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MBL2  -  mannose-binding lectin (protein C) 2, soluble

Homo sapiens

Synonyms: COLEC1, Collectin-1, HSMBPC, MBL, MBL2D, ...
 
 
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Disease relevance of MBL2

 

Psychiatry related information on MBL2

 

High impact information on MBL2

  • Upon recognition of the infectious agent, MBL and the ficolins initiate the lectin pathway of complement activation through attached serine proteases (MASPs), whereas SP-A and SP-D rely on other effector mechanisms: direct opsonization, neutralization, and agglutination [14].
  • A particular genotype, in which glycine is substituted by aspartic acid at codon 54 of MBP in the fifth collagen repeat, shows apparent concordance with the clinical phenotype [15].
  • Human mannose binding protein (MBP) is a C-type serum lectin involved in first-line host defense against a variety of bacterial, fungal and viral pathogens [15].
  • MBL is structurally related to the complement C1 subcomponent, C1q, and seems to activate the complement system through an associated serine protease known as MASP (ref. 4) or p100 (ref. 5), which is similar to C1r and C1s of the classical pathway [16].
  • Thus complement activation through MBL, like the classical pathway, involves two serine proteases and may antedate the development of the specific immune system of vertebrates [16].
 

Chemical compound and disease context of MBL2

 

Biological context of MBL2

  • Deficiency of human mannose-binding lectin (MBL) caused by mutations in the coding part of the MBL2 gene is associated with increased risk and severity of infections and autoimmunity [21].
  • The results of this study suggest that additional 5' variants as well as markers of distinct 3' haplotype blocks in MBL2 may contribute to circulating protein levels, but further studies are required to confirm these observations [22].
  • We studied whether the MBL2 codon 54 B allele affected serum MBL levels, admissions for infective exacerbation in COPD and disease susceptibility [2].
  • MBL binds to specific carbohydrate structures found on the surface of a range of microorganisms, including bacteria, yeasts, parasitic protozoa and viruses, and exhibits antibacterial activity through killing mediated by the terminal, lytic complement components or by promoting phagocytosis [16].
  • These findings indicate that serum ficolins are structurally and functionally similar to MBL and have the capacity to activate the lectin pathway and thus have a role in innate immunity [23].
 

Anatomical context of MBL2

 

Associations of MBL2 with chemical compounds

  • Mannose-binding lectin (MBL) is also a collagenous lectin in serum that is specific for GlcNAc and mannose binding [23].
  • When sialic acid residues were removed from the parent organism by neuraminidase treatment, the binding of both MBL and C4 increased significantly [5].
  • Complexes of MBL-MASP2 are able to activate the complement system in an Ab and C1-independent fashion after binding of the lectin to appropriate microbial sugar arrays [10].
  • Incubating human serum (HS) with N-acetyl-D-glucosamine or anti-human MBL monoclonal antibody attenuated MBL and C3 deposition on purified CK1 (ELISA) [24].
  • Mannose (or mannan)-binding lectin (MBL) is an oligomeric serum lectin that plays a role in innate immunity by activating the complement system [28].
 

Physical interactions of MBL2

  • There were also no significant differences between MBL/MASP-1 positive cases and negative cases in the plasma levels of circulating immune complexes or soluble C5b-9 [17].
  • The lectin pathway of the complement system is activated when mannan-binding lectin (MBL) in complex with MBL-associated serine protease 2 (MASP-2) binds to carbohydrate structures on microorganisms [29].
  • Structural superimposition of hSP-D with mannose- binding protein C (MBP-C) complexed with GlcNAc reveals steric clashes between the ligand and the side chain of Arg343 in hSP-D [30].
  • Preincubation of the MASPs with soluble MBL inhibited subsequent binding to immobilized L-ficolin/P35 and, conversely, suggesting that these lectins compete with each other for binding to the MASPs in vivo [31].
  • Analysis of thymocytes reveals increased MBP binding and GII association with CD45 in double-positive thymocytes compared with either double-negative or single-positive thymocytes [32].
 

Enzymatic interactions of MBL2

 

Regulatory relationships of MBL2

 

Other interactions of MBL2

 

Analytical, diagnostic and therapeutic context of MBL2

  • The HLA haplotype was established by allelic specific PCR while the MBL2 genotype was resolved by melting temperature assay [1].
  • Immunohistochemistry and TUNEL findings support a role of MBL2 in the clearance of apoptotic cells [1].
  • Using flow cytometry, it was possible to detect strong MBL binding to the cps- and cpsD- mutants over a wide range of concentrations [5].
  • Sequence analysis of the MBP gene in three children with recurrent infections, the opsonic defect, and low serum MBP concentrations showed a point mutation at base 230 of exon 1 causing a change of codon 54 from GGC to GAC [43].
  • It was predicted that both homozygous and heterozygous individuals would have profoundly reduced serum levels of the protein and this was confirmed by immunoassay as was the reduced capacity of such sera to activate complement through the MBP initiated classical pathway [44].

References

  1. Evidence of a correlation between mannose binding lectin and celiac disease: a model for other autoimmune diseases. Boniotto, M., Braida, L., Baldas, V., Not, T., Ventura, A., Vatta, S., Radillo, O., Tedesco, F., Percopo, S., Montico, M., Amoroso, A., Crovella, S. J. Mol. Med. (2005) [Pubmed]
  2. Mannose-binding lectin gene polymorphism predicts hospital admissions for COPD infections. Yang, I.A., Seeney, S.L., Wolter, J.M., Anders, E.M., McCormack, J.G., Tunnicliffe, A.M., Rabnott, G.C., Shaw, J.G., Dent, A.G., Kim, S.T., Zimmerman, P.V., Fong, K.M. Genes Immun. (2003) [Pubmed]
  3. Genetic polymorphisms in molecules of innate immunity and susceptibility to infection with Wuchereria bancrofti in South India. Choi, E.H., Zimmerman, P.A., Foster, C.B., Zhu, S., Kumaraswami, V., Nutman, T.B., Chanock, S.J. Genes Immun. (2001) [Pubmed]
  4. MBL2 polymorphisms screening in a regional Italian CF Center. Trevisiol, C., Boniotto, M., Giglio, L., Poli, F., Morgutti, M., Crovella, S. J. Cyst. Fibros. (2005) [Pubmed]
  5. Activation of complement by mannose-binding lectin on isogenic mutants of Neisseria meningitidis serogroup B. Jack, D.L., Dodds, A.W., Anwar, N., Ison, C.A., Law, A., Frosch, M., Turner, M.W., Klein, N.J. J. Immunol. (1998) [Pubmed]
  6. Independent effects of genetic variations in mannose-binding lectin influence the course of HIV disease: the advantage of heterozygosity for coding mutations. Catano, G., Agan, B.K., Kulkarni, H., Telles, V., Marconi, V.C., Dolan, M.J., Ahuja, S.K. J. Infect. Dis. (2008) [Pubmed]
  7. Mannose binding lectin gene deficiency increases susceptibility to traumatic brain injury in mice. Yager, P.H., You, Z., Qin, T., Kim, H.H., Takahashi, K., Ezekowitz, A.B., Stahl, G.L., Carroll, M.C., Whalen, M.J. J. Cereb. Blood Flow Metab. (2008) [Pubmed]
  8. Mannose-binding lectin concentrations, MBL2 polymorphisms, and susceptibility to respiratory tract infections in young men. Rantala, A., Lajunen, T., Juvonen, R., Bloigu, A., Silvennoinen-Kassinen, S., Peitso, A., Saikku, P., Vainio, O., Leinonen, M. J. Infect. Dis. (2008) [Pubmed]
  9. Mannose-binding lectin deficiency confers risk for bacterial infections in a large Hungarian cohort of patients with liver cirrhosis. Altorjay, I., Vitalis, Z., Tornai, I., Palatka, K., Kacska, S., Farkas, G., Udvardy, M., Harsfalvi, J., Dinya, T., Orosz, P., Lombay, B., Par, G., Par, A., Csak, T., Osztovits, J., Szalay, F., Csepregi, A., Lakatos, P.L., Papp, M. J. Hepatol. (2010) [Pubmed]
  10. Enhancement of complement activation and opsonophagocytosis by complexes of mannose-binding lectin with mannose-binding lectin-associated serine protease after binding to Staphylococcus aureus. Neth, O., Jack, D.L., Johnson, M., Klein, N.J., Turner, M.W. J. Immunol. (2002) [Pubmed]
  11. Role of hypoxia on increased blood pressure in patients with obstructive sleep apnoea. Okabe, S., Hida, W., Kikuchi, Y., Taguchi, O., Ogawa, H., Mizusawa, A., Miki, H., Shirato, K. Thorax (1995) [Pubmed]
  12. Chromosome 18q paracentric inversion in a family with mental retardation and hearing loss. Keppler-Noreuil, K.M., Carroll, A.J., Finley, S.C., Descartes, M., Cody, J.D., DuPont, B.R., Gay, C.T., Leach, R.J. Am. J. Med. Genet. (1998) [Pubmed]
  13. The deceit continues: an updated literature review of Munchausen Syndrome by Proxy. Sheridan, M.S. Child abuse & neglect. (2003) [Pubmed]
  14. Collections and ficolins: humoral lectins of the innate immune defense. Holmskov, U., Thiel, S., Jensenius, J.C. Annu. Rev. Immunol. (2003) [Pubmed]
  15. Distinct and overlapping functions of allelic forms of human mannose binding protein. Super, M., Gillies, S.D., Foley, S., Sastry, K., Schweinle, J.E., Silverman, V.J., Ezekowitz, R.A. Nat. Genet. (1992) [Pubmed]
  16. A second serine protease associated with mannan-binding lectin that activates complement. Thiel, S., Vorup-Jensen, T., Stover, C.M., Schwaeble, W., Laursen, S.B., Poulsen, K., Willis, A.C., Eggleton, P., Hansen, S., Holmskov, U., Reid, K.B., Jensenius, J.C. Nature (1997) [Pubmed]
  17. Glomerular deposition of mannose-binding lectin (MBL) indicates a novel mechanism of complement activation in IgA nephropathy. Endo, M., Ohi, H., Ohsawa, I., Fujita, T., Matsushita, M., Fujita, T. Nephrol. Dial. Transplant. (1998) [Pubmed]
  18. Mannose-binding lectin-2 genetic variation and stomach cancer risk. Baccarelli, A., Hou, L., Chen, J., Lissowska, J., El-Omar, E.M., Grillo, P., Giacomini, S.M., Yaeger, M., Bernig, T., Zatonski, W., Fraumeni, J.F., Chanock, S.J., Chow, W.H. Int. J. Cancer (2006) [Pubmed]
  19. Mannose-binding lectin binds to Ebola and Marburg envelope glycoproteins, resulting in blocking of virus interaction with DC-SIGN and complement-mediated virus neutralization. Ji, X., Olinger, G.G., Aris, S., Chen, Y., Gewurz, H., Spear, G.T. J. Gen. Virol. (2005) [Pubmed]
  20. Glycosylation inhibitors and neuraminidase enhance human immunodeficiency virus type 1 binding and neutralization by mannose-binding lectin. Hart, M.L., Saifuddin, M., Spear, G.T. J. Gen. Virol. (2003) [Pubmed]
  21. Disease-associated mutations in human mannose-binding lectin compromise oligomerization and activity of the final protein. Larsen, F., Madsen, H.O., Sim, R.B., Koch, C., Garred, P. J. Biol. Chem. (2004) [Pubmed]
  22. An analysis of genetic variation across the MBL2 locus in Dutch Caucasians indicates that 3' haplotypes could modify circulating levels of mannose-binding lectin. Bernig, T., Breunis, W., Brouwer, N., Hutchinson, A., Welch, R., Roos, D., Kuijpers, T., Chanock, S. Hum. Genet. (2005) [Pubmed]
  23. Ficolins and the lectin complement pathway. Matsushita, M., Fujita, T. Immunol. Rev. (2001) [Pubmed]
  24. Endothelial oxidative stress activates the lectin complement pathway: role of cytokeratin 1. Collard, C.D., Montalto, M.C., Reenstra, W.R., Buras, J.A., Stahl, G.L. Am. J. Pathol. (2001) [Pubmed]
  25. Alloiococcus otitidis is a ligand for collectins and Toll-like receptor 2, and its phagocytosis is enhanced by collectins. Konishi, M., Nishitani, C., Mitsuzawa, H., Shimizu, T., Sano, H., Harimaya, A., Fujii, N., Himi, T., Kuroki, Y. Eur. J. Immunol. (2006) [Pubmed]
  26. Expression of H-ficolin/Hakata antigen, mannose-binding lectin-associated serine protease (MASP)-1 and MASP-3 by human glioma cell line T98G. Kuraya, M., Matsushita, M., Endo, Y., Thiel, S., Fujita, T. Int. Immunol. (2003) [Pubmed]
  27. Mannan-binding protein levels in human amniotic fluid during gestation and its interaction with collectin receptor from amnion cells. Malhotra, R., Willis, A.C., Lopez Bernal, A., Thiel, S., Sim, R.B. Immunology (1994) [Pubmed]
  28. Proteolytic activities of two types of mannose-binding lectin-associated serine protease. Matsushita, M., Thiel, S., Jensenius, J.C., Terai, I., Fujita, T. J. Immunol. (2000) [Pubmed]
  29. Novel MASP2 variants detected among North African and Sub-Saharan individuals. Lozano, F., Suárez, B., Muñoz, A., Jensenius, J.C., Mensa, J., Vives, J., Horcajada, J.P. Tissue Antigens (2005) [Pubmed]
  30. Arg343 in human surfactant protein D governs discrimination between glucose and N-acetylglucosamine ligands. Allen, M.J., Laederach, A., Reilly, P.J., Mason, R.J., Voelker, D.R. Glycobiology (2004) [Pubmed]
  31. Characterization of the interaction between L-ficolin/p35 and mannan-binding lectin-associated serine proteases-1 and -2. Cseh, S., Vera, L., Matsushita, M., Fujita, T., Arlaud, G.J., Thielens, N.M. J. Immunol. (2002) [Pubmed]
  32. Developmentally regulated changes in glucosidase II association with, and carbohydrate content of, the protein tyrosine phosphatase CD45. Baldwin, T.A., Ostergaard, H.L. J. Immunol. (2001) [Pubmed]
  33. MASP-2, the C3 convertase generating protease of the MBLectin complement activating pathway. Vorup-Jensen, T., Jensenius, J.C., Thiel, S. Immunobiology (1998) [Pubmed]
  34. Assays for the functional activity of the mannan-binding lectin pathway of complement activation. Thiel, S., Møller-Kristensen, M., Jensen, L., Jensenius, J.C. Immunobiology (2002) [Pubmed]
  35. Mannose binding lectin (MBL) and HIV. Ji, X., Gewurz, H., Spear, G.T. Mol. Immunol. (2005) [Pubmed]
  36. A keratin peptide inhibits mannose-binding lectin. Montalto, M.C., Collard, C.D., Buras, J.A., Reenstra, W.R., McClaine, R., Gies, D.R., Rother, R.P., Stahl, G.L. J. Immunol. (2001) [Pubmed]
  37. Characterization of an equine mannose-binding lectin and its roles in disease. Podolsky, M.J., Lasker, A., Flaminio, M.J., Gowda, L.D., Ezekowitz, R.A., Takahashi, K. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  38. Mannose binding lectin enhances IL-1beta and IL-10 induction by non-lipopolysaccharide (LPS) components of Neisseria meningitidis. Sprong, T., Jack, D.L., Klein, N.J., Turner, M.W., van der Ley, P., Steeghs, L., Jacobs, L., van der Meer, J.W., van Deuren, M. Cytokine (2004) [Pubmed]
  39. The Mad2 spindle checkpoint protein undergoes similar major conformational changes upon binding to either Mad1 or Cdc20. Luo, X., Tang, Z., Rizo, J., Yu, H. Mol. Cell (2002) [Pubmed]
  40. C1q and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells. Ogden, C.A., deCathelineau, A., Hoffmann, P.R., Bratton, D., Ghebrehiwet, B., Fadok, V.A., Henson, P.M. J. Exp. Med. (2001) [Pubmed]
  41. Activation of the lectin complement pathway by H-ficolin (Hakata antigen). Matsushita, M., Kuraya, M., Hamasaki, N., Tsujimura, M., Shiraki, H., Fujita, T. J. Immunol. (2002) [Pubmed]
  42. Polymorphisms in CD14, mannose-binding lectin, and Toll-like receptor-2 are associated with increased prevalence of infection in critically ill adults. Sutherland, A.M., Walley, K.R., Russell, J.A. Crit. Care Med. (2005) [Pubmed]
  43. Molecular basis of opsonic defect in immunodeficient children. Sumiya, M., Super, M., Tabona, P., Levinsky, R.J., Arai, T., Turner, M.W., Summerfield, J.A. Lancet (1991) [Pubmed]
  44. High frequencies in African and non-African populations of independent mutations in the mannose binding protein gene. Lipscombe, R.J., Sumiya, M., Hill, A.V., Lau, Y.L., Levinsky, R.J., Summerfield, J.A., Turner, M.W. Hum. Mol. Genet. (1992) [Pubmed]
 
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