Genomes and Genes
Gene Symbol: SERPINA1
Description: serpin family A member 1
Alias: A1A, A1AT, AAT, PI1, PRO2275, alpha1AT, nNIF, alpha-1-antitrypsin, alpha-1 antitrypsin, alpha-1 protease inhibitor, alpha-1-antiproteinase, alpha-1-antitrypsin null, alpha-1-antitrypsin short transcript variant 1C4, alpha-1-antitrypsin short transcript variant 1C5, protease inhibitor 1 (anti-elastase), alpha-1-antitrypsin, serine (or cysteine) proteinase inhibitor, clade A, member 1, serpin A1, serpin peptidase inhibitor clade A (alpha-1antiproteinase, antitrypsin) member 1, serpin peptidase inhibitor clade A member 1, serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1
- Ezzikouri S, El Feydi A, El Kihal L, Afifi R, Benazzouz M, Hassar M, et al. Prevalence of common HFE and SERPINA1 mutations in patients with hepatocellular carcinoma in a Moroccan population. Arch Med Res. 2008;39:236-41 pubmed publisherHereditary hemochromatosis and SERPINA1 mutation were reported to affect liver functions...
- Nyon M, Segu L, Cabrita L, LÃ©vy G, Kirkpatrick J, Roussel B, et al. Structural dynamics associated with intermediate formation in an archetypal conformational disease. Structure. 2012;20:504-12 pubmed publisher..Conformational disease intermediates may best be defined using powerful but minimally perturbing techniques, mild disease mutants, and physiological conditions. ..
- Schmidt B, Perlmutter D. Grp78, Grp94, and Grp170 interact with alpha1-antitrypsin mutants that are retained in the endoplasmic reticulum. Am J Physiol Gastrointest Liver Physiol. 2005;289:G444-55 pubmed..Agents that perturb the synthesis and/or activity of ER chaperones such as tunicamycin and calcium ionophore A23187, have different effects on the solubility and degradation of alpha1-AT Z as well as on its residual secretion. ..
- van t Wout E, van Schadewijk A, Savage N, Stolk J, Hiemstra P. ?1-antitrypsin production by proinflammatory and antiinflammatory macrophages and dendritic cells. Am J Respir Cell Mol Biol. 2012;46:607-13 pubmed publisher1)-Antitrypsin (AAT) acts as an important neutrophil elastase inhibitor in the lung...
- Kolarich D, Weber A, Turecek P, Schwarz H, Altmann F. Comprehensive glyco-proteomic analysis of human alpha1-antitrypsin and its charge isoforms. Proteomics. 2006;6:3369-80 pubmed..Fucosylation of diantennary structures was marginal and of the core alpha1,6 type. ..
- Huntington J, Read R, Carrell R. Structure of a serpin-protease complex shows inhibition by deformation. Nature. 2000;407:923-6 pubmed..It is this ability of the conformational mechanism to crush as well as inhibit proteases that provides the serpins with their selective advantage. ..
- Kim S, Woo J, Seo E, Yu M, Ryu S. A 2.1 A resolution structure of an uncleaved alpha(1)-antitrypsin shows variability of the reactive center and other loops. J Mol Biol. 2001;306:109-19 pubmed..The high-resolution structure of active alpha(1)-antitrypsin also provides evidence for the existence of localized van-der-Waals strain in the central hydrophobic core. ..
- Zorzetto M, Russi E, Senn O, Imboden M, Ferrarotti I, Tinelli C, et al. SERPINA1 gene variants in individuals from the general population with reduced alpha1-antitrypsin concentrations. Clin Chem. 2008;54:1331-8 pubmed publisher..We decided to perform an exhaustive investigation of SERPINA1 gene variants in individuals from the general population with a moderately reduced serum AAT concentration, ..
- Perlino E, Cortese R, Ciliberto G. The human alpha 1-antitrypsin gene is transcribed from two different promoters in macrophages and hepatocytes. EMBO J. 1987;6:2767-71 pubmed..In addition, in macrophages two distinct mRNAs are generated transcript by alternative splicing. These results suggest that alpha 1-AT gene transcription responds to two different cell-specific regulatory mechanisms. ..
- Graham A, Kalsheker N, Newton C, Bamforth F, Powell S, Markham A. Molecular characterisation of three alpha-1-antitrypsin deficiency variants: proteinase inhibitor (Pi) nullcardiff (Asp256----Val); PiMmalton (Phe51----deletion) and PiI (Arg39----Cys). Hum Genet. 1989;84:55-8 pubmed..Examination of the protein tertiary structure suggests that all of these mutations are likely to result in folding abnormalities that may explain the deficiency states. ..
- Christianson J, Shaler T, Tyler R, Kopito R. OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD. Nat Cell Biol. 2008;10:272-82 pubmed publisher..These data suggest that XTP3-B and OS-9 are components of distinct, partially redundant, quality control surveillance pathways that coordinate protein folding with membrane dislocation and ubiquitin conjugation in mammalian cells. ..
- Lawless M, Greene C, Mulgrew A, Taggart C, O Neill S, McElvaney N. Activation of endoplasmic reticulum-specific stress responses associated with the conformational disease Z alpha 1-antitrypsin deficiency. J Immunol. 2004;172:5722-6 pubmed..Z alpha1-antitrypsin (A1AT) deficiency is a genetic disease associated with accumulation of misfolded A1AT in the endoplasmic reticulum (ER) ..
- Cordelier P, Strayer D. Mechanisms of alpha1-antitrypsin inhibition of cellular serine proteases and HIV-1 protease that are essential for HIV-1 morphogenesis. Biochim Biophys Acta. 2003;1638:197-207 pubmed..The simultaneous inhibition of two different steps in HIV morphogenesis both increases alpha(1)AT antilentiviral activity and decreases the possibility that HIV mutations will allow escape from inhibition. ..
- Denden S, Haj Khelil A, Perrin P, Daimi H, Leban N, Ouaja A, et al. Alpha 1 antitrypsin polymorphism in the Tunisian population with special reference to pulmonary disease. Pathol Biol (Paris). 2008;56:106-10 pubmedThe study investigated alpha 1 antitrypsin (AAT) gene polymorphism in the Tunisian population. We aimed to analyze the correlation between Pi polymorphism and the risk of developing chronic obstructive pulmonary disease (COPD)...
- Medicina D, Montani N, Fra A, Tiberio L, Corda L, Miranda E, et al. Molecular characterization of the new defective P(brescia) alpha1-antitrypsin allele. Hum Mutat. 2009;30:E771-81 pubmed publisher..Among the known mutations of the alpha(1)AT gene (SERPINA1) causing alpha(1)AT deficiency, a few alleles, particularly the Z allele, may also predispose adults to liver ..
- Frazier G, Siewertsen M, Hofker M, Brubacher M, Cox D. A null deficiency allele of alpha 1-antitrypsin, QOludwigshafen, with altered tertiary structure. J Clin Invest. 1990;86:1878-84 pubmed..A total of 13 different alpha 1AT deficiency alleles, 6 of them null alleles, have been sequenced to date. ..
- Dementiev A, Simonovic M, Volz K, Gettins P. Canonical inhibitor-like interactions explain reactivity of alpha1-proteinase inhibitor Pittsburgh and antithrombin with proteinases. J Biol Chem. 2003;278:37881-7 pubmed..This suggests a general, limited, canonical-like interaction between serpins and proteinases in their Michaelis complexes. ..
- Banauch G, Brantly M, Izbicki G, Hall C, Shanske A, Chavko R, et al. Accelerated spirometric decline in New York City firefighters with α₁-antitrypsin deficiency. Chest. 2010;138:1116-24 pubmed publisher..Antitrypsin (AAT) deficiency is a risk factor for obstructive airway disease...
- Takahashi H, Crystal R. Alpha 1-antitrypsin Null(isola di procida): an alpha 1-antitrypsin deficiency allele caused by deletion of all alpha 1-antitrypsin coding exons. Am J Hum Genet. 1990;47:403-13 pubmed..CTGT) bracketing the deletion, and a novel inserted 4-bp sequence (CCTG) at the breakpoint, suggesting that the mechanism of the deletion may have been "slipped mispairing." ..
- Bristow C, Mercatante D, Kole R. HIV-1 preferentially binds receptors copatched with cell-surface elastase. Blood. 2003;102:4479-86 pubmed
- Yang P, Sun Z, Krowka M, Aubry M, Bamlet W, Wampfler J, et al. Alpha1-antitrypsin deficiency carriers, tobacco smoke, chronic obstructive pulmonary disease, and lung cancer risk. Arch Intern Med. 2008;168:1097-103 pubmed publisher..Our results suggest that alpha(1)ATD carriers are at a 70% to 100% increased risk of lung cancer and may account for 11% to 12% of the patients with lung cancer in our study. ..
- Denden S, Zorzetto M, Amri F, Knani J, Ottaviani S, Scabini R, et al. Screening for Alpha 1 antitrypsin deficiency in Tunisian subjects with obstructive lung disease: a feasibility report. Orphanet J Rare Dis. 2009;4:12 pubmed publisher..We found that 6/120 OLD patients carried an AAT deficient allele, 1 PI*MZ, 1 PI*MPlowel, 3 PI*MMmalton, 1 PI*MMwurzburg...
- Dahl M, Tybjaerg Hansen A, Sillesen H, Jensen G, Steffensen R, Nordestgaard B. Blood pressure, risk of ischemic cerebrovascular and ischemic heart disease, and longevity in alpha(1)-antitrypsin deficiency: the Copenhagen City Heart Study. Circulation. 2003;107:747-52 pubmed..Because MZ heterozygosity was associated with increased age, MZ heterozygosity could be a beneficial condition. ..
- de Serres F, Blanco I, Fernandez Bustillo E. Health implications of alpha1-antitrypsin deficiency in Sub-Sahara African countries and their emigrants in Europe and the New World. Genet Med. 2005;7:175-84 pubmedTo determine the frequencies of the protease inhibitor (PI) deficiency alleles of alpha1-antitrypsin deficiency (AAT Deficiency) in indigenous populations in 12 countries in Sub-Sahara Africa because of their potential impact on the ..
- Fischer H, Ortiz Pallardo M, Ko Y, Esch C, Zhou H. Chronic liver disease in heterozygous alpha1-antitrypsin deficiency PiZ. J Hepatol. 2000;33:883-92 pubmed..It can aggravate or can be aggravated by advanced coexistent chronic liver diseases. PiZ immunohistochemistry is an easy, highly specific method to detect this metabolic defect on liver biopsies. ..
- Fra A, Gooptu B, Ferrarotti I, Miranda E, Scabini R, Ronzoni R, et al. Three new alpha1-antitrypsin deficiency variants help to define a C-terminal region regulating conformational change and polymerization. PLoS ONE. 2012;7:e38405 pubmed publisherAlpha1-antitrypsin (AAT) deficiency is a hereditary disorder associated with reduced AAT plasma levels, predisposing adults to pulmonary emphysema...
- Jardi R, Rodriguez F, Miravitlles M, Vidal R, Cotrina M, Quer J, et al. Identification and molecular characterization of the new alpha-1-antitrypsin deficient allele PI Y barcelona (Asp256-->Val and Pro391-->His). Mutations in brief no. 174. Online. Hum Mutat. 1998;12:213 pubmedTo characterize the molecular basis of the "new" alpha1-antitrypsin (alpha1AT) deficient variant, PI Y barcelona, DNA sequence analysis of the coding exons of the alpha1AT gene was carried out using an amplification DNA ..
- Winkler I, Hendy J, Coughlin P, Horvath A, Levesque J. Serine protease inhibitors serpina1 and serpina3 are down-regulated in bone marrow during hematopoietic progenitor mobilization. J Exp Med. 2005;201:1077-88 pubmed..activity of these neutrophil serine proteases is regulated by the expression of naturally occurring inhibitors (serpina1 and serpina3) produced locally within the bone marrow...
- Thun G, Ferrarotti I, Imboden M, Rochat T, Gerbase M, Kronenberg F, et al. SERPINA1 PiZ and PiS heterozygotes and lung function decline in the SAPALDIA cohort. PLoS ONE. 2012;7:e42728 pubmed publisher..The SAPALDIA population includes over 4600 subjects from whom SERPINA1 genotypes for S and Z alleles, spirometry and respiratory symptoms at baseline and after 11 years follow-up, as ..
- Carroll T, Greene C, O Connor C, Nolan A, O Neill S, McElvaney N. Evidence for unfolded protein response activation in monocytes from individuals with alpha-1 antitrypsin deficiency. J Immunol. 2010;184:4538-46 pubmed publisherThe hereditary disorder alpha-1 antitrypsin (AAT) deficiency results from mutations in the SERPINA1 gene and presents with emphysema in young adults and liver disease in childhood...
- Elliott P, Abrahams J, Lomas D. Wild-type alpha 1-antitrypsin is in the canonical inhibitory conformation. J Mol Biol. 1998;275:419-25 pubmed..This pocket may provide a target for rational drug design to prevent the formation of polymers and the associated plasma deficiency, liver cirrhosis and emphysema. ..
- Sørheim I, Bakke P, Gulsvik A, Pillai S, Johannessen A, Gaarder P, et al. α₁-Antitrypsin protease inhibitor MZ heterozygosity is associated with airflow obstruction in two large cohorts. Chest. 2010;138:1125-32 pubmed publisher..Our results suggest that PI MZ individuals may be slightly more susceptible to the development of airflow obstruction than PI MM individuals. ..
- Lomas D, Lourbakos A, Cumming S, Belorgey D. Hypersensitive mousetraps, alpha1-antitrypsin deficiency and dementia. Biochem Soc Trans. 2002;30:89-92 pubmed..This must now be achieved in vivo if we are to treat the associated clinical syndromes. ..
- Xie L, Zhao C, Cai S, Xu Y, Huang L, Bian J, et al. Novel proteomic strategy reveal combined alpha1 antitrypsin and cathepsin D as biomarkers for colorectal cancer early screening. J Proteome Res. 2010;9:4701-9 pubmed publisher..Two glycol-proteins, alpha1 antitrypsin (A1AT) and cathepsin D (CTSD), which play central role in proteasome regulation, were further examined due to their ..
- Graham A, Kalsheker N, Bamforth F, Newton C, Markham A. Molecular characterisation of two alpha-1-antitrypsin deficiency variants: proteinase inhibitor (Pi) Null(Newport) (Gly115----Ser) and (Pi) Z Wrexham (Ser-19----Leu). Hum Genet. 1990;85:537-40 pubmedTwo single point mutations in the alpha-1-antitrypsin gene, resulting in AAT deficiency, have been characterised in heterozygotes by DNA amplification and direct sequencing...
- de Serres F, Blanco I, Fernandez Bustillo E. Genetic epidemiology of alpha-1 antitrypsin deficiency in southern Europe: France, Italy, Portugal and Spain. Clin Genet. 2003;63:490-509 pubmedAlpha-1-antitrypsin deficiency (AAT deficiency) is one of the most common serious hereditary disorders in the world because it affects all major racial subgroups worldwide and there are at least 120...
- Fregonese L, Stolk J, Frants R, Veldhuisen B. Alpha-1 antitrypsin Null mutations and severity of emphysema. Respir Med. 2008;102:876-84 pubmed publisherAlpha-1 antitrypsin (AAT) deficiency is an autosomal-codominant disorder, caused by mutations in the SERPINA1 gene on chromosome 14...
- Pei D, Majmudar G, Weiss S. Hydrolytic inactivation of a breast carcinoma cell-derived serpin by human stromelysin-3. J Biol Chem. 1994;269:25849-55 pubmed
- Hamrita B, Chahed K, Trimeche M, Guillier C, Hammann P, Chaieb A, et al. Proteomics-based identification of alpha1-antitrypsin and haptoglobin precursors as novel serum markers in infiltrating ductal breast carcinomas. Clin Chim Acta. 2009;404:111-8 pubmed publisher..These proteins may constitute new and useful markers of breast cancer that offer a clue to a better understanding of inflammatory pathways and carcinogenesis events linked to breast cancer progression. ..
- de Serres F, Blanco I, Fernandez Bustillo E. PI S and PI Z alpha-1 antitrypsin deficiency worldwide. A review of existing genetic epidemiological data. Monaldi Arch Chest Dis. 2007;67:184-208 pubmedb>AAT deficiency is not a rare disease, but one of the most common congenital disorders increasing susceptibility of deficiency individuals to both lung and liver disease as well as other several adverse health effects...
- Elliott P, Pei X, Dafforn T, Lomas D. Topography of a 2.0 A structure of alpha1-antitrypsin reveals targets for rational drug design to prevent conformational disease. Protein Sci. 2000;9:1274-81 pubmed..This structure allows us to define five cavities that are potential targets for rational drug design to develop agents that will prevent conformational transitions and ameliorate the associated disease. ..
- Kok K, van Soest H, van Herwaarden A, van Oijen M, Boland G, Halangk J, et al. Influence of alpha-1 antitrypsin heterozygosity on treatment efficacy of HCV combination therapy. Eur J Gastroenterol Hepatol. 2010;22:808-12 pubmed publisherThe role of heterozygosity for alpha-1 antitrypsin (A1AT) alleles in patients with chronic hepatitis C virus (HCV) is unclear...
- Wadsworth M, Vinall L, Jones A, Hardy R, Whitehouse D, Butterworth S, et al. Alpha1-antitrypsin as a risk for infant and adult respiratory outcomes in a national birth cohort. Am J Respir Cell Mol Biol. 2004;31:559-64 pubmedReduced alpha1-antitrypsin (AAT) encoded by the gene SERPINA1 is a potential risk for pulmonary disease...
- Dahl M, Tybjaerg Hansen A, Lange P, Vestbo J, Nordestgaard B. Change in lung function and morbidity from chronic obstructive pulmonary disease in alpha1-antitrypsin MZ heterozygotes: A longitudinal study of the general population. Ann Intern Med. 2002;136:270-9 pubmed..In the population at large, MZ heterozygosity may account for a fraction of COPD cases---on the order of 2%, similar to the percentage of persons with COPD who have the severe but rare ZZ genotype. ..
- Kalsheker N, Morley S, Morgan K. Gene regulation of the serine proteinase inhibitors alpha1-antitrypsin and alpha1-antichymotrypsin. Biochem Soc Trans. 2002;30:93-8 pubmed..The most abundant serpins in human plasma are alpha(1)-antitrypsin (AAT) and alpha(1)-antichymotrypsin (ACT)...
- Im H, Woo M, Hwang K, Yu M. Interactions causing the kinetic trap in serpin protein folding. J Biol Chem. 2002;277:46347-54 pubmed..Mutational analyses suggest strongly that interactions not found in the final stable form cause the kinetic trap in serpin protein folding. ..
- Lomas D, Mahadeva R. Alpha1-antitrypsin polymerization and the serpinopathies: pathobiology and prospects for therapy. J Clin Invest. 2002;110:1585-90 pubmed
- Devlin G, Chow M, Howlett G, Bottomley S. Acid Denaturation of alpha1-antitrypsin: characterization of a novel mechanism of serpin polymerization. J Mol Biol. 2002;324:859-70 pubmed..However, they more closely resemble those formed by the pathological variant M(malton). Taken together, these data describe a novel kinetic mechanism of serine proteinase inhibitor polymerization. ..
- Okayama H, Brantly M, Holmes M, Crystal R. Characterization of the molecular basis of the alpha 1-antitrypsin F allele. Am J Hum Genet. 1991;48:1154-8 pubmed
- Cameron P, Chevet E, Pluquet O, Thomas D, Bergeron J. Calnexin phosphorylation attenuates the release of partially misfolded alpha1-antitrypsin to the secretory pathway. J Biol Chem. 2009;284:34570-9 pubmed publisher..This is the first report in which the phosphorylation of calnexin is linked to the efficiency of secretion of a cargo glycoprotein. ..
- Yamasaki M, Sendall T, Harris L, Lewis G, Huntington J. Loop-sheet mechanism of serpin polymerization tested by reactive center loop mutations. J Biol Chem. 2010;285:30752-8 pubmed publisher..These results argue strongly against the loop-sheet hypothesis and suggest that, in serpin polymers, the P8-P6 region is only a small part of an extensive domain swap. ..
- Chappell S, Hadzic N, Stockley R, Guetta Baranes T, Morgan K, Kalsheker N. A polymorphism of the alpha1-antitrypsin gene represents a risk factor for liver disease. Hepatology. 2008;47:127-32 pubmed..of abnormally folded protein in hepatocytes, the principal producers of circulating alpha(1)-antitrypsin (AAT)...
- Hayes V, Gardiner Garden M. Are polymorphic markers within the alpha-1-antitrypsin gene associated with risk of human immunodeficiency virus disease?. J Infect Dis. 2003;188:1205-8 pubmed..to determine whether variants of the human alpha-1-antitrypsin (AAT) gene, also known as "PI," or "SERPINA1," are associated with human immunodeficiency virus (HIV) infection in 2 African-based populations from HIV-..
- Perlmutter D. Liver injury in alpha1-antitrypsin deficiency: an aggregated protein induces mitochondrial injury. J Clin Invest. 2002;110:1579-83 pubmed
- Mahadeva R, Dafforn T, Carrell R, Lomas D. 6-mer peptide selectively anneals to a pathogenic serpin conformation and blocks polymerization. Implications for the prevention of Z alpha(1)-antitrypsin-related cirrhosis. J Biol Chem. 2002;277:6771-4 pubmed..Furthermore they demonstrate how a conformational disease process can be selectively inhibited with a small peptide. ..
- Chappell S, Daly L, Morgan K, Guetta Baranes T, Roca J, Rabinovich R, et al. Cryptic haplotypes of SERPINA1 confer susceptibility to chronic obstructive pulmonary disease. Hum Mutat. 2006;27:103-9 pubmed..The most widely recognized candidate gene in COPD is SERPINA1, although it has been suggested that SERPINA3 may also play a role...
- Seo E, Lee C, Yu M. Concerted regulation of inhibitory activity of alpha 1-antitrypsin by the native strain distributed throughout the molecule. J Biol Chem. 2002;277:14216-20 pubmed..The results suggest that the native strain of alpha(1)-antitrypsin distributed throughout the molecule regulates the inhibitory function in a concerted manner. ..
- Wang Y, He Y, Abraham B, Rouhani F, Brantly M, Scott D, et al. Cytosolic, autocrine alpha-1 proteinase inhibitor (A1PI) inhibits caspase-1 and blocks IL-1? dependent cytokine release in monocytes. PLoS ONE. 2012;7:e51078 pubmed publisher..Therapeutic approaches which limit inflammasome responses in patients with A1PI deficiency, in combination with A1PI augmentation, may provide additional respiratory tissue-sparing benefits. ..
- Bergin D, Reeves E, Meleady P, Henry M, McElvaney O, Carroll T, et al. ?-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8. J Clin Invest. 2010;120:4236-50 pubmed publisherHereditary deficiency of the protein ?-1 antitrypsin (AAT) causes a chronic lung disease in humans that is characterized by excessive mobilization of neutrophils into the lung...
- Salahuddin P. Genetic variants of alpha1-antitrypsin. Curr Protein Pept Sci. 2010;11:101-17 pubmed..The examples of some of the null variants are QOcardiff, QOhong kong, QOgranite falls, QObellingham, QOmattawa, QObolton, and QOludwigshafen. The molecular basis of deficiency of these variants also forms the theme of this review. ..
- Lomas D. Molecular mousetraps, alpha1-antitrypsin deficiency and the serpinopathies. Clin Med (Lond). 2005;5:249-57 pubmed..In view of the common mechanism underlying these conditions, we have grouped them together as the serpinopathies. ..
- Hidvegi T, Schmidt B, Hale P, Perlmutter D. Accumulation of mutant alpha1-antitrypsin Z in the endoplasmic reticulum activates caspases-4 and -12, NFkappaB, and BAP31 but not the unfolded protein response. J Biol Chem. 2005;280:39002-15 pubmedIn alpha(1)-antitrypsin (alpha1AT) deficiency, a polymerogenic mutant form of the secretory glycoprotein alpha1AT, alpha1ATZ, is retained in the endoplasmic reticulum (ER) of liver cells...
- Yamasaki M, Li W, Johnson D, Huntington J. Crystal structure of a stable dimer reveals the molecular basis of serpin polymerization. Nature. 2008;455:1255-8 pubmed publisher..This structure explains the extreme stability of serpin polymers, the molecular basis of their rapid propagation, and provides critical new insights into the structural changes which initiate irreversible beta-sheet expansion. ..
- Kim M, Jung C, Im H. Characterization and suppression of dysfunctional human alpha1-antitrypsin variants. Biochem Biophys Res Commun. 2006;343:295-302 pubmed
- Settin A, El Bendary M, Abo Al Kassem R, El Baz R. Molecular analysis of A1AT (S and Z) and HFE (C282Y and H63D) gene mutations in Egyptian cases with HCV liver cirrhosis. J Gastrointestin Liver Dis. 2006;15:131-5 pubmedAlpha-1-antitrypsin (A1AT) S and Z deficiency alleles and hemochromatosis (HFE) mutant C282Y, H63D alleles were reported to potentially affect the liver even if present in a heterozygous state...
- Curiel D, Brantly M, Curiel E, Stier L, Crystal R. Alpha 1-antitrypsin deficiency caused by the alpha 1-antitrypsin Nullmattawa gene. An insertion mutation rendering the alpha 1-antitrypsin gene incapable of producing alpha 1-antitrypsin. J Clin Invest. 1989;83:1144-52 pubmed..The identification of the Nullmattawa gene supports the concept that Null alpha 1AT alleles represent a heterogenous group in which very different mechanisms cause the identical phenotypic state. ..
- Krishnan B, Gierasch L. Dynamic local unfolding in the serpin ?-1 antitrypsin provides a mechanism for loop insertion and polymerization. Nat Struct Mol Biol. 2011;18:222-6 pubmed publisher..Mutations in ??AT that cause polymerization-induced serpinopathies map to the labile region, suggesting that the evolution of serpin function required sampling of high risk conformations on a dynamic energy landscape. ..
- Li Y, Krowka M, Qi Y, Katzmann J, Song Y, Li Y, et al. Alpha1-antitrypsin deficiency carriers, serum alpha 1-antitrypsin concentration, and non-small cell lung cancer survival. J Thorac Oncol. 2011;6:291-5 pubmed publisher..44; 95% CI: 1.21-1.71). Being an ??ATD carrier had no significant effect on NSCLC survival. The increased serum ??AT concentration was a poor prognosis marker for NSCLC, regardless of carrier status. ..
- Knaupp A, Levina V, Robertson A, Pearce M, Bottomley S. Kinetic instability of the serpin Z alpha1-antitrypsin promotes aggregation. J Mol Biol. 2010;396:375-83 pubmed publisher..Kinetic analysis of the unfolding transition showed that Z alpha(1)AT unfolds at least 1.5-fold faster than the wild type. The biological implications of these data are discussed. ..
- Namciu S, Friedman R, Marsden M, Sarausad L, Jasoni C, Fournier R. Sequence organization and matrix attachment regions of the human serine protease inhibitor gene cluster at 14q32.1. Mamm Genome. 2004;15:162-78 pubmed..Several differences between the MAR-Wiz predictions and the results of biochemical tests were observed. The genomic organization of the serpin gene cluster is discussed. ..
- Normandin K, Péant B, Le Page C, de Ladurantaye M, Ouellet V, Tonin P, et al. Protease inhibitor SERPINA1 expression in epithelial ovarian cancer. Clin Exp Metastasis. 2010;27:55-69 pubmed publisher..b>SERPINA1 was selected for further study due to its high expression in the majority of LMP tumors and its low expression in ..
- Lindor N, Yang P, Evans I, Schowalter K, de Andrade M, Li J, et al. Alpha-1-antitrypsin deficiency and smoking as risk factors for mismatch repair deficient colorectal cancer: a study from the colon cancer family registry. Mol Genet Metab. 2010;99:157-9 pubmed publisherIn a previous study, alpha-1-antitrypsin (A1AT) deficiency alleles were found to be over represented among individuals with microsatellite unstable (MSI-high) colorectal cancers, and this was most significant in former or current smokers...
- Mahadeva R, Atkinson C, Li Z, Stewart S, Janciauskiene S, Kelley D, et al. Polymers of Z alpha1-antitrypsin co-localize with neutrophils in emphysematous alveoli and are chemotactic in vivo. Am J Pathol. 2005;166:377-86 pubmed..These findings may also explain the progression of emphysema in some individuals despite alpha(1)-antitrypsin replacement therapy. ..
- Dahl M, Hersh C, Ly N, Berkey C, Silverman E, Nordestgaard B. The protease inhibitor PI*S allele and COPD: a meta-analysis. Eur Respir J. 2005;26:67-76 pubmedIn many countries, the protease inhibitor (SERPINA1) PI*S allele is more common than PI*Z, the allele responsible for most cases of chronic obstructive pulmonary disease (COPD) due to severe alpha 1-antitrypsin deficiency...
- Ortiz Muñoz G, Houard X, Martin Ventura J, Ishida B, Loyau S, Rossignol P, et al. HDL antielastase activity prevents smooth muscle cell anoikis, a potential new antiatherogenic property. FASEB J. 2009;23:3129-39 pubmed publisher..Using mass spectrometry and Western blotting, we showed the presence of alpha(1)-antitrypsin (AAT) (SERPINA1, serpin peptidase inhibitor, clade A, an elastase inhibitor) in HDL, isolated either by ultracentrifugation or by ..
- Knappstein S, Ide T, Schmidt M, Heusipp G. Alpha 1-antitrypsin binds to and interferes with functionality of EspB from atypical and typical enteropathogenic Escherichia coli strains. Infect Immun. 2004;72:4344-50 pubmed..for putative host cell proteins interacting with EspB of atypical EPEC strains and identified alpha(1)-antitrypsin (AAT) as a binding partner for EspB...
- Hersh C, Dahl M, Ly N, Berkey C, Nordestgaard B, Silverman E. Chronic obstructive pulmonary disease in alpha1-antitrypsin PI MZ heterozygotes: a meta-analysis. Thorax. 2004;59:843-9 pubmed..Future studies that adjust for smoking and include other COPD related phenotypes are required to conclusively determine the risk of COPD in PI MZ heterozygotes. ..
- Rudnick D, Perlmutter D. Alpha-1-antitrypsin deficiency: a new paradigm for hepatocellular carcinoma in genetic liver disease. Hepatology. 2005;42:514-21 pubmedLiver disease in alpha-1-antitrypsin (alpha1AT) deficiency is caused by a gain-of-toxic function mechanism engendered by the accumulation of a mutant glycoprotein in the endoplasmic reticulum (ER)...
- Cichy J, Potempa J, Travis J. Biosynthesis of alpha1-proteinase inhibitor by human lung-derived epithelial cells. J Biol Chem. 1997;272:8250-5 pubmed
- Anderson E, Thomas L, Hayflick J, Thomas G. Inhibition of HIV-1 gp160-dependent membrane fusion by a furin-directed alpha 1-antitrypsin variant. J Biol Chem. 1993;268:24887-91 pubmed..The potential use of alpha 1-PDX in manipulating the activation of proproteins in a tissue- and time-specific manner is discussed. ..
- Long G, Chandra T, Woo S, Davie E, Kurachi K. Complete sequence of the cDNA for human alpha 1-antitrypsin and the gene for the S variant. Biochemistry. 1984;23:4828-37 pubmed
- Janciauskiene S, Nita I, Stevens T. Alpha1-antitrypsin, old dog, new tricks. Alpha1-antitrypsin exerts in vitro anti-inflammatory activity in human monocytes by elevating cAMP. J Biol Chem. 2007;282:8573-82 pubmed..Regulation of serine protease activity is considered to be the sole mechanism for the function of alpha1-antitrypsin (AAT)...
- Hayes V. Genetic diversity of the alpha-1-antitrypsin gene in Africans identified using a novel genotyping assay. Hum Mutat. 2003;22:59-66 pubmedThe highly polymorphic human alpha-1-antitrypsin (AAT) gene, more recently named SERPINA1, codes for the most abundant circulating plasma serine protease inhibitor, protease inhibitor 1 (PI)...
- Wu Y, Swulius M, Moremen K, Sifers R. Elucidation of the molecular logic by which misfolded alpha 1-antitrypsin is preferentially selected for degradation. Proc Natl Acad Sci U S A. 2003;100:8229-34 pubmed..For newly synthesized alpha1-antitrypsin (AAT), the modification of its asparagine-linked oligosaccharides by a slow-acting mannosidase partitions the misfolded ..
- Blanco I, de Serres F, Fernandez Bustillo E, Lara B, Miravitlles M. Estimated numbers and prevalence of PI*S and PI*Z alleles of alpha1-antitrypsin deficiency in European countries. Eur Respir J. 2006;27:77-84 pubmed..A remarkable lack in number of reliable epidemiological studies and marked differences among these European countries and regions within a given country was also found. ..
- Congote L. Serpin A1 and CD91 as host instruments against HIV-1 infection: are extracellular antiviral peptides acting as intracellular messengers?. Virus Res. 2007;125:119-34 pubmedb>Serpin A1 (alpha1-antitrypsin, alpha1-proteinase inhibitor) has been shown to be a non-cytolytic antiviral factor present in blood and effective against HIV infection...