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SFTPC  -  surfactant protein C

Homo sapiens

 
 
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Disease relevance of SFTPC

 

High impact information on SFTPC

 

Chemical compound and disease context of SFTPC

 

Biological context of SFTPC

 

Anatomical context of SFTPC

  • The SFTPC mutation, designated g.1728 G --> A, results in the deletion of exon4, generating a truncated form of SP-C (SP-C(Deltaexon4)). cDNA encoding SP-C(Deltaexon4) was constitutively expressed in type II epithelial cells of transgenic mice [1].
  • We have determined the entire nucleotide sequence of two distinct genes encoding SP-C from a genomic library prepared from human leukocytes [11].
  • Although its solubility in organic solvents and avidity for lipid membranes impart properties important for its biophysical activity, SP-C represents a structurally and functionally challenging protein for the alveolar type II cell that must synthesize and traffic the peptide through the regulated secretory pathway [12].
  • SP-A, SP-C, and/or SP-D transcripts were detected in 11 (84.6%) of 13 lymph nodes with histologically identifiable metastases of pulmonary adenocarcinomas and in 10 (55.5%) of 18 lymph nodes that were tumor free on routine histological examination [13].
  • Surfactant protein C (SP-C) is synthesized by alveolar type II cells as a 21-kDa propeptide (proSP-C21) which is proteolytically processed in subcellular compartments distal to the trans-Golgi network to yield a 35-residue mature form [14].
 

Associations of SFTPC with chemical compounds

  • These results prove that native SP-C is a lipopeptide with two palmitoyl groups covalently linked to the polypeptide chain [15].
  • Hydrophobic surfactant-associated polypeptides: SP-C is a lipopeptide with two palmitoylated cysteine residues, whereas SP-B lacks covalently linked fatty acyl groups [15].
  • Treatment of SP-C with KOH releases fatty acids (palmitic acid to more than 85%) in molar ratios of 1.8-2.0 relative to the polypeptide [15].
  • The mutation is predicted to substitute a glutamine for a conserved leucine residue and may hinder processing of SP-C precursor protein [2].
  • However, unlike SP-C, SP-C(i) exhibited a very poor ability to promote phospholipid adsorption, gave high surface tension during cyclic film compression, and did not bind lipopolysaccharide in vitro [16].
 

Physical interactions of SFTPC

  • The TTF-1/TAP26 complex differentially modulates surfactant protein-B (SP-B) and -C (SP-C) promoters in lung cells [17].
 

Enzymatic interactions of SFTPC

  • Furthermore, addition of control SP-B can improve samples containing oxidized SP-C, but not vice versa [18].
 

Regulatory relationships of SFTPC

  • To test the role of this bridge in SP-B function in vivo, a construct was generated in which cysteine residues 235 and 246 of the human SP-B proprotein were mutated to serine and cloned under the control of the 3.7-kilobase hSP-C promoter (hSP-B(C235S/C246S)) [19].
 

Other interactions of SFTPC

 

Analytical, diagnostic and therapeutic context of SFTPC

  • Of the 10 patients with abnormal pro-SP-C processing, as suggested from analysis of broncho-alveolar lavage (BAL) fluid, two distinct heterozygous SFTPC missense mutations were identified [22].
  • We have purified a hydrophobic surfactant protein of approximately 5 kDa that we term SP5 from bronchopulmonary lavage fluid from a patient with alveolar proteinosis and shown that it promotes rapid surface film formation by simple mixtures of phospholipids [10].
  • Northern blot studies showed lung-specific expression of the full-length SFTPC transcript, appearing in 50-day-old fetus and increasing during lung development [25].
  • Both SFTPC transcripts were detected mainly in lung by real-time RT-PCR and they were significantly down-regulated in necrotic lungs of pigs infected with Actinobacillus pleuropneumoniae [25].
  • By Western blot analysis, all of these recognized a low molecular weight surfactant species (9 kd) that could be either SP-B or SP-C [26].

References

  1. Expression of a human surfactant protein C mutation associated with interstitial lung disease disrupts lung development in transgenic mice. Bridges, J.P., Wert, S.E., Nogee, L.M., Weaver, T.E. J. Biol. Chem. (2003) [Pubmed]
  2. Heterozygosity for a surfactant protein C gene mutation associated with usual interstitial pneumonitis and cellular nonspecific interstitial pneumonitis in one kindred. Thomas, A.Q., Lane, K., Phillips, J., Prince, M., Markin, C., Speer, M., Schwartz, D.A., Gaddipati, R., Marney, A., Johnson, J., Roberts, R., Haines, J., Stahlman, M., Loyd, J.E. Am. J. Respir. Crit. Care Med. (2002) [Pubmed]
  3. Mapping of the pulmonary surfactant SP5 (SFTP2) locus to 8p21 and characterization of a microsatellite repeat marker that shows frequent loss of heterozygosity in human carcinomas. Wood, S., Yaremko, M.L., Schertzer, M., Kelemen, P.R., Minna, J., Westbrook, C.A. Genomics (1994) [Pubmed]
  4. Respiratory epithelial cell expression of human transforming growth factor-alpha induces lung fibrosis in transgenic mice. Korfhagen, T.R., Swantz, R.J., Wert, S.E., McCarty, J.M., Kerlakian, C.B., Glasser, S.W., Whitsett, J.A. J. Clin. Invest. (1994) [Pubmed]
  5. Regulation of messenger RNAs for the hydrophobic surfactant proteins in human lung. Liley, H.G., White, R.T., Warr, R.G., Benson, B.J., Hawgood, S., Ballard, P.L. J. Clin. Invest. (1989) [Pubmed]
  6. Genetics of pediatric interstitial lung disease. Nogee, L.M. Curr. Opin. Pediatr. (2006) [Pubmed]
  7. Nonspecific interstitial pneumonia, alveolar proteinosis, and abnormal proprotein trafficking resulting from a spontaneous mutation in the surfactant protein C gene. Stevens, P.A., Pettenazzo, A., Brasch, F., Mulugeta, S., Baritussio, A., Ochs, M., Morrison, L., Russo, S.J., Beers, M.F. Pediatr. Res. (2005) [Pubmed]
  8. Interstitial lung disease in a baby with a de novo mutation in the SFTPC gene. Brasch, F., Griese, M., Tredano, M., Johnen, G., Ochs, M., Rieger, C., Mulugeta, S., Müller, K.M., Bahuau, M., Beers, M.F. Eur. Respir. J. (2004) [Pubmed]
  9. Adaptation and increased susceptibility to infection associated with constitutive expression of misfolded SP-C. Bridges, J.P., Xu, Y., Na, C.L., Wong, H.R., Weaver, T.E. J. Cell Biol. (2006) [Pubmed]
  10. Low molecular weight human pulmonary surfactant protein (SP5): isolation, characterization, and cDNA and amino acid sequences. Warr, R.G., Hawgood, S., Buckley, D.I., Crisp, T.M., Schilling, J., Benson, B.J., Ballard, P.L., Clements, J.A., White, R.T. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  11. Two SP-C genes encoding human pulmonary surfactant proteolipid. Glasser, S.W., Korfhagen, T.R., Perme, C.M., Pilot-Matias, T.J., Kister, S.E., Whitsett, J.A. J. Biol. Chem. (1988) [Pubmed]
  12. Synthesis and post-translational processing of surfactant protein C. Solarin, K.O., Wang, W.J., Beers, M.F. Pediatric pathology & molecular medicine. (2001) [Pubmed]
  13. Surfactant protein gene expression in metastatic and micrometastatic pulmonary adenocarcinomas and other non-small cell lung carcinomas: detection by reverse transcriptase-polymerase chain reaction. Betz, C., Papadopoulos, T., Buchwald, J., Dämmrich, J., Müller-Hermelink, H.K. Cancer Res. (1995) [Pubmed]
  14. Synthetic processing of surfactant protein C by alevolar epithelial cells. The COOH terminus of proSP-C is required for post-translational targeting and proteolysis. Beers, M.F., Lomax, C.A., Russo, S.J. J. Biol. Chem. (1998) [Pubmed]
  15. Hydrophobic surfactant-associated polypeptides: SP-C is a lipopeptide with two palmitoylated cysteine residues, whereas SP-B lacks covalently linked fatty acyl groups. Curstedt, T., Johansson, J., Persson, P., Eklund, A., Robertson, B., Löwenadler, B., Jörnvall, H. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  16. N-terminally extended surfactant protein (SP) C isolated from SP-B-deficient children has reduced surface activity and inhibited lipopolysaccharide binding. Li, J., Ikegami, M., Na, C.L., Hamvas, A., Espinassous, Q., Chaby, R., Nogee, L.M., Weaver, T.E., Johansson, J. Biochemistry (2004) [Pubmed]
  17. The TTF-1/TAP26 complex differentially modulates surfactant protein-B (SP-B) and -C (SP-C) promoters in lung cells. Yang, M.C., Guo, Y., Liu, C.C., Weissler, J.C., Yang, Y.S. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  18. Reactive oxygen species inactivation of surfactant involves structural and functional alterations to surfactant proteins SP-B and SP-C. Rodríguez-Capote, K., Manzanares, D., Haines, T., Possmayer, F. Biophys. J. (2006) [Pubmed]
  19. Ablation of a critical surfactant protein B intramolecular disulfide bond in transgenic mice. Beck, D.C., Na, C.L., Whitsett, J.A., Weaver, T.E. J. Biol. Chem. (2000) [Pubmed]
  20. Alterations in SP-B and SP-C expression in neonatal lung disease. Nogee, L.M. Annu. Rev. Physiol. (2004) [Pubmed]
  21. Monoclonal antibody 7F9 recognizes rat protein homologous to human carboxypeptidase-M in developing and adult rat lung. Fujiwara, N., Ikeda, M., Hirabayashi, S., Mori, H., Shirasawa, M., Kansaku, A., Sunamori, M., Hata, Y. Respirology (2007) [Pubmed]
  22. Mutation of SFTPC in infantile pulmonary alveolar proteinosis with or without fibrosing lung disease. Tredano, M., Griese, M., Brasch, F., Schumacher, S., de Blic, J., Marque, S., Houdayer, C., Elion, J., Couderc, R., Bahuau, M. Am. J. Med. Genet. A (2004) [Pubmed]
  23. Surfactant protein A and B genetic variants predispose to idiopathic pulmonary fibrosis. Selman, M., Lin, H.M., Montaño, M., Jenkins, A.L., Estrada, A., Lin, Z., Wang, G., DiAngelo, S.L., Guo, X., Umstead, T.M., Lang, C.M., Pardo, A., Phelps, D.S., Floros, J. Hum. Genet. (2003) [Pubmed]
  24. VEGF induces airway epithelial cell proliferation in human fetal lung in vitro. Brown, K.R., England, K.M., Goss, K.L., Snyder, J.M., Acarregui, M.J. Am. J. Physiol. Lung Cell Mol. Physiol. (2001) [Pubmed]
  25. Molecular characterization of the porcine surfactant, pulmonary-associated protein C gene. Cirera, S., Nyg??rd, A.B., Jensen, H.E., Skovgaard, K., Boye, M., Fredholm, M. Genomics (2006) [Pubmed]
  26. Antigenicity of low molecular weight surfactant species. Strayer, D.S., Merritt, T.A., Makunike, C., Hallman, M. Am. J. Pathol. (1989) [Pubmed]
 
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