ID A1AT_HUMAN Reviewed; 418 AA. AC P01009; A6PX14; B2RDQ8; Q0PVP5; Q13672; Q53XB8; Q5U0M1; Q7M4R2; AC Q86U18; Q86U19; Q96BF9; Q96ES1; Q9P1P0; Q9UCE6; Q9UCM3; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 3. DT 13-FEB-2019, entry version 253. DE RecName: Full=Alpha-1-antitrypsin; DE AltName: Full=Alpha-1 protease inhibitor; DE AltName: Full=Alpha-1-antiproteinase; DE AltName: Full=Serpin A1; DE Contains: DE RecName: Full=Short peptide from AAT; DE Short=SPAAT; DE Flags: Precursor; GN Name=SERPINA1; Synonyms=AAT, PI; ORFNames=PRO0684, PRO2209; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=6319097; DOI=10.1089/dna.1983.2.255; RA Bollen A., Herzog A., Cravador A., Herion P., Chuchana P., RA van der Straten A., Loriau R., Jacobs P., van Elsen A.; RT "Cloning and expression in Escherichia coli of full-length RT complementary DNA coding for human alpha 1-antitrypsin."; RL DNA 2:255-264(1983). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=6093867; DOI=10.1021/bi00316a003; RA Long G.L., Chandra T., Woo S.L.C., Davie E.W., Kurachi K.; RT "Complete sequence of the cDNA for human alpha 1-antitrypsin and the RT gene for the S variant."; RL Biochemistry 23:4828-4837(1984). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND MUTAGENESIS OF MET-382. RX PubMed=6387509; DOI=10.1038/312077a0; RA Rosenberg S., Barr P.J., Najarian R.C., Hallewell R.A.; RT "Synthesis in yeast of a functional oxidation-resistant mutant of RT human alpha-antitrypsin."; RL Nature 312:77-80(1984). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=2985281; DOI=10.1016/S0092-8674(85)80026-X; RA Ciliberto G., Dente L., Cortese R.; RT "Cell-specific expression of a transfected human alpha 1-antitrypsin RT gene."; RL Cell 41:531-540(1985). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND CHARACTERIZATION OF VARIANT Z. RX PubMed=3491072; RA Nukiwa T., Satoh K., Brantly M.L., Ogushi F., Fells G.A., Courtney M., RA Crystal R.G.; RT "Identification of a second mutation in the protein-coding sequence of RT the Z type alpha 1-antitrypsin gene."; RL J. Biol. Chem. 261:15989-15994(1986). RN [6] RP ERRATUM. RA Nukiwa T., Satoh K., Brantly M.L., Ogushi F., Fells G.A., Courtney M., RA Crystal R.G.; RL J. Biol. Chem. 262:10412-10412(1987). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ALA-237 AND RP ASP-400. RC TISSUE=Liver; RX PubMed=17650587; RA Shasany A.K., Shukla A.K., Darokar M.P., Saraiya M., Chaturvedi N., RA Tewari L., Khanuja S.P.; RT "An alpha-1 antitrypsin genetic variant from India."; RL Indian J. Biochem. Biophys. 44:176-178(2007). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS TRP-172; ALA-237 AND RP LYS-366. RC TISSUE=Lymphocyte; RA Balduyck M., Porchet N., Aubert J.-P., Zerimech F., Douchain F., RA Verchain S.; RT "Characterization of a new variant of alpha1 antitrypsin M Lille RT (p.Gly148Trp)."; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Fetal liver; RA Zhang C., Yu Y., Zhang S., Ouyang S., Luo L., Wei H., Zhou G., RA Zhou W., Bi J., Zhang Y., Liu M., He F.; RT "Functional prediction of the coding sequences of 32 new genes deduced RT by analysis of cDNA clones from human fetal liver."; RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). RC TISSUE=Fetal liver, and Placenta; RA Li W.B., Gruber C., Jessee J., Polayes D.; RT "Full-length cDNA libraries and normalization."; RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Synovium; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT RP ALA-237. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [13] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Colon, and Ovary; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [14] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-67; 196-255 AND 387-418. RX PubMed=6979715; DOI=10.1038/297655a0; RA Leicht M., Long G.L., Chandra T., Kurachi K., Kidd V.J., Mace M. Jr., RA Davie E.W., Woo S.L.C.; RT "Sequence homology and structural comparison between the chromosomal RT human alpha 1-antitrypsin and chicken ovalbumin genes."; RL Nature 297:655-659(1982). RN [15] RP PRELIMINARY PROTEIN SEQUENCE OF 25-418 (ISOFORM 1). RA Chan S.K.; RT "The covalent structure of human alpha1-protease inhibitor."; RL Fed. Proc. 41:1016-1016(1982). RN [16] RP PROTEIN SEQUENCE OF 25-418 (ISOFORM 1). RX PubMed=7045697; DOI=10.1038/298329a0; RA Carrell R.W., Jeppsson J.-O., Laurell C.-B., Brennan S.O., Owen M.C., RA Vaughan L., Boswell D.R.; RT "Structure and variation of human alpha 1-antitrypsin."; RL Nature 298:329-334(1982). RN [17] RP PROTEIN SEQUENCE OF 25-418 (ISOFORM 1), VARIANTS ABERRANT FORM RP 190-GLY--ARG-198 AND VAL-288, AND FUNCTION. RC TISSUE=Blood; RA Sinha A.K., Girish G.V.; RT "Appearance of an aberrant form of alpha-antitrypsin in the RT circulation of chronic cigarette smokers and its effect on the insulin RT induced NO synthesis in blood platelets."; RL Submitted (AUG-2007) to UniProtKB. RN [18] RP PROTEIN SEQUENCE OF 25-39, AND FUNCTION. RC TISSUE=Ascites; RX PubMed=1906855; DOI=10.1111/j.1349-7006.1991.tb01905.x; RA Tanaka N., Sekiya S., Takamizawa H., Kato N., Moriyama Y., RA Fujimura S.; RT "Characterization of a 54 kDa, alpha 1-antitrypsin-like protein RT isolated from ascitic fluid of an endometrial cancer patient."; RL Jpn. J. Cancer Res. 82:693-700(1991). RN [19] RP PROTEIN SEQUENCE OF 30-48 AND 248-257 (ISOFORMS 1/2/3), GLYCOSYLATION RP AT ASN-70; ASN-107 AND ASN-271, STRUCTURE OF CARBOHYDRATES, RP CYSTEINE-BINDING, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=16622833; DOI=10.1002/pmic.200500751; RA Kolarich D., Weber A., Turecek P.L., Schwarz H.P., Altmann F.; RT "Comprehensive glyco-proteomic analysis of human alpha1-antitrypsin RT and its charge isoforms."; RL Proteomics 6:3369-3380(2006). RN [20] RP PROTEIN SEQUENCE OF 47-66. RC TISSUE=Urine; RX PubMed=8323530; DOI=10.1006/bbrc.1993.1731; RA Umekawa T., Kohri K., Amasaki N., Yamate T., Yoshida K., Yamamoto K., RA Suzuki Y., Sinohara H., Kurita T.; RT "Sequencing of a urinary stone protein, identical to alpha-one RT antitrypsin, which lacks 22 amino acids."; RL Biochem. Biophys. Res. Commun. 193:1049-1053(1993). RN [21] RP PROTEIN SEQUENCE OF 50-63 AND 161-178 (ISOFORMS 1/2/3), AND RP IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Brain, and Cajal-Retzius cell; RA Lubec G., Afjehi-Sadat L.; RL Submitted (MAR-2007) to UniProtKB. RN [22] RP NUCLEOTIDE SEQUENCE [MRNA] OF 292-418 (ISOFORM 1). RX PubMed=3876243; DOI=10.1016/0014-5793(85)81056-5; RA Riley J.H., Bathurst I.C., Edbrooke M.R., Carrell R.W., Craig R.K.; RT "Alpha 1-antitrypsin and serum albumin mRNA accumulation in normal, RT acute phase and ZZ human liver."; RL FEBS Lett. 189:361-366(1985). RN [23] RP NUCLEOTIDE SEQUENCE [MRNA] OF 350-418 (ISOFORM 1). RX PubMed=7031661; DOI=10.1073/pnas.78.11.6826; RA Kurachi K., Chandra T., Friezner Degen S.J., White T.T., RA Marchioro T.L., Woo S.L.C., Davie E.W.; RT "Cloning and sequence of cDNA coding for alpha 1-antitrypsin."; RL Proc. Natl. Acad. Sci. U.S.A. 78:6826-6830(1981). RN [24] RP PROTEIN SEQUENCE OF 375-414, IDENTIFICATION OF SPAAT, FUNCTION, AND RP SUBCELLULAR LOCATION. RC TISSUE=Placenta; RX PubMed=1406456; RA Niemann M.A., Narkates A.J., Miller E.J.; RT "Isolation and serine protease inhibitory activity of the 44-residue, RT C-terminal fragment of alpha 1-antitrypsin from human placenta."; RL Matrix 12:233-241(1992). RN [25] RP NUCLEOTIDE SEQUENCE [MRNA] OF 387-418 (ISOFORM 1). RX PubMed=3873938; RA Coutelle C., Speer A., Rogers J., Kalsheker N., Humphries S., RA Williamson R.; RT "Construction and partial characterization of a human liver cDNA RT library."; RL Biomed. Biochim. Acta 44:421-431(1985). RN [26] RP GLYCOSYLATION AT ASN-70 AND ASN-271. RX PubMed=12754519; DOI=10.1038/nbt827; RA Zhang H., Li X.-J., Martin D.B., Aebersold R.; RT "Identification and quantification of N-linked glycoproteins using RT hydrazide chemistry, stable isotope labeling and mass spectrometry."; RL Nat. Biotechnol. 21:660-666(2003). RN [27] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-70 AND ASN-271. RC TISSUE=Bile; RX PubMed=15084671; DOI=10.1074/mcp.M400015-MCP200; RA Kristiansen T.Z., Bunkenborg J., Gronborg M., Molina H., RA Thuluvath P.J., Argani P., Goggins M.G., Maitra A., Pandey A.; RT "A proteomic analysis of human bile."; RL Mol. Cell. Proteomics 3:715-728(2004). RN [28] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-70 AND ASN-271. RC TISSUE=Plasma; RX PubMed=14760718; DOI=10.1002/pmic.200300556; RA Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.; RT "Screening for N-glycosylated proteins by liquid chromatography mass RT spectrometry."; RL Proteomics 4:454-465(2004). RN [29] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-70; ASN-107 AND ASN-271. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., RA Moore R.J., Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [30] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-70. RC TISSUE=Platelet; RX PubMed=16263699; DOI=10.1074/mcp.M500324-MCP200; RA Lewandrowski U., Moebius J., Walter U., Sickmann A.; RT "Elucidation of N-glycosylation sites on human platelet proteins: a RT glycoproteomic approach."; RL Mol. Cell. Proteomics 5:226-233(2006). RN [31] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-70; ASN-107 AND ASN-271. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of RT multiple enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [32] RP GLYCOSYLATION AT ASN-107 AND ASN-271. RX PubMed=19139490; DOI=10.1074/mcp.M800504-MCP200; RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., RA Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., RA Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.; RT "A strategy for precise and large scale identification of core RT fucosylated glycoproteins."; RL Mol. Cell. Proteomics 8:913-923(2009). RN [33] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-70; ASN-107 AND ASN-271, RP AND STRUCTURE OF CARBOHYDRATES. RC TISSUE=Cerebrospinal fluid; RX PubMed=19838169; DOI=10.1038/nmeth.1392; RA Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., RA Brinkmalm G., Larson G.; RT "Enrichment of glycopeptides for glycan structure and attachment site RT identification."; RL Nat. Methods 6:809-811(2009). RN [34] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [35] RP GLYCOSYLATION AT ASN-70 AND ASN-271, STRUCTURE OF CARBOHYDRATES, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=22171320; DOI=10.1074/mcp.M111.013649; RA Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.; RT "Human urinary glycoproteomics; attachment site specific analysis of RT N-and O-linked glycosylations by CID and ECD."; RL Mol. Cell. Proteomics 11:1-17(2012). RN [36] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-383, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [37] RP PHOSPHORYLATION AT SER-38. RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028; RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J., RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N., RA Pinna L.A., Pagliarini D.J., Dixon J.E.; RT "A single kinase generates the majority of the secreted RT phosphoproteome."; RL Cell 161:1619-1632(2015). RN [38] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., RA Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [39] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS). RX PubMed=6332197; DOI=10.1016/0022-2836(84)90298-5; RA Loebermann H., Tokuoka R., Deisenhofer J., Huber R.; RT "Human alpha 1-proteinase inhibitor. Crystal structure analysis of two RT crystal modifications, molecular model and preliminary analysis of the RT implications for function."; RL J. Mol. Biol. 177:531-556(1984). RN [40] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS). RX PubMed=2785270; DOI=10.1093/protein/2.6.407; RA Engh R., Loebermann H., Schneider M., Wiegand G., Huber R., RA Laurell C.-B.; RT "The S variant of human alpha 1-antitrypsin, structure and RT implications for function and metabolism."; RL Protein Eng. 2:407-415(1989). RN [41] RP X-RAY CRYSTALLOGRAPHY (3.46 ANGSTROMS) OF 25-418. RX PubMed=8543039; DOI=10.1016/0014-5793(95)01331-8; RA Song H.K., Lee K.N., Kwon K.-S., Yu M.-H., Suh S.W.; RT "Crystal structure of an uncleaved alpha 1-antitrypsin reveals the RT conformation of its inhibitory reactive loop."; RL FEBS Lett. 377:150-154(1995). RN [42] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 26-418. RX PubMed=8756325; DOI=10.1038/nsb0896-676; RA Elliott P.R., Lomas D.A., Carrell R.W., Abrahams J.P.; RT "Inhibitory conformation of the reactive loop of alpha 1- RT antitrypsin."; RL Nat. Struct. Biol. 3:676-681(1996). RN [43] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 45-418. RX PubMed=8939743; DOI=10.1016/S0969-2126(96)00126-8; RA Ryu S.-E., Choi H.-J., Kwon K.-S., Lee K.N., Yu M.-H.; RT "The native strains in the hydrophobic core and flexible reactive loop RT of a serine protease inhibitor: crystal structure of an uncleaved RT alpha1-antitrypsin at 2.7 A."; RL Structure 4:1181-1192(1996). RN [44] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 26-418. RX PubMed=9466920; DOI=10.1006/jmbi.1997.1458; RA Elliott P.R., Abrahams J.P., Lomas D.A.; RT "Wild-type alpha 1-antitrypsin is in the canonical inhibitory RT conformation."; RL J. Mol. Biol. 275:419-425(1998). RN [45] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 48-418 IN COMPLEX WITH BOVINE RP TRYPSIN. RX PubMed=11057674; DOI=10.1038/35038119; RA Huntington J.A., Read R.J., Carrell R.W.; RT "Structure of a serpin-protease complex shows inhibition by RT deformation."; RL Nature 407:923-926(2000). RN [46] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 44-418. RX PubMed=10716194; DOI=10.1110/ps.9.2.417; RA Dunstone M.A., Dai W., Whisstock J.C., Rossjohn J., Pike R.N., RA Feil S.C., Le Bonniec B.F., Parker M.W., Bottomley S.P.; RT "Cleaved antitrypsin polymers at atomic resolution."; RL Protein Sci. 9:417-420(2000). RN [47] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS). RX PubMed=10933492; DOI=10.1110/ps.9.7.1274; RA Elliott P.R., Pei X.Y., Dafforn T.R., Lomas D.A.; RT "Topography of a 2.0 A structure of alpha1-antitrypsin reveals targets RT for rational drug design to prevent conformational disease."; RL Protein Sci. 9:1274-1281(2000). RN [48] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 25-418. RX PubMed=11178897; DOI=10.1006/jmbi.2000.4357; RA Kim S.-J., Woo J.-R., Seo E.J., Yu M.-H., Ryu S.-E.; RT "A 2.1 A resolution structure of an uncleaved alpha(1)-antitrypsin RT shows variability of the reactive center and other loops."; RL J. Mol. Biol. 306:109-119(2001). RN [49] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 25-418. RX PubMed=12244055; DOI=10.1074/jbc.M207682200; RA Im H., Woo M.-S., Hwang K.Y., Yu M.-H.; RT "Interactions causing the kinetic trap in serpin protein folding."; RL J. Biol. Chem. 277:46347-46354(2002). RN [50] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 26-418 OF VARIANT PITTSBURGH RP ARG-382. RX PubMed=12860985; DOI=10.1074/jbc.M305195200; RA Dementiev A., Simonovic M., Volz K., Gettins P.G.; RT "Canonical inhibitor-like interactions explain reactivity of alpha1- RT proteinase inhibitor Pittsburgh and antithrombin with proteinases."; RL J. Biol. Chem. 278:37881-37887(2003). RN [51] RP REVIEW. RX PubMed=2669992; DOI=10.1007/BF01115992; RA Kalsheker N.; RT "Alpha 1-antitrypsin: structure, function and molecular biology of the RT gene."; RL Biosci. Rep. 9:129-138(1989). RN [52] RP REVIEW. RX PubMed=1859394; DOI=10.1002/bies.950130404; RA Wu Y., Foreman R.C.; RT "The molecular genetics of alpha 1 antitrypsin deficiency."; RL Bioessays 13:163-169(1991). RN [53] RP CHARACTERIZATION OF VARIANT M2, AND POLYMORPHISM. RX PubMed=2901226; RA Nukiwa T., Brantly M.L., Ogushi F., Fells G.A., Crystal R.G.; RT "Characterization of the gene and protein of the common alpha 1- RT antitrypsin normal M2 allele."; RL Am. J. Hum. Genet. 43:322-330(1988). RN [54] RP VARIANT M3 ASP-400. RX PubMed=2394452; DOI=10.1007/BF00206766; RA Graham A., Hayes K., Weidinger S., Newton C.R., Markham A.F., RA Kalsheker N.A.; RT "Characterisation of the alpha-1-antitrypsin M3 gene, a normal RT variant."; RL Hum. Genet. 85:381-382(1990). RN [55] RP VARIANT F CYS-247. RX PubMed=2035534; RA Okayama H., Brantly M., Holmes M., Crystal R.G.; RT "Characterization of the molecular basis of the alpha 1-antitrypsin F RT allele."; RL Am. J. Hum. Genet. 48:1154-1158(1991). RN [56] RP VARIANT M-HEERLEN LEU-393. RX PubMed=2784123; DOI=10.1007/BF00279001; RA Hofker M.H., Nukiwa T., van Paassen H.M.B., Nelen M., Kramps J.A., RA Klasen E.C., Frants R.R., Crystal R.G.; RT "A Pro-->Leu substitution in codon 369 of the alpha-1-antitrypsin RT deficiency variant PI M-Heerlen."; RL Hum. Genet. 81:264-268(1989). RN [57] RP VARIANT M-MALTON PHE-75 DEL. RX PubMed=2786335; RA Fraizer G.C., Harrold T.R., Hofker M.H., Cox D.W.; RT "In-frame single codon deletion in the M-Malton deficiency allele of RT alpha 1-antitrypsin."; RL Am. J. Hum. Genet. 44:894-902(1989). RN [58] RP VARIANT M-MINERAL SPRINGS GLU-91. RX PubMed=1967187; DOI=10.1128/MCB.10.1.47; RA Curiel D.T., Vogelmeier C., Hubbard R.C., Stier L.E., Crystal R.G.; RT "Molecular basis of alpha 1-antitrypsin deficiency and emphysema RT associated with the alpha 1-antitrypsin M-Mineral springs allele."; RL Mol. Cell. Biol. 10:47-56(1990). RN [59] RP VARIANT M-NICHINAN PHE-75 DEL. RX PubMed=2309708; RA Matsunaga E., Shiokawa S., Nakamura H., Maruyama T., Tsuda K., RA Fukumaki Y.; RT "Molecular analysis of the gene of the alpha 1-antitrypsin deficiency RT variant, M-Nichinan."; RL Am. J. Hum. Genet. 46:602-612(1990). RN [60] RP VARIANT M-PROCIDA PRO-65. RX PubMed=3262617; RA Takahashi H., Nukiwa T., Satoh K., Ogushi F., Brantly M., Fells G., RA Stier L., Courtney M., Crystal R.G.; RT "Characterization of the gene and protein of the alpha 1-antitrypsin RT 'deficiency' allele M-Procida."; RL J. Biol. Chem. 263:15528-15534(1988). RN [61] RP VARIANT P-DUARTE VAL-280. RX PubMed=8364590; DOI=10.1002/humu.1380020311; RA Hildesheim J., Kinsley G., Bissell M., Pierce J., Brantly M.; RT "Genetic diversity from a limited repertoire of mutations on different RT common allelic backgrounds: alpha 1-antitrypsin deficiency variant P- RT Duarte."; RL Hum. Mutat. 2:221-228(1993). RN [62] RP VARIANT PITTSBURGH ARG-382. RX PubMed=6604220; DOI=10.1056/NEJM198309223091203; RA Owen M.C., Brennan S.O., Lewis J.H., Carrell R.W.; RT "Mutation of antitrypsin to antithrombin. Alpha 1-antitrypsin RT Pittsburgh (358 Met leads to Arg), a fatal bleeding disorder."; RL N. Engl. J. Med. 309:694-698(1983). RN [63] RP INVOLVEMENT IN A1ATD, AND VARIANT S-IIYAMA PHE-77. RX PubMed=1905728; RA Seyama K., Nukiwa T., Takabe K., Takahashi H., Miyake K., Kira S.; RT "Siiyama (serine 53 (TCC) to phenylalanine 53 (TTC)). A new alpha 1- RT antitrypsin-deficient variant with mutation on a predicted conserved RT residue of the serpin backbone."; RL J. Biol. Chem. 266:12627-12632(1991). RN [64] RP VARIANT V-MUNICH ALA-26. RX PubMed=2316526; RA Holmes M.D., Brantly M.L., Curiel D.T., Weidinger S., Crystal R.G.; RT "Characterization of the normal alpha 1-antitrypsin allele V-Munich: a RT variant associated with a unique protein isoelectric focusing RT pattern."; RL Am. J. Hum. Genet. 46:810-816(1990). RN [65] RP INVOLVEMENT IN A1ATD, AND VARIANT W-BETHESDA THR-360. RX PubMed=2390072; DOI=10.1016/0006-291X(90)90493-7; RA Holmes M.D., Brantly M.L., Fells G.A., Crystal R.G.; RT "Alpha 1-antitrypsin W-Bethesda: molecular basis of an unusual alpha RT 1-antitrypsin deficiency variant."; RL Biochem. Biophys. Res. Commun. 170:1013-1020(1990). RN [66] RP VARIANT Z-AUGSBURG LYS-366. RX PubMed=2339709; RA Faber J.-P., Weidinger S., Olek K.; RT "Sequence data of the rare deficient alpha 1-antitrypsin variant PI RT Zaugsburg."; RL Am. J. Hum. Genet. 46:1158-1162(1990). RN [67] RP INVOLVEMENT IN A1ATD, AND VARIANTS Z-WREXHAM LEU-4 AND Q0-NEWPORT RP SER-139. RX PubMed=2227940; DOI=10.1007/BF00194233; RA Graham A., Kalsheker N.A., Bamforth F.J., Newton C.R., Markham A.F.; RT "Molecular characterisation of two alpha-1-antitrypsin deficiency RT variants: proteinase inhibitor (Pi) Null(Newport) (Gly115-->Ser) and RT (Pi) Z Wrexham (Ser-19-->Leu)."; RL Hum. Genet. 85:537-540(1990). RN [68] RP VARIANTS P-CARDIFF VAL-280; I CYS-63 AND M-MALTON PHE-75 DEL. RX PubMed=2606478; DOI=10.1007/BF00210671; RA Graham A., Kalsheker N.A., Newton C.R., Bamforth F.J., Powell S.J., RA Markham A.F.; RT "Molecular characterisation of three alpha-1-antitrypsin deficiency RT variants: proteinase inhibitor (Pi) nullcardiff (Asp256-->Val); PiM- RT Malton (Phe51-->deletion) and PiI (Arg39-->Cys)."; RL Hum. Genet. 84:55-58(1989). RN [69] RP VARIANT QO-LUDWIGSHAFEN ASN-116. RX PubMed=2254451; DOI=10.1172/JCI114919; RA Fraizer G.C., Siewertsen M.A., Hofker M.H., Brubacher M.G., Cox D.W.; RT "A null deficiency allele of alpha 1-antitrypsin, QO-Ludwigshafen, RT with altered tertiary structure."; RL J. Clin. Invest. 86:1878-1884(1990). RN [70] RP VARIANTS M5-KARLSRUHE THR-58; M6-BONN PHE-69; M-PALERMO PHE-75 DEL; RP M6-PASSAU THR-84; M5-BERLIN THR-112; V ARG-172; M2-OBERNBURG TRP-172; RP L-FRANKFURT GLU-180; S-MUNICH PHE-354; P-DONAUWOERTH ASN-365 AND RP L-OFFENBACH THR-386. RX PubMed=7977369; RA Faber J.-P., Poller W., Weidinger S., Kirchgesser M., Schwaab R., RA Bidlingmaier F., Olek K.; RT "Identification and DNA sequence analysis of 15 new alpha 1- RT antitrypsin variants, including two PI*Q0 alleles and one deficient RT PI*M allele."; RL Am. J. Hum. Genet. 55:1113-1121(1994). RN [71] RP VARIANT Z-BRISTOL MET-109. RX PubMed=9459000; DOI=10.1017/S0003480097006404; RA Lovegrove J.U., Jeremiah S., Gillett G.T., Temple I.K., Povey S., RA Whitehouse D.B.; RT "A new alpha 1-antitrypsin mutation, Thr-Met 85, (PI ZBristol) RT associated with novel electrophoretic properties."; RL Ann. Hum. Genet. 61:385-391(1997). RN [72] RP VARIANTS Y-BARCELONA VAL-280 AND HIS-415. RX PubMed=10651487; RA Jardi R., Rodriguez F., Miravitlles M., Vidal R., Cotrina M., Quer J., RA Pascual C., Weidinger S.; RT "Identification and molecular characterization of the new alpha-1- RT antitrypsin deficient allele PI YBarcelona (Asp256Val and RT Pro391His)."; RL Hum. Mutat. 12:213-213(1998). RN [73] RP VARIANT SAO TOME HIS-386. RA Seixas S., Trovoada M.J., Santos M.T., Rocha J.; RT "A novel alpha-1-antitrypsin P362H variant found in a population RT sample from Sao Tome e Principe (Gulf of Guinea, West Africa)."; RL Hum. Mutat. 13:414-414(1999). RN [74] RP VARIANT BASQUE ARG-305 DEL. RX PubMed=10612848; RX DOI=10.1002/(SICI)1098-1004(200001)15:1<121::AID-HUMU37>3.0.CO;2-U; RA Seixas S., Garcia O., Amorim A., Rocha J.; RT "A novel alpha-1-antitrypsin r281del variant found in a population RT sample from the Basque country."; RL Hum. Mutat. 15:121-122(2000). RN [75] RP VARIANTS Z ALA-237 AND LYS-366, VARIANT S VAL-288, SUBCELLULAR RP LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION, AND INTERACTION WITH CANX RP AND PDIA3. RX PubMed=23826168; DOI=10.1371/journal.pone.0066889; RA Marques P.I., Ferreira Z., Martins M., Figueiredo J., Silva D.I., RA Castro P., Morales-Hojas R., Simoes-Correia J., Seixas S.; RT "SERPINA2 is a novel gene with a divergent function from SERPINA1."; RL PLoS ONE 8:E66889-E66889(2013). RN [76] RP CHARACTERIZATION OF VARIANT PITTSBURGH ARG-382. RX PubMed=26797521; DOI=10.1016/j.bbrc.2016.01.069; RA Sheffield W.P., Bhakta V.; RT "The M358R variant of alpha(1)-proteinase inhibitor inhibits RT coagulation factor VIIa."; RL Biochem. Biophys. Res. Commun. 470:710-713(2016). CC -!- FUNCTION: Inhibitor of serine proteases. Its primary target is CC elastase, but it also has a moderate affinity for plasmin and CC thrombin. Irreversibly inhibits trypsin, chymotrypsin and CC plasminogen activator. The aberrant form inhibits insulin-induced CC NO synthesis in platelets, decreases coagulation time and has CC proteolytic activity against insulin and plasmin. CC -!- FUNCTION: Short peptide from AAT: reversible chymotrypsin CC inhibitor. It also inhibits elastase, but not trypsin. Its major CC physiological function is the protection of the lower respiratory CC tract against proteolytic destruction by human leukocyte elastase CC (HLE). CC -!- SUBUNIT: The variants S and Z interact with CANX AND PDIA3. CC {ECO:0000269|PubMed:11057674}. CC -!- INTERACTION: CC Self; NbExp=7; IntAct=EBI-986224, EBI-986224; CC P00760:- (xeno); NbExp=5; IntAct=EBI-986224, EBI-986385; CC P00772:CELA1 (xeno); NbExp=2; IntAct=EBI-986224, EBI-986248; CC P71213:espB (xeno); NbExp=3; IntAct=EBI-986224, EBI-2615322; CC P43307:SSR1; NbExp=4; IntAct=EBI-986224, EBI-714168; CC -!- SUBCELLULAR LOCATION: Secreted. Endoplasmic reticulum. Note=The S CC and Z allele are not secreted effectively and accumulate CC intracellularly in the endoplasmic reticulum. CC -!- SUBCELLULAR LOCATION: Short peptide from AAT: Secreted, CC extracellular space, extracellular matrix. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P01009-1; Sequence=Displayed; CC Name=2; CC IsoId=P01009-2; Sequence=VSP_028889; CC Note=No experimental confirmation available.; CC Name=3; CC IsoId=P01009-3; Sequence=VSP_028890; CC Note=No experimental confirmation available. May be produced at CC very low levels due to a premature stop codon in the mRNA, CC leading to nonsense-mediated mRNA decay.; CC -!- TISSUE SPECIFICITY: Ubiquitous. Expressed in leukocytes and CC plasma. {ECO:0000269|PubMed:23826168}. CC -!- DOMAIN: The reactive center loop (RCL) extends out from the body CC of the protein and directs binding to the target protease. The CC protease cleaves the serpin at the reactive site within the RCL, CC establishing a covalent linkage between the carboxyl group of the CC serpin reactive site and the serine hydroxyl of the protease. The CC resulting inactive serpin-protease complex is highly stable. CC -!- PTM: N-glycosylated. Differential glycosylation produces a number CC of isoforms. N-linked glycan at Asn-107 is alternatively di- CC antennary, tri-antennary or tetra-antennary. The glycan at Asn-70 CC is di-antennary with trace amounts of tri-antennary. Glycan at CC Asn-271 is exclusively di-antennary. Structure of glycans at Asn- CC 70 and Asn-271 is Hex5HexNAc4. The structure of the antennae is CC Neu5Ac(alpha1-6)Gal(beta1-4)GlcNAc attached to the core structure CC Man(alpha1-6)[Man(alpha1-3)]Man(beta1-4)GlcNAc(beta1-4)GlcNAc. CC Some antennae are fucosylated, which forms a Lewis-X determinant. CC {ECO:0000269|PubMed:12754519, ECO:0000269|PubMed:14760718, CC ECO:0000269|PubMed:15084671, ECO:0000269|PubMed:16263699, CC ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:16622833, CC ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218, CC ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:22171320, CC ECO:0000269|PubMed:23826168}. CC -!- PTM: Proteolytic processing may yield the truncated form that CC ranges from Asp-30 to Lys-418. CC -!- POLYMORPHISM: The sequence shown is that of the M1V allele which CC is the most common form of PI (44 to 49%). Other frequent alleles CC are: M1A 20 to 23%; M2 10 to 11%; M3 14 to 19%. CC {ECO:0000269|PubMed:2901226}. CC -!- DISEASE: Alpha-1-antitrypsin deficiency (A1ATD) [MIM:613490]: A CC disorder whose most common manifestation is emphysema, which CC becomes evident by the third to fourth decade. A less common CC manifestation of the deficiency is liver disease, which occurs in CC children and adults, and may result in cirrhosis and liver CC failure. Environmental factors, particularly cigarette smoking, CC greatly increase the risk of emphysema at an earlier age. CC {ECO:0000269|PubMed:1905728, ECO:0000269|PubMed:2227940, CC ECO:0000269|PubMed:2390072}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- MISCELLANEOUS: The aberrant form is found in the plasma of chronic CC smokers, and persists after smoking is ceased. It can still be CC found ten years after smoking has ceased. CC -!- SIMILARITY: Belongs to the serpin family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAD62334.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC Sequence=CAD62585.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Alpha-1 antitrypsin entry; CC URL="https://en.wikipedia.org/wiki/Alpha_1-antitrypsin"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; K01396; AAB59375.1; -; mRNA. DR EMBL; K02212; AAB59495.1; -; Genomic_DNA. DR EMBL; X01683; CAA25838.1; -; mRNA. DR EMBL; M11465; AAA51546.1; -; mRNA. DR EMBL; J02619; AAA51547.1; -; Genomic_DNA. DR EMBL; DQ682455; ABG73380.1; -; mRNA. DR EMBL; AM048838; CAJ15161.1; -; Genomic_DNA. DR EMBL; AF113676; AAF29581.1; -; mRNA. DR EMBL; AF130068; AAG35496.1; -; mRNA. DR EMBL; BX161449; CAD61914.1; -; mRNA. DR EMBL; BX247968; CAD62306.1; -; mRNA. DR EMBL; BX248002; CAD62334.1; ALT_INIT; mRNA. DR EMBL; BX248257; CAD62585.1; ALT_INIT; mRNA. DR EMBL; AK315637; BAG38005.1; -; mRNA. DR EMBL; BT019455; AAV38262.1; -; mRNA. DR EMBL; BC011991; AAH11991.1; -; mRNA. DR EMBL; BC015642; AAH15642.1; -; mRNA. DR EMBL; J00064; AAB59369.1; -; Genomic_DNA. DR EMBL; J00066; AAB59370.1; -; Genomic_DNA. DR EMBL; J00065; AAB59370.1; JOINED; Genomic_DNA. DR EMBL; J00067; AAB59371.1; -; Genomic_DNA. DR EMBL; X02920; CAA26677.1; -; mRNA. DR EMBL; V00496; CAA23755.1; -; mRNA. DR EMBL; M26123; AAA51545.1; -; mRNA. DR CCDS; CCDS9925.1; -. [P01009-1] DR PIR; A21853; ITHU. DR PIR; A61391; A61391. DR RefSeq; NP_000286.3; NM_000295.4. [P01009-1] DR RefSeq; NP_001002235.1; NM_001002235.2. [P01009-1] DR RefSeq; NP_001002236.1; NM_001002236.2. [P01009-1] DR RefSeq; NP_001121172.1; NM_001127700.1. [P01009-1] DR RefSeq; NP_001121173.1; NM_001127701.1. [P01009-1] DR RefSeq; NP_001121174.1; NM_001127702.1. [P01009-1] DR RefSeq; NP_001121175.1; NM_001127703.1. [P01009-1] DR RefSeq; NP_001121176.1; NM_001127704.1. [P01009-1] DR RefSeq; NP_001121177.1; NM_001127705.1. [P01009-1] DR RefSeq; NP_001121178.1; NM_001127706.1. [P01009-1] DR RefSeq; NP_001121179.1; NM_001127707.1. [P01009-1] DR RefSeq; XP_016876859.1; XM_017021370.1. [P01009-1] DR UniGene; Hs.525557; -. DR PDB; 1ATU; X-ray; 2.70 A; A=45-418. DR PDB; 1D5S; X-ray; 3.00 A; A=44-377, B=378-418. DR PDB; 1EZX; X-ray; 2.60 A; A=48-382, B=383-418. DR PDB; 1HP7; X-ray; 2.10 A; A=25-418. DR PDB; 1IZ2; X-ray; 2.20 A; A=25-418. DR PDB; 1KCT; X-ray; 3.46 A; A=25-418. DR PDB; 1OO8; X-ray; 2.65 A; A=26-418. DR PDB; 1OPH; X-ray; 2.30 A; A=26-418. DR PDB; 1PSI; X-ray; 2.92 A; A=26-418. DR PDB; 1QLP; X-ray; 2.00 A; A=26-418. DR PDB; 1QMB; X-ray; 2.60 A; A=49-376, B=377-418. DR PDB; 2D26; X-ray; 3.30 A; A=25-382, B=383-418. DR PDB; 2QUG; X-ray; 2.00 A; A=25-418. DR PDB; 3CWL; X-ray; 2.44 A; A=25-418. DR PDB; 3CWM; X-ray; 2.51 A; A=25-418. DR PDB; 3DRM; X-ray; 2.20 A; A=26-418. DR PDB; 3DRU; X-ray; 3.20 A; A/B/C=26-418. DR PDB; 3NDD; X-ray; 1.50 A; A=46-382, B=383-418. DR PDB; 3NDF; X-ray; 2.70 A; A=46-382, B=383-418. DR PDB; 3NE4; X-ray; 1.81 A; A=48-418. DR PDB; 3T1P; X-ray; 3.90 A; A=48-418. DR PDB; 4PYW; X-ray; 1.91 A; A=26-418. DR PDB; 5IO1; X-ray; 3.34 A; A/B=29-418. DR PDB; 5NBU; X-ray; 1.67 A; A=43-418. DR PDB; 5NBV; X-ray; 1.73 A; A=43-418. DR PDB; 7API; X-ray; 3.00 A; A=36-382, B=383-418. DR PDB; 8API; X-ray; 3.10 A; A=36-382, B=383-418. DR PDB; 9API; X-ray; 3.00 A; A=36-382, B=383-418. DR PDBsum; 1ATU; -. DR PDBsum; 1D5S; -. DR PDBsum; 1EZX; -. DR PDBsum; 1HP7; -. DR PDBsum; 1IZ2; -. DR PDBsum; 1KCT; -. DR PDBsum; 1OO8; -. DR PDBsum; 1OPH; -. DR PDBsum; 1PSI; -. DR PDBsum; 1QLP; -. DR PDBsum; 1QMB; -. DR PDBsum; 2D26; -. DR PDBsum; 2QUG; -. DR PDBsum; 3CWL; -. DR PDBsum; 3CWM; -. DR PDBsum; 3DRM; -. DR PDBsum; 3DRU; -. DR PDBsum; 3NDD; -. DR PDBsum; 3NDF; -. DR PDBsum; 3NE4; -. DR PDBsum; 3T1P; -. DR PDBsum; 4PYW; -. DR PDBsum; 5IO1; -. DR PDBsum; 5NBU; -. DR PDBsum; 5NBV; -. DR PDBsum; 7API; -. DR PDBsum; 8API; -. DR PDBsum; 9API; -. DR ProteinModelPortal; P01009; -. DR SMR; P01009; -. DR BioGrid; 111283; 46. DR CORUM; P01009; -. DR DIP; DIP-35493N; -. DR IntAct; P01009; 22. DR MINT; P01009; -. DR STRING; 9606.ENSP00000348068; -. DR DrugBank; DB03345; Beta-Mercaptoethanol. DR DrugBank; DB05481; Recombinant alpha 1-antitrypsin. DR MEROPS; I04.001; -. DR CarbonylDB; P01009; -. DR GlyConnect; 20; -. DR iPTMnet; P01009; -. DR PhosphoSitePlus; P01009; -. DR UniCarbKB; P01009; -. DR BioMuta; SERPINA1; -. DR DMDM; 1703025; -. DR DOSAC-COBS-2DPAGE; P01009; -. DR OGP; P01009; -. DR REPRODUCTION-2DPAGE; IPI00553177; -. DR REPRODUCTION-2DPAGE; P01009; -. DR SWISS-2DPAGE; P01009; -. DR UCD-2DPAGE; P01009; -. DR EPD; P01009; -. DR jPOST; P01009; -. DR MaxQB; P01009; -. DR PaxDb; P01009; -. DR PeptideAtlas; P01009; -. DR PRIDE; P01009; -. DR ProteomicsDB; 51300; -. DR ProteomicsDB; 51301; -. [P01009-2] DR ProteomicsDB; 51302; -. [P01009-3] DR DNASU; 5265; -. DR Ensembl; ENST00000355814; ENSP00000348068; ENSG00000197249. [P01009-1] DR Ensembl; ENST00000393087; ENSP00000376802; ENSG00000197249. [P01009-1] DR Ensembl; ENST00000393088; ENSP00000376803; ENSG00000197249. [P01009-1] DR Ensembl; ENST00000402629; ENSP00000386094; ENSG00000197249. [P01009-2] DR Ensembl; ENST00000404814; ENSP00000385960; ENSG00000197249. [P01009-1] DR Ensembl; ENST00000437397; ENSP00000408474; ENSG00000197249. [P01009-1] DR Ensembl; ENST00000440909; ENSP00000390299; ENSG00000197249. [P01009-1] DR Ensembl; ENST00000448921; ENSP00000416066; ENSG00000197249. [P01009-1] DR Ensembl; ENST00000449399; ENSP00000416354; ENSG00000197249. [P01009-1] DR Ensembl; ENST00000489769; ENSP00000451525; ENSG00000197249. [P01009-3] DR Ensembl; ENST00000636712; ENSP00000490054; ENSG00000197249. [P01009-1] DR GeneID; 5265; -. DR KEGG; hsa:5265; -. DR UCSC; uc001ycx.5; human. [P01009-1] DR CTD; 5265; -. DR DisGeNET; 5265; -. DR EuPathDB; HostDB:ENSG00000197249.12; -. DR GeneCards; SERPINA1; -. DR GeneReviews; SERPINA1; -. DR HGNC; HGNC:8941; SERPINA1. DR HPA; CAB013211; -. DR HPA; CAB016648; -. DR HPA; CAB073396; -. DR HPA; HPA000927; -. DR HPA; HPA001292; -. DR MalaCards; SERPINA1; -. DR MIM; 107400; gene. DR MIM; 613490; phenotype. DR neXtProt; NX_P01009; -. DR OpenTargets; ENSG00000197249; -. DR Orphanet; 60; Alpha-1-antitrypsin deficiency. DR Orphanet; 178396; Hemorrhagic disease due to alpha-1-antitrypsin Pittsburgh mutation. DR PharmGKB; PA35509; -. DR eggNOG; KOG2392; Eukaryota. DR eggNOG; COG4826; LUCA. DR GeneTree; ENSGT00940000154493; -. DR HOVERGEN; HBG005957; -. DR InParanoid; P01009; -. DR KO; K03984; -. DR OMA; FFLPDEG; -. DR OrthoDB; 131191at2759; -. DR PhylomeDB; P01009; -. DR TreeFam; TF343201; -. DR Reactome; R-HSA-114608; Platelet degranulation. DR Reactome; R-HSA-204005; COPII-mediated vesicle transport. DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs). DR Reactome; R-HSA-5694530; Cargo concentration in the ER. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation. DR SIGNOR; P01009; -. DR ChiTaRS; SERPINA1; human. DR EvolutionaryTrace; P01009; -. DR GeneWiki; Alpha_1-antitrypsin; -. DR GenomeRNAi; 5265; -. DR PMAP-CutDB; P01009; -. DR PRO; PR:P01009; -. DR Proteomes; UP000005640; Chromosome 14. DR Bgee; ENSG00000197249; Expressed in 207 organ(s), highest expression level in liver. DR ExpressionAtlas; P01009; baseline and differential. DR Genevisible; P01009; HS. DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL. DR GO; GO:0030134; C:COPII-coated ER to Golgi transport vesicle; TAS:Reactome. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; IEA:GOC. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0002020; F:protease binding; IPI:UniProtKB. DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IDA:MGI. DR GO; GO:0006953; P:acute-phase response; IEA:UniProtKB-KW. DR GO; GO:0007596; P:blood coagulation; IEA:UniProtKB-KW. DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome. DR GO; GO:0048208; P:COPII vesicle coating; TAS:Reactome. DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; TAS:Reactome. DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central. DR GO; GO:0043312; P:neutrophil degranulation; TAS:Reactome. DR GO; GO:0002576; P:platelet degranulation; TAS:Reactome. DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome. DR InterPro; IPR023795; Serpin_CS. DR InterPro; IPR023796; Serpin_dom. DR InterPro; IPR000215; Serpin_fam. DR InterPro; IPR036186; Serpin_sf. DR PANTHER; PTHR11461; PTHR11461; 1. DR Pfam; PF00079; Serpin; 1. DR SMART; SM00093; SERPIN; 1. DR SUPFAM; SSF56574; SSF56574; 1. DR PROSITE; PS00284; SERPIN; 1. PE 1: Evidence at protein level; KW 3D-structure; Acute phase; Alternative splicing; Blood coagulation; KW Complete proteome; Direct protein sequencing; Endoplasmic reticulum; KW Extracellular matrix; Glycoprotein; Hemostasis; Phosphoprotein; KW Polymorphism; Protease inhibitor; Reference proteome; Secreted; KW Serine protease inhibitor; Signal. FT SIGNAL 1 24 {ECO:0000269|PubMed:1906855}. FT CHAIN 25 418 Alpha-1-antitrypsin. FT {ECO:0000269|PubMed:6093867}. FT /FTId=PRO_0000032377. FT PEPTIDE 375 418 Short peptide from AAT. FT /FTId=PRO_0000364030. FT REGION 368 392 RCL. FT SITE 382 383 Reactive bond. FT MOD_RES 38 38 Phosphoserine; by FAM20C. FT {ECO:0000269|PubMed:26091039}. FT MOD_RES 256 256 S-cysteinyl cysteine. FT MOD_RES 383 383 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT CARBOHYD 70 70 N-linked (GlcNAc...) (complex) FT asparagine. {ECO:0000269|PubMed:12754519, FT ECO:0000269|PubMed:14760718, FT ECO:0000269|PubMed:15084671, FT ECO:0000269|PubMed:16263699, FT ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:16622833, FT ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:19838169, FT ECO:0000269|PubMed:22171320}. FT CARBOHYD 107 107 N-linked (GlcNAc...) (complex) FT asparagine. {ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:16622833, FT ECO:0000269|PubMed:19139490, FT ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:19838169}. FT CARBOHYD 271 271 N-linked (GlcNAc...) (complex) FT asparagine. {ECO:0000269|PubMed:12754519, FT ECO:0000269|PubMed:14760718, FT ECO:0000269|PubMed:15084671, FT ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:16622833, FT ECO:0000269|PubMed:19139490, FT ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:19838169, FT ECO:0000269|PubMed:22171320}. FT VAR_SEQ 307 418 Missing (in isoform 3). FT {ECO:0000303|Ref.10}. FT /FTId=VSP_028890. FT VAR_SEQ 356 418 AVHKAVLTIDEKGTEAAGAMFLEAIPMSIPPEVKFNKPFVF FT LMIEQNTKSPLFMGKVVNPTQK -> VRSP (in FT isoform 2). {ECO:0000303|Ref.10}. FT /FTId=VSP_028889. FT VARIANT 4 4 S -> L (in Z-Wrexham). FT {ECO:0000269|PubMed:2227940}. FT /FTId=VAR_006978. FT VARIANT 26 26 D -> A (in V-Munich; dbSNP:rs199422212). FT {ECO:0000269|PubMed:2316526}. FT /FTId=VAR_006979. FT VARIANT 37 37 T -> A (in dbSNP:rs11558262). FT /FTId=VAR_051938. FT VARIANT 58 58 A -> T (in M5-Karlsruhe; FT dbSNP:rs149319176). FT {ECO:0000269|PubMed:7977369}. FT /FTId=VAR_006980. FT VARIANT 63 63 R -> C (in I; dbSNP:rs28931570). FT {ECO:0000269|PubMed:2606478}. FT /FTId=VAR_006981. FT VARIANT 65 65 L -> P (in M-Procida; dbSNP:rs28931569). FT {ECO:0000269|PubMed:3262617}. FT /FTId=VAR_006982. FT VARIANT 69 69 S -> F (in M6-Bonn; dbSNP:rs199687431). FT {ECO:0000269|PubMed:7977369}. FT /FTId=VAR_006983. FT VARIANT 75 75 Missing (in M-Malton, M-Nichinan and M- FT Palermo; associated with very low serum FT levels of AAT; homozygosity for allele M- FT Malton may be associated with a risk for FT chronic emphysema or infantile liver FT cirrhosis). {ECO:0000269|PubMed:2309708, FT ECO:0000269|PubMed:2606478, FT ECO:0000269|PubMed:2786335, FT ECO:0000269|PubMed:7977369}. FT /FTId=VAR_006984. FT VARIANT 77 77 S -> F (in S-Iiyama; dbSNP:rs55819880). FT {ECO:0000269|PubMed:1905728}. FT /FTId=VAR_006985. FT VARIANT 84 84 A -> T (in M6-Passau; dbSNP:rs111850950). FT {ECO:0000269|PubMed:7977369}. FT /FTId=VAR_006986. FT VARIANT 91 91 G -> E (in M-Mineral springs; causes FT reduced AAT secretion; dbSNP:rs28931568). FT {ECO:0000269|PubMed:1967187}. FT /FTId=VAR_006987. FT VARIANT 92 92 T -> I (in QO-Lisbon; deficient AAT with FT very low serum levels; FT dbSNP:rs1490133295). FT /FTId=VAR_006988. FT VARIANT 109 109 T -> M (in Z-Bristol; deficient AA; FT disrupts the N-glycosylation site N-107; FT dbSNP:rs199422213). FT {ECO:0000269|PubMed:9459000}. FT /FTId=VAR_011620. FT VARIANT 112 112 P -> T (in M5-Berlin; dbSNP:rs886044322). FT {ECO:0000269|PubMed:7977369}. FT /FTId=VAR_006989. FT VARIANT 116 116 I -> N (in QO-Ludwigshafen; FT dbSNP:rs28931572). FT {ECO:0000269|PubMed:2254451}. FT /FTId=VAR_006990. FT VARIANT 125 125 R -> H (in M2; associated with D-400; FT dbSNP:rs709932). FT /FTId=VAR_006991. FT VARIANT 139 139 G -> S (in QO-Newport; dbSNP:rs11558261). FT {ECO:0000269|PubMed:2227940}. FT /FTId=VAR_006992. FT VARIANT 172 172 G -> R (in V and M-Nichinan; FT dbSNP:rs112030253). FT {ECO:0000269|PubMed:7977369}. FT /FTId=VAR_006993. FT VARIANT 172 172 G -> W (in M2-Obernburg; FT dbSNP:rs112030253). FT {ECO:0000269|PubMed:7977369, FT ECO:0000269|Ref.8}. FT /FTId=VAR_006994. FT VARIANT 180 180 Q -> E (in L-Frankfurt; FT dbSNP:rs864622051). FT {ECO:0000269|PubMed:7977369}. FT /FTId=VAR_006995. FT VARIANT 190 198 QGKIVDLVK -> GFQNAILVR (in Aberrant FT form). FT /FTId=VAR_036746. FT VARIANT 228 228 E -> K (in X; dbSNP:rs199422208). FT /FTId=VAR_006996. FT VARIANT 237 237 V -> A (in M1A and Z; associated with K- FT 366 in Z; dbSNP:rs6647). FT {ECO:0000269|PubMed:17650587, FT ECO:0000269|PubMed:23826168, FT ECO:0000269|Ref.12, ECO:0000269|Ref.8}. FT /FTId=VAR_006997. FT VARIANT 247 247 R -> C (in F; dbSNP:rs28929470). FT {ECO:0000269|PubMed:2035534}. FT /FTId=VAR_006998. FT VARIANT 280 280 D -> V (in P-Duarte/P-Cardiff/P-Lowell; FT associated with H-415 in Y-Barcelona; FT dbSNP:rs121912714). FT {ECO:0000269|PubMed:10651487, FT ECO:0000269|PubMed:2606478, FT ECO:0000269|PubMed:8364590}. FT /FTId=VAR_006999. FT VARIANT 288 288 E -> V (in S and T; dbSNP:rs17580). FT {ECO:0000269|PubMed:23826168, FT ECO:0000269|Ref.17}. FT /FTId=VAR_007000. FT VARIANT 305 305 Missing (in Basque). FT {ECO:0000269|PubMed:10612848}. FT /FTId=VAR_009216. FT VARIANT 354 354 S -> F (in S-Munich; dbSNP:rs201788603). FT {ECO:0000269|PubMed:7977369}. FT /FTId=VAR_007001. FT VARIANT 360 360 A -> T (in W-Bethesda; dbSNP:rs1802959). FT {ECO:0000269|PubMed:2390072}. FT /FTId=VAR_007002. FT VARIANT 365 365 D -> N (in P-St.Albans/P-Donauwoerth; FT dbSNP:rs143370956). FT {ECO:0000269|PubMed:7977369}. FT /FTId=VAR_007003. FT VARIANT 366 366 E -> K (in Z/Z-Augsburg/Z-Tun; associated FT with A-237 in Z; dbSNP:rs28929474). FT {ECO:0000269|PubMed:2339709, FT ECO:0000269|PubMed:23826168, FT ECO:0000269|Ref.8}. FT /FTId=VAR_007004. FT VARIANT 382 382 M -> R (in Pittsburgh; has antithrombin FT activity; inhibits factor VIIa activity; FT causes fatal bleeding diathesis; FT dbSNP:rs121912713). FT {ECO:0000269|PubMed:12860985, FT ECO:0000269|PubMed:26797521, FT ECO:0000269|PubMed:6604220}. FT /FTId=VAR_007005. FT VARIANT 386 386 P -> H (in Sao Tome; dbSNP:rs569384943). FT {ECO:0000269|Ref.73}. FT /FTId=VAR_007006. FT VARIANT 386 386 P -> T (in L-Offenbach; dbSNP:rs12233). FT {ECO:0000269|PubMed:7977369}. FT /FTId=VAR_007007. FT VARIANT 387 387 E -> K (in Christchurch; FT dbSNP:rs121912712). FT /FTId=VAR_007008. FT VARIANT 393 393 P -> L (in M-Heerlen; dbSNP:rs199422209). FT {ECO:0000269|PubMed:2784123}. FT /FTId=VAR_007009. FT VARIANT 400 400 E -> D (in M2 and M3; associated with H- FT 125 in M2; dbSNP:rs1303). FT {ECO:0000269|PubMed:17650587, FT ECO:0000269|PubMed:2394452}. FT /FTId=VAR_007010. FT VARIANT 415 415 P -> H (in Y-Barcelona; associated with FT V-280). {ECO:0000269|PubMed:10651487}. FT /FTId=VAR_007011. FT MUTAGEN 382 382 M->V: Oxidation-resistant inhibitor of FT therapeutic importance. FT {ECO:0000269|PubMed:6387509}. FT CONFLICT 12 12 Missing (in Ref. 4; AAA51546). FT {ECO:0000305}. FT CONFLICT 23 23 L -> P (in Ref. 11; BAG38005). FT {ECO:0000305}. FT CONFLICT 26 26 D -> H (in Ref. 18; AA sequence). FT {ECO:0000305}. FT CONFLICT 39 39 H -> L (in Ref. 18; AA sequence). FT {ECO:0000305}. FT CONFLICT 61 61 L -> P (in Ref. 9; AAF29581). FT {ECO:0000305}. FT CONFLICT 96 96 T -> A (in Ref. 7; ABG73380). FT {ECO:0000305}. FT CONFLICT 139 140 GN -> DG (in Ref. 1; AAB59375). FT {ECO:0000305}. FT CONFLICT 174 174 T -> H (in Ref. 4; AAA51546). FT {ECO:0000305}. FT CONFLICT 229 229 E -> D (in Ref. 4; AAA51546). FT {ECO:0000305}. FT CONFLICT 273 273 T -> N (in Ref. 1; AAB59375). FT {ECO:0000305}. FT CONFLICT 280 280 D -> G (in Ref. 7; ABG73380). FT {ECO:0000305}. FT CONFLICT 326 326 V -> I (in Ref. 3; CAA25838). FT {ECO:0000305}. FT CONFLICT 410 410 G -> L (in Ref. 24; AA sequence). FT {ECO:0000305}. FT CONFLICT 414 414 N -> S (in Ref. 24; AA sequence). FT {ECO:0000305}. FT TURN 48 50 {ECO:0000244|PDB:1HP7}. FT HELIX 51 68 {ECO:0000244|PDB:3NDD}. FT STRAND 70 72 {ECO:0000244|PDB:5NBU}. FT STRAND 74 76 {ECO:0000244|PDB:3NDD}. FT HELIX 78 89 {ECO:0000244|PDB:3NDD}. FT HELIX 94 103 {ECO:0000244|PDB:3NDD}. FT TURN 108 110 {ECO:0000244|PDB:3NDD}. FT HELIX 113 127 {ECO:0000244|PDB:3NDD}. FT STRAND 135 145 {ECO:0000244|PDB:3NDD}. FT STRAND 146 148 {ECO:0000244|PDB:1ATU}. FT HELIX 152 162 {ECO:0000244|PDB:3NDD}. FT STRAND 164 169 {ECO:0000244|PDB:3NDD}. FT STRAND 171 173 {ECO:0000244|PDB:1ATU}. FT HELIX 174 188 {ECO:0000244|PDB:3NDD}. FT TURN 189 191 {ECO:0000244|PDB:3NDD}. FT STRAND 206 220 {ECO:0000244|PDB:3NDD}. FT HELIX 224 226 {ECO:0000244|PDB:3NDD}. FT STRAND 228 235 {ECO:0000244|PDB:3NDD}. FT STRAND 238 256 {ECO:0000244|PDB:3NDD}. FT TURN 257 260 {ECO:0000244|PDB:3NDD}. FT STRAND 261 279 {ECO:0000244|PDB:3NDD}. FT STRAND 280 282 {ECO:0000244|PDB:1ATU}. FT HELIX 284 290 {ECO:0000244|PDB:3NDD}. FT HELIX 293 301 {ECO:0000244|PDB:3NDD}. FT STRAND 306 313 {ECO:0000244|PDB:3NDD}. FT STRAND 315 322 {ECO:0000244|PDB:3NDD}. FT HELIX 324 329 {ECO:0000244|PDB:3NDD}. FT HELIX 334 336 {ECO:0000244|PDB:3NDD}. FT TURN 337 339 {ECO:0000244|PDB:1QMB}. FT TURN 343 345 {ECO:0000244|PDB:3NDD}. FT STRAND 347 349 {ECO:0000244|PDB:3NDD}. FT STRAND 351 364 {ECO:0000244|PDB:3NDD}. FT STRAND 366 381 {ECO:0000244|PDB:3NDD}. FT STRAND 387 389 {ECO:0000244|PDB:3NDD}. FT STRAND 394 400 {ECO:0000244|PDB:3NDD}. FT TURN 401 403 {ECO:0000244|PDB:3NDD}. FT STRAND 406 414 {ECO:0000244|PDB:3NDD}. SQ SEQUENCE 418 AA; 46737 MW; 7016555F273B7F16 CRC64; MPSSVSWGIL LLAGLCCLVP VSLAEDPQGD AAQKTDTSHH DQDHPTFNKI TPNLAEFAFS LYRQLAHQSN STNIFFSPVS IATAFAMLSL GTKADTHDEI LEGLNFNLTE IPEAQIHEGF QELLRTLNQP DSQLQLTTGN GLFLSEGLKL VDKFLEDVKK LYHSEAFTVN FGDTEEAKKQ INDYVEKGTQ GKIVDLVKEL DRDTVFALVN YIFFKGKWER PFEVKDTEEE DFHVDQVTTV KVPMMKRLGM FNIQHCKKLS SWVLLMKYLG NATAIFFLPD EGKLQHLENE LTHDIITKFL ENEDRRSASL HLPKLSITGT YDLKSVLGQL GITKVFSNGA DLSGVTEEAP LKLSKAVHKA VLTIDEKGTE AAGAMFLEAI PMSIPPEVKF NKPFVFLMIE QNTKSPLFMG KVVNPTQK //