Alpha-2-macroglobulin (P01023)

Uniprot ID P01023
Protein Name Alpha-2-macroglobulin
Gene Name A2M
Species Homo sapiens (Human)
Signal peptide(a) N Secretome P(b) 0.57
Function Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bait region, a conformational change is induced in the protein which traps the proteinase. The entrapped enzyme remains active against low molecular weight substrates (activity against high molecular weight substrates is greatly reduced). Following cleavage in the bait region, a thioester bond is hydrolyzed and mediates the covalent binding of the protein to the proteinase.
GO - Molecular function
  • calcium-dependent protein binding : IPI:AgBase
  • endopeptidase inhibitor activity : IBA:GO_Central
  • enzyme binding : IPI:UniProtKB
  • growth factor binding : IDA:UniProtKB
  • interleukin-1 binding : IDA:UniProtKB
  • interleukin-8 binding : IPI:UniProtKB
  • protease binding : IPI:BHF-UCL
  • serine-type endopeptidase inhibitor activity : IDA:UniProtKB
  • signaling receptor binding : IMP:AgBase
  • tumor necrosis factor binding : IDA:UniProtKB
GO - Biological process
  • blood coagulation, intrinsic pathway : TAS:Reactome
  • extracellular matrix disassembly : TAS:Reactome
  • negative regulation of complement activation, lectin pathway : IDA:UniProtKB
  • platelet degranulation : TAS:Reactome
  • regulation of small GTPase mediated signal transduction : TAS:Reactome
  • stem cell differentiation : IEA:Ensembl
(a) The Signal peptide D-score cutoff for "YES"(having signal peptide) is 0.45.
(b) Non-classically secreted proteins should obtain an NN-score(Neural Networks score) exceeding the normal threshold of 0.5, but not at the same time be predicted to contain a signal peptide.