alpha-2-Macroglobulin (alpha-2M) is a homotetrameric serum protein consisting of four identical subunits that form dimers through disulfide bonds. Initially, alpha-2M was characterized as a pan-proteinase inhibitor that was able to “bait” proteinases into cleaving specific peptide sequences on alpha-2M. This interaction induces a conformational change in alpha-2M, thus enabling it to “trap” the proteinase and further inhibit its activity. Subsequently, alpha-2M has been shown to function as a carrier protein and regulator of cytokines during inflammation. Circulating transforming growth factor beta (TGF beta) in serum is primarily bound to alpha-2M, which renders TGF∫ inactive. Mutations and deletions in the gene encoding alpha-2M are associated with an increased incidence of Alzheimer's Disease (AD). Alpha-2-macroglobulin-like protein 1 (alpha2ML1) is a related protein that is expressed in the epidermis and may play a role in keratinocyte differentiation.
Function:
A2ML1 is a new member of the alpha 2-macroglobulin protease inhibitor family, and shares most the characteristics of this family. It is the first family member detected in the epidermis and may play an important role during desquamation by inhibiting extracellular proteases. The alpha-macroglobulin (AM) superfamily of proteins contains both complement components and protease inhibitors, including A2M and A2ML1. AM proteins display a unique trap mechanism of inhibition, by which the AM inhibitor undergoes a major conformational change upon its cleavage by a protease, thus trapping the protease and blocking it from subsequent substrate binding.
Subunit:
Monomer.
Subcellular Location:
Secreted
Tissue Specificity:
In the epidermis, expressed predominantly in the granular layer at the apical edge of keratinocytes (at protein level). Also detected in placenta, testis and thymus but not in epithelia of kidney, lung, small intestine or colon.
Similarity:
Belongs to the protease inhibitor I39 (alpha-2-macroglobulin) family.
SWISS:
A8K2U0
Gene ID:
144568
Database links:
Entrez Gene: 144568 Human
Omim: 610627 Human
SwissProt: A8K2U0 Human
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