CD59
Function
Potent inhibitor of the complement membrane attack complex (MAC) action, which protects human cells from damage during complement activation (PubMed:11882685, PubMed:1698710, PubMed:2475111, PubMed:2475570, PubMed:2606909, PubMed:9053451). Acts by binding to the beta-haipins of C8 (C8A and C8B) components of the assembling MAC, forming an intermolecular beta-sheet that prevents incorporation of the multiple copies of C9 required for complete formation of the osmolytic pore (PubMed:11882685, PubMed:1698710, PubMed:36797260).
The soluble form from urine retains its specific complement binding activity, but exhibits greatly reduced ability to inhibit complement membrane attack complex (MAC) assembly on cell membranes.
Involvement in disease
Hemolytic anemia, CD59-mediated, with or without polyneuropathy
HACD59
An autosomal recessive disorder characterized by infantile onset of chronic hemolysis and a relapsing-remitting polyneuropathy, often exacerbated by infection, and manifested as hypotonia, limb muscle weakness, and hyporeflexia.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
N- and O-glycosylated. The N-glycosylation mainly consists of a family of biantennary complex-type structures with and without lactosamine extensions and outer arm fucose residues. Also significant amounts of triantennary complexes (22%). Variable sialylation also present in the Asn-43 oligosaccharide. The predominant O-glycans are mono-sialylated forms of the disaccharide, Gal-beta-1,3GalNAc, and their sites of attachment are probably on Thr-76 and Thr-77. The GPI-anchor of soluble urinary CD59 has no inositol-associated phospholipid, but is composed of seven different GPI-anchor variants of one or more monosaccharide units. Major variants contain sialic acid, mannose and glucosamine. Sialic acid linked to an N-acetylhexosamine-galactose arm is present in two variants.
Glycated (PubMed:10805801). Glycation is found in diabetic subjects, but only at minimal levels in nondiabetic subjects. Glycated CD59 lacks MAC-inhibitory function and confers to vascular complications of diabetes (PubMed:10805801).
Cellular localization
- Cell membrane
- Lipid-anchor
- GPI-anchor
- Secreted
- Localizes to the cell surface (PubMed:36797260). Soluble form found in a number of tissues (PubMed:8670172).
Alternative names
CD59, MIC11, MIN1, MIN2, MIN3, MSK21, CD59 glycoprotein, 1F5 antigen, 20 kDa homologous restriction factor, MAC-inhibitory protein, MEM43 antigen, Membrane attack complex inhibition factor, Membrane inhibitor of reactive lysis, Protectin, HRF-20, HRF20, MAC-IP, MACIF, MIRL