Alpha-1-microglobulin (IPR002968)

Short name: A1-microglobln

Overlapping homologous superfamilies

Family relationships

  • Alpha-1-microglobulin (IPR002968)


The lipocalin family can be subdivided into kernal and outlier sets. The kernal lipocalins form the largest self consistent group, comprising the subfamily of alpha-1-microglobulins. The outlier lipocalins form several smaller distinct subgroups: the OBPs, the von Ebner's gland proteins, alpha-1-acid glycoproteins, tick histamine binding proteins and the nitrophorins.

Alpha-1-microglobulin (A1M), also known as protein HC (for Heterogeneous Charge), is a low molecular weight protein component of plasma first discovered in pathological human urine. It is a member of the lipocalin superfamily. Although much is now known of its structure and properties, the function and physiological role of A1M remains unclear, although evidence suggests that it functions in the regulation of the immune system. A1M is known to exist in both a free form and complexed to other macromolecules: immunoglobulin A (IgA) in humans and alpha-1-inhibitor-3 in the rat. Free A1M is a monomeric protein composed of one 188 residue polypeptide and contains three cysteines, two of which (residues 75 and 173) form a conserved intra-molecular disulphide link [PMID: 1696404]. A1M is glycosylated by three separate carbohydrate chains: two complex carbohydrates are N-linked to asparagines at residues 17 and 96, and the other simple carbohydrate is O-linked to threonine at position 5. 22% of the total molecular mass of the protein is derived from carbohydrate. Free A1M is extremely heterogeneous in charge, and is found tightly associated with a chromophore. This chromophoric group is covalently bound to the free cysteine residue at position 34. It also binds retinol as a major ligand, but this is probably distinct from the its covalent chromophore. The glycosylation is different between species.

The principal sites of A1M synthesis are the liver and kidney. Half of all human plasma A1M (about 0.03mg/ml) forms a 1:1 complex with about 5% of plasma immunoglobulin A. The resulting macromolecular complex has a molecular weight of 200000, and a plasma concentration of 0.3mg/ml. It can exhibit both antibody activity and affect many of the biological actions of free A1M [PMID: 1696404]. A1M has many affects on the immune system. It inhibits stimulation of cultured lymphocytes by protein antigens; it can induce cell division of lymphocytes, a mitogenic effect that can either be enhanced or inhibited by the action of other plasma components; it inhibits neutrophil granulocyte migration in vitro; and it inhibits chemotaxis.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.