Bordini J, et al. Limiting hepatic Bmp-Smad signaling by matriptase-2 is required for erythropoietin-mediated hepcidin suppression in mice. Blood. 2016;127:2327-36 pubmed publisher
    ..We concluded that the function of matriptase-2 is dominant over that of ERFE and is essential in facilitating hepcidin suppression by attenuating the BMP-SMAD signaling. ..
  21. Willemetz A, Lenoir A, Deschemin J, Lopez Otin C, Ramsay A, Vaulont S, et al. Matriptase-2 is essential for hepcidin repression during fetal life and postnatal development in mice to maintain iron homeostasis. Blood. 2014;124:441-4 pubmed publisher
  22. Ramsay A, Reid J, Velasco G, Quigley J, Hooper J. The type II transmembrane serine protease matriptase-2--identification, structural features, enzymology, expression pattern and potential roles. Front Biosci. 2008;13:569-79 pubmed
    ..Here we overview the identification of matriptase-2, summarise its structural features, biochemistry, expression pattern and disease associations and discuss its potential functions. ..
  23. Stirnberg M, Maurer E, Arenz K, Babler A, Jahnen Dechent W, Gütschow M. Cell surface serine protease matriptase-2 suppresses fetuin-A/AHSG-mediated induction of hepcidin. Biol Chem. 2015;396:81-93 pubmed publisher
    ..Fetuin-A deficiency in mice resulted in decreased hepcidin mRNA levels. These findings implicate a role of fetuin-A in iron homeostasis and provide new insights into the mechanism of how matriptase-2 might modulate hepcidin expression. ..
  24. Moroishi T, Nishiyama M, Takeda Y, Iwai K, Nakayama K. The FBXL5-IRP2 axis is integral to control of iron metabolism in vivo. Cell Metab. 2011;14:339-51 pubmed publisher
    ..The liver-specific mutant mice died with acute liver failure when fed a high-iron diet. Thus, our results uncover a major role for FBXL5 in ensuring an appropriate supply of iron to cells. ..
  25. Truksa J, Gelbart T, Peng H, Beutler E, Beutler B, Lee P. Suppression of the hepcidin-encoding gene Hamp permits iron overload in mice lacking both hemojuvelin and matriptase-2/TMPRSS6. Br J Haematol. 2009;147:571-81 pubmed publisher
    ..This phenotype is consistent with hemojuvelin being a major substrate for matriptase-2/TMPRSS6 protease activity. ..