Decay-accelerating factor

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Complement decay-accelerating factor, also known as CD55 or DAF, is a protein that, in humans, is encoded by the CD55 gene.[1]

DAF regulates the complement system on the cell surface. It recognizes C4b and C3b fragments that are created during activation of C4 (classical or lectin pathway) or C3 (alternative pathway). Interaction of DAF with cell-associated C4b of the classical and lectin pathways interferes with the conversion of C2 to C2b, thereby preventing formation of the C4b2b C3-convertase, and interaction of DAF with C3b of the alternative pathway interferes with the conversion of factor B to Bb by factor D, thereby preventing formation of the C3bBb C3 convertase of the alternative pathway. Thus, by limiting the amplification convertases of the complement cascade, DAF indirectly blocks the formation of the membrane attack complex.[2]

This glycoprotein is broadly distributed among hematopoietic and non-hematopoietic cells. It is a determinant for the Cromer blood group system.

Structure

DAF is a 70 kDa membrane protein that attaches to cell membrane via a glycophosphatidylinositol (GPI) anchor.

DAF contains four complement control protein (CCP) repeats with a single N-linked glycan positioned between CCP1 and CCP2. CCP2, CCP3, CCP4 and three consecutive lysine residues in a positively charged pocket between CCP2 and CCP3 are involved in its inhibition of the alternate complement pathway. CCP2 and CCP3 alone are involved in its inhibition of the classical pathway.[3]

Pathology

Paroxysmal nocturnal hemoglobinuria

Because DAF is a GPI-anchored protein, its expression is reduced in persons with mutations that reduce GPI levels such as those with paroxysmal nocturnal hemoglobinuria; in that disorder, red blood cells with very low levels of DAF and CD59 undergo complement-mediated hemolysis.[4]

Infectious diseases

DAF is used as a receptor by some coxsackieviruses and other enteroviruses.[5] Recombinant soluble DAF-Fc has been tested in mice as an anti-enterovirus therapy for heart damage;[6] however, the human enterovirus that was tested binds much more strongly to human DAF than to mouse or rat DAF. Echoviruses and coxsackie B viruses that use human decay-accelerating factor (DAF) as a receptor do not bind the rodent analogues of DAF.[7] and DAF-Fc has yet to be tested in humans.

See also

References

  1. Medof ME, Lublin DM, Holers VM, Ayers DJ, Getty RR, Leykam JF, Atkinson JP, Tykocinski ML (April 1987). "Cloning and characterization of cDNAs encoding the complete sequence of decay-accelerating factor of human complement". Proc. Natl. Acad. Sci. U.S.A. 84 (7): 2007–11. doi:10.1073/pnas.84.7.2007. PMC 304572. PMID 2436222.
  2. "Molecular function for CD55 Gene".
  3. Brodbeck WG, Kuttner-Kondo L, Mold C, Medof ME (Sep 2000). "Structure/function studies of human decay-accelerating factor". immunology. 101 (1): 104–11. doi:10.1046/j.1365-2567.2000.00086.x. PMC 2327052. PMID 11012760.
  4. Parker C, Omine M, Richards S, et al. (2005). "Diagnosis and management of paroxysmal nocturnal hemoglobinuria". Blood. 106 (12): 3699–709. doi:10.1182/blood-2005-04-1717. PMC 1895106. PMID 16051736.
  5. Karnauchow TM, Tolson DL, Harrison BA, Altman E, Lublin DM, Dimock K (August 1996). "The HeLa cell receptor for enterovirus 70 is decay-accelerating factor (CD55)". J. Virol. 70 (8): 5143–52. PMC 190469. PMID 8764022.
  6. Yanagawa B, Spiller OB, Choy J, Luo H, Cheung P, Zhang HM, Goodfellow IG, Evans DJ, Suarez A, Yang D, McManus BM (January 2003). "Coxsackievirus B3-associated myocardial pathology and viral load reduced by recombinant soluble human decay-accelerating factor in mice". Lab. Invest. 83 (1): 75–85. doi:10.1097/01.lab.0000049349.56211.09. PMID 12533688.
  7. Spiller OB, Goodfellow IG, Evans DJ, Almond JW, Morgan BP (January 2000). "Echoviruses and coxsackie B viruses that use human decay-accelerating factor (DAF) as a receptor do not bind the rodent analogues of DAF". J. Infect. Dis. 181 (1): 340–3. doi:10.1086/315210. PMID 10608785.

Further reading

  • Selinka HC, Wolde A, Sauter M, et al. (2004). "Virus-receptor interactions of coxsackie B viruses and their putative influence on cardiotropism". Med. Microbiol. Immunol. 193 (2–3): 127–31. doi:10.1007/s00430-003-0193-y. PMID 12920584.
  • Mikesch JH, Schier K, Roetger A, et al. (2007). "The expression and action of decay-accelerating factor (CD55) in human malignancies and cancer therapy". Cell. Oncol. 28 (5–6): 223–32. PMID 17167176.

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