Tbio A2M Alpha-2-macroglobulin

Protein Summary

Description

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. The protein encoded by this gene is a protease inhibitor and cytokine transporter. It uses a bait-and-trap mechanism to inhibit a broad spectrum of proteases, including trypsin, thrombin and collagenase. It can also inhibit inflammatory cytokines, and it thus disrupts inflammatory cascades. Mutations in this gene are a cause of alpha-2-macroglobulin deficiency. This gene is implicated in Alzheimer's disease (AD) due to its ability to mediate the clearance and degradation of A-beta, the major component of beta-amyloid deposits. A related pseudogene, which is also located on the p arm of chromosome 12, has been identified. [provided by RefSeq, Nov 2016]

Uniprot Accession IDs

• P01023
• Q13677
• Q59F47
• Q5QTS0
• Q68DN2
• Q6PIY3
• Q6PN97
• Alpha-2-M

Gene Name

• A2M

Ensembl ID

• ENST00000318602
• ENSP00000323929
• ENSG00000175899

Symbol

• CPAMD5
• A2MD
• CPAMD5
• FWP007
• S863-7

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
gene perturbation	1
protein domain	1
PubMedID	0.98
small molecule perturbation	0.83
biological term	0.82

Protein Classes

PANTHER Classes

Protein / Signaling Molecule / Cytokine / Alpha-2-macroglobulin

Protein / Enzyme Modulator / Protease Inhibitor / Serine Protease Inhibitor / Alpha-2-macroglobulin

Protein / Defense/immunity Protein / Complement Component / Alpha-2-macroglobulin

DTO Classes

Protein / Enzyme Modulator / Protease Inhibitor / Serine Protease Inhibitor / Alpha-2-macroglobulin

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1350.92   (req: < 5)

Gene RIFs: 127   (req: <= 3)

Antibodies: 862   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1350.92   (req: >= 5)

Gene RIFs: 127   (req: > 3)

Antibodies: 862   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 16

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0