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UniProtKB/Swiss-Prot entry P01009

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Entry information
Entry name A1AT_HUMAN
Primary accession number P01009
Secondary accession numbers A6PX14 Q0PVP5 Q13672 Q53XB8 Q5U0M1 Q7M4R2 Q86U18 Q86U19 Q96BF9 Q96ES1 Q9P1P0
Integrated into Swiss-Prot on July 21, 1986
Sequence was last modified on October 1, 1996 (Sequence version 3)
Annotations were last modified on    September 2, 2008 (Entry version 140)
Name and origin of the protein
Protein name Alpha-1-antitrypsin [Precursor]
Synonyms Alpha-1 protease inhibitor
Alpha-1-antiproteinase
Gene name
Name: SERPINA1
Synonyms: AAT, PI
ORFNames: PRO0684, PRO2209
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
 NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
PubMed=6319097 [NCBI, ExPASy, EBI, Israel, Japan]
Bollen A., Herzog A., Cravador A., Herion P., Chuchana P., van der Straten A., Loriau R., Jacobs P., van Elsen A.;
"Cloning and expression in Escherichia coli of full-length complementary DNA coding for human alpha 1-antitrypsin.";
DNA 2:255-264(1983).
[2]
 NUCLEOTIDE SEQUENCE [GENOMIC DNA].
DOI=10.1021/bi00316a003; PubMed=6093867 [NCBI, ExPASy, EBI, Israel, Japan]
Long G.L., Chandra T., Woo S.L.C., Davie E.W., Kurachi K.;
"Complete sequence of the cDNA for human alpha 1-antitrypsin and the gene for the S variant.";
Biochemistry 23:4828-4837(1984).
[3]
 NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND MUTAGENESIS OF MET-382.
DOI=10.1038/312077a0; PubMed=6387509 [NCBI, ExPASy, EBI, Israel, Japan]
Rosenberg S., Barr P.J., Najarian R.C., Hallewell R.A.;
"Synthesis in yeast of a functional oxidation-resistant mutant of human alpha-antitrypsin.";
Nature 312:77-80(1984).
[4]
 NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
DOI=10.1016/S0092-8674(85)80026-X; PubMed=2985281 [NCBI, ExPASy, EBI, Israel, Japan]
Ciliberto G., Dente L., Cortese R.;
"Cell-specific expression of a transfected human alpha 1-antitrypsin gene.";
Cell 41:531-540(1985).
[5]
 NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND CHARACTERIZATION OF VARIANT Z.
PubMed=3491072 [NCBI, ExPASy, EBI, Israel, Japan]
Nukiwa T., Satoh K., Brantly M.L., Ogushi F., Fells G.A., Courtney M., Crystal R.G.;
"Identification of a second mutation in the protein-coding sequence of the Z type alpha 1-antitrypsin gene.";
J. Biol. Chem. 261:15989-15994(1986).
[6]
 ERRATUM.
Nukiwa T., Satoh K., Brantly M.L., Ogushi F., Fells G.A., Courtney M., Crystal R.G.;
J. Biol. Chem. 262:10412-10412(1987).
[7]
 NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ALA-237 AND ASP-400.
TISSUE=Liver;
PubMed=17650587 [NCBI, ExPASy, EBI, Israel, Japan]
Shasany A.K., Shukla A.K., Darokar M.P., Saraiya M., Chaturvedi N., Tewari L., Khanuja S.P.;
"An alpha-1 antitrypsin genetic variant from India.";
Indian J. Biochem. Biophys. 44:176-178(2007).
[8]
 NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS TRP-172; ALA-237 AND LYS-366.
TISSUE=Lymphocyte;
Balduyck M., Porchet N., Aubert J.-P., Zerimech F., Douchain F., Verchain S.;
"Characterization of a new variant of alpha1 antitrypsin M Lille (p.Gly148Trp).";
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[9]
 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Fetal liver;
Zhang C., Yu Y., Zhang S., Ouyang S., Luo L., Wei H., Zhou G., Zhou W., Bi J., Zhang Y., Liu M., He F.;
"Functional prediction of the coding sequences of 32 new genes deduced by analysis of cDNA clones from human fetal liver.";
Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
[10]
 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
TISSUE=Fetal liver, and Placenta;
Li W.B., Gruber C., Jessee J., Polayes D.;
"Full-length cDNA libraries and normalization.";
Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
[11]
 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ALA-237.
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.;
"Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
[12]
 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Colon, and Ovary;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[13]
 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-67; 196-255 AND 387-418.
DOI=10.1038/297655a0; PubMed=6979715 [NCBI, ExPASy, EBI, Israel, Japan]
Leicht M., Long G.L., Chandra T., Kurachi K., Kidd V.J., Mace M. Jr., Davie E.W., Woo S.L.C.;
"Sequence homology and structural comparison between the chromosomal human alpha 1-antitrypsin and chicken ovalbumin genes.";
Nature 297:655-659(1982).
[14]
 PROTEIN SEQUENCE OF 25-418 (ISOFORM 1).
DOI=10.1038/298329a0; PubMed=7045697 [NCBI, ExPASy, EBI, Israel, Japan]
Carrell R.W., Jeppsson J.-O., Laurell C.-B., Brennan S.O., Owen M.C., Vaughan L., Boswell D.R.;
"Structure and variation of human alpha 1-antitrypsin.";
Nature 298:329-334(1982).
[15]
 PRELIMINARY PROTEIN SEQUENCE OF 25-418 (ISOFORM 1).
Chan S.K.;
"The covalent structure of human alpha1-protease inhibitor.";
Fed. Proc. 41:1016-1016(1982).
[16]
 PROTEIN SEQUENCE OF 25-418 (ISOFORM 1), VARIANTS ABERRANT FORM 190-GLY--ARG-198 AND VAL-288, AND FUNCTION.
TISSUE=Blood;
Sinha A.K., Girish G.V.;
"Appearance of an aberrant form of alpha-antitrypsin in the circulation of chronic cigarette smokers and its effect on the insulin induced NO synthesis in blood platelets.";
Submitted (AUG-2007) to UniProtKB.
[17]
 PROTEIN SEQUENCE OF 25-39, AND FUNCTION.
TISSUE=Ascites;
PubMed=1906855 [NCBI, ExPASy, EBI, Israel, Japan]
Tanaka N., Sekiya S., Takamizawa H., Kato N., Moriyama Y., Fujimura S.;
"Characterization of a 54 kDa, alpha 1-antitrypsin-like protein isolated from ascitic fluid of an endometrial cancer patient.";
Jpn. J. Cancer Res. 82:693-700(1991).
[18]
 PROTEIN SEQUENCE OF 30-48 AND 248-257 (ISOFORMS 1/2/3), GLYCOSYLATION AT ASN-70; ASN-107 AND ASN-271, STRUCTURE OF CARBOHYDRATES, CYSTEINE BINDING, AND MASS SPECTROMETRY.
DOI=10.1002/pmic.200500751; PubMed=16622833 [NCBI, ExPASy, EBI, Israel, Japan]
Kolarich D., Weber A., Turecek P.L., Schwarz H.P., Altmann F.;
"Comprehensive glyco-proteomic analysis of human alpha1-antitrypsin and its charge isoforms.";
Proteomics 6:3369-3380(2006).
[19]
 PROTEIN SEQUENCE OF 50-63 AND 161-178 (ISOFORMS 1/2/3), AND MASS SPECTROMETRY.
TISSUE=Brain, and Cajal-Retzius cell;
Lubec G., Afjehi-Sadat L.;
Submitted (MAR-2007) to UniProtKB.
[20]
 NUCLEOTIDE SEQUENCE [MRNA] OF 292-418 (ISOFORM 1).
DOI=10.1016/0014-5793(85)81056-5; PubMed=3876243 [NCBI, ExPASy, EBI, Israel, Japan]
Riley J.H., Bathurst I.C., Edbrooke M.R., Carrell R.W., Craig R.K.;
"Alpha 1-antitrypsin and serum albumin mRNA accumulation in normal, acute phase and ZZ human liver.";
FEBS Lett. 189:361-366(1985).
[21]
 NUCLEOTIDE SEQUENCE [MRNA] OF 350-418 (ISOFORM 1).
PubMed=7031661 [NCBI, ExPASy, EBI, Israel, Japan]
Kurachi K., Chandra T., Friezner Degen S.J., White T.T., Marchioro T.L., Woo S.L.C., Davie E.W.;
"Cloning and sequence of cDNA coding for alpha 1-antitrypsin.";
Proc. Natl. Acad. Sci. U.S.A. 78:6826-6830(1981).
[22]
 NUCLEOTIDE SEQUENCE [MRNA] OF 387-418 (ISOFORM 1).
PubMed=3873938 [NCBI, ExPASy, EBI, Israel, Japan]
Coutelle C., Speer A., Rogers J., Kalsheker N., Humphries S., Williamson R.;
"Construction and partial characterization of a human liver cDNA library.";
Biomed. Biochim. Acta 44:421-431(1985).
[23]
 GLYCOSYLATION AT ASN-70 AND ASN-271.
DOI=10.1038/nbt827; PubMed=12754519 [NCBI, ExPASy, EBI, Israel, Japan]
Zhang H., Li X.-J., Martin D.B., Aebersold R.;
"Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry.";
Nat. Biotechnol. 21:660-666(2003).
[24]
 GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-70 AND ASN-271, AND MASS SPECTROMETRY.
TISSUE=Bile;
DOI=10.1074/mcp.M400015-MCP200; PubMed=15084671 [NCBI, ExPASy, EBI, Israel, Japan]
Kristiansen T.Z., Bunkenborg J., Gronborg M., Molina H., Thuluvath P.J., Argani P., Goggins M.G., Maitra A., Pandey A.;
"A proteomic analysis of human bile.";
Mol. Cell. Proteomics 3:715-728(2004).
[25]
 GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-70 AND ASN-271, AND MASS SPECTROMETRY.
TISSUE=Plasma;
DOI=10.1002/pmic.200300556; PubMed=14760718 [NCBI, ExPASy, EBI, Israel, Japan]
Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.;
"Screening for N-glycosylated proteins by liquid chromatography mass spectrometry.";
Proteomics 4:454-465(2004).
[26]
 GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-70; ASN-107 AND ASN-271, AND MASS SPECTROMETRY.
TISSUE=Plasma;
DOI=10.1021/pr0502065; PubMed=16335952 [NCBI, ExPASy, EBI, Israel, Japan]
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.;
"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry.";
J. Proteome Res. 4:2070-2080(2005).
[27]
 GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-70, AND MASS SPECTROMETRY.
TISSUE=Platelet;
DOI=10.1074/mcp.M500324-MCP200; PubMed=16263699 [NCBI, ExPASy, EBI, Israel, Japan]
Lewandrowski U., Moebius J., Walter U., Sickmann A.;
"Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach.";
Mol. Cell. Proteomics 5:226-233(2006).
[28]
 X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
DOI=10.1016/0022-2836(84)90298-5; PubMed=6332197 [NCBI, ExPASy, EBI, Israel, Japan]
Loebermann H., Tokuoka R., Deisenhofer J., Huber R.;
"Human alpha 1-proteinase inhibitor. Crystal structure analysis of two crystal modifications, molecular model and preliminary analysis of the implications for function.";
J. Mol. Biol. 177:531-556(1984).
[29]
 X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
DOI=10.1093/protein/2.6.407; PubMed=2785270 [NCBI, ExPASy, EBI, Israel, Japan]
Engh R., Loebermann H., Schneider M., Wiegand G., Huber R., Laurell C.-B.;
"The S variant of human alpha 1-antitrypsin, structure and implications for function and metabolism.";
Protein Eng. 2:407-415(1989).
[30]
 X-RAY CRYSTALLOGRAPHY (3.46 ANGSTROMS) OF 25-418.
DOI=10.1016/0014-5793(95)01331-8; PubMed=8543039 [NCBI, ExPASy, EBI, Israel, Japan]
Song H.K., Lee K.N., Kwon K.-S., Yu M.-H., Suh S.W.;
"Crystal structure of an uncleaved alpha 1-antitrypsin reveals the conformation of its inhibitory reactive loop.";
FEBS Lett. 377:150-154(1995).
[31]
 X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 26-418.
DOI=10.1038/nsb0896-676; PubMed=8756325 [NCBI, ExPASy, EBI, Israel, Japan]
Elliott P.R., Lomas D.A., Carrell R.W., Abrahams J.P.;
"Inhibitory conformation of the reactive loop of alpha 1-antitrypsin.";
Nat. Struct. Biol. 3:676-681(1996).
[32]
 X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 45-418.
DOI=10.1016/S0969-2126(96)00126-8; PubMed=8939743 [NCBI, ExPASy, EBI, Israel, Japan]
Ryu S.-E., Choi H.-J., Kwon K.-S., Lee K.N., Yu M.-H.;
"The native strains in the hydrophobic core and flexible reactive loop of a serine protease inhibitor: crystal structure of an uncleaved alpha1-antitrypsin at 2.7 A.";
Structure 4:1181-1192(1996).
[33]
 X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 26-418.
DOI=10.1006/jmbi.1997.1458; PubMed=9466920 [NCBI, ExPASy, EBI, Israel, Japan]
Elliott P.R., Abrahams J.P., Lomas D.A.;
"Wild-type alpha 1-antitrypsin is in the canonical inhibitory conformation.";
J. Mol. Biol. 275:419-425(1998).
[34]
 X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 48-418 IN COMPLEX WITH BOVINE TRYPSIN.
DOI=10.1038/35038119; PubMed=11057674 [NCBI, ExPASy, EBI, Israel, Japan]
Huntington J.A., Read R.J., Carrell R.W.;
"Structure of a serpin-protease complex shows inhibition by deformation.";
Nature 407:923-926(2000).
[35]
 X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 44-418.
PubMed=10716194 [NCBI, ExPASy, EBI, Israel, Japan]
Dunstone M.A., Dai W., Whisstock J.C., Rossjohn J., Pike R.N., Feil S.C., Le Bonniec B.F., Parker M.W., Bottomley S.P.;
"Cleaved antitrypsin polymers at atomic resolution.";
Protein Sci. 9:417-420(2000).
[36]
 X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
PubMed=10933492 [NCBI, ExPASy, EBI, Israel, Japan]
Elliott P.R., Pei X.Y., Dafforn T.R., Lomas D.A.;
"Topography of a 2.0 A structure of alpha1-antitrypsin reveals targets for rational drug design to prevent conformational disease.";
Protein Sci. 9:1274-1281(2000).
[37]
 X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 25-418.
DOI=10.1006/jmbi.2000.4357; PubMed=11178897 [NCBI, ExPASy, EBI, Israel, Japan]
Kim S.-J., Woo J.-R., Seo E.J., Yu M.-H., Ryu S.-E.;
"A 2.1 A resolution structure of an uncleaved alpha(1)-antitrypsin shows variability of the reactive center and other loops.";
J. Mol. Biol. 306:109-119(2001).
[38]
 X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 25-418.
DOI=10.1074/jbc.M207682200; PubMed=12244055 [NCBI, ExPASy, EBI, Israel, Japan]
Im H., Woo M.-S., Hwang K.Y., Yu M.-H.;
"Interactions causing the kinetic trap in serpin protein folding.";
J. Biol. Chem. 277:46347-46354(2002).
[39]
 X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 26-418 OF VARIANT PITTSBURGH ARG-382.
DOI=10.1074/jbc.M305195200; PubMed=12860985 [NCBI, ExPASy, EBI, Israel, Japan]
Dementiev A., Simonovic M., Volz K., Gettins P.G.;
"Canonical inhibitor-like interactions explain reactivity of alpha1-proteinase inhibitor Pittsburgh and antithrombin with proteinases.";
J. Biol. Chem. 278:37881-37887(2003).
[40]
 REVIEW.
DOI=10.1007/BF01115992; PubMed=2669992 [NCBI, ExPASy, EBI, Israel, Japan]
Kalsheker N.;
"Alpha 1-antitrypsin: structure, function and molecular biology of the gene.";
Biosci. Rep. 9:129-138(1989).
[41]
 REVIEW.
PubMed=1859394 [NCBI, ExPASy, EBI, Israel, Japan]
Wu Y., Foreman R.C.;
"The molecular genetics of alpha 1 antitrypsin deficiency.";
Bioessays 13:163-169(1991).
[42]
 CHARACTERIZATION OF VARIANT M2.
PubMed=2901226 [NCBI, ExPASy, EBI, Israel, Japan]
Nukiwa T., Brantly M.L., Ogushi F., Fells G.A., Crystal R.G.;
"Characterization of the gene and protein of the common alpha 1-antitrypsin normal M2 allele.";
Am. J. Hum. Genet. 43:322-330(1988).
[43]
 VARIANT M3 ASP-400.
DOI=10.1007/BF00206766; PubMed=2394452 [NCBI, ExPASy, EBI, Israel, Japan]
Graham A., Hayes K., Weidinger S., Newton C.R., Markham A.F., Kalsheker N.A.;
"Characterisation of the alpha-1-antitrypsin M3 gene, a normal variant.";
Hum. Genet. 85:381-382(1990).
[44]
 VARIANT F CYS-247.
PubMed=2035534 [NCBI, ExPASy, EBI, Israel, Japan]
Okayama H., Brantly M., Holmes M., Crystal R.G.;
"Characterization of the molecular basis of the alpha 1-antitrypsin F allele.";
Am. J. Hum. Genet. 48:1154-1158(1991).
[45]
 VARIANT M-HEERLEN LEU-393.
DOI=10.1007/BF00279001; PubMed=2784123 [NCBI, ExPASy, EBI, Israel, Japan]
Hofker M.H., Nukiwa T., van Paassen H.M.B., Nelen M., Kramps J.A., Klasen E.C., Frants R.R., Crystal R.G.;
"A Pro-->Leu substitution in codon 369 of the alpha-1-antitrypsin deficiency variant PI M-Heerlen.";
Hum. Genet. 81:264-268(1989).
[46]
 VARIANT M-MALTON PHE-75 DEL.
PubMed=2786335 [NCBI, ExPASy, EBI, Israel, Japan]
Fraizer G.C., Harrold T.R., Hofker M.H., Cox D.W.;
"In-frame single codon deletion in the M-Malton deficiency allele of alpha 1-antitrypsin.";
Am. J. Hum. Genet. 44:894-902(1989).
[47]
 VARIANT M-MINERAL SPRINGS GLU-91.
PubMed=1967187 [NCBI, ExPASy, EBI, Israel, Japan]
Curiel D.T., Vogelmeier C., Hubbard R.C., Stier L.E., Crystal R.G.;
"Molecular basis of alpha 1-antitrypsin deficiency and emphysema associated with the alpha 1-antitrypsin M-Mineral springs allele.";
Mol. Cell. Biol. 10:47-56(1990).
[48]
 VARIANT M-NICHINAN PHE-75 DEL.
PubMed=2309708 [NCBI, ExPASy, EBI, Israel, Japan]
Matsunaga E., Shiokawa S., Nakamura H., Maruyama T., Tsuda K., Fukumaki Y.;
"Molecular analysis of the gene of the alpha 1-antitrypsin deficiency variant, M-Nichinan.";
Am. J. Hum. Genet. 46:602-612(1990).
[49]
 VARIANT M-PROCIDA PRO-65.
PubMed=3262617 [NCBI, ExPASy, EBI, Israel, Japan]
Takahashi H., Nukiwa T., Satoh K., Ogushi F., Brantly M., Fells G., Stier L., Courtney M., Crystal R.G.;
"Characterization of the gene and protein of the alpha 1-antitrypsin 'deficiency' allele M-Procida.";
J. Biol. Chem. 263:15528-15534(1988).
[50]
 VARIANT P-DUARTE VAL-280.
PubMed=8364590 [NCBI, ExPASy, EBI, Israel, Japan]
Hildesheim J., Kinsley G., Bissell M., Pierce J., Brantly M.;
"Genetic diversity from a limited repertoire of mutations on different common allelic backgrounds: alpha 1-antitrypsin deficiency variant P-Duarte.";
Hum. Mutat. 2:221-228(1993).
[51]
 VARIANT PITTSBURGH ARG-382.
PubMed=6604220 [NCBI, ExPASy, EBI, Israel, Japan]
Owen M.C., Brennan S.O., Lewis J.H., Carrell R.W.;
"Mutation of antitrypsin to antithrombin. Alpha 1-antitrypsin Pittsburgh (358 Met leads to Arg), a fatal bleeding disorder.";
N. Engl. J. Med. 309:694-698(1983).
[52]
 VARIANT S-IIYAMA PHE-77.
PubMed=1905728 [NCBI, ExPASy, EBI, Israel, Japan]
Seyama K., Nukiwa T., Takabe K., Takahashi H., Miyake K., Kira S.;
"Siiyama (serine 53 (TCC) to phenylalanine 53 (TTC)). A new alpha 1-antitrypsin-deficient variant with mutation on a predicted conserved residue of the serpin backbone.";
J. Biol. Chem. 266:12627-12632(1991).
[53]
 VARIANT V-MUNICH ALA-26.
PubMed=2316526 [NCBI, ExPASy, EBI, Israel, Japan]
Holmes M.D., Brantly M.L., Curiel D.T., Weidinger S., Crystal R.G.;
"Characterization of the normal alpha 1-antitrypsin allele V-Munich: a variant associated with a unique protein isoelectric focusing pattern.";
Am. J. Hum. Genet. 46:810-816(1990).
[54]
 VARIANT W-BETHESDA THR-360.
DOI=10.1016/0006-291X(90)90493-7; PubMed=2390072 [NCBI, ExPASy, EBI, Israel, Japan]
Holmes M.D., Brantly M.L., Fells G.A., Crystal R.G.;
"Alpha 1-antitrypsin W-Bethesda: molecular basis of an unusual alpha 1-antitrypsin deficiency variant.";
Biochem. Biophys. Res. Commun. 170:1013-1020(1990).
[55]
 VARIANT Z-AUGSBURG LYS-366.
PubMed=2339709 [NCBI, ExPASy, EBI, Israel, Japan]
Faber J.-P., Weidinger S., Olek K.;
"Sequence data of the rare deficient alpha 1-antitrypsin variant PI Zaugsburg.";
Am. J. Hum. Genet. 46:1158-1162(1990).
[56]
 VARIANTS Z-WREXHAM LEU-4 AND Q0-NEWPORT SER-139.
DOI=10.1007/BF00194233; PubMed=2227940 [NCBI, ExPASy, EBI, Israel, Japan]
Graham A., Kalsheker N.A., Bamforth F.J., Newton C.R., Markham A.F.;
"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. 85:537-540(1990).
[57]
 VARIANTS P-CARDIFF VAL-280; I CYS-63 AND M-MALTON PHE-75 DEL.
DOI=10.1007/BF00210671; PubMed=2606478 [NCBI, ExPASy, EBI, Israel, Japan]
Graham A., Kalsheker N.A., Newton C.R., Bamforth F.J., Powell S.J., Markham A.F.;
"Molecular characterisation of three alpha-1-antitrypsin deficiency variants: proteinase inhibitor (Pi) nullcardiff (Asp256-->Val); PiM-Malton (Phe51-->deletion) and PiI (Arg39-->Cys).";
Hum. Genet. 84:55-58(1989).
[58]
 VARIANT QO-LUDWIGSHAFEN ASN-116.
PubMed=2254451 [NCBI, ExPASy, EBI, Israel, Japan]
Fraizer G.C., Siewertsen M.A., Hofker M.H., Brubacher M.G., Cox D.W.;
"A null deficiency allele of alpha 1-antitrypsin, QO-Ludwigshafen, with altered tertiary structure.";
J. Clin. Invest. 86:1878-1884(1990).
[59]
 VARIANTS.
PubMed=7977369 [NCBI, ExPASy, EBI, Israel, Japan]
Faber J.-P., Poller W., Weidinger S., Kirchgesser M., Schwaab R., Bidlingmaier F., Olek K.;
"Identification and DNA sequence analysis of 15 new alpha 1-antitrypsin variants, including two PI*Q0 alleles and one deficient PI*M allele.";
Am. J. Hum. Genet. 55:1113-1121(1994).
[60]
 VARIANT Z-BRISTOL MET-109.
PubMed=9459000 [NCBI, ExPASy, EBI, Israel, Japan]
Lovegrove J.U., Jeremiah S., Gillett G.T., Temple I.K., Povey S., Whitehouse D.B.;
"A new alpha 1-antitrypsin mutation, Thr-Met 85, (PI ZBristol) associated with novel electrophoretic properties.";
Ann. Hum. Genet. 61:385-391(1997).
[61]
 VARIANTS Y-BARCELONA VAL-280 AND HIS-415.
PubMed=10651487 [NCBI, ExPASy, EBI, Israel, Japan]
Jardi R., Rodriguez F., Miravitlles M., Vidal R., Cotrina M., Quer J., Pascual C., Weidinger S.;
"Identification and molecular charaterization of the new alpha-1-antitrypsin deficient allele PI YBarcelona (Asp256Val and Pro391His).";
Hum. Mutat. 12:213-213(1998).
[62]
 VARIANT SAO TOME HIS-386.
Seixas S., Trovoada M.J., Santos M.T., Rocha J.;
"A novel alpha-1-antitrypsin P362H variant found in a population sample from Sao Tome e Principe (Gulf of Guinea, West Africa).";
Hum. Mutat. 13:414-414(1999).
[63]
 VARIANT BASQUE ARG-305 DEL.
DOI=10.1002/(SICI)1098-1004(200001)15:1<121::AID-HUMU37>3.0.CO;2-U; PubMed=10612848 [NCBI, ExPASy, EBI, Israel, Japan]
Seixas S., Garcia O., Amorim A., Rocha J.;
"A novel alpha-1-antitrypsin r281del variant found in a population sample from the Basque country.";
Hum. Mutat. 15:121-122(2000).
Comments
  • FUNCTION: Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Inhibits trypsin, chymotrypsin and plasminogen activator. The aberrant form inhibits insulin-induced NO synthesis in platelets, decreases coagulation time and has proteolytic activity against insulin and plasmin.
  • INTERACTION:
    P00760:- (xeno); NbExp=1; IntAct=EBI-986224, EBI-986385;
    P00772:ELA1 (xeno); NbExp=1; IntAct=EBI-986224, EBI-986248;
  • SUBCELLULAR LOCATION: Secreted.
  • ALTERNATIVE PRODUCTS: 3 named isoforms [FASTA] produced by alternative splicing.
    Name1
    Isoform IDP01009-1
    This is the isoform sequence displayed in this entry.
    Name2
    Isoform IDP01009-2
    Note: No experimental confirmation available.
    Features which should be applied to build the isoform sequence: VSP_028889.
    Name3
    Isoform IDP01009-3
    Note: No experimental confirmation available.
    Features which should be applied to build the isoform sequence: VSP_028890.
  • TISSUE SPECIFICITY: Plasma.
  • DOMAIN: The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable.
  • PTM: Several isomers are observed, resulting from the combination of different N-linked glycan structures and mature N-terminus. N-linked glycan at Asn-107 is alternatively di-antennary, tri-antennary or tetra-antennary, whereas glycan at Asn-70 is di-antennary with trace amounts of tri-antennary, and glycan at Asn-271 is exclusively di-antennary. The structure of the antennas is Neu5Ac(alpha1-6)Gal(beta1-4)GlcNAc attached to the core structure Man(alpha1-6)[Man(alpha1-3)]Man(beta1-4)GlcNAc(beta1-4)GlcNAc. Some antennas are fucosylated, which forms a Lewis-X determinant.
  • PTM: Proteolytic processing may yield the truncated form that ranges from Asp-30 to Lys-418.
  • POLYMORPHISM: The sequence shown is that of the M1V allele which is the most common form of PI (44 to 49%). Other frequent alleles are: M1A 20 to 23%; M2 10 to 11%; M3 14 to 19%.
  • DISEASE: The major physiological function of AAT is the protection of the lower respiratory tract against proteolytic destruction by human leukocyte elastase (HLE). A hereditary deficiency of AAT, is associated with a 20-30 fold increased risk of developing chronic obstructive pulmonary disease.
  • DISEASE: Deficiency of the normal inhibitor in individuals homozygous for allele Z or M-Malton can result in the development of chronic emphysema or infantile liver cirrhosis.
  • DISEASE: Variant Pittsburgh is the cause of bleeding diathesis.
  • MISCELLANEOUS: The aberrant form is found in the plasma of chronic smokers, and persists after smoking is ceased. It can still be found ten years after smoking has ceased.
  • SIMILARITY: Belongs to the serpin family.
  • WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=SERPINA1";.
  • WEB RESOURCE: Name=Wikipedia; Note=Alpha-1 antitrypsin entry; URL="http://en.wikipedia.org/wiki/Alpha_1-antitrypsin";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
K01396; AAB59375.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
K02212; AAB59495.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X01683; CAA25838.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M11465; AAA51546.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
J02619; AAA51547.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
DQ682455; ABG73380.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AM048838; CAJ15161.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF113676; AAF29581.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF130068; AAG35496.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BX161449; CAD61914.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BX247968; CAD62306.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BX248002; CAD62334.1; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BX248257; CAD62585.1; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BT019455; AAV38262.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC011991; AAH11991.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC015642; AAH15642.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
J00064; AAB59369.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
J00066; AAB59370.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
J00065; AAB59370.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
J00067; AAB59371.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X02920; CAA26677.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
V00496; CAA23755.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26123; AAA51545.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A21853; ITHU.
A61391; A61391.
RefSeq NP_000286.3; -.
NP_001002235.1; -.
NP_001002236.1; -.
NP_001121172.1; -.
NP_001121173.1; -.
NP_001121174.1; -.
NP_001121175.1; -.
NP_001121176.1; -.
NP_001121177.1; -.
NP_001121178.1; -.
NP_001121179.1; -.
UniGene Hs.525557
3D structure databases
PDB
1ATU; X-ray; 2.70 A; A=45-418.[ExPASy / RCSB / EBI]
1D5S; X-ray; 3.00 A; A=44-377, B=378-418.[ExPASy / RCSB / EBI]
1EZX; X-ray; 2.60 A; A=48-382, B=383-418.[ExPASy / RCSB / EBI]
1HP7; X-ray; 2.10 A; A=25-418.[ExPASy / RCSB / EBI]
1IZ2; X-ray; 2.20 A; A=25-418.[ExPASy / RCSB / EBI]
1KCT; X-ray; 3.46 A; A=25-418.[ExPASy / RCSB / EBI]
1OO8; X-ray; 2.65 A; A=26-418.[ExPASy / RCSB / EBI]
1OPH; X-ray; 2.30 A; A=26-418.[ExPASy / RCSB / EBI]
1PSI; X-ray; 2.92 A; A=26-418.[ExPASy / RCSB / EBI]
1QLP; X-ray; 2.00 A; A=26-418.[ExPASy / RCSB / EBI]
1QMB; X-ray; 2.60 A; A=49-376, B=377-418.[ExPASy / RCSB / EBI]
2D26; X-ray; 3.30 A; A=26-382, B=383-418.[ExPASy / RCSB / EBI]
7API; X-ray; 3.00 A; A=36-382, B=383-418.[ExPASy / RCSB / EBI]
8API; X-ray; 3.10 A; A=36-382, B=383-418.[ExPASy / RCSB / EBI]
9API; X-ray; 3.00 A; A=36-382, B=383-418.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1ATU; -.
1D5S; -.
1EZX; -.
1HP7; -.
1IZ2; -.
1KCT; -.
1OO8; -.
1OPH; -.
1PSI; -.
1QLP; -.
1QMB; -.
2D26; -.
7API; -.
8API; -.
9API; -.
ModBase P01009.
Protein-protein interaction databases
IntAct P01009; -.
Protein family/group databases
MEROPS I04.001; -.
PTM databases
GlycoSuiteDB P01009; -.
Enzyme and pathway databases
Reactome REACT_604; Hemostasis.
2D gel databases
SWISS-2DPAGE P01009; -.
Cornea-2DPAGE P01009; -.
DOSAC-COBS-2DPAGE P01009; -.
HSC-2DPAGE P01009; -.
OGP P01009; -.
REPRODUCTION-2DPAGE IPI00553177; -.
P01009; -.
Siena-2DPAGE P01009; -.
Organism-specific databases
H-InvDB HIX0011929; -.
HGNC HGNC:8941; SERPINA1.
GenAtlas SERPINA1.
HPA CAB013211; -.
CAB016648; -.
HPA000927; -.
HPA001292; -.
MIM 107400; gene+phenotype. [NCBI / EBI]
Orphanet 60; Alpha-1 antitrypsin deficiency.
PharmGKB PA35509; -.
GeneCards P01009.
Gene expression databases
ArrayExpress P01009; -.
GermOnline ENSG00000197249; Homo sapiens.
Ontologies
GO
GO:0005615; Cellular component: extracellular space (inferred from mutant phenotype from UniProtKB).
GO:0031093; Cellular component: platelet alpha granule lumen (inferred from experiment from Reactome).
GO:0005515; Molecular function: protein binding (inferred from physical interaction from UniProtKB).
GO:0004867; Molecular function: serine-type endopeptidase inhibitor activity (non-traceable author statement from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR000215; Protease_inhib_I4_serpin.
Graphical view of domain structure.
PANTHER PTHR11461; Prot_inh_serpin; 1.
Pfam PF00079; Serpin; 1.
Pfam graphical view of domain structure.
SMART SM00093; SERPIN; 1.
SMART graphical view of domain structure.
PROSITE PS00284; SERPIN; 1.
BLOCKS P01009.
Other
SWISS-3DIMAGE P01009.
Genome annotation databases
Ensembl ENSG00000197249; Homo sapiens. [Contig view]
GeneID 5265; -.
KEGG hsa:5265; -.
Phylogenomic databases
HOGENOM P01009; -.
HOVERGEN P01009; -.
Other