Alpha-2-Macroglobulin

Alpha-2-Macroglobulin, also known as α2-macroglobulin (α2M and A2M), is an abundant protein of the plasma of vertebrates and members of several invertebrate phyla and functions as a broad-spectrum protease-binding protein. Alpha-2-Macroglobulin is produced by the liver, and is a major component of the alpha-2 band in protein electrophoresis. Alpha-2-Macroglobulin is a large plasma glycoprotein that has long been known as an irreversible inhibitor of a variety of proteinases. More recently, it has been reported that numerous growth factors, cytokines and hormones bind to alpha 2M through diverse mechanisms. A2M is also produced in the brain where it binds multiple extracellular ligands and is internalized by neurons and astrocytes. In the brain of Alzheimer's disease (AD) patients, A2M has been localized to diffuse amyloid plaques. A2M also binds soluble beta-amyloid, of which it mediates degradation. Protease-conjugated alpha2-macroglobulin is selectively bound by cells contacting the body fluids and alpha2-macroglobulin and its protease cargo are then internalized and degraded in secondary lysosomes of those cells. In addition to this function as an agent for protease clearance, alpha2-macroglobulin binds a variety of other ligands, including several peptide growth factors and modulates the activity of a lectin-dependent cytolytic pathway in arthropods.

Alpha-2-Macroglobulin Related Areas

Enzyme>>Protease & Regulator>>Aspartate Protease & Regulator>>Alpha-2-Macroglobulin/A2M

Enzyme>>Protease & Regulator>>Cysteine Protease & Regulator>>Alpha-2-Macroglobulin/A2M

Enzyme>>Protease & Regulator>>Metalloprotease & Regulator>>Alpha-2-Macroglobulin/A2M

Enzyme>>Protease & Regulator>>Serine Protease & Regulator>>Alpha-2-Macroglobulin/A2M

Alpha-2-Macroglobulin Alternative Names

Alpha-2-Macroglobulin, A2M, FWP007, CPAMD5, DKFZp779B086, S863-7 [Homo sapiens]

Alpha-2-Macroglobulin, A2m, A2mp [Mus musculus]

Summaries for Alpha-2-Macroglobulin

Entrez Gene summary for Alpha-2-Macroglobulin:

Alpha-2-Macroglobulin is a protease inhibitor and cytokine transporter. It inhibits many proteases, including trypsin, thrombin and collagenase. A2M is implicated in Alzheimer disease (AD) due to its ability to mediate the clearance and degradation of A-beta, the major component of beta-amyloid deposits

OMIM - description for Alpha-2-Macroglobulin:

A2M is a 718-kD homotetrameric glycoprotein of plasma and extracellular spaces that was first recognized as a broad spectrum protease inhibitor. A2M is activated by proteases with which it interacts, and this proteolytic activation causes a conformational change that traps the protease within the A2M homotetramer. In addition, A2M contains several independent domains that function as carriers of specific growth factors and/or binding sites for receptors. Activation of A2M by proteases alters the interaction of A2M with these ligands and induces cell signaling

Wikipedia summary for Alpha-2-Macroglobulin:

Alpha-2-Macroglobulin, also known as α2-macroglobulin and abbreviated as α2M and A2M, is a large plasma protein found in the blood. It is produced by the liver, and is a major component of the alpha-2 band in protein electrophoresis. Alpha 2-Macroglobulin is the largest major nonimmunoglobulin protein in plasma. The alpha 2-macroglobulin molecule is synthesized mainly in liver, but also locally by macrophages, fibroblasts, and adrenocortical cells. Alpha 2 macroglobulin acts as an antiprotease and is able to inactivate an enormous variety of proteinases. It functions as an inhibitor of fibrinolysis by inhibiting plasmin and kallikrein. It functions as an inhibitor of coagulation by inhibiting thrombin. Alpha 2-macroglobulin may act as a carrier protein because it also binds to numerous growth factors and cytokines, such as platelet-derived growth factor, basic fibroblast growth factor, TGF-β, insulin, and IL-1β. No specific deficiency with associated disease has been recognized, and no disease state is attributed to low concentrations of Alpha 2 macroglobulin. The concentration of alpha 2 macroglobulin rises 10-fold or more in the nephrotic syndrome when other lower molecular weight proteins are lost in the urine. The loss of alpha 2 macroglobulin into urine is prevented by its large size. The net result is that alpha 2 macroglobulin reaches serum levels equal to or greater than those of albumin in the nephrotic syndrome, which has the effect of maintaining oncotic pressure.

Human Alpha-2-Macroglobulin Protein General Information

 

• Protein names: Recommended name: Alpha-2-Macroglobulin Short name=Alpha-2-M
• Sequence length: 1474 AA.
• Domain: Bait region Signal
• Sequence similarities: Belongs to the protease inhibitor I39 (Alpha-2-Macroglobulin) family. [View classification]
• Sequence caution: The sequence AAT02228.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence BAD92851.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.
• Subunit structure: Homotetramer; disulfide-linked.
• Subcellular location: Secreted
• Tissue specificity: Secreted in plasma.

General information above from UniProt

Function for Alpha-2-Macroglobulin Protein

UniProtKB:

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.

Genatlas:

• Alpha-2-Macroglobulin protease inhibitor I39 (alpha-2- macroglobulin) family
• serum protease inhibitor mediating the clearance and degradation of A-beta, the major component of beta-amyloid deposits
• Alpha-2-Macroglobulin protease inhibitor and cytokine transporter

Homology for human Alpha-2-Macroglobulin

• homolog to murine A2m

Phenotype Information for Alpha-2-Macroglobulin

• Gene/Locus: A2M , A2MD
• Phenotype: Alpha-2-Macroglobulin deficiency
  {Alzheimer disease, susceptibility to}

Phenotype Information for Alpha-2-Macroglobulin from OMIM (Online Mendelian Inheritance in Man)