|CD59||MIRL, MACIF, P-18, protectin|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
|18 / 18|
19 / 19
25 / 25
|CD59 is expressed widely on cells in all tissues such as leukocytes, erythrocytes, platelets, a variety of endothelial and epithelial cells, placenta and spermatozoa. Expression on erthrocytes is important for their survival. It is also found in a number of bodily fluids including blood plasma, saliva, amniotic fluid, seminal fluid and urine.|
|MOLECULAR FAMILY NAME: Belongs to the Ly6 superfamily.|
CD59 is a single-pass GPI-anchored glycoprotein. It is structurally related to snake venom neurotoxins. There are 5 disulfide bonds that are shown by NMR to be: 1-5, 2-3, 4-6, 7-8, 9-10. The bonds are described from the NMR studies as a relatively flat, disk-shaped molecule, with a 2-stranded b-sheet finger loosely packed against a core formed by a 3-stranded b-sheet and a short helix.
POST-TRANSCRIPTIONAL MODIFICATION: No information.
POST- TRANSLATIONAL MODIFICATION
Residue 18 is used as a site for N-glycanation. N-glycanation is not essential for function as determined by mutagenesis studies.
|CD59 binds complement components C8 and C9. A proposed interaction with CD2 has not been confirmed.|
LIGANDS AND MOLECULES ASSOCIATED WITH CD59
There is a possible interaction with CD2. Some studies demonstrate adhesion with blocking antibodies and recombinant protein.
|CD59 is a membrane inhibitor of reactive lysis (protectin), regulates complement-mediated cell lysis, polymerization and is involved in lymphocyte signal transduction. Binding to C9 inhibits its incorporation into C5b-8, thereby blocking the terminal steps of polymerization of the complement membrane attack complex (MAC) on the plasma membrane, thus protecting cells from complement mediated lysis. It does not block the lytic activity of perforin by cell-mediated cytotoxicity. CD59 expression is essential for erythrocyte survival. It is unlikely that CD59 is synthesized by all cells on which it is expressed. CD59 has a signaling role, as a GPI-anchored molecule, in T cell activation and appears to have some role in cell adhesion through CD2 but is controversial. CD59 can be transferred between cells via fluid phase vesicles and other non-membranous complexes, which also explains its presence in many body fluids. Paroxysmal nocturnal hemoglobinuria (PNH) is likely to be the direct consequence of the reduction or loss of CD59 expression on the cell surface, although in most cases, it results from defects in the synthesis of GPI-anchors. CD59 and the 2 other complement regulatory proteins, CD46 and CD55, have received much attention for their role in reproduction and xenotransplantation (see CD46).|
CD59 associates with C9, inhibiting incorporation into C5b-8 and preventing terminal steps in polymerization of the MAC in plasma membranes thus protecting cells from complement-mediated lysis.
DISEASE RELEVANCE AND FUNCTION OF CD59 IN INTACT ANIMAL
Genetic defects in GPI-anchor attachment that cause a reduction or loss of both CD59 and CD55 on erythrocytes produce the symptoms of the disease PNH. CD59 transgenic pigs are being studied for use of their tissues in xenotransplantation. CD59 is incorporated in HIV envelope and protects virus and HIV infected cells against complement deposition.
MOLECULAR INTERACTIONS -
Database accession numbers
Revised June 25, 2008