A2ML1 explained

Alpha-2-macroglobulin-like 1 abbreviated as α2ML1 is a protein that in humans is encoded by the A2ML1 gene.^[1] α2ML1 is a large, 180 kDa protein found in the epidermis. It is able to the inhibit the chymotryptic activity of KLK7.^[2]

Function

This gene encodes a member of the alpha-macroglobulin superfamily. The encoded protein acts as an inhibitor for several proteases, and has been reported as the p170 antigen recognized by autoantibodies in the autoimmune disease paraneoplastic pemphigus (PNP).^[3] Alternative splicing results in multiple transcript variants.^[1]

Clinical significance

Mutations in A2ML1 are associated to Noonan-like syndrome.^[4]

Further reading

• Chapuis J, Hot D, Hansmannel F, Kerdraon O, Ferreira S, Hubans C, Maurage CA, Huot L, Bensemain F, Laumet G, Ayral AM, Fievet N, Hauw JJ, DeKosky ST, Lemoine Y, Iwatsubo T, Wavrant-Devrièze F, Dartigues JF, Tzourio C, Buée L, Pasquier F, Berr C, Mann D, Lendon C, Alpérovitch A, Kamboh MI, Amouyel P, Lambert JC . Transcriptomic and genetic studies identify IL-33 as a candidate gene for Alzheimer's disease . Mol. Psychiatry . 14 . 11 . 1004–16 . 2009 . 19204726 . 2860783 . 10.1038/mp.2009.10 .
• Galliano MF, Toulza E, Jonca N, Gonias SL, Serre G, Guerrin M . Binding of alpha2ML1 to the low density lipoprotein receptor-related protein 1 (LRP1) reveals a new role for LRP1 in the human epidermis . PLOS ONE . 3 . 7 . e2729 . 2008 . 18648652 . 2453322 . 10.1371/journal.pone.0002729 . 2008PLoSO...3.2729G . free .
• Toulza E, Mattiuzzo NR, Galliano MF, Jonca N, Dossat C, Jacob D, de Daruvar A, Wincker P, Serre G, Guerrin M . Large-scale identification of human genes implicated in epidermal barrier function . Genome Biol. . 8 . 6 . R107 . 2007 . 17562024 . 2394760 . 10.1186/gb-2007-8-6-r107 . free .

Notes and References

1. Web site: Entrez Gene: Alpha-2-macroglobulin-like 1 .
2. Galliano MF, Toulza E, Gallinaro H, Jonca N, Ishida-Yamamoto A, Serre G, Guerrin M . A novel protease inhibitor of the alpha2-macroglobulin family expressed in the human epidermis . J Biol Chem . 281 . 9 . 5780–5789 . November 2005 . 16298998. 10.1074/jbc.m508017200. free .
3. Schepens I, Jaunin F, Begre N, Läderach U, Marcus K, Hashimoto T, Favre B, Borradori L . The protease inhibitor alpha-2-macroglobulin-like-1 is the p170 antigen recognized by paraneoplastic pemphigus autoantibodies in human . PLOS ONE . 5 . 8 . e12250 . 2010 . 20805888 . 2923615 . 10.1371/journal.pone.0012250 . 2010PLoSO...512250S . free .
4. Vissers LE, Bonetti M, Paardekooper Overman J, Nillesen WM, Frints SG, de Ligt J, Zampino G, Justino A, Machado JC, Schepens M, Brunner HG, Veltman JA, Scheffer H, Gros P, Costa JL, Tartaglia M, van der Burgt I, Yntema HG, den Hertog J . Heterozygous germline mutations in A2ML1 are associated with a disorder clinically related to Noonan syndrome . Eur. J. Hum. Genet. . 2014 . 24939586 . 10.1038/ejhg.2014.115 . 23 . 3 . 317–24 . 4326711.