properdin

Summary

Summary: A 53-kDa protein that is a positive regulator of the alternate pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It stabilizes the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) and protects it from rapid inactivation, thus facilitating the cascade of COMPLEMENT ACTIVATION and the formation of MEMBRANE ATTACK COMPLEX. Individuals with mutation in the PFC gene exhibit properdin deficiency and have a high susceptibility to infections.

Top Publications

  1. Derry J, Barnard P. Physical linkage of the A-raf-1, properdin, synapsin I, and TIMP genes on the human and mouse X chromosomes. Genomics. 1992;12:632-8 pubmed
    ..SYN1), the glycoprotein tissue inhibitor of metalloproteinases (TIMP), the proto-oncogene A-raf-1 (ARAF1), and properdin (PFC), a positive regulator of the alternative pathway of human complement, lie within a conserved synteny ..
  2. Goundis D, Reid K. Properdin, the terminal complement components, thrombospondin and the circumsporozoite protein of malaria parasites contain similar sequence motifs. Nature. 1988;335:82-5 pubmed
    b>Properdin is a plasma glycoprotein which stabilizes the C3bnBb enzyme complex of the alternative pathway of the complement system...
  3. Gupta Bansal R, Parent J, Brunden K. Inhibition of complement alternative pathway function with anti-properdin monoclonal antibodies. Mol Immunol. 2000;37:191-201 pubmed
    ..These blocking antibodies bind human properdin with high avidity and prevent its interaction with the alternative pathway C3 convertase...
  4. Fredrikson G, Gullstrand B, Westberg J, Sjoholm A, Uhlen M, Truedsson L. Expression of properdin in complete and incomplete deficiency: normal in vitro synthesis by monocytes in two cases with properdin deficiency type II due to distinct mutations. J Clin Immunol. 1998;18:272-82 pubmed
    Three properdin deficiency phenotypes have been reported--complete deficiency (type I), incomplete deficiency (type II), and dysfunction of properdin protein (type III)--all associated with increased susceptibility to meningococcal ..
  5. Farries T, Lachmann P, Harrison R. Analysis of the interactions between properdin, the third component of complement (C3), and its physiological activation products. Biochem J. 1988;252:47-54 pubmed
    The interactions of properdin with both surface-bound and fluid-phase C3 (the third component of complement) and its activation products have been investigated by using a purified preparation of the 'native' form...
  6. Bathum L, Hansen H, Teisner B, Koch C, Garred P, Rasmussen K, et al. Association between combined properdin and mannose-binding lectin deficiency and infection with Neisseria meningitidis. Mol Immunol. 2006;43:473-9 pubmed
    Individuals genetically deficient of properdin are more susceptible to meningococcal disease...
  7. Kimura Y, Miwa T, Zhou L, Song W. Activator-specific requirement of properdin in the initiation and amplification of the alternative pathway complement. Blood. 2008;111:732-40 pubmed
    b>Properdin is a positive regulator of alternative pathway (AP) complement. The current understanding of properdin function is that it facilitates AP complement activation by stabilizing the C3 convertase C3bBb...
  8. Kemper C, Atkinson J, Hourcade D. Properdin: emerging roles of a pattern-recognition molecule. Annu Rev Immunol. 2010;28:131-55 pubmed publisher
    ..b>Properdin, a plasma component that is also released by activated neutrophils, is critical in the stabilization of ..
  9. Smith K, Nolan K, Reid K, Perkins S. Neutron and X-ray scattering studies on the human complement protein properdin provide an analysis of the thrombospondin repeat. Biochemistry. 1991;30:8000-8 pubmed
    b>Properdin is a regulatory glycoprotein of the alternative pathway of the complement system of immune defense. It is responsible for the stabilization of the C3 convertase complex formed between C3b and the Bb fragment of factor B...

More Information

Publications62

  1. Miwa T, Sato S, Gullipalli D, Nangaku M, Song W. Blocking properdin, the alternative pathway, and anaphylatoxin receptors ameliorates renal ischemia-reperfusion injury in decay-accelerating factor and CD59 double-knockout mice. J Immunol. 2013;190:3552-9 pubmed publisher
    ..mice with mice deficient in various complement components or receptors including C3, C4, factor B (fB), factor properdin (fP), mannose-binding lectin, C3aR, C5aR, or Ig and assessed renal IRI in the resulting mutant strains...
  2. Griffiss J, Jarvis G, O BRIEN J, Eads M, Schneider H. Lysis of Neisseria gonorrhoeae initiated by binding of normal human IgM to a hexosamine-containing lipooligosaccharide epitope(s) is augmented by strain-specific, properdin-binding-dependent alternative complement pathway activation. J Immunol. 1991;147:298-305 pubmed
    ..Analyses of the absorbed sera revealed that the gonococci had variously depleted properdin from NHS as assessed by using an Ag-capture solid-phase RIA...
  3. Ruseva M, Vernon K, Lesher A, Schwaeble W, Ali Y, Botto M, et al. Loss of properdin exacerbates C3 glomerulopathy resulting from factor H deficiency. J Am Soc Nephrol. 2013;24:43-52 pubmed publisher
    Complement factor H (CFH) is a negative regulator of the alternative pathway of complement, and properdin is the sole positive regulator...
  4. Kostavasili I, Sahu A, Friedman H, Eisenberg R, Cohen G, Lambris J. Mechanism of complement inactivation by glycoprotein C of herpes simplex virus. J Immunol. 1997;158:1763-71 pubmed
    ..We found that gC-1, but not gC-2, inhibited the binding of C5 and properdin to C3b and also inhibited the alternative pathway-mediated lysis of rabbit erythrocytes...
  5. Gauvreau D, Roy C, Tom F, Lu H, Miegueu P, Richard D, et al. A new effector of lipid metabolism: complement factor properdin. Mol Immunol. 2012;51:73-81 pubmed publisher
    ..b>Properdin stabilizes C3 convertase following alternative complement activation...
  6. Wirthmueller U, Dewald B, Thelen M, Schafer M, Stover C, Whaley K, et al. Properdin, a positive regulator of complement activation, is released from secondary granules of stimulated peripheral blood neutrophils. J Immunol. 1997;158:4444-51 pubmed
    b>Properdin is an important regulatory constituent of the complement system. In contrast to most other components of complement, biosynthesis of properdin is restricted to a few cell types only, i.e...
  7. Pangburn M. Analysis of the natural polymeric forms of human properdin and their functions in complement activation. J Immunol. 1989;142:202-7 pubmed
    Many of the anomalies observed in studies or properdin may be explained on the basis of its ability to form a series of multi-subunit polymers and by differences in the functions of these forms of properdin...
  8. Vuagnat B, Mach J, Le Doussal J. Activation of the alternative pathway of human complement by autologous cells expressing transmembrane recombinant properdin. Mol Immunol. 2000;37:467-78 pubmed
    b>Properdin (P) is a serum glycoprotein that stabilizes the labile C3 convertase (C3bBb) of the alternative pathway of the complement system (AP)...
  9. Stoiber H, Schneider R, Janatova J, Dierich M. Human complement proteins C3b, C4b, factor H and properdin react with specific sites in gp120 and gp41, the envelope proteins of HIV-1. Immunobiology. 1995;193:98-113 pubmed
    ..e. activated C4 (C4b) and activated C3 (C3b) and the complement regulator proteins factor H and properdin. In this study we analyze these interactions in detail...
  10. Tyson K, Elkins C, de Silva A. A novel mechanism of complement inhibition unmasked by a tick salivary protein that binds to properdin. J Immunol. 2008;180:3964-8 pubmed
    ..In this study, we demonstrate that the target of Salp20 is properdin. Properdin is a natural, positive regulator of the alternative pathway that binds to the C3 convertase, ..
  11. Perdikoulis M, Kishore U, Reid K. Expression and characterisation of the thrombospondin type I repeats of human properdin. Biochim Biophys Acta. 2001;1548:265-77 pubmed
    b>Properdin, an upregulator of the alternative complement pathway, is central to deposition of the activated complement fragment C3b on the surfaces of the pathogens, which it achieves by preventing the dissociation of the Bb catalytic ..
  12. de Paula P, Barbosa J, Junior P, Ferriani V, Latorre M, Nudelman V, et al. Ontogeny of complement regulatory proteins - concentrations of factor h, factor I, c4b-binding protein, properdin and vitronectin in healthy children of different ages and in adults. Scand J Immunol. 2003;58:572-7 pubmed
    ..year, 1-6 years and 6-13 years) and in adults: factor H (fH), factor I (fI), C4b-binding protein (C4 BP), properdin and vitronectin...
  13. Tanuma Y, Ohi H, Hatano M. Two types of C3 nephritic factor: properdin-dependent C3NeF and properdin-independent C3NeF. Clin Immunol Immunopathol. 1990;56:226-38 pubmed
    ..Two types of C3NeF were detected, of which one was heat sensitive (56 degrees C for 30 min) and properdin dependent (C3NeF:P) but the other was heat stable and properdin independent (C3NeF:nP)...
  14. Stover C, Luckett J, Echtenacher B, Dupont A, Figgitt S, Brown J, et al. Properdin plays a protective role in polymicrobial septic peritonitis. J Immunol. 2008;180:3313-8 pubmed
    b>Properdin is a positive regulator of complement activation so far known to be instrumental in the survival of infections with certain serotypes of Neisseria meningitidis...
  15. Sun Z, Reid K, Perkins S. The dimeric and trimeric solution structures of the multidomain complement protein properdin by X-ray scattering, analytical ultracentrifugation and constrained modelling. J Mol Biol. 2004;343:1327-43 pubmed
    b>Properdin regulates the alternative pathway of the complement system of immune defence by stabilising the C3 convertase complex. It contains six thrombospondin repeat type I (TSR-1 to TSR-6) domains and an N-terminal domain...
  16. Kemper C, Mitchell L, Zhang L, Hourcade D. The complement protein properdin binds apoptotic T cells and promotes complement activation and phagocytosis. Proc Natl Acad Sci U S A. 2008;105:9023-8 pubmed publisher
    ..Here we demonstrate for the first time, to our knowledge, that the human complement protein properdin binds to early apoptotic T cells and initiates complement activation, leading to C3b opsonization and ingestion ..
  17. Lesher A, Zhou L, Kimura Y, Sato S, Gullipalli D, Herbert A, et al. Combination of factor H mutation and properdin deficiency causes severe C3 glomerulonephritis. J Am Soc Nephrol. 2013;24:53-65 pubmed publisher
    Factor H (fH) and properdin both modulate complement; however, fH inhibits activation, and properdin promotes activation of the alternative pathway of complement...
  18. Schwaeble W, Huemer H, Most J, Dierich M, Strobel M, Claus C, et al. Expression of properdin in human monocytes. Eur J Biochem. 1994;219:759-64 pubmed
    b>Properdin is the only known positive regulator of the alternative pathway of complement activation...
  19. Nolan K, Schwaeble W, Kaluz S, Dierich M, Reid K. Molecular cloning of the cDNA coding for properdin, a positive regulator of the alternative pathway of human complement. Eur J Immunol. 1991;21:771-6 pubmed
    Northern blot analysis indicated that the mRNA for human properdin is approximately 1.5 kb long and that its level in U-937 cells is increased by pretreating the cells with phorbol 12-myristate 13-acetate (PMA)...
  20. Schlesinger M, Nave Z, Levy Y, Slater P, Fishelson Z. Prevalence of hereditary properdin, C7 and C8 deficiencies in patients with meningococcal infections. Clin Exp Immunol. 1990;81:423-7 pubmed
    ..study revealed 11 non-related patients with complete C deficiency: five deficient in C7, three in C8, two in properdin and one in C2...
  21. Farries T, Lachmann P, Harrison R. Analysis of the interaction between properdin and factor B, components of the alternative-pathway C3 convertase of complement. Biochem J. 1988;253:667-75 pubmed
    The interactions between Factor B (B), its activation products Ba and Bb, properdin (P) and C3i or C3b, components that together form the alternative-pathway C3 convertase enzyme of human complement, have been analysed...
  22. Panetti T, Kudryk B, Mosher D. Interaction of recombinant procollagen and properdin modules of thrombospondin-1 with heparin and fibrinogen/fibrin. J Biol Chem. 1999;274:430-7 pubmed
    Many properties have been assigned to the procollagen and properdin (Type I) modules of thrombospondin-1 (TSP1) based on activities of large proteolytic fragments of TSP1 or peptides containing TSP1-derived sequences...
  23. Farries T, Atkinson J. Biosynthesis of properdin. J Immunol. 1989;142:842-7 pubmed
    b>Properdin (P) is synthesized by the human promyelocytic cell line, HL-60, after differentiation with DMSO. The secreted P was physiochemically indistinguishable from purified plasma P...
  24. Schejbel L, Rosenfeldt V, Marquart H, Valerius N, Garred P. Properdin deficiency associated with recurrent otitis media and pneumonia, and identification of male carrier with Klinefelter syndrome. Clin Immunol. 2009;131:456-62 pubmed publisher
    b>Properdin is an initiator and stabilizer of the alternative complement activation pathway (AP)...
  25. Lesher A, Nilsson B, Song W. Properdin in complement activation and tissue injury. Mol Immunol. 2013;56:191-8 pubmed publisher
    The plasma protein properdin is the only known positive regulator of complement activation...
  26. Tuszynski G, Rothman V, Deutch A, Hamilton B, Eyal J. Biological activities of peptides and peptide analogues derived from common sequences present in thrombospondin, properdin, and malarial proteins. J Cell Biol. 1992;116:209-17 pubmed
    ..polypeptide chains of TSP and show homology with peptide sequences found in a number of other proteins including properdin, malarial circumsporozoite, and a blood-stage antigen of Plasmodium falciparum...
  27. Sjoholm A, Selander B, Ostenson S, Holmstrom E, Soderstrom C. Normal human serum depleted of C1q, factor D and properdin: its use in studies of complement activation. APMIS. 1991;99:1120-8 pubmed
    Normal human sera were depleted of C1q, factor D (D) and properdin (P) by a simple and reproducible procedure providing reagents for analysis of complement-dependent functions...
  28. Zaferani A, Vivès R, van der Pol P, Hakvoort J, Navis G, van Goor H, et al. Identification of tubular heparan sulfate as a docking platform for the alternative complement component properdin in proteinuric renal disease. J Biol Chem. 2011;286:5359-67 pubmed publisher
    b>Properdin binds to proximal tubular epithelial cells (PTEC) and activates the complement system via the alternative pathway in vitro. Cellular ligands for properdin in the kidney have not yet been identified...
  29. Agarwal S, Ferreira V, Cortes C, Pangburn M, Rice P, Ram S. An evaluation of the role of properdin in alternative pathway activation on Neisseria meningitidis and Neisseria gonorrhoeae. J Immunol. 2010;185:507-16 pubmed publisher
    b>Properdin, a positive regulator of the alternative pathway (AP) of complement is important in innate immune defenses against invasive neisserial infections...
  30. Siezenga M, van der Geest R, Mallat M, Rabelink T, Daha M, Berger S. Urinary properdin excretion is associated with intrarenal complement activation and poor renal function. Nephrol Dial Transplant. 2010;25:1157-61 pubmed publisher
    ..Recent experimental evidence suggests an important role for properdin in promoting intrarenal complement activation...
  31. Chondrou M, Papanastasiou A, Spyroulias G, Zarkadis I. Three isoforms of complement properdin factor P in trout: cloning, expression, gene organization and constrained modeling. Dev Comp Immunol. 2008;32:1454-66 pubmed publisher
    b>Properdin is a plasma glycoprotein and the only known naturally occurring positive regulator of the complement system, stabilizing the alternative pathway convertase (C3bBb)...
  32. Hartmann S, Hofsteenge J. Properdin, the positive regulator of complement, is highly C-mannosylated. J Biol Chem. 2000;275:28569-74 pubmed
    b>Properdin is the positive regulator of the alternative pathway of complement activation...
  33. Genel F, Atlihan F, Gulez N, Sjöholm A, Skattum L, Truedsson L. Properdin deficiency in a boy with fulminant meningococcal septic shock. Acta Paediatr. 2006;95:1498-1500 pubmed
    ..invasive diseases and meningitis have been associated with late complement component deficiencies and properdin deficiency...
  34. Ivanovska N, Dimitrova P, Luckett J, El Rachkidy Lonnen R, Schwaeble W, Stover C. Properdin deficiency in murine models of nonseptic shock. J Immunol. 2008;180:6962-9 pubmed
    Hereditary properdin deficiency is linked to susceptibility to meningococcal disease (Neisseria meningitidis serotypes Y and W-135) with high mortality...
  35. Cortes C, Ferreira V, Pangburn M. Native properdin binds to Chlamydia pneumoniae and promotes complement activation. Infect Immun. 2011;79:724-31 pubmed publisher
    ..Recently, properdin, a positive regulator of the alternative pathway of complement, has been shown to bind to surfaces and promote ..
  36. Saggu G, Cortes C, Emch H, Ramirez G, Worth R, Ferreira V. Identification of a novel mode of complement activation on stimulated platelets mediated by properdin and C3(H2O). J Immunol. 2013;190:6457-67 pubmed publisher
    ..leukocytes, which interact directly with platelets in response to vascular injury, are among the main sources of properdin, a positive regulator of the alternative pathway...
  37. Schwaeble W, Dippold W, Schafer M, Pohla H, Jonas D, Luttig B, et al. Properdin, a positive regulator of complement activation, is expressed in human T cell lines and peripheral blood T cells. J Immunol. 1993;151:2521-8 pubmed
    b>Properdin plays an important regulatory role in the activation of the complement system. Here we report the biosynthesis of properdin in four different human T cell lines and in T cells purified from peripheral blood...
  38. Higgins J, Wiedemann H, Timpl R, Reid K. Characterization of mutant forms of recombinant human properdin lacking single thrombospondin type I repeats. Identification of modules important for function. J Immunol. 1995;155:5777-85 pubmed
    b>Properdin is a serum glycoprotein that up-regulates the alternative pathway of complement by stabilizing the C3b-Bb complex. It also binds sulfated glycoconjugates, such as sulfatide, in vitro...
  39. Sjoholm A, Braconier J, Soderstrom C. Properdin deficiency in a family with fulminant meningococcal infections. Clin Exp Immunol. 1982;50:291-7 pubmed
    Three males in a large family showed a selective deficiency of properdin (P). One of the P deficient individuals died from a fulminant infection with Neisseria meningitidis group C...
  40. Harboe M, Garred P, Lindstad J, Pharo A, Muller F, Stahl G, et al. The role of properdin in zymosan- and Escherichia coli-induced complement activation. J Immunol. 2012;189:2606-13 pubmed publisher
    b>Properdin is well known as an enhancer of the alternative complement amplification loop when C3 is activated, whereas its role as a recognition molecule of exogenous pathogen-associated molecular patterns and initiator of complement ..
  41. Zhou H, Yan H, Stover C, Fernandez T, Rodriguez de Cordoba S, Song W, et al. Antibody directs properdin-dependent activation of the complement alternative pathway in a mouse model of abdominal aortic aneurysm. Proc Natl Acad Sci U S A. 2012;109:E415-22 pubmed publisher
    ..However, the mechanism by which complement AP is initiated remains undefined. The complement protein properdin, traditionally viewed as a positive regulator of the AP, may also initiate complement activation by binding ..
  42. Zhang Y, Meyer N, Wang K, Nishimura C, Frees K, Jones M, et al. Causes of alternative pathway dysregulation in dense deposit disease. Clin J Am Soc Nephrol. 2012;7:265-74 pubmed publisher
    ..C3Nefs were detected by: ELISA, C3 convertase surface assay (C3CSA), C3CSA with properdin (C3CSAP), two-dimensional immunoelectrophoresis (2DIEP), and immunofixation electrophoresis (IFE)...
  43. Kimura Y, Zhou L, Miwa T, Song W. Genetic and therapeutic targeting of properdin in mice prevents complement-mediated tissue injury. J Clin Invest. 2010;120:3545-54 pubmed
    ..Dysfunction of AP regulatory proteins has been linked to several human inflammatory disorders. Properdin is a positive regulator of AP complement activation that has been shown to extend the half-life of cell surface..
  44. Sjoholm A, Soderstrom C, Nilsson L. A second variant of properdin deficiency: the detection of properdin at low concentrations in affected males. Complement. 1988;5:130-40 pubmed
    A selective deficiency of properdin (P) was identified in a 58-year-old male and in his 29-year-old nephew, both of whom were clinically healthy...
  45. Ferreira V, Cortes C, Pangburn M. Native polymeric forms of properdin selectively bind to targets and promote activation of the alternative pathway of complement. Immunobiology. 2010;215:932-40 pubmed publisher
    b>Properdin, a positive regulator of the complement system, has recently been reported to bind to certain pathogenic microorganisms, to early or late apoptotic and necrotic cells, and to particular live human cell lines, thus providing a ..
  46. Dimitrova P, Ivanovska N, Schwaeble W, Gyurkovska V, Stover C. The role of properdin in murine zymosan-induced arthritis. Mol Immunol. 2010;47:1458-66 pubmed publisher
    Using properdin-deficient and wild-type mice, we have investigated the role of properdin in development and progression of zymosan-induced arthritis...
  47. Kemper C, Hourcade D. Properdin: New roles in pattern recognition and target clearance. Mol Immunol. 2008;45:4048-56 pubmed publisher
    b>Properdin was first described over 50 years ago by Louis Pillemer and his collaborators as a vital component of an antibody-independent complement activation pathway...
  48. Robson K, Hall J, Jennings M, Harris T, Marsh K, Newbold C, et al. A highly conserved amino-acid sequence in thrombospondin, properdin and in proteins from sporozoites and blood stages of a human malaria parasite. Nature. 1988;335:79-82 pubmed
    ..WSPCSVTCG), present in three copies in region I of thrombospondin (TSP), six copies in properdin (P) and one copy in all the circumsporozoite (CS) proteins sequenced so far...
  49. Nolan K, Kaluz S, Higgins J, Goundis D, Reid K. Characterization of the human properdin gene. Biochem J. 1992;287 ( Pt 1):291-7 pubmed
    A cosmid clone containing the complete coding sequence of the human properdin gene has been characterized. The gene is located at one end of the approximately 40 kb cosmid insert and approximately 8...
  50. Nielsen H, Koch C, Mansa B, Magnussen P, Bergmann O. Complement and immunoglobulin studies in 15 cases of chronic meningococcemia: properdin deficiency and hypoimmunoglobulinemia. Scand J Infect Dis. 1990;22:31-6 pubmed
    ..We found one individual with complete deficiency of properdin, a component of the alternative complement pathway. In the other patients, the complement system was normal...
  51. Zaferani A, Vivès R, van der Pol P, Navis G, Daha M, van Kooten C, et al. Factor h and properdin recognize different epitopes on renal tubular epithelial heparan sulfate. J Biol Chem. 2012;287:31471-81 pubmed publisher
    ..Recently, we showed that properdin binds to tubular heparan sulfates (HS)...
  52. Lane A, Truong Tran Q, Myers A, Bickel C, Schleimer R. Serum amyloid A, properdin, complement 3, and toll-like receptors are expressed locally in human sinonasal tissue. Am J Rhinol. 2006;20:117-23 pubmed
    ..recognition receptors known as toll-like receptors (TLRs) and the effector molecules complement factor 3 (C3), properdin, and serum amyloid A (SAA) were examined in human sinonasal mucosa obtained from control subjects and patients ..
  53. Gaarkeuken H, Siezenga M, Zuidwijk K, van Kooten C, Rabelink T, Daha M, et al. Complement activation by tubular cells is mediated by properdin binding. Am J Physiol Renal Physiol. 2008;295:F1397-403 pubmed publisher
    ..Recent studies on mechanisms of complement activation indicate a key role for properdin in the initiation of an alternative pathway...