9nrc

Structural highlights

Disease

TMPS6_HUMAN IRIDA syndrome. The disease is caused by variants affecting the gene represented in this entry. Mutations leading to abrogation of TMPRSS6 activity are associated with IRIDA due to elevated levels of hepcidin, a negative regulator of plasma iron pool (PubMed:20232450).^[1]

Function

TMPS6_HUMAN Membrane-bound serine protease (PubMed:18976966, PubMed:20518742, PubMed:25156943, PubMed:25588876). Through the cleavage of cell surface hemojuvelin (HJV), a regulator of the expression of the iron absorption-regulating hormone hepicidin/HAMP, plays a role in iron homeostasis (PubMed:18408718, PubMed:18976966, PubMed:25156943).^{[2] [3] [4] [5] [6] [7]}

References

1. ↑ De Falco L, Totaro F, Nai A, Pagani A, Girelli D, Silvestri L, Piscopo C, Campostrini N, Dufour C, Al Manjomi F, Minkov M, Van Vuurden DG, Feliu A, Kattamis A, Camaschella C, Iolascon A. Novel TMPRSS6 mutations associated with iron-refractory iron deficiency anemia (IRIDA). Hum Mutat. 2010 May;31(5):E1390-405. PMID:20232450 doi:10.1002/humu.21243
2. ↑ Finberg KE, Heeney MM, Campagna DR, Aydinok Y, Pearson HA, Hartman KR, Mayo MM, Samuel SM, Strouse JJ, Markianos K, Andrews NC, Fleming MD. Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA). Nat Genet. 2008 May;40(5):569-71. PMID:18408718 doi:10.1038/ng.130
3. ↑ Silvestri L, Pagani A, Nai A, De Domenico I, Kaplan J, Camaschella C. The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin. Cell Metab. 2008 Dec;8(6):502-11. PMID:18976966 doi:10.1016/j.cmet.2008.09.012
4. ↑ Stirnberg M, Maurer E, Horstmeyer A, Kolp S, Frank S, Bald T, Arenz K, Janzer A, Prager K, Wunderlich P, Walter J, Gütschow M. Proteolytic processing of the serine protease matriptase-2: identification of the cleavage sites required for its autocatalytic release from the cell surface. Biochem J. 2010 Aug 15;430(1):87-95. PMID:20518742 doi:10.1042/BJ20091565
5. ↑ De Falco L, Silvestri L, Kannengiesser C, Morán E, Oudin C, Rausa M, Bruno M, Aranda J, Argiles B, Yenicesu I, Falcon-Rodriguez M, Yilmaz-Keskin E, Kocak U, Beaumont C, Camaschella C, Iolascon A, Grandchamp B, Sanchez M. Functional and clinical impact of novel TMPRSS6 variants in iron-refractory iron-deficiency anemia patients and genotype-phenotype studies. Hum Mutat. 2014 Nov;35(11):1321-9. PMID:25156943 doi:10.1002/humu.22632
6. ↑ McDonald CJ, Ostini L, Bennett N, Subramaniam N, Hooper J, Velasco G, Wallace DF, Subramaniam VN. Functional analysis of matriptase-2 mutations and domains: insights into the molecular basis of iron-refractory iron deficiency anemia. Am J Physiol Cell Physiol. 2015 Apr 1;308(7):C539-47. PMID:25588876 doi:10.1152/ajpcell.00264.2014
7. ↑ De Falco L, Silvestri L, Kannengiesser C, Morán E, Oudin C, Rausa M, Bruno M, Aranda J, Argiles B, Yenicesu I, Falcon-Rodriguez M, Yilmaz-Keskin E, Kocak U, Beaumont C, Camaschella C, Iolascon A, Grandchamp B, Sanchez M. Functional and clinical impact of novel TMPRSS6 variants in iron-refractory iron-deficiency anemia patients and genotype-phenotype studies. Hum Mutat. 2014 Nov;35(11):1321-9. PMID:25156943 doi:10.1002/humu.22632