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Gene Review

SFTPA1B  -  surfactant protein A1B

Homo sapiens

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Disease relevance of SFTPA1


Psychiatry related information on SFTPA1


High impact information on SFTPA1

  • 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 [8].
  • It has been known for several years that surfactant lipids suppress a variety of immune cell functions, most notably lymphocyte proliferation, which, conversely, is augmented by SP-A [9].
  • On the C57BL/6J background, they develop a fatal disease characterized by pulmonary chronic interstitial inflammation and alveolar proteinosis, inflammation of the glandular stomach and skin resulting in scarring due to constant itching, and hyperplasia of lymphoid cells, haematopoietic cells and the forestomach epithelium [10].
  • SPA1: a gene important for chromosome segregation and other mitotic functions in S. cerevisiae [11].
  • Although steady-state hematopoiesis was unimpaired in homozygous mutant animals, all animals developed the progressive accumulation of surfactant lipids and proteins in the alveolar space, the defining characteristic of the idiopathic human disorder pulmonary alveolar proteinosis [12].

Chemical compound and disease context of SFTPA1


Biological context of SFTPA1

  • Finally, out of five intragenic haplotypes identified in the SFTPA1 gene and nine identified in the SFTPA2 gene, 1A ( 3 ) was most significantly associated with tuberculosis susceptibility (P=0.026) [18].
  • In the present study, 88 infants with RDS and 88 control infants that were matched for degree of prematurity, prenatal glucocorticoid therapy, and sex were analyzed for SP-A genotypes [19].
  • In this study, we found that O(2) also was permissive for IL-1 induction of SP-A expression and for cAMP and IL-1 stimulation of type II cell nuclear protein binding to the TBE [3].
  • Cyclic AMP (cAMP) stimulation of SP-A expression in lung type II cells is O(2) dependent and mediated by increased phosphorylation and binding of thyroid transcription factor 1 (TTF-1) to an upstream response element (TTF-1-binding element [TBE]) [3].
  • Surfactant protein A (SP-A), a major component of lung surfactant, participates in the innate immune response and can enhance phagocytosis [13].

Anatomical context of SFTPA1


Associations of SFTPA1 with chemical compounds

  • The newly expressed MR likely came from intracellular pools because: 1) up-regulation of the MR by SP-A occurred by 1 h, 2) new protein synthesis was not necessary for MR up-regulation, and 3) pinocytosis of mannose BSA via MR recycling was increased [13].
  • We also found that exposure of mice to 90% O2 for 4 days, sufficient to lead to consumption of glutathione, oxidation of protein thiols, and accumulation of airspace protein-associated carbonyl moieties, blocked the permeabilizing activity of lavage fluid from SP-A+/+ mice [24].
  • Activity at pH 7.4 was approximately 50% less, and inhibition by SP-A was partially dependent on Ca(2+) [25].
  • SP-A also prevented C1q and C1 from binding to immune complexes [22].
  • SP-A triggered the increase in cytosolic Ca2+ by inducing activation of phospholipase C, which leads to the hydrolysis of membrane phospholipids, yielding inositol 1,4,5-trisphosphate and mobilizing intracellularly stored Ca2+ by inositol triphosphate-sensitive channels [20].

Physical interactions of SFTPA1

  • Glycoprotein-340 (gp-340) was first identified as a surfactant protein (SP)-D-binding molecule purified from lung lavage of patients with alveolar proteinosis (Holmskov, et al., J. Biol. Chem. 1997;272:13743) [26].
  • We also determined whether specific SP-B variants interact with RDS susceptibility or protective SP-A variants to enhance or reduce risk for RDS [27].
  • Surfactant-associated protein A (SP-A) is a component of pulmonary surfactant that binds to a specific receptor (SPAR) on the surface of type II alveolar cells of the lung and regulates gene expression and surfactant secretion [28].
  • SP-A and SP-D also bind lipids and SP-A is involved in organization of alveolar surfactant phospholipids [29].
  • To obtain a better understanding of how lung collectins modulate cellular responses, the authors investigated whether SP-A interacts with the toll-like receptor 2 (TLR2) [30].

Co-localisations of SFTPA1


Regulatory relationships of SFTPA1

  • SP-A appeared to induce prostaglandin E(2) synthesis in chorionic trophoblasts via induction of cyclooxygenase type 2 expression [32].
  • SP-A mRNA and protein are downregulated by phorbol esters (TPA) via inhibition of gene transcription [33].
  • To test whether SP-A induced Smad signaling, a Smad3/4-specific reporter gene was transfected in primary human CD4(+) T lymphocytes [34].
  • Because surfactant protein A (SP-A) is capable of modulating other functions of human monocytic cells, we hypothesized that SP-A may regulate MMP-9 expression [35].
  • We speculate that SP-A may influence the protease/antiprotease balance in the lungs of patients with quantitative and/or qualitative changes in surfactant constituents favoring an abnormal breakdown of extracellular matrix components [35].

Other interactions of SFTPA1

  • In the present study, we identified a GT box (GGGGTGGGG) at -61 bp of SP-A2 5'-flanking sequence that is highly conserved among the SP-A genes of different species [36].
  • Cortisol (10(-7) and 10(-6) m, 24 h) induced SP-A expression in cultured chorionic trophoblasts, which could be blocked by the glucocorticoid receptor antagonist RU486 [32].
  • Treatment of chorionic trophoblasts with SP-A (10-100 mug/ml, 24 h) caused a dose-dependent increase of prostaglandin E(2) release and an induction of cyclooxygenase type 2 but not cytosolic phospholipase A(2) and microsomal prostaglandin E synthase expression [32].
  • In contrast to lung surfactant protein D (SP-D), which is generally expressed on mucosal surfaces, SP-A seems to be restricted to the respiratory system [37].
  • RESULTS: At baseline, high levels of anti-GM-CSF antibodies and increased SP-A and SP-B levels were seen in all patients, and LDH was raised in 83% [38].

Analytical, diagnostic and therapeutic context of SFTPA1


  1. Tumor necrosis factor-alpha inhibits expression of pulmonary surfactant protein. Wispé, J.R., Clark, J.C., Warner, B.B., Fajardo, D., Hull, W.E., Holtzman, R.B., Whitsett, J.A. J. Clin. Invest. (1990) [Pubmed]
  2. Surfactant proteins A and D inhibit the growth of Gram-negative bacteria by increasing membrane permeability. Wu, H., Kuzmenko, A., Wan, S., Schaffer, L., Weiss, A., Fisher, J.H., Kim, K.S., McCormack, F.X. J. Clin. Invest. (2003) [Pubmed]
  3. Permissive effects of oxygen on cyclic AMP and interleukin-1 stimulation of surfactant protein A gene expression are mediated by epigenetic mechanisms. Islam, K.N., Mendelson, C.R. Mol. Cell. Biol. (2006) [Pubmed]
  4. Direct binding of Toll-like receptor 2 to zymosan, and zymosan-induced NF-kappa B activation and TNF-alpha secretion are down-regulated by lung collectin surfactant protein A. Sato, M., Sano, H., Iwaki, D., Kudo, K., Konishi, M., Takahashi, H., Takahashi, T., Imaizumi, H., Asai, Y., Kuroki, Y. J. Immunol. (2003) [Pubmed]
  5. Pulmonary surfactant protein A modulates the cellular response to smooth and rough lipopolysaccharides by interaction with CD14. Sano, H., Sohma, H., Muta, T., Nomura, S., Voelker, D.R., Kuroki, Y. J. Immunol. (1999) [Pubmed]
  6. Mostly separate distributions of CLAC- versus Abeta40- or thioflavin S-reactivities in senile plaques reveal two distinct subpopulations of beta-amyloid deposits. Kowa, H., Sakakura, T., Matsuura, Y., Wakabayashi, T., Mann, D.M., Duff, K., Tsuji, S., Hashimoto, T., Iwatsubo, T. Am. J. Pathol. (2004) [Pubmed]
  7. Interaction of pulmonary surfactant protein A with phospholipid liposomes: a kinetic study on head group and fatty acid specificity. Meyboom, A., Maretzki, D., Stevens, P.A., Hofmann, K.P. Biochim. Biophys. Acta (1999) [Pubmed]
  8. Collections and ficolins: humoral lectins of the innate immune defense. Holmskov, U., Thiel, S., Jensenius, J.C. Annu. Rev. Immunol. (2003) [Pubmed]
  9. Immunomodulatory functions of surfactant. Wright, J.R. Physiol. Rev. (1997) [Pubmed]
  10. The itchy locus encodes a novel ubiquitin protein ligase that is disrupted in a18H mice. Perry, W.L., Hustad, C.M., Swing, D.A., O'Sullivan, T.N., Jenkins, N.A., Copeland, N.G. Nat. Genet. (1998) [Pubmed]
  11. SPA1: a gene important for chromosome segregation and other mitotic functions in S. cerevisiae. Snyder, M., Davis, R.W. Cell (1988) [Pubmed]
  12. Involvement of granulocyte-macrophage colony-stimulating factor in pulmonary homeostasis. Dranoff, G., Crawford, A.D., Sadelain, M., Ream, B., Rashid, A., Bronson, R.T., Dickersin, G.R., Bachurski, C.J., Mark, E.L., Whitsett, J.A. Science (1994) [Pubmed]
  13. Pulmonary surfactant protein A up-regulates activity of the mannose receptor, a pattern recognition receptor expressed on human macrophages. Beharka, A.A., Gaynor, C.D., Kang, B.K., Voelker, D.R., McCormack, F.X., Schlesinger, L.S. J. Immunol. (2002) [Pubmed]
  14. Interaction of SP-A (surfactant protein A) with bacterial rough lipopolysaccharide (Re-LPS), and effects of SP-A on the binding of Re-LPS to CD14 and LPS-binding protein. García-Verdugo, I., Sánchez-Barbero, F., Soldau, K., Tobias, P.S., Casals, C. Biochem. J. (2005) [Pubmed]
  15. Surfactant protein A, but not surfactant protein D, is an opsonin for influenza A virus phagocytosis by rat alveolar macrophages. Benne, C.A., Benaissa-Trouw, B., van Strijp, J.A., Kraaijeveld, C.A., van Iwaarden, J.F. Eur. J. Immunol. (1997) [Pubmed]
  16. Protective role of lung surfactant protein D in a murine model of invasive pulmonary aspergillosis. Madan, T., Kishore, U., Singh, M., Strong, P., Hussain, E.M., Reid, K.B., Sarma, P.U. Infect. Immun. (2001) [Pubmed]
  17. Combined SP-A-bleomycin effect on cytokines by THP-1 cells: impact of surfactant lipids on this effect. Huang, W., Wang, G., Phelps, D.S., Al-Mondhiry, H., Floros, J. Am. J. Physiol. Lung Cell Mol. Physiol. (2002) [Pubmed]
  18. Variants of the SFTPA1 and SFTPA2 genes and susceptibility to tuberculosis in Ethiopia. Malik, S., Greenwood, C.M., Eguale, T., Kifle, A., Beyene, J., Habte, A., Tadesse, A., Gebrexabher, H., Britton, S., Schurr, E. Hum. Genet. (2006) [Pubmed]
  19. Association between the surfactant protein A (SP-A) gene locus and respiratory-distress syndrome in the Finnish population. Rämet, M., Haataja, R., Marttila, R., Floros, J., Hallman, M. Am. J. Hum. Genet. (2000) [Pubmed]
  20. Pulmonary surfactant protein A activates a phosphatidylinositol 3-kinase/calcium signal transduction pathway in human macrophages: participation in the up-regulation of mannose receptor activity. Beharka, A.A., Crowther, J.E., McCormack, F.X., Denning, G.M., Lees, J., Tibesar, E., Schlesinger, L.S. J. Immunol. (2005) [Pubmed]
  21. Purification of a cell-surface receptor for surfactant protein A. Chroneos, Z.C., Abdolrasulnia, R., Whitsett, J.A., Rice, W.R., Shepherd, V.L. J. Biol. Chem. (1996) [Pubmed]
  22. Surfactant protein A regulates complement activation. Watford, W.T., Wright, J.R., Hester, C.G., Jiang, H., Frank, M.M. J. Immunol. (2001) [Pubmed]
  23. Immunogold localization of SP-A in lungs of infants dying from respiratory distress syndrome. deMello, D.E., Heyman, S., Phelps, D.S., Floros, J. Am. J. Pathol. (1993) [Pubmed]
  24. Surfactant protein A is a principal and oxidation-sensitive microbial permeabilizing factor in the alveolar lining fluid. Kuzmenko, A.I., Wu, H., Wan, S., McCormack, F.X. J. Biol. Chem. (2005) [Pubmed]
  25. Interaction of surfactant protein a with peroxiredoxin 6 regulates phospholipase A2 activity. Wu, Y.Z., Manevich, Y., Baldwin, J.L., Dodia, C., Yu, K., Feinstein, S.I., Fisher, A.B. J. Biol. Chem. (2006) [Pubmed]
  26. Glycoprotein-340 binds surfactant protein-A (SP-A) and stimulates alveolar macrophage migration in an SP-A-independent manner. Tino, M.J., Wright, J.R. Am. J. Respir. Cell Mol. Biol. (1999) [Pubmed]
  27. Surfactant protein (SP) B associations and interactions with SP-A in white and black subjects with respiratory distress syndrome. Floros, J., Fan, R., Diangelo, S., Guo, X., Wert, J., Luo, J. Pediatrics international : official journal of the Japan Pediatric Society. (2001) [Pubmed]
  28. Natural protection from apoptosis by surfactant protein A in type II pneumocytes. White, M.K., Baireddy, V., Strayer, D.S. Exp. Cell Res. (2001) [Pubmed]
  29. Molecular structures and interactions of pulmonary surfactant components. Johansson, J., Curstedt, T. Eur. J. Biochem. (1997) [Pubmed]
  30. Regulation of inflammation and bacterial clearance by lung collectins. Sano, H., Kuronuma, K., Kudo, K., Mitsuzawa, H., Sato, M., Murakami, S., Kuroki, Y. Respirology (2006) [Pubmed]
  31. Microfibril-associated protein 4 binds to surfactant protein A (SP-A) and colocalizes with SP-A in the extracellular matrix of the lung. Schlosser, A., Thomsen, T., Shipley, J.M., Hein, P.W., Brasch, F., Tornøe, I., Nielsen, O., Skjødt, K., Palaniyar, N., Steinhilber, W., McCormack, F.X., Holmskov, U. Scand. J. Immunol. (2006) [Pubmed]
  32. Induction of surfactant protein a expression by cortisol facilitates prostaglandin synthesis in human chorionic trophoblasts. Sun, K., Brockman, D., Campos, B., Pitzer, B., Myatt, L. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  33. Signal transduction events involved in TPA downregulation of SP-A gene expression. Miakotina, O.L., Snyder, J.M. Am. J. Physiol. Lung Cell Mol. Physiol. (2004) [Pubmed]
  34. TGF-beta1 in SP-A preparations influence immune suppressive properties of SP-A on human CD4+ T lymphocytes. Kunzmann, S., Wright, J.R., Steinhilber, W., Kramer, B.W., Blaser, K., Speer, C.P., Schmidt-Weber, C. Am. J. Physiol. Lung Cell Mol. Physiol. (2006) [Pubmed]
  35. Surfactant protein A increases matrix metalloproteinase-9 production by THP-1 cells. Vazquez de Lara, L.G., Umstead, T.M., Davis, S.E., Phelps, D.S. Am. J. Physiol. Lung Cell Mol. Physiol. (2003) [Pubmed]
  36. A GT box element is essential for basal and cyclic adenosine 3',5'-monophosphate regulation of the human surfactant protein A2 gene in alveolar type II cells: evidence for the binding of lung nuclear factors distinct from Sp1. Young, P.P., Mendelson, C.R. Mol. Endocrinol. (1997) [Pubmed]
  37. Expression and localization of lung surfactant protein A in human tissues. Madsen, J., Tornoe, I., Nielsen, O., Koch, C., Steinhilber, W., Holmskov, U. Am. J. Respir. Cell Mol. Biol. (2003) [Pubmed]
  38. Relationship of anti-GM-CSF antibody concentration, surfactant protein A and B levels, and serum LDH to pulmonary parameters and response to GM-CSF therapy in patients with idiopathic alveolar proteinosis. Seymour, J.F., Doyle, I.R., Nakata, K., Presneill, J.J., Schoch, O.D., Hamano, E., Uchida, K., Fisher, R., Dunn, A.R. Thorax (2003) [Pubmed]
  39. Surfactant protein A gene deletion and prognostics for patients with stage I non-small cell lung cancer. Jiang, F., Caraway, N.P., Nebiyou Bekele, B., Zhang, H.Z., Khanna, A., Wang, H., Li, R., Fernandez, R.L., Zaidi, T.M., Johnston, D.A., Katz, R.L. Clin. Cancer Res. (2005) [Pubmed]
  40. Surfactant protein A2 gene expression by human airway submucosal gland cells. Saitoh, H., Okayama, H., Shimura, S., Fushimi, T., Masuda, T., Shirato, K. Am. J. Respir. Cell Mol. Biol. (1998) [Pubmed]
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