• Decay accelerating factor, DAF

MAJOR LINKS FOR CD55  

• NCBI LocusLink Record: 1604
• Mendelian Inheritance in Man (OMIM): 125240
• SwissProt annotated protein record: P08174

• Binds C3b and C4b to inhibit formation of the C3 convertases
• Binds C3bBb (alternative pathway convertase) and C4b2a (classical pathway
• convertase) to accelerate decay of the C3 convertases
• Functions with human complement much more efficiently than complement of
• other species (hence, commonly said to show homologous restriction)
• Receptor for CD97
• Receptor for echovirus and Coxsackie B virus

CELLULAR FUNCTION OF CD55  

• Sets a protective barrier threshold against inappropriate complement activation and deposition on plasma membranes, especially by the classical pathway of complement activation, by limiting formation and half-life of the C3 convertases
• Has been implicated as a ligand or protective molecule in fertilization
• 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

DISEASE RELEVANCE OF CD55 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). Whilst 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 ten Cromer blood group antigens are located on CD55, including a null
• allele generated by a premature stop codon; and amino acid substitutions in SCR3 for Dr-alpha and in SCR4 for Cr(a-)
• Some soluble CD55 found in plasma and secretions at concentrations not expected to provide significant effects. 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

• Families in which CD55 is a member
  • CD55-->Glycosyl phosphatidyl inositol anchored
  • CD55-->regulators of complement activation gene

MOLECULAR STRUCTURE OF CD55  

• Single chain, glycosylphosphatidylinositol (GPI)-anchored, type I cell surface protein*
• Four N-terminal short consensus repeat (SCR) modules (also known as "Sushi" domains and as CCP (complement control protein) repeats: 4 Cys in 1-3,2-4 linkage) with C3b/C4b binding & regulatory activity in SCR2,3,4*
• Heavily glycosylated membrane-proximal extracellular sequence
• SCR1 is not required for complement regulatory function
• Several novel forms of DAF have been reported: **
• 1) DAF-A (63kDa) and DAF-B (55kDa) have been isolated form human erythrocytes. These forms do not appear to have a GPI anchor. Seya et al. (1987) J. Immunol. 139, 1260-1267**
• 2) DAF-U1 (55-65kDa) and DAF-U2 (60-80kDa) have been isolated from urine. DAF-U2 is thought to be inactive. Nakano et al. (1991) Biochim. Biophys. Acta. 1074, 326-330**
• 3) Two forms have been found in tears (a 70 kDa and 100 kDa form). Lass et al. (1990) Invest. Opthamol. Vis. Sci. 31, 1136-1148**
• 4) A dimeric form (not disulfide bonded) has been isolated from human erythrocytes. Kinoshita et al. (1987) J. Immunol. 138, 2994-2998**

MOLECULAR MASS OF CD55  

POST-TRANSCRIPTIONAL MODIFICATION OF CD55  

• Note that there are two papers that initially reported the cloning of CD55. One of them [Caras et al., (1987) Nature 325, 545-549] reported that there may be an alternatively spliced form of CD55 that might in fact be secreted, not GPI linked. The expressed protein has not yet been demonstrated**
• Alternate forms have been noted (see preceding section) but it is not clear if these are splice variants**

POST-TRANSLATIONAL MODIFICATION OF CD55  

• Heavily glycosylated membrane-proximal extracellular sequence
• Single N-linked glycosylation site at the carboxy terminal end of SCR 1*
• Formation of GPI-anchor

SUBSTRATES FOR CD55   - No information

ENZYMES WHICH MODIFY CD55   - No information

LIGANDS FOR CD55 AND MOLECULES ASSOCIATED WITH CD55  

• Note 1 - 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. [Pangburn (1986) J. Immunol. 136, 2216-2221; Fujita et al. (1987) J. Exp. Med. 166, 1221-1228.]. However, in support of C3b binding it should be noted that physical crosslinking of CD55 to C3b has been achieved (Kinoshita et al. (1986) J. Immunol. 136, 3390-3395)

• Widely expressed on cells throughout the body
• Low expression on NK cells
• Erythrocytes

• CD55 is a key molecule to protect 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

SELECTION OF OTHER CD55-SPECIFIC REFERENCE MAB  

REVIEWS

1. Garratty G Blood group antigens as tumor markers, parasitic/bacterial/viral receptors, and their association with immunologically important proteins. Immunol Invest 1995 24:213 PubMed

2. Liszewski MK,Farries TC,Lublin DM,Rooney IA,Atkinson JP Control of the complement system. Adv Immunol 1996 61:201 PubMed

3. Lublin DM,Atkinson JP Decay-accelerating factor and membrane cofactor protein. Curr Top Microbiol Immunol 1990 153:123 PubMed

4. Nicholson-Weller A,Wang CE Structure and function of decay accelerating factor CD55. J Lab Clin Med 1994 123:485 PubMed

5. Vanderpuye OA,Labarrere CA,McIntyre JA The complement system in human reproduction. Am J Reprod Immunol 1992 27:145 PubMed

PRIMARY CITATIONS

6. Bergelson JM,Mohanty JG,Crowell RL,St John NF,Lublin DM,Finberg RW Coxsackievirus B3 adapted to growth in RD cells binds to decay- accelerating factor (CD55). J Virol 1995 69:1903 PubMed

7. Brodbeck WG,Liu D,Sperry J,Mold C,Medof ME Localization of classical and alternative pathway regulatory activity within the decay-accelerating factor. J Immunol 1996 156:2528 PubMed

8. Caras IW,Davitz MA,Rhee L,Weddell G,Martin DW Jr,Nussenzweig V Cloning of decay-accelerating factor suggests novel use of splicing to generate two proteins. Nature 1987 325:545 PubMed

9. Clarkson NA,Kaufman R,Lublin DM,Ward T,Pipkin PA,Minor PD,Evans DJ,Almond JW Characterization of the echovirus 7 receptor: domains of CD55 critical for virus binding. J Virol 1995 69:5497 PubMed

10. Finberg RW,White W,Nicholson-Weller A Decay-accelerating factor expression on either effector or target cells inhibits cytotoxicity by human natural killer cells. J Immunol 1992 149:2055 PubMed

11. Hatanaka M,Seya T,Matsumoto M,Hara T,Nonaka M,Inoue N,Takeda J,Shimizu A Mechanisms by which the surface expression of the glycosyl- phosphatidylinositol-anchored complement regulatory proteins decay- accelerating factor (CD55) and CD59 is lost in human leukaemia cell lines. Biochem J 1996 314:969 PubMed

12. Karnauchow TM,Tolson DL,Harrison BA,Altman E,Lublin DM,Dimock K The HeLa cell receptor for enterovirus 70 is decay-accelerating factor (CD55). J Virol 1996 70:5143 PubMed

13. Medof ME,Lublin DM,Holers VM,Ayers DJ,Getty RR,Leykam JF,Atkinson JP,Tykocinski ML Cloning and characterization of cDNAs encoding the complete sequence of decay-accelerating factor of human complement. Proc Natl Acad Sci U S A 1987 84:2007 PubMed

14. Niehans GA,Cherwitz DL,Staley NA,Knapp DJ,Dalmasso AP Human carcinomas variably express the complement inhibitory proteins CD46 (membrane cofactor protein), CD55 (decay-accelerating factor), and CD59 (protectin). Am J Pathol 1996 149:129 PubMed

15. Pham T,Kaul A,Hart A,Goluszko P,Moulds J,Nowicki S,Lublin DM,Nowicki BJ dra-related X adhesins of gestational pyelonephritis-associated Escherichia coli recognize SCR-3 and SCR-4 domains of recombinant decay- accelerating factor. Infect Immun 1995 63:1663 PubMed

16. Post TW,Arce MA,Liszewski MK,Thompson ES,Atkinson JP,Lublin DM Structure of the gene for human complement protein decay accelerating factor. J Immunol 1990 144:740 PubMed

17. Shafren DR,Bates RC,Agrez MV,Herd RL,Burns GF,Barry RD Coxsackieviruses B1, B3, and B5 use decay accelerating factor as a receptor for cell attachment. J Virol 1995 69:3873 PubMed

18. Shenoy-Scaria AM,Kwong J,Fujita T,Olszowy MW,Shaw AS,Lublin DM Signal transduction through decay-accelerating factor. Interaction of glycosyl-phosphatidylinositol anchor and protein tyrosine kinases p56lck and p59fyn 1. J Immunol 1992 149:3535 PubMed

19. Spear GT,Lurain NS,Parker CJ,Ghassemi M,Payne GH,Saifuddin M Host cell-derived complement control proteins CD55 and CD59 are incorporated into the virions of two unrelated enveloped viruses. Human T cell leukemia/lymphoma virus type I (HTLV-I) and human cytomegalovirus (HCMV). J Immunol 1995 155:4376 PubMed

20. Stoiber H,Pinter C,Siccardi AG,Clivio A,Dierich MP Efficient destruction of human immunodeficiency virus in human serum by inhibiting the protective action of complement factor H and decay accelerating factor (DAF, CD55). J Exp Med 1996 183:307 PubMed

21. Telen MJ Glycosyl phosphatidylinositol-linked blood group antigens and paroxysmal nocturnal hemoglobinuria. Transfus Clin Biol 1995 2:277 PubMed

22. Thomas DJ,Lublin DM Identification of 5'-flanking regions affecting the expression of the human decay accelerating factor gene and their role in tissue-specific expression. J Immunol 1993 150:151 PubMed

23. Venneker GT,Das PK,Naafs B,Tigges AJ,Bos JD,Asghar SS Morphoea lesions are associated with aberrant expression of membrane cofactor protein and decay accelerating factor in vascular endothelium. Br J Dermatol 1994 131:237 PubMed

WWW RESOURCES

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Modified 10/14/99   mpr@mail.nih.gov