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Gene Review

SERPINA1  -  serpin peptidase inhibitor, clade A (alpha...

Homo sapiens

Synonyms: A1A, A1AT, AAT, Alpha-1 protease inhibitor, Alpha-1-antiproteinase, ...
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Disease relevance of SERPINA1

  • We demonstrate that a plasmid carrying the full SERPINA1 on a 19-kb genomic fragment and the EBV gene EBNA1 and its family of repeats binding sites undergoes efficient extrachromosomal replication in dividing mammalian tissue culture cells [1].
  • Although the consequences to the individual (i.e., emphysema) are identical to those associated with the common homozygous Z mutation, the homozygous null bellingham form of alpha 1AT deficiency has a very different genetic basis [2].
  • We show here that synthetic peptides based on the sequence of this region bind specifically and saturably to human hepatoma cells and human monocytes (Kd = 4.0 X 10(-8) M, 4.5 X 10(5) plasma membrane receptors per cell) and mediate increases in synthesis of alpha 1-AT [3].
  • Inhibition of HIV-1 gp160-dependent membrane fusion by a furin-directed alpha 1-antitrypsin variant [4].
  • The ratio of functional to antigenic levels of alpha 1AT in SF of patients with inflammatory joint diseases was similar to that of alpha 1AT in normal plasma, whereas that of alpha 1ACT was significantly decreased [5].

Psychiatry related information on SERPINA1


High impact information on SERPINA1


Chemical compound and disease context of SERPINA1


Biological context of SERPINA1


Anatomical context of SERPINA1


Associations of SERPINA1 with chemical compounds

  • The Vmunich allele differed from the common normal M1(Val213) alpha 1AT allele by a single nucleotide substitution of cytosine for adenosine, with the resultant amino acid change Asp2 GAT----Ala GCT [20].
  • alpha(1)-Antitrypsin (AAT) is the major serine proteinase inhibitor (SERPIN A1) in human plasma [26].
  • We now show that when MCF-7(ML) cells (a subline synthesizing low levels of alpha 1-AT) are grown in soft agar in medium depleted of its trypsin inhibitory capacity (i.e. alpha 1-AT-free), addition of alpha 1-AT (50 micrograms/ml) significantly reduces colony formation in both the presence and absence of estradiol (34% and 44%, respectively) [27].
  • We also found that a variety of inflammatory mediators, cytokines, and steroid hormones are able to stimulate synthesis of alpha 1-AT and alpha 1-ACHY by MCF-7 cells [27].
  • The disease process is exacerbated by cigarette smoke, which is capable of oxidizing a critical methionine residue at the active site, rendering AAT an inefficient inhibitor of NE [28].

Physical interactions of SERPINA1


Enzymatic interactions of SERPINA1


Regulatory relationships of SERPINA1


Other interactions of SERPINA1

  • Binding of peptide 105Y is also blocked by peptides with sequence corresponding to carboxy-terminal fragments of the serpins AT III and alpha 1-ACT, but not by peptides having the sequence of the extreme amino terminus of alpha 1-AT [3].
  • Although much is known about the function, structure, and inhibitory mechanism of circulating serpins such as alpha(1)-antitrypsin (SERPINA1) and antithrombin III (SERPINC1), relatively little is known about the function of the vertebrate intracellular (clade B) serpins [38].
  • In the context of the maintenance of tissue homeostasis, we hypothesized that neutrophils may be able to store alpha 1-AT, thus having it available for release concordantly with NE [39].
  • Western blot analysis showed the majority of alpha 1AT and SLPI molecules to be complexed and/or degraded [40].
  • For instance, the addition of 30 microM alpha 1-AT increased the KD of transferrin from 8.46 +/- 1.51 nM to 21.6 +/- 3.04 nM; the Bmax. values were 1.17 +/- 0.18 pmol/mg of protein and 1.04 +/- 0.25 pmol/mg of protein respectively [30].

Analytical, diagnostic and therapeutic context of SERPINA1


  1. Epstein-Barr virus/human vector provides high-level, long-term expression of alpha1-antitrypsin in mice. Stoll, S.M., Sclimenti, C.R., Baba, E.J., Meuse, L., Kay, M.A., Calos, M.P. Mol. Ther. (2001) [Pubmed]
  2. Emphysema associated with complete absence of alpha 1- antitrypsin in serum and the homozygous inheritance [corrected] of a stop codon in an alpha 1-antitrypsin-coding exon. Satoh, K., Nukiwa, T., Brantly, M., Garver, R.I., Hofker, M., Courtney, M., Crystal, R.G. Am. J. Hum. Genet. (1988) [Pubmed]
  3. Identification of a serpin-enzyme complex receptor on human hepatoma cells and human monocytes. Perlmutter, D.H., Glover, G.I., Rivetna, M., Schasteen, C.S., Fallon, R.J. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  4. Inhibition of HIV-1 gp160-dependent membrane fusion by a furin-directed alpha 1-antitrypsin variant. Anderson, E.D., Thomas, L., Hayflick, J.S., Thomas, G. J. Biol. Chem. (1993) [Pubmed]
  5. Proteolytic inactivation of alpha 1-antitrypsin and alpha 1-antichymotrypsin by neutrophils in arthritic joints. Abbink, J.J., Kamp, A.M., Nuijens, J.H., Swaak, T.J., Hack, C.E. Arthritis Rheum. (1993) [Pubmed]
  6. Immunohistochemical localization of lysozyme, lactoferrin, alpha 1-antichymotrypsin, and alpha 1-antitrypsin in salivary gland of human fetuses. Lee, S.K., Lim, C.Y., Chi, J.G., Yamada, K., Kunikata, M., Hashimura, K., Mori, M. Acta Histochem. (1990) [Pubmed]
  7. Association between the PI*M3 allele of alpha 1-antitrypsin and Alzheimer's disease? A preliminary report. Kowalska, A., Danker-Hopfe, H., Wender, M., Florczak, J., Walter, H. Hum. Genet. (1996) [Pubmed]
  8. Survival in relation to lung function and smoking cessation in patients with severe hereditary alpha 1-antitrypsin deficiency. Seersholm, N., Kok-Jensen, A. Am. J. Respir. Crit. Care Med. (1995) [Pubmed]
  9. Antiproteases and Down's syndrome in an Australian population. McPhee, H., Ananthakrishnan, R., Taft, L.I. J. Med. Genet. (1980) [Pubmed]
  10. Long-term follow-up of a cohort of children with alpha-1-antitrypsin deficiency. Wall, M., Moe, E., Eisenberg, J., Powers, M., Buist, N., Buist, A.S. J. Pediatr. (1990) [Pubmed]
  11. Adenovirus-mediated in vivo gene transfer and expression in normal rat liver. Jaffe, H.A., Danel, C., Longenecker, G., Metzger, M., Setoguchi, Y., Rosenfeld, M.A., Gant, T.W., Thorgeirsson, S.S., Stratford-Perricaudet, L.D., Perricaudet, M. Nat. Genet. (1992) [Pubmed]
  12. Replacement therapy for alpha 1-antitrypsin deficiency associated with emphysema. Wewers, M.D., Casolaro, M.A., Sellers, S.E., Swayze, S.C., McPhaul, K.M., Wittes, J.T., Crystal, R.G. N. Engl. J. Med. (1987) [Pubmed]
  13. Risk of cirrhosis and primary liver cancer in alpha 1-antitrypsin deficiency. Eriksson, S., Carlson, J., Velez, R. N. Engl. J. Med. (1986) [Pubmed]
  14. Role of alpha-1-antichymotrypsin deficiency in promoting cirrhosis in two siblings with heterozygous alpha-1-antitrypsin deficiency phenotype SZ. Yoon, D., Kueppers, F., Genta, R.M., Klintmalm, G.B., Khaoustov, V.I., Yoffe, B. Gut (2002) [Pubmed]
  15. Immunohistochemical localization of alpha 1-antitrypsin and alpha 1-antichymotrypsin in salivary pleomorphic adenomas. Murase, N., Kobayashi, K., Mitani, H., Mori, M. Virchows Archiv. A, Pathological anatomy and histopathology. (1985) [Pubmed]
  16. Alpha-1-antitrypsin deficiency: a new paradigm for hepatocellular carcinoma in genetic liver disease. Rudnick, D.A., Perlmutter, D.H. Hepatology (2005) [Pubmed]
  17. Recombinant alpha 1-antitrypsin Pittsburgh (Met 358----Arg) is a potent inhibitor of plasma kallikrein and activated factor XII fragment. Schapira, M., Ramus, M.A., Jallat, S., Carvallo, D., Courtney, M. J. Clin. Invest. (1986) [Pubmed]
  18. Glucose removal from N-linked oligosaccharides is required for efficient maturation of certain secretory glycoproteins from the rough endoplasmic reticulum to the Golgi complex. Lodish, H.F., Kong, N. J. Cell Biol. (1984) [Pubmed]
  19. Sequence homology and structural comparison between the chromosomal human alpha 1-antitrypsin and chicken ovalbumin genes. Leicht, M., Long, G.L., Chandra, T., Kurachi, K., Kidd, V.J., Mace, M., Davie, E.W., Woo, S.L. Nature (1982) [Pubmed]
  20. Characterization of the normal alpha 1-antitrypsin allele Vmunich: a variant associated with a unique protein isoelectric focusing pattern. Holmes, M.D., Brantly, M.L., Curiel, D.T., Weidinger, S., Crystal, R.G. Am. J. Hum. Genet. (1990) [Pubmed]
  21. Characterization of the molecular basis of the alpha 1-antitrypsin F allele. Okayama, H., Brantly, M., Holmes, M., Crystal, R.G. Am. J. Hum. Genet. (1991) [Pubmed]
  22. Characterization of the gene and protein of the common alpha 1-antitrypsin normal M2 allele. Nukiwa, T., Brantly, M.L., Ogushi, F., Fells, G.A., Crystal, R.G. Am. J. Hum. Genet. (1988) [Pubmed]
  23. Molecular basis of alpha 1-antitrypsin deficiency and emphysema associated with the alpha 1-antitrypsin Mmineral springs allele. Curiel, D.T., Vogelmeier, C., Hubbard, R.C., Stier, L.E., Crystal, R.G. Mol. Cell. Biol. (1990) [Pubmed]
  24. The acute-phase protein alpha 1-antitrypsin inhibits growth and proliferation of human early erythroid progenitor cells (burst-forming units-erythroid) and of human erythroleukemic cells (K562) in vitro by interfering with transferrin iron uptake. Graziadei, I., Gaggl, S., Kaserbacher, R., Braunsteiner, H., Vogel, W. Blood (1994) [Pubmed]
  25. Development of a transgenic mouse system for the analysis of stages in liver carcinogenesis using tissue-specific expression of SV40 large T-antigen controlled by regulatory elements of the human alpha-1-antitrypsin gene. Sepulveda, A.R., Finegold, M.J., Smith, B., Slagle, B.L., DeMayo, J.L., Shen, R.F., Woo, S.L., Butel, J.S. Cancer Res. (1989) [Pubmed]
  26. Oncostatin M induced alpha1-antitrypsin (AAT) gene expression in Hep G2 cells is mediated by a 3' enhancer. Morgan, K., Marsters, P., Morley, S., van Gent, D., Hejazi, A., Backx, M., Thorpe, E.R., Kalsheker, N. Biochem. J. (2002) [Pubmed]
  27. alpha 1-Antitrypsin- and anchorage-independent growth of MCF-7 breast cancer cells. Finlay, T.H., Tamir, S., Kadner, S.S., Cruz, M.R., Yavelow, J., Levitz, M. Endocrinology (1993) [Pubmed]
  28. Molecular pathology of alpha 1-antitrypsin deficiency and its significance to clinical medicine. Kalsheker, N.A. QJM : monthly journal of the Association of Physicians. (1994) [Pubmed]
  29. Therapeutic level of functional human alpha 1 antitrypsin (hAAT) secreted from murine muscle transduced by adeno-associated virus (rAAV1) vector. Lu, Y., Choi, Y.K., Campbell-Thompson, M., Li, C., Tang, Q., Crawford, J.M., Flotte, T.R., Song, S. The journal of gene medicine. (2006) [Pubmed]
  30. The hepatic acute-phase proteins alpha 1-antitrypsin and alpha 2-macroglobulin inhibit binding of transferrin to its receptor. Graziadei, I., Kaserbacher, R., Braunsteiner, H., Vogel, W. Biochem. J. (1993) [Pubmed]
  31. Within-subject variation of elastase/alpha 1-protease inhibitor complexes and lactoferrin in plasma. Antonsen, S. Scand. J. Clin. Lab. Invest. (1993) [Pubmed]
  32. Safety and efficacy of recombinant alpha(1)-antitrypsin therapy in cystic fibrosis. Martin, S.L., Downey, D., Bilton, D., Keogan, M.T., Edgar, J., Elborn, J.S. Pediatric pulmonology. (2006) [Pubmed]
  33. Turnover of *I-protein C inhibitor and *I-alpha 1-antitrypsin and their complexes with activated protein C. Laurell, M., Stenflo, J., Carlson, T.H. Blood (1990) [Pubmed]
  34. A method for screening hypochlorous acid scavengers by inhibition of the oxidation of 5-thio-2-nitrobenzoic acid: application to anti-asthmatic drugs. Ching, T.L., de Jong, J., Bast, A. Anal. Biochem. (1994) [Pubmed]
  35. Oxidation of plasma alpha 1-antitrypsin in smokers and nonsmokers and by an oxidizing agent. Cox, D.W., Billingsley, G.D. Am. Rev. Respir. Dis. (1984) [Pubmed]
  36. Function of a rare variant of alpha-1-antitrypsin, phenotype P(i) EFranklin S, a poor inhibitor of human neutrophil elastase. Cook, L., Knight, K.R., Burdon, J.G., Brenton, S., Hunt, J.M. Research in experimental medicine. Zeitschrift für die gesamte experimentelle Medizin einschliesslich experimenteller Chirurgie. (1997) [Pubmed]
  37. The acute-phase protein alpha 1-antitrypsin inhibits transferrin-receptor binding and proliferation of human skin fibroblasts. Graziadei, I., Kähler, C.M., Wiedermann, C.J., Vogel, W. Biochim. Biophys. Acta (1998) [Pubmed]
  38. SRP-2 is a cross-class inhibitor that participates in postembryonic development of the nematode Caenorhabditis elegans: initial characterization of the clade L serpins. Pak, S.C., Kumar, V., Tsu, C., Luke, C.J., Askew, Y.S., Askew, D.J., Mills, D.R., Brömme, D., Silverman, G.A. J. Biol. Chem. (2004) [Pubmed]
  39. Activated neutrophils secrete stored alpha 1-antitrypsin. Pääkkö, P., Kirby, M., du Bois, R.M., Gillissen, A., Ferrans, V.J., Crystal, R.G. Am. J. Respir. Crit. Care Med. (1996) [Pubmed]
  40. Protease-antiprotease imbalance in the lungs of children with cystic fibrosis. Birrer, P., McElvaney, N.G., Rüdeberg, A., Sommer, C.W., Liechti-Gallati, S., Kraemer, R., Hubbard, R., Crystal, R.G. Am. J. Respir. Crit. Care Med. (1994) [Pubmed]
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