CD55 DAF (decay accelerating factor)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
GPI anchor
Epithelia
Stomach
Endothelium
Breast
Erythrocyte
Colon
Nervous system
Tumor Cell
Plasma Cell
Hematopoietic Cell
50 / 50
70 / 70
80 / 80

Expression
CD55 is expressed on erythrocytes but is low on NK cells.  CD55 is widely expressed on cells through out the body and on all cells in contact with serum, including all hematopoietic cells and the vascular endothelium.  It is widely expressed on epithelia in the gastointestinal and genitourinary tracts and the central nervous system.  A soluble form of CD55 is present in plasma and body fluids.  CD55 is expressed on various tumors, breast, colon and stomach.
 


Structure
MOLECULAR FAMILY NAME: Belongs to the regulators of complement activation gene  family.

CD55 is a single-pass GPI-anchored 376 aa glycoprotein.  It contains an extracellular domain which contains 4 N-terminal complement control protein (CCP) domains, also known as short consensus repeat (SCR) domains.  The extracellular domain is heavily glycosylated but there is 1 N-linked glycosylation site at the C-terminal end of SCR1.   C3b/C4b binding and regulatory activity is found in SCR2,3,4 but not in SCR1.  SCR1 is not required for complement regulatory function.  Several novel forms of CD55 have been reported.  DAF-A, a 63 kDa, and DAF-B, 55 kDa.  DAF-A lacks the GPI anchor and is secreted, whereas DAF-V is the membrane anchored form.  Both isoforms can be further modified by varying glycosylation patterns.  The difference in molecular weight between CD55 found on human erythrocytes and that of lymphocytes is due to glycosylation differences.  DAF-U1, a 55-65 kDa, and DAF-U2, a 60-80 kDa, have been isolated from urine.  DAF-U2 is thought to be inactive.  There have been found 2 forms found in tears, a 70 kDa and 100 kDa form.  A dimeric form but not disulfide bonded has been isolated from human erythrocytes.  CD55 expressed on a Chinese hamster ovary cell line defective in O-glycosylation is rapidly degraded, suggesting that the carbohydrate structures serve to protect CD55 from proteolysis.  The glycoprotein is GPI-anchored at Ser319.  A minor form of CD55 mRNA arises from alternate splicing of an additional exon, but a corresponding protein has not been identified.  A co-valently linked homodimeric form has been described.

MOLECULAR MASS
Cell Type Unreduced Reduced Comment
Lymphocytes 70 kDa 80 kDa
Nucleated cells
Erythrocytes
55 kDa

50 kDa
The molecular mass of CD55 is about 5 kDa less on erythrocytes than on nucleated cells. This is due to glycosylation differences

POST-TRANSCRIPTIONAL MODIFICATION

Alternatively splicing yields 2 different isoforms expressed as DAF-A and DAF-B. 

POST-TRANSLATIONAL MODIFICATION

CD55 has a heavily glycosylated membrane-proximal extracellular sequence and has 1 N-linked glycosylation site at the carboxy terminal end of SCR with formation of a GPI-anchor.

Ligands
CD55 interacts with complement components and CD97 and a 7-transmembrane domain protein which also contains 3 extracellular EGF domains.

LIGANDS AND MOLECULES ASSOCIATED WITH CD55
Molecule Comment
C3b/C3bBb convertase Binds through SCR2,3,4. Ligands C3b/C4b: There is a body of evidence that suggests Bb or C2a within the convertase may be the actual ligand for CD55.  However, affinity of CD55 for the convertase itself is much higher than for individual components, suggesting that the binding site may involve a neoepitope generated through conformational changes (particularly of C3b) or through juxtaposition of the two molecules. However, in support of C3b binding it should be noted that physical crosslinking of CD55 to C3b has been achieved.


C4b/C4b2a convertase Binds through SCR2,3. Ligands C3b/C4b: There is a body of evidence that suggests Bb or C2a within the convertase may be the actual ligand for CD55. However, affinity of CD55 for the convertase itself is much higher than for individual components, suggesting that the binding site may involve a neoepitope generated through conformational changes (particularly of C3b) or through juxtaposition of the two molecules. However, in support of C3b binding it should be noted that physical crosslinking of CD55 to C3b has been achieved.


Coxsackie viruses (B1, B3, B5) Receptor (probably via SCR1 and SCR3)
CD97 CD97 has recently been implicated as a ligand for CD55
Echoviruses (type 7) Binding via SCR2,3,4 has been implicated
E. coli Dr-adhesins Receptor (via SCR3/4)
Enterovirus 70 Receptor
Protein tyrosine kinases Lck and Fyn, but not Src





Function
CD55 is a member of the regulator of complement activation (RCA) family of proteins (see CD35).  CD55 protects against inappropriate complement activation and disposition on plasma membrane by binding C3b and C4b to inhibit C3 convertase formation, and by limiting formation and half-life of the C3 convertases.  It accelerates the dissociation of the components of the C3-convertases, namely C2a from C4b in the C4b2a complex, a C3-convertase of the classical pathway, and factor Bb from the C3bBb complex, a C3-convertase of the alternative pathway.  CD55 expression increases upon T cell activation and antibodies to CD55 are mitogenic in the presence of phorbol esters.  CD55 and the 2 other complement regulatory proteins, CD46 and CD59, have received much attention in their role in reproduction and xenotransplantation (see CD46).  CD55 has been implicated as a ligand or protective molecule in fertilization by protecting sperm from complement deposition in the female reproductive system.  Crosslinking CD55, as for many GPI-anchored molecules, induces signal transduction.  This has been studied in T cell activation, where protein tyrosine kinases are activated.  CD55 expression on NK cells or their targets has been associated with reduced efficiency of cell lysis.

BIOCHEMICAL ACTIVITY

CD55 binds C3b and C4b to inhibit formation of the C3 convertases and binds C3bBb, an alternative pathway convertase, and C4b2a, a classical pathway convertase, to accelerate decay of the C3 convertases.  Functions with human complement are much more efficient than complement of other species hence, are commonly said to show homologous restriction. 

DISEASE RELEVANCE AND FUNCTION OF CD55 IN INTACT ANIMAL

Genetic defects in the CD55 gene or GPI-anchor attachment cause reduction or loss of CD55 and CD59 on erythrocytes, and thus symptoms of the disease paroxysmal nocturnal hemoglobinuria (PNH).  While CD55 does have an important role in protection of erythrocytes from homologous complement lysis, these cells can survive without it.  Individuals with the Inab phenotype express no CD55 but do express CD59.  However, they do not suffer overt erythrocyte hemolysis.  CD55 deficiencies are found in psoriatic skin lesions.  Expression may be related to tumorigenesis.  The 10 Cromer blood group antigens are located on CD55, including a null allele generated by a premature stop codon and aa substitutions in SCR3 for Dr-a and in SCR4 for Cr(a-).  Some soluble CD55 is found in plasma and secretions. The concentrations are not expected to provide significant effects but microenvironment concentrations may be effective.  HIV and HIV-infected cells are resistant to complement deposition, due to protective associations with CD55 and factor H.  CMV incorporates CD55 into the membrane.  CD55 transgenic pigs are being assessed as possible xenograft organ donors.  CD55 is a possible target for tumor therapy and has a potential use in xenotransplantation to protect against inappropriate complement activation.  CD55 also served as a receptor for CD97 for coxsackie B viruses, echoviruses, enterovirus and E. coli Dr-adhesins.

Comments
The mouse has 2 genes for CD55, 1 codes for a GPI-anchored protein and the 2nd for a transmembrane protein.  Analysis of mRNA expression showed that the GPI-anchored form is detected in most tissues, whereas the transmembrane form is highly expressed in the testes, and is also detected in bone marrow, lymph nodes, lung and liver.  CD55 expressed on mouse erythrocytes is resistant to phosphatidylinositol-specific phospholipase C treatment whereas CD55 on the surface of spleen and PBMCs is removed by phospholipase C, suggesting that the 2 forms of CD55 are expressed on different cell types.  This is another example of the lack of conservation between species of genes in the RCA complex (see CD35).

MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD55: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD55: No information.

ADDITIONAL INSIGHTS

CD55 is a key molecule that protects cells against inappropriate complement activation, especially evident in PNH and classical pathway activation, and as such is being utilized in transgenic animals for xenotransplantation studies.  The relevance of the T cell signal transduction studies to physiological functions of the molecule is not clear.  The multiple receptor functions for microorganisms are intriguing.  The associations of NK target lysis and CD55 expression may be important to NK mechanisms of killing.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 1604P08174
MouseL41366
MouseL41365
Antibodies
67   View Reactivity
IA10   View Reactivity

Revised June 25, 2008


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