alpha-2-macroglobulin; alpha-2-M; C3 & PZP-like alpha-2-macroglobulin domain-containing protein 5 (A2M, CPAMD5, FWP007)
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Function
- binds proteases
- alpha-2 Macroglobulin contributes more than 1/4 of the thrombin inhibition normally present in plasma
- when alpha-2 macroglobulin reacts with proteinase, it undergoes a major conformational change that has been termed protease trapping
- protease trapping is accompanied by hydrolysis of a gamma-glutamyl Cys & activation of alpha-2 macroglobulin
- activated alpha-2 macrogloblulin is the ligand for the alpha-2 macroglobulin receptor LRP
- the alpha-2 macroglobulin/Receptor complex may provide a mechanism for protease clearance
- able to inhibit all four classes of proteinases trapping mechanism
Structure
- homotetramer; disulfide-linked
- belongs to the protease inhibitor I39 (alpha-2-macroglobulin) family
- peptide stretch, called the 'bait region' contains specific cleavage sites for different proteinases
Compartment
Expression
- secreted in plasma
- contrary to the rat protein, which is an acute phase protein, this protein is always present at high levels in circulation
Pathology
- it has been proposed that a common isoform of the gene for alpha-2 macroglobulin increases risk of Alzheimer's disease[4]
- plasma levels are elevated in
- nephrotic syndrome
- protein-losing gastroenteropathies
- hepatic cirrhosis
- diabetes mellitus
Laboratory
- serum protein electrophoresis
- alpha-2 Macroglobulin normally accounts for 25% of the alpha-2 band
- its large size contributes to selective retention on the gel
More general terms
- acute phase protein
- alpha 2 globulin
- macroglobulin
- oligomerizing protein
- regulatory molecule
- protease inhibitor
- sialoglycoprotein
Additional terms
- alpha-2-macroglobulin-like protein 1 (C3 & PZP-like alpha-2-macroglobulin domain-containing protein 9, A2ML1, CPAMD9)
- CD91, low density lipoprotein (LDL) receptor related protein (LRP) 1, apolipoprotein E [apoE] receptor 1, chylomicron remnant receptor or alpha-2 macroglobulin receptor
References
- ↑ Clinical Diagnosis & Management by Laboratory Methods, J.B. Henry (ed), W.B. Saunders Co., Philadelphia, PA. 1991, pg 222
- ↑ Clinical Chemistry, Principles, Procedures, Correlations, 2nd ed., Bishop, Duben-Engelkirk, Fody (eds), JB Lippincott, Philadelphia, 1991 pg 184
- ↑ Wolf BB et al Characterization and immunohistochemical localization of alpha 2-macroglobulin receptor (low-density lipoprotein receptor-related protein) in human brain. Am J Pathol 141:37 1992 PMID: https://www.ncbi.nlm.nih.gov/pubmed/1632469
- ↑ 4.0 4.1 Blacker D et al Alpha-2 macroglobulin is genetically associated with Alzheimer disease. Nat Genet. 1998 Aug;19(4):357-60. PMID: https://www.ncbi.nlm.nih.gov/pubmed/9697696
- ↑ Entrez Gene http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=2
- ↑ UniProt http://www.uniprot.org/uniprot/P01023.html
- ↑ Wikipedia; Note: alpha-2 macroglobulin entry http://en.wikipedia.org/wiki/alpha_2-macroglobulin