Transmembrane Protease, Serine 6 (TMPRSS6)

Matriptase-2

SPN	Q990
HGNC	16517
MGI	1919003
PubMed	21622652
RGD	1307138
UniProt	Q8IU80
Wiki	TMPRSS6

TMPRSS6 shares 35% sequence identity with human matriptase/ST14 and spinesin/TMPRSS5, and 84.3% identity with mouse Tmprss6. It contains structural features characteristic of type II serine proteinases, including a short hydrophobic domain, a type II transmembrane sequence, 2 CUB domains, 3 LDL receptor repeats, and a C-terminal catalytic domain with structural hallmarks of serine proteinases. A potential phosphorylation domain is present at the cytoplasmic tail. Sequence alignment of the catalytic domains of TMPRSS6 and other type II serine proteinase family members permitted the identification of several conserved domains. Northern blot analysis of multiple human tissues revealed expression of a 3.5-kb TMPRSS6 transcript exclusively in fetal and adult liver.

Reference

"Matriptase-2, a membrane-bound mosaic serine proteinase predominantly expressed in human liver and showing degrading activity against extracellular matrix proteins."
J. Biol. Chem. 277:37637-37646(2002) [PubMed] [Europe PMC] [Abstract]

"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]

"A genome annotation-driven approach to cloning the human ORFeome."
Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence of human chromosome 22."
Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Membrane anchored serine proteases: a rapidly expanding group of cell surface proteolytic enzymes with potential roles in cancer."
Cancer Metastasis Rev. 22:237-258(2003) [PubMed] [Europe PMC] [Abstract]

"The type II transmembrane serine protease matriptase-2 --identification, structural features, enzymology, expression pattern and potential roles."
Front. Biosci. 13:569-579(2008) [PubMed] [Europe PMC] [Abstract]

"A mutation in the TMPRSS6 gene, encoding a transmembrane serine protease that suppresses hepcidin production, in familial iron deficiency anemia refractory to oral iron."
Haematologica 93:1473-1479(2008) [PubMed] [Europe PMC] [Abstract]

"Molecular mechanisms of the defective hepcidin inhibition in TMPRSS6 mutations associated with iron-refractory iron deficiency anemia."
Blood 113:5605-5608(2009) [PubMed] [Europe PMC] [Abstract]

"A novel splice site mutation c.2278 (-1) G>C in the TMPRSS6 gene causes deletion of the substrate binding site of the serine protease resulting in refractory iron deficiency anaemia."
Br. J. Haematol. 147:766-769(2009) [PubMed] [Europe PMC] [Abstract]

"Proteolytic processing of the serine protease matriptase-2: identification of the cleavage sites required for its autocatalytic release from the cell surface."
Biochem. J. 430:87-95(2010) [PubMed] [Europe PMC] [Abstract]

"A novel TMPRSS6 mutation that prevents protease auto-activation causes IRIDA."
Biochem. J. 431:363-371(2010) [PubMed] [Europe PMC] [Abstract]

"The consensus coding sequences of human breast and colorectal cancers."
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]

"Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA)."
Nat. Genet. 40:569-571(2008) [PubMed] [Europe PMC] [Abstract]

"Haematologic data, iron parameters and molecular findings in two new cases of iron-refractory iron deficiency anaemia."
Eur. J. Haematol. 83:595-602(2009) [PubMed] [Europe PMC] [Abstract]

"Matriptase-2 mutations in iron-refractory iron deficiency anemia patients provide new insights into protease activation mechanisms."
Hum. Mol. Genet. 18:3673-3683(2009) [PubMed] [Europe PMC] [Abstract]

"Polymorphisms and mutations of human TMPRSS6 in iron deficiency anemia."
Blood Cells Mol. Dis. 44:16-21(2010) [PubMed] [Europe PMC] [Abstract]

"Novel TMPRSS6 mutations associated with iron-refractory iron deficiency anemia (IRIDA)."
Hum. Mutat. 31:E1390-E1405(2010) [PubMed] [Europe PMC] [Abstract]

"Novel missense mutation in the TMPRSS6 gene in a Japanese female with iron-refractory iron deficiency anemia."
Int. J. Hematol. 94:101-103(2011) [PubMed] [Europe PMC] [Abstract]

"Inactive matriptase-2 mutants found in IRIDA patients still repress hepcidin in a transfection assay despite having lost their serine protease activity."
Hum. Mutat. 33:1388-1396(2012) [PubMed] [Europe PMC] [Abstract]

"A novel mutation Gly603Arg of TMPRSS6 in a Korean female with iron-refractory iron deficiency anemia."
Pediatr. Blood Cancer 58:640-642(2012) [PubMed] [Europe PMC] [Abstract]

"Functional and clinical impact of novel TMPRSS6 variants in iron-refractory iron-deficiency anemia patients and genotype-phenotype studies."
Hum. Mutat. 35:1321-1329(2014) [PubMed] [Europe PMC] [Abstract]

"Functional analysis of Matriptase-2 mutations and domains: Insights into the molecular basis of iron refractory iron deficiency anemia."
Am. J. Physiol. 000:C264-C264(2015) [PubMed] [Europe PMC] [Abstract]