Genomes and Genes
Gene Symbol: TMPRSS6
Description: transmembrane protease, serine 6
Alias: IRIDA, matriptase-2, membrane-bound mosaic serine proteinase matriptase-2, transmembrane protease serine 6, type II transmembrane serine protease 6
- Pathogenesis and management of iron deficiency anemia: emerging role of celiac disease, helicobacter pylori, and autoimmune gastritisChaim Hershko
Department of Hematology, Shaare Zedek Medical Center and Hebrew University of Jerusalem, Israel
Semin Hematol 46:339-50. 2009..However, abnormal iron absorption caused by hereditary iron-refractory iron deficiency anemia (IRIDA) or acquired disease is increasingly recognized as an important cause of unexplained iron deficiency...
- Down-regulation of Bmp/Smad signaling by Tmprss6 is required for maintenance of systemic iron homeostasisKarin E Finberg
Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA
Blood 115:3817-26. 2010..Previously, we showed that IRIDA patients harbor loss-of-function mutations in TMPRSS6, a type II transmembrane serine protease primarily expressed by the liver...
- Identification of a common variant in the TFR2 gene implicated in the physiological regulation of serum iron levelsIrene Pichler
Institute of Genetic Medicine, European Academy Bozen Bolzano, 39100 Bolzano, Italy
Hum Mol Genet 20:1232-40. 2011..an association between the HFE locus and ferritin and confirmed previously reported associations with the TF, TMPRSS6 and HFE genes...
- Association of HFE and TMPRSS6 genetic variants with iron and erythrocyte parameters is only in part dependent on serum hepcidin concentrationsMichela Traglia
Division of Genetics and Cell Biology, San Raffaele Research Institute, Milano, Italy
J Med Genet 48:629-34. 2011..Hepcidin is the main regulator of iron homeostasis: inappropriate production of hepcidin results in iron overload or iron deficiency and anaemia...
- Common variants in TMPRSS6 are associated with iron status and erythrocyte volumeBeben Benyamin
Queensland Institute of Medical Research, Brisbane, Queensland, Australia
Nat Genet 41:1173-5. 2009..1 x 10(-10)). We also find suggestive evidence of association with blood hemoglobin levels (combined P = 5.3 x 10(-7)). These findings demonstrate the involvement of TMPRSS6 in control of iron homeostasis and in normal erythropoiesis.
- Variants in TF and HFE explain approximately 40% of genetic variation in serum-transferrin levelsBeben Benyamin
Queensland Institute of Medical Research, Brisbane 4029, Australia
Am J Hum Genet 84:60-5. 2009....
- Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA)Karin E Finberg
Pathology Service, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
Nat Genet 40:569-71. 2008..Here, we show that iron deficiency anemia refractory to oral iron therapy can be caused by germline mutations in TMPRSS6, which encodes a type II transmembrane serine protease produced by the liver that regulates the expression of the ..
- Genetic variability of TMPRSS6 and its association with iron deficiency anaemiaPaola Delbini
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, University of Milan, Italy
Br J Haematol 151:281–4. 2010Transmembrane Protease, Serine 6 (TMPRSS6) has an important role in iron homeostasis and its mutations, performed in TMPRSS6-deficient mice, have been recently associated with iron-refractory iron deficiency anaemia (IRIDA)...
- Inherited disorders of iron metabolismClara Camaschella
Vita Salute University, San Raffaele Scientific Institute, Milan, Italy
Curr Opin Pediatr 23:14-20. 2011..To discuss inherited iron disorders, their pathophysiology and clinical implications in the light of the recent advances in our knowledge of iron metabolism and its regulation...
- TMPRSS6 rs855791 modulates hepcidin transcription in vitro and serum hepcidin levels in normal individualsAntonella Nai
Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Verona, Italy
Blood 118:4459-62. 2011The iron hormone hepcidin is inhibited by matriptase-2 (MT2), a liver serine protease encoded by the TMPRSS6 gene...
- A genome-wide association analysis of serum iron concentrationsToshiko Tanaka
MedStar Research Institute, Baltimore, MD, USA
Blood 115:94-6. 2010..12 x 10(-9)), located in exon 13 of the transmembrane protease serine 6 (TMPRSS6) gene, an enzyme that promotes iron absorption and recycling by inhibiting hepcidin ..
- Matriptase-2 (TMPRSS6): a proteolytic regulator of iron homeostasisAndrew J Ramsay
Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain
Haematologica 94:840-9. 2009..The type-two transmembrane serine protease (TTSP), matriptase-2 (also known as TMPRSS6), is attracting significant amounts of interest due to its recently described role in iron homeostasis...
- Matriptase-2 (TMPRSS6) is directly up-regulated by hypoxia inducible factor-1: identification of a hypoxia-responsive element in the TMPRSS6 promoter regionEva Maurer
Pharmaceutical Institute, University of Bonn, An der Immenburg 4, D 53121 Bonn, Germany
Biol Chem 393:535-40. 2012The type II transmembrane serine protease matriptase-2 (TMPRSS6) down-regulates the expression of hepcidin, the main regulator of systemic iron homeostasis, and increases in this way iron plasma levels...
- The A736V TMPRSS6 polymorphism influences hepatic iron overload in nonalcoholic fatty liver diseaseLuca Valenti
Department of Pathophysiology and Transplantation, Section Internal Medicine, Universita degli Studi, Fondazione Cà Granda IRCCS Ospedale Maggiore Policlinico, Milano, Italy
PLoS ONE 7:e48804. 2012..The p.Ala736Val TMPRSS6 variant influences iron metabolism regulating the transcription of the hepatic hormone hepcidin, but its role in ..
- Effect of the A736V TMPRSS6 polymorphism on the penetrance and clinical expression of hereditary hemochromatosisLuca Valenti
Department of Internal Medicine, UO Medicina Interna 1B, Universita degli Studi, Fondazione Cà Granda IRCCS Ospedale Maggiore Policlinico, Milano, Italy
J Hepatol 57:1319-25. 2012..The rs855791 polymorphism, encoding for the p.A736V variant of TMPRSS6 regulating hepcidin, influences iron status in the population...
- Genome-wide association study identifies variants in TMPRSS6 associated with hemoglobin levelsJohn C Chambers
Department of Epidemiology and Public Health, Imperial College London, London, UK
Nat Genet 41:1170-2. 2009..most closely associated SNP (rs855791) results in nonsynonymous (V736A) change in the serine protease domain of TMPRSS6 and a blood hemoglobin concentration 0.13 (95% CI 0.09-0.17) g/dl lower per copy of allele A (P = 1.6 x 10(-13))...
- A novel TMPRSS6 mutation that prevents protease auto-activation causes IRIDASandro Altamura
Department of Pediatric Oncology, Haematology and Immunology, University Hospital of Heidelberg, Germany
Biochem J 431:363-71. 2010..The disease is caused by mutations in the transmembrane serine protease TMPRSS6 (transmembrane protease serine 6) that prevent inactivation of HJV (haemojuvelin), an activator of hepcidin transcription...
- The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelinLaura Silvestri
Vita Salute San Raffaele University, Istituto di Ricovero e Cura a Carattere Scientifico IRCCS San Raffaele, Milan, Italy
Cell Metab 8:502-11. 2008..The transmembrane serine protease matriptase-2 (TMPRSS6) inhibits the hepcidin response and its mutational inactivation causes iron-deficient anemia in mice and humans...
- Novel TMPRSS6 mutations associated with iron-refractory iron deficiency anemia (IRIDA)Luigia De Falco
CEINGE, Centro di Ingegneria Genetica e Biotecnologie Avanzate, Via Comunale Margherita 482, Naples, Italy
Hum Mutat 31:E1390-405. 2010..In this paper we describe 12 IRIDA patients belonging to 7 unrelated families and identify 10 (9 novel) TMPRSS6 mutations spread along the gene sequence: 5 missense, 1 non sense and 4 frameshift...
- A mutation in the TMPRSS6 gene, encoding a transmembrane serine protease that suppresses hepcidin production, in familial iron deficiency anemia refractory to oral ironMaria Antonietta Melis
Dipartimento di Scienze Biomediche e Biotecnologie, Universita di Cagliari, Cagliari, Italy
Haematologica 93:1473-9. 2008..Defective hepcidin synthesis causes iron loading, while overproduction results in defective reticuloendothelial iron release and iron absorption...
- Molecular mechanisms of the defective hepcidin inhibition in TMPRSS6 mutations associated with iron-refractory iron deficiency anemiaLaura Silvestri
Vita Salute University, San Raffaele Scientific Institute, Milan, Italy
Blood 113:5605-8. 2009..Our results underline the importance of LDLRA and CUB domains of matriptase-2...
- Role of matriptase-2 (TMPRSS6) in iron metabolismPauline Lee
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037, USA
Acta Haematol 122:87-96. 2009..Mutations in a type II serine protease, matriptase-2/TMPRSS6, were recently identified to be associated with severe iron deficiency caused by inappropriately high levels of ..
- The type II transmembrane serine protease matriptase-2--identification, structural features, enzymology, expression pattern and potential rolesAndrew J Ramsay
Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland 4059, Australia
Front Biosci 13:569-79. 2008Matriptase-2 (also known as TMPRSS6) is a recently identified member of the type II transmembrane serine protease (TTSP) family...
- Matriptase-2, a membrane-bound mosaic serine proteinase predominantly expressed in human liver and showing degrading activity against extracellular matrix proteinsGloria Velasco
Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
J Biol Chem 277:37637-46. 2002....
- Matriptase-2 mutations in iron-refractory iron deficiency anemia patients provide new insights into protease activation mechanismsAndrew J Ramsay
Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
Hum Mol Genet 18:3673-83. 2009..Here we describe two novel heterozygous mutations within the matriptase-2 (TMPRSS6) gene of monozygotic twin girls exhibiting an IRIDA phenotype...
- Inflammation Regulates TMPRSS6 Expression via STAT5Delphine Meynard
Program in Anemia Signaling Research, Division of Nephrology, Program in Membrane Biology, Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
PLoS ONE 8:e82127. 2013b>TMPRSS6 is a regulated gene, with a crucial role in the regulation of iron homeostasis by inhibiting hepcidin expression...
- Is the acronym IRIDA acceptable for slow responders to iron in the presence of TMPRSS6 mutations?Ebru Yımaz Keskin
Division of Pediatric Hematology, Department of Pediatrics, Gazi University Faculty of Medicine, Ankara, Turkey
Turk J Pediatr 55:479-84. 2013..iron deficiency anemia (IRIDA) is a recently described autosomal recessive disorder caused by mutations in TMPRSS6, the gene encoding matriptase-2. Patients have inappropriately high levels of hepcidin...
- Liver iron modulates hepcidin expression during chronically elevated erythropoiesis in miceVictor Díaz
Institute of Veterinary Physiology, Vetsuisse Faculty, and Zurich Center for Integrative Human Physiology ZIHP, and University of Zurich, Switzerland Department of Health and Human Performance, Faculty of Sports Science, INEF, Technical University of Madrid, Spain
Hepatology 58:2122-32. 2013..pathway targets showed that inhibitor of DNA binding 1 (ID1) and SMAD7, but not transmembrane serine protease 6 (TMPRSS6), were up-regulated by increased iron availability and thus may be involved in setting the upper limit of ..
- Associations of common variants in HFE and TMPRSS6 with iron parameters are independent of serum hepcidin in a general population: a replication studyTessel E Galesloot
Department for Health Evidence, Radboud University Medical Centre, Nijmegen, The Netherlands
J Med Genet 50:593-8. 2013Genome-wide association studies have convincingly shown that single nucleotide polymorphisms (SNPs) in HFE and TMPRSS6 are associated with iron parameters...
- Hepatocyte growth factor activator inhibitor type 2 (HAI-2) modulates hepcidin expression by inhibiting the cell surface protease matriptase-2Eva Maurer
Pharmaceutical Institute, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany
Biochem J 450:583-93. 2013....
- A strong anti-inflammatory signature revealed by liver transcription profiling of Tmprss6-/- miceMichela Riba
Center for Translational Genomics and Bioinformatics, San Raffaele Scientific Institute, Milan, Italy
PLoS ONE 8:e69694. 2013..anemia (IDA)-low hepcidin show a pro-inflammatory response that is blunted in iron deficient-high hepcidin Tmprss6 KO mice...
- TMPRSS6, but not TF, TFR2 or BMP2 variants are associated with increased risk of iron-deficiency anemiaPeng An
Key Laboratory of Nutrition and Metabolism, Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China
Hum Mol Genet 21:2124-31. 2012..elderly Chinese women: rs3811647 (TF), rs7385804 (TFR2), rs235756 (BMP2), and rs855791(V736A) and rs4820268 (TMPRSS6, encoding matriptase-2)...
- Deletion of TMPRSS6 attenuates the phenotype in a mouse model of β-thalassemiaAntonella Nai
Vita Salute San Raffaele University, Milan, Italy
Blood 119:5021-9. 2012..The BMP pathway is inactivated by the serine protease TMPRSS6 that cleaves the BMP coreceptor hemojuvelin...
- Iron refractory iron deficiency anemiaLuigia De Falco
CEINGE, Biotecnologie Avanzate, Naples, Italy
Haematologica 98:845-53. 2013Iron refractory iron deficiency anemia is a hereditary recessive anemia due to a defect in the TMPRSS6 gene encoding Matriptase-2...
- Decreased hemojuvelin protein levels in mask mice lacking matriptase-2-dependent proteolytic activityJ Frýdlová
Institute of Pathophysiology, First Faculty of Medicine, Charles University, Prague, Czech Republic
Physiol Res 62:405-11. 2013Matriptase-2, a membrane protein encoded by the Tmprss6 gene, is a negative regulator of hepcidin expression...
- Administration of recombinant erythropoietin alone does not improve the phenotype in iron refractory iron deficiency anemia patientsKai Lehmberg
Department of Pediatric Hematology and Oncology, University Medical Center Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany
Ann Hematol 92:387-94. 2013Mutations in transmembrane protease, serine 6 (TMPRSS6) cause iron refractory iron deficiency anemia (IRIDA). Parenteral iron administration may slightly improve hemoglobin level but is troublesome for patients...
- Matriptase-2, a regulatory protease of iron homeostasis: possible substrates, cleavage sites and inhibitorsMarit Stirnberg
Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, An der Immenburg 4, D 53121 Bonn, Germany
Curr Pharm Des 19:1052-61. 2013..Mutations in matriptase- 2 cause iron-refractory iron deficiency anemia (IRIDA), an iron deficiency disorder where the level of hepcidin is inappropriately high...
- Neogenin interacts with matriptase-2 to facilitate hemojuvelin cleavageCaroline A Enns
Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, Oregon 97239, USA
J Biol Chem 287:35104-17. 2012..The complex facilitates HJV cleavage by MT2, and release of the cleaved HJV from the cell occurs after a retrograde trafficking through the TGN/Golgi compartments...
- Genetic variants influencing biomarkers of nutrition are not associated with cognitive capability in middle-aged and older adultsTamuno Alfred
School of Social and Community Medicine, University of Bristol, Bristol, UK
J Nutr 143:606-12. 2013..for polymorphisms associated with circulating concentrations of iron [rs4820268 transmembrane protease, serine 6 (TMPRSS6) and rs1800562 hemochromatosis (HFE)], vitamin B-12 [(rs492602 fucosyltransferase 2 (FUT2)], vitamin D ([..
- The influence of matriptase-2 on prostate cancer in vitro: a possible role for β-cateninSiobhan L Webb
Metastasis and Angiogenesis Research Group, Institute of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, UK
Oncol Rep 28:1491-7. 2012....
- Reducing TMPRSS6 ameliorates hemochromatosis and β-thalassemia in miceShuling Guo
Isis Pharmaceuticals, Carlsbad, California 92010, USA
J Clin Invest 123:1531-41. 2013..HAMP expression is controlled by activation of the SMAD1,5,8/SMAD4 complex. TMPRSS6 is a serine protease that reduces SMAD activation and blocks HAMP expression...
- Race-ethnic differences in the association of genetic loci with HbA1c levels and mortality in U.S. adults: the third National Health and Nutrition Examination Survey (NHANES III)Jonna L Grimsby
General Medicine Division, Massachusetts General Hospital, Boston, MA, USA
BMC Med Genet 13:30. 2012..is race-ethnic variation in 1) HbA1c-associated risk allele frequencies (RAFs) for SNPs near SPTA1, HFE, ANK1, HK1, ATP11A, FN3K, TMPRSS6, G6PC2, GCK, MTNR1B; 2) association of SNPs with HbA1c and 3) association of SNPs with mortality.
- An RNAi therapeutic targeting Tmprss6 decreases iron overload in Hfe(-/-) mice and ameliorates anemia and iron overload in murine β-thalassemia intermediaPaul J Schmidt
Department of Pathology, Children s Hospital Boston and Harvard Medical School, Boston, MA 02115, USA
Blood 121:1200-8. 2013..b>Tmprss6 is postulated to regulate hepcidin production by cleaving Hemojuvelin (Hjv), a key modulator of hepcidin ..
- A novel mutation Gly603Arg of TMPRSS6 in a Korean female with iron-refractory iron deficiency anemiaHyoung Soo Choi
Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Korea
Pediatr Blood Cancer 58:640-2. 2012..The genetic background of IRIDA is mutations in the TMPRSS6 gene encoding matriptase-2 (TMPRSS6) that prevent inactivation of hemojuvelin, an activator of hepcidin ..
- Common TMPRSS6 mutations and iron, erythrocyte, and pica phenotypes in 48 women with iron deficiency or depletionPauline L Lee
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA, USA
Blood Cells Mol Dis 48:124-7. 2012b>TMPRSS6 A736V is associated with lower transferrin saturation (TS), hemoglobin (Hb), and mean corpuscular volume (MCV) levels in general adult populations...
- Severe microcytic anemia but increased erythropoiesis in mice lacking Hfe or Tfr2 and Tmprss6Pauline Lee
The Scripps Research Institute, Department of Molecular and Experimental Medicine, La Jolla, CA, USA
Blood Cells Mol Dis 48:173-8. 2012Cell surface proteins Hfe, Tfr2, hemojuvelin and Tmprss6 play key roles in iron homeostasis. Hfe and Tfr2 induce transcription of hepcidin, a small peptide that promotes the degradation of the iron transporter ferroportin...
- Responsiveness to oral iron and ascorbic acid in a patient with IRIDAMilena Cau
Dipartimento di Scienze Biomediche e Biotecnologie, Universita di Cagliari, Italy
Blood Cells Mol Dis 48:121-3. 2012Mutations in TMPRSS6 gene cause iron-refractory iron deficiency anemia, a rare autosomal recessive disorder characterized by hypochromic microcytic anemia not responsive to oral iron therapy and partially responsive to parenteral iron ..
- Association of TMPRSS6 polymorphisms with ferritin, hemoglobin, and type 2 diabetes risk in a Chinese Han populationWei Gan
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China
Am J Clin Nutr 95:626-32. 2012b>Transmembrane protease serine 6 (TMPRSS6) regulates iron homeostasis by inhibiting the expression of hepcidin...
- Candidate gene sequencing of SLC11A2 and TMPRSS6 in a family with severe anaemia: common SNPs, rare haplotypes, no causative mutationAnita Kloss-Brandstätter
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria
PLoS ONE 7:e35015. 2012..iron deficiency anaemia (IRIDA) is a rare disorder which was linked to mutations in two genes (SLC11A2 and TMPRSS6). Common polymorphisms within these genes were associated with serum iron levels...
- Membrane-bound serine protease matriptase-2 (Tmprss6) is an essential regulator of iron homeostasisAlicia R Folgueras
Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, Spain
Blood 112:2539-45. 2008..Here we show that matriptase-2 (Tmprss6), a recently described member of the TTSP family, is an essential regulator of iron homeostasis...
- Iron-refractory iron deficiency anemiaKarin E Finberg
Department of Pathology, Duke University Medical Center, Durham, NC
Semin Hematol 46:378-86. 2009..IRIDA has recently been shown to be caused by mutations in the gene TMPRSS6, which encodes a transmembrane serine protease (also known as matriptase-2) expressed by the liver...
- Genetic upregulation of matriptase-2 reduces the aggressiveness of prostate cancer cells in vitro and in vivo and affects FAK and paxillin localisationAndrew J Sanders
Metastasis and Angiogenesis Research Group, Cardiff University School of Medicine, Cardiff, UK
J Cell Physiol 216:780-9. 2008..Furthermore, the data presented implies a possible connection between matriptase-2 and the paxillin and FAK adhesion molecules which may ultimately contribute to the reduced migration rates seen in this study...
- Polymorphisms and mutations of human TMPRSS6 in iron deficiency anemiaE Beutler
Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Blood Cells Mol Dis 44:16-21. 2010..with iron deficiency from the general population were examined for polymorphisms or sporadic mutations in TMPRSS6 to identify genetic risk factors for iron deficiency anemia...
- Sequence variants in three loci influence monocyte counts and erythrocyte volumeManuel A R Ferreira
Queensland Institute of Medical Research QIMR, Brisbane, QLD 4029, Australia
Am J Hum Genet 85:745-9. 2009..001, 9.9x10(-5), and 7x10(-5), respectively). The identification of these QTL provides new opportunities for furthering our understanding of the mechanisms regulating hemopoietic cell fate...
- Matriptase-2 inhibits breast tumor growth and invasion and correlates with favorable prognosis for breast cancer patientsChristian Parr
Metastasis and Angiogenesis Research Group, School of Medicine, Cardiff University, Cardiff, United Kingdom
Clin Cancer Res 13:3568-76. 2007..The role of matriptase-2 and its cellular function in cancer is unknown. This study aimed to provide new insights into the significance of matriptase-2 in cancer...
- Refinement of the 22q12-q13 breast cancer--associated region: evidence of TMPRSS6 as a candidate gene in an eastern Finnish populationJaana M Hartikainen
Department of Pathology, University of Kuopio, Finland
Clin Cancer Res 12:1454-62. 2006..A SNP (rs733655) in matriptase-2 gene (TMPRSS6) was detected to associate with breast cancer risk...
- Membrane anchored serine proteases: a rapidly expanding group of cell surface proteolytic enzymes with potential roles in cancerSarah Netzel-Arnett
Vascular Biology Department, Jerome H Holland Laboratory for the Biological Sciences, American Red Cross, 15601 Crabbs Branch Way, Rockville, MD 20855, USA
Cancer Metastasis Rev 22:237-58. 2003..Diagnostic or therapeutic targeting of the membrane anchored serine proteases has potential as promising new approaches for the treatment of cancer and other diseases...
- Multiple loci influence erythrocyte phenotypes in the CHARGE ConsortiumSanthi K Ganesh
National Human Genome Research Institute, Division of Intramural Research, Bethesda, MD, USA
Nat Genet 41:1191-8. 2009..Our findings include loci previously associated with these traits (HBS1L-MYB, HFE, TMPRSS6, TFR2, SPTA1) as well as new associations (EPO, TFRC, SH2B3 and 15 other loci)...
- Iron-refractory iron deficiency anemia: new molecular mechanismsYujie Cui
Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Soochow University, Suzhou, China
Kidney Int 76:1137-41. 2009..In mice, defects in the Tmprss6 gene encoding matriptase-2 result in high hepcidin expression and cause severe microcytic anemia...
- Fine tuning of hepcidin expression by positive and negative regulatorsMartina U Muckenthaler
Department of Pediatric Oncology, Haematology and Immunology, University Hospital of Heidelberg, Molecular Medicine Partnership Unit, Im Neuenheimer Feld 156, 69120 Heidelberg, Germany
Cell Metab 8:1-3. 2008..Three recent publications now identify a novel hepcidin suppressor, the transmembrane serine protease TMPRSS6 (also known as matriptase-2), which is required to sense iron deficiency.
- Two nonsense mutations in the TMPRSS6 gene in a patient with microcytic anemia and iron deficiencyFlavia Guillem
Assistance publique des Hôpitaux de Paris APHP, Laboratoire de Génétique et Biochimie Hormonale, Hopital Bichat, Paris, France
Blood 112:2089-91. 2008..with poor intestinal absorption and defective iron utilization of IV iron is caused by inherited mutations in TMPRSS6, a liver-expressed gene that encodes a membrane-bound serine protease of previously unknown role that was ..
- Interacting signals in the control of hepcidin expressionDeepak Darshan
Iron Metabolism Laboratory, Queensland Institute of Medical Research and the University of Queensland, PO Royal Brisbane Hospital, Brisbane, QLD, Australia
Biometals 22:77-87. 2009..levels by acting through hepatocyte cell surface proteins including HFE, transferrin receptor 2, hemojuvelin, TMPRSS6 and the IL-6R...
- Hepcidin downregulation by repeated bleeding is not mediated by soluble hemojuvelinJ Krijt
Institute of Pathophysiology and Center of Experimental Hematology, Charles University in Prague, First Faculty of Medicine, Prague, Czech Republic
Physiol Res 59:53-9. 2010..Liver and muscle furin mRNA content was not significantly changed. No effect on hepatic Tmprss6 mRNA content was observed...
- SELDI-TOF MS detection of urinary hepcidinSandro Altamura
Department of Pediatric Oncology, Haematology and Immunology, University Hospital of Heidelberg Molecular Medicine Partnership Unit, Im Neuenheimer Feld 156, 69120 Heidelberg, Germany
Biochimie 91:1335-8. 2009..retention in the anemias of inflammation and plays a pathogenic role in iron-refractory iron-deficiency anemia (IRIDA)...
- Regulation of type II transmembrane serine proteinase TMPRSS6 by hypoxia-inducible factors: new link between hypoxia signaling and iron homeostasisSamira Lakhal
Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford OX3 7BN, United Kingdom
J Biol Chem 286:4090-7. 2011..Type II transmembrane serine proteinase (TMPRSS6) antagonizes hepcidin induction by BMPs by cleaving HJV from the cell membrane...
- The serine protease TMPRSS6 is required to sense iron deficiencyXin Du
Department of Genetics, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Science 320:1088-92. 2008..caused by high levels of hepcidin and is due to a splicing defect in the transmembrane serine protease 6 gene Tmprss6. Overexpression of normal TMPRSS6 protein suppresses activation of the Hamp promoter, and the TMPRSS6 cytoplasmic ..
- Suppression of the hepcidin-encoding gene Hamp permits iron overload in mice lacking both hemojuvelin and matriptase-2/TMPRSS6Jaroslav Truksa
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
Br J Haematol 147:571-81. 2009..is countered through a pathway involving the hepatocyte-specific plasma membrane protease matriptase-2 encoded by TMPRSS6, leading to suppression of HAMP expression...
- Haematologic data, iron parameters and molecular findings in two new cases of iron-refractory iron deficiency anaemiaIsabelle Tchou
Geneva University Hospitals, Switzerland
Eur J Haematol 83:595-602. 2009Matriptase-2 (Tmprss6), a type II transmembrane serine protease, has an essential role in iron homoeostasis as a hepcidin regulator...
- Recent advances in iron metabolism and related disordersClara Camaschella
Università Vita Salute e IRCCS San Raffaele, Via Olgettina 60, Milan, Italy
Intern Emerg Med 5:393-400. 2010..The study of genetic conditions such as hemochromatosis and iron-refractory-iron-deficiency anemia (IRIDA) has provided crucial insights into the molecular mechanisms controlling iron homeostasis...
- Immunoassay for human serum hemojuvelinCarole Brasse-Lagnel
Laboratoire de Biochimie Medicale, hôpital universitaire de Rouen, EA4309 Endothélium Microvasculaire et Lésions Cérébrales Néonatales, Universite de Rouen, Rouen, France
Haematologica 95:2031-7. 2010..can be produced by secretion following furin cleavage or by proteolytic cleavage of the membrane-bound form by matriptase 2 (TMPRSS6). These forms contribute to down-regulation of hepcidin expression upon iron deficiency or hypoxia...
- A novel SNaPshot assay to detect genetic mutations related to iron metabolismStefania Bertoncini
Department of Biology, Anthropology Unit, University of Pisa, Pisa, Italy
Genet Test Mol Biomarkers 15:173-9. 2011..targets 10 autosomal mutations in genes, or regions near to them, reported to be involved in iron metabolism: TMPRSS6, TF, and HFE...
- [Iron deficiency anaemia due to a matriptase-2 mutation]M L H Marloes Cuijpers
Universitair Medisch Centrum St Radboud, Nijmegen, Afd Hematologie, The Netherlands
Ned Tijdschr Geneeskd 154:A1038. 2010..hepcidin-regulating proteins the patient was found to be compound heterozygous for two different mutations in the TMPRSS6 gene. This leads to a dysfunctional matriptase-2 protein for which the gene codes...
- Novel association to the proprotein convertase PCSK7 gene locus revealed by analysing soluble transferrin receptor (sTfR) levelsKonrad Oexle
Institute of Human Genetics, MRI, Technische Universitat Munchen, Munich, Germany
Hum Mol Genet 20:1042-7. 2011..of five genome-wide association studies on sTfR and ferritin revealed novel association to the PCSK7 and TMPRSS6 loci for sTfR and the HFE locus for both parameters...
- Suppression of hepatic hepcidin expression in response to acute iron deprivation is associated with an increase of matriptase-2 proteinAn Sheng Zhang
Department of Cell and Developmental Biology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
Blood 117:1687-99. 2011..demonstrate a pivotal role for bone morphogenic protein-6 (BMP6) and matriptase-2, a protein encoded by the TMPRSS6 gene, in the induction and suppression of hepatic hepcidin expression, respectively...
- Iron-deficiency anemia secondary to mutations in genes controlling hepcidinMilena Cau
Dipartimento di Scienze Biomediche e Biotecnologie Università di Cagliari, Ospedale Regionale Microcitemie ASL Cagliari, Via Jenner s n, Cagliari, Italy
Expert Rev Hematol 3:205-16. 2010..In 2008, a new gene, TMPRSS6, was identified that encodes a negative regulator of hepcidin expression...
- Common variants at 10 genomic loci influence hemoglobin A₁(C) levels via glycemic and nonglycemic pathwaysNicole Soranzo
Human Genetics, Wellcome Trust Sanger Institute, Hinxton, U K
Diabetes 59:3229-39. 2010..We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA₁(c) levels...
- Tmprss6 is a genetic modifier of the Hfe-hemochromatosis phenotype in miceKarin E Finberg
Department of Pathology, Duke University School of Medicine, Durham, NC, USA
Blood 117:4590-9. 2011..b>TMPRSS6, a transmembrane serine protease mutated in iron-refractory iron deficiency anemia, inhibits hepcidin expression ..
- Liver hemojuvelin protein levels in mice deficient in matriptase-2 (Tmprss6)Jan Krijt
Institute of Pathophysiology and Center of Experimental Hematology, Charles University in Prague, Czech Republic
Blood Cells Mol Dis 47:133-7. 2011Mutations of the TMPRSS6 gene, encoding the serine protease matriptase-2, lead to iron-refractory iron deficiency anemia. Matriptase-2 is a potent negative regulator of hepcidin...
- A close association of abnormal iron metabolism with steatosis in the mice fed a choline-deficient dietHiroyuki Tsuchiya
Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Yonago, Tottori 683 8504, Japan
Biol Pharm Bull 33:1101-4. 2010..significantly downregulated hepcidin while increases in hemojuvelin and transferrin receptor 2 and a decrease in Tmprss6 expression were observed...
- Molecular mechanisms of hepcidin regulation in sea bass (Dicentrarchus labrax)J V Neves
Iron and Innate Immunity, Instituto de Biologia Molecular e Celular IBMC, Rua do Campo Alegre 823, 4150 180 Porto, Portugal
Fish Shellfish Immunol 31:1154-61. 2011..labrax) several coding sequences of known molecules involved on these pathways in mammals, namely jak3, stat3, tmprss6, bmp6, bmpr2, hjv, smad4, smad5, tfr1 and tfr2...
- [Iron deficiency and overload. Implications in oxidative stress and cardiovascular health]L Toxqui
Departamento de Metabolismo y Nutricion, Instituto de Ciencia y Tecnología de Alimentos y Nutrición ICTAN, Instituto del Frio, Consejo Superior de Investigaciones Cientificas CSIC, Madrid, Spain
Nutr Hosp 25:350-65. 2010..overload and iron deficiency anaemia, involves mutations in several genes such as HFE, TFR2,HAMP, HJV, Tf and TMPRSS6. Iron has the capacity to accept and donate electrons easily and can catalyze reactions of free radicals ..
- Rapid, accurate detection of TMPRSS6 gene causative mutations with a high-resolution melting assayHe ming Wu
Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, PR China
Blood Cells Mol Dis 47:198-204. 2011Mutations of the TMPRSS6 gene are considered the major genetic factors for iron-refractory iron deficiency anemia (IRIDA)...
- Essential role of endocytosis of the type II transmembrane serine protease TMPRSS6 in regulating its functionalityFrançois Béliveau
Department of Pharmacology, Faculty of Medicine and Health Sciences, Universite de Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada
J Biol Chem 286:29035-43. 2011The type II transmembrane serine protease TMPRSS6 (also known as matriptase-2) controls iron homeostasis through its negative regulation of expression of hepcidin, a key hormone involved in iron metabolism...
- Novel missense mutation in the TMPRSS6 gene in a Japanese female with iron-refractory iron deficiency anemiaTsutomu Sato
Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, South 1, West 16, Chuo Ku, Sapporo, 060 8543, Japan
Int J Hematol 94:101-3. 2011..The disease is caused by mutations in TMPRSS6 (transmembrane protease serine 6) that prevent inactivation of membrane-bound hemojuvelin, an activator of hepcidin transcription...
- Low hepcidin accounts for the proinflammatory status associated with iron deficiencyAlessia Pagani
Vita Salute San Raffaele University and Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy
Blood 118:736-46. 2011..b>Tmprss6(-/-) mice, characterized by iron deficiency and high hepcidin, show a blunted inflammatory response when ..
- Regulation of TMPRSS6 by BMP6 and iron in human cells and miceDelphine Meynard
Program in Membrane Biology, Division of Nephrology, Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Blood 118:747-56. 2011Mutations in transmembrane protease, serine 6 (TMPRSS6), encoding matriptase-2, are responsible for the familial anemia disorder iron-refractory iron deficiency anemia (IRIDA)...
- Matriptase-2- and proprotein convertase-cleaved forms of hemojuvelin have different roles in the down-regulation of hepcidin expressionJulia E Maxson
Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, Oregon 97239, USA
J Biol Chem 285:39021-8. 2010..These results suggest that the matriptase-2 and proprotein convertase-cleavage products have different roles in the regulation of hepcidin expression...
- Hemochromatosis - Epidemiology and Molecular MechanismsPauline Lee; Fiscal Year: 2009..We have recently discovered that a serum protease encoded by the Tmprss6 gene is a potent downregulator of hepcidin...
- Hemochromatosis - Epidemiology and Molecular MechanismsPauline L Lee; Fiscal Year: 2010..We have recently discovered that a serum protease encoded by the Tmprss6 gene is a potent downregulator of hepcidin...
- Mechanistic Characterization and Genetic Analysis of Systemic Iron HomeostasisXin Du; Fiscal Year: 2010..Mask phenotype was traced to a splicing error affecting the type II transmembrane serine protease 6 (TMPRSS6)...
- Mechanistic Characterization and Genetic Analysis of Systemic Iron HomeostasisXin Du; Fiscal Year: 2009..Mask phenotype was traced to a splicing error affecting the type II transmembrane serine protease 6 (TMPRSS6)...
- Genes that modify Iron loading in miceNancy Catherine Andrews; Fiscal Year: 2010..iron content and (2) carry out genetic screens for novel genes involved in iron homeostasis using mice lacking Tmprss6, a key inhibitor of production of the iron regulatory hormone hepcidin...
- Iron Status: A Pathway Analysis in Multiple EthnicitiesChristine McLaren; Fiscal Year: 2009..Potential study results could be used to identify individuals at risk for iron deficiency and to develop innovative prevention and treatment strategies. ..
- Study of the HFE Transferrin Receptor interaction in mammalian iron homeostasisPaul Schmidt; Fiscal Year: 2007..Most importantly, this award will assist in the transition of the candidate to become a fully independent investigator in the field of iron metabolism. ..
- Iron Status: A Pathway Analysis in Multiple EthnicitiesChristine McLaren; Fiscal Year: 2007..Potential study results could be used to identify individuals at risk for iron deficiency and to develop innovative prevention and treatment strategies. ..
- Functional investigation of hemojuvelin in regulation of hepcidin expressionAn Sheng Zhang; Fiscal Year: 2010..Elucidation of the role of HFE2, the juvenile HH-causing gene (Papanikolaou et al., 2004), will lead to a full understanding of the regulation of body iron homeostasis as well as more effective cures for iron overload disorders. ..
- Functional investigation of hemojuvelin in regulation of hepcidin expressionAn Sheng Zhang; Fiscal Year: 2009..Elucidation of the role of HFE2, the juvenile HH-causing gene (Papanikolaou et al., 2004), will lead to a full understanding of the regulation of body iron homeostasis as well as more effective cures for iron overload disorders. ..