CD59  MIRL, MACIF, P-18, protectin
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
GPI anchor
Blood Cell
Leukocyte
Erythrocyte
Platelet
Endothelial Cell
Epithelial Cell
Plasma Cell
Placenta
18 / 18
19 / 19
25 / 25

Expression
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.


Structure
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. 

MOLECULAR MASS
Cell Type Unreduced Reduced Comment
Lymphocytes 18-25 kDa 19-25 kDa

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.

Ligands
CD59 binds complement components C8 and C9.  A proposed interaction with CD2 has not been confirmed.

LIGANDS AND MOLECULES ASSOCIATED WITH CD59
Molecule Comment
C8-a 
C9 Inhibits incorporation into C5b-8
Lck Protein tyrosine kinases, acts with Lck and Fyn, but not Src
Fyn Protein tyrosine kinases, acts with Lck and Fyn, but not Src


There is a possible interaction with CD2.  Some studies demonstrate adhesion with blocking antibodies and recombinant protein.



Function
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).

BIOCHEMICAL ACTIVITY

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. 

Comments

 

MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD59: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD59: No information.

ADDITIONAL INSIGHTS

CD59 has been widely studied because of its roles in paroxysmal nocturnal hemoglobinuria and kinase signaling as a GPI-anchored protein.  Homologous proteins have been found in many mammalian species, and the function is less efficient with complement components obtained from non-homologous species.  It is highly efficient at protecting cells through inhibition of MAC formation, and can be viewed as "catching" inappropriately activated complement that has escaped the multiple inhibitors at the C3/C5 amplification steps. 



Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 966P13987
RatS53340P27274U48255
Antibodies
MUC93A   View Reactivity
p282   View Reactivity

Revised June 25, 2008


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