ID A1AT_HUMAN Reviewed; 418 AA. AC P01009; A6PX14; B2RDQ8; Q0PVP5; Q13672; Q53XB8; Q5U0M1; Q7M4R2; Q86U18; AC Q86U19; Q96BF9; Q96ES1; Q9P1P0; Q9UCE6; Q9UCM3; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 3. DT 27-MAR-2024, entry version 283. DE RecName: Full=Alpha-1-antitrypsin {ECO:0000305}; 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 {ECO:0000312|HGNC:HGNC:8941}; Synonyms=AAT, PI; GN ORFNames=PRO0684, PRO2209; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC 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 complementary RT 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 gene RT 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 human RT 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; DOI=10.1016/s0021-9258(18)66664-5; 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 the RT Z type alpha 1-antitrypsin gene."; RL J. Biol. Chem. 261:15989-15994(1986). RN [6] RP ERRATUM OF PUBMED:3491072. 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 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., Zhou W., RA Bi J., Zhang Y., Liu M., He F.; RT "Functional prediction of the coding sequences of 32 new genes deduced by RT 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., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., 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., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA 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 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 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 project: RT 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 human RT 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-GLN--LYS-198 DELINS GLY-PHE-GLN-ASN-ALA-ILE-LEU-VAL-ARG AND VAL-288, RP AND FUNCTION. RC TISSUE=Blood; RA Sinha A.K., Girish G.V.; RT "Appearance of an aberrant form of alpha-antitrypsin in the circulation of RT chronic cigarette smokers and its effect on the insulin induced NO RT 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., Fujimura S.; RT "Characterization of a 54 kDa, alpha 1-antitrypsin-like protein isolated RT 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 AT RP ASN-70; ASN-107 AND ASN-271, STRUCTURE OF CARBOHYDRATES, CYSTEINE-BINDING, RP 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 and its RT 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 antitrypsin, RT 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 IDENTIFICATION RP 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, acute RT 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., Marchioro T.L., RA 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; DOI=10.1016/s0934-8832(11)80066-1; RA Niemann M.A., Narkates A.J., Miller E.J.; RT "Isolation and serine protease inhibitory activity of the 44-residue, C- RT 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 library."; RL Biomed. Biochim. Acta 44:421-431(1985). RN [26] RP CLEAVAGE BY STAPHYLOCOCCUS AUREUS PROTEASES (MICROBIAL INFECTION). RX PubMed=3533918; DOI=10.1016/s0021-9258(18)67022-x; RA Potempa J., Watorek W., Travis J.; RT "The inactivation of human plasma alpha 1-proteinase inhibitor by RT proteinases from Staphylococcus aureus."; RL J. Biol. Chem. 261:14330-14334(1986). RN [27] 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 [28] 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., Thuluvath P.J., RA 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 [29] 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 [30] 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., Moore R.J., RA 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 [31] 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 [32] 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 multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [33] 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., Zheng Z.B., RA Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L., RA Ying W.T., He S.M., Qian X.H.; RT "A strategy for precise and large scale identification of core fucosylated RT glycoproteins."; RL Mol. Cell. Proteomics 8:913-923(2009). RN [34] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-70; ASN-107 AND ASN-271, AND RP 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., Brinkmalm G., RA Larson G.; RT "Enrichment of glycopeptides for glycan structure and attachment site RT identification."; RL Nat. Methods 6:809-811(2009). RN [35] 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., Buerckstuemmer T., RA 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 [36] 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 N- and RT O-linked glycosylations by CID and ECD."; RL Mol. Cell. Proteomics 11:1-17(2012). RN [37] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-383, AND IDENTIFICATION BY RP 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., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [38] 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 phosphoproteome."; RL Cell 161:1619-1632(2015). RN [39] 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., Ayoub D., RA 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 [40] RP INTERACTION WITH CELA2A. RX PubMed=31358993; DOI=10.1038/s41588-019-0470-3; RA Esteghamat F., Broughton J.S., Smith E., Cardone R., Tyagi T., Guerra M., RA Szabo A., Ugwu N., Mani M.V., Azari B., Kayingo G., Chung S., Fathzadeh M., RA Weiss E., Bender J., Mane S., Lifton R.P., Adeniran A., Nathanson M.H., RA Gorelick F.S., Hwa J., Sahin-Toth M., Belfort-DeAguiar R., Kibbey R.G., RA Mani A.; RT "CELA2A mutations predispose to early-onset atherosclerosis and metabolic RT syndrome and affect plasma insulin and platelet activation."; RL Nat. Genet. 51:1233-1243(2019). RN [41] RP INTERACTION WITH ERGIC3 AND LMAN1. RX PubMed=31142615; DOI=10.1074/jbc.ra119.007435; RA Yoo W., Cho E.B., Kim S., Yoon J.B.; RT "The E3 ubiquitin ligase MARCH2 regulates ERGIC3-dependent trafficking of RT secretory proteins."; RL J. Biol. Chem. 294:10900-10912(2019). RN [42] 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 [43] 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., Laurell C.-B.; RT "The S variant of human alpha 1-antitrypsin, structure and implications for RT function and metabolism."; RL Protein Eng. 2:407-415(1989). RN [44] 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 [45] 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-antitrypsin."; RL Nat. Struct. Biol. 3:676-681(1996). RN [46] 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 of a RT serine protease inhibitor: crystal structure of an uncleaved alpha1- RT antitrypsin at 2.7 A."; RL Structure 4:1181-1192(1996). RN [47] 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 [48] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 48-418 IN COMPLEX WITH BOVINE RP PRSS1, AND INTERACTION WITH BOVINE PRSS1. 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 deformation."; RL Nature 407:923-926(2000). RN [49] 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., Feil S.C., RA 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 [50] 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 for RT rational drug design to prevent conformational disease."; RL Protein Sci. 9:1274-1281(2000). RN [51] 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 shows RT variability of the reactive center and other loops."; RL J. Mol. Biol. 306:109-119(2001). RN [52] 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 [53] 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 [54] 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 [55] 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 [56] 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-antitrypsin RT normal M2 allele."; RL Am. J. Hum. Genet. 43:322-330(1988). RN [57] 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 variant."; RL Hum. Genet. 85:381-382(1990). RN [58] 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 [59] 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 [60] 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 alpha RT 1-antitrypsin."; RL Am. J. Hum. Genet. 44:894-902(1989). RN [61] RP VARIANT M-MINERAL SPRINGS GLU-91. RX PubMed=1967187; DOI=10.1128/mcb.10.1.47-56.1990; 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 associated RT with the alpha 1-antitrypsin M-Mineral springs allele."; RL Mol. Cell. Biol. 10:47-56(1990). RN [62] RP VARIANT M-NICHINAN PHE-75 DEL. RX PubMed=2309708; RA Matsunaga E., Shiokawa S., Nakamura H., Maruyama T., Tsuda K., 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 [63] RP VARIANT M-PROCIDA PRO-65. RX PubMed=3262617; DOI=10.1016/s0021-9258(19)37620-3; 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 [64] 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 [65] 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 Pittsburgh RT (358 Met leads to Arg), a fatal bleeding disorder."; RL N. Engl. J. Med. 309:694-698(1983). RN [66] RP INVOLVEMENT IN A1ATD, AND VARIANT S-IIYAMA PHE-77. RX PubMed=1905728; DOI=10.1016/s0021-9258(18)98945-3; 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 [67] 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 pattern."; RL Am. J. Hum. Genet. 46:810-816(1990). RN [68] 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 1- RT antitrypsin deficiency variant."; RL Biochem. Biophys. Res. Commun. 170:1013-1020(1990). RN [69] 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 [70] RP INVOLVEMENT IN A1ATD, AND VARIANTS LEU-4 AND 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 variants: RT proteinase inhibitor (Pi) Null(Newport) (Gly115-->Ser) and (Pi) Z Wrexham RT (Ser-19-->Leu)."; RL Hum. Genet. 85:537-540(1990). RN [71] RP VARIANTS CYS-63; PHE-75 DEL AND VAL-280. 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-Malton RT (Phe51-->deletion) and PiI (Arg39-->Cys)."; RL Hum. Genet. 84:55-58(1989). RN [72] RP VARIANT 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, with RT altered tertiary structure."; RL J. Clin. Invest. 86:1878-1884(1990). RN [73] RP VARIANTS THR-58; PHE-69; PHE-75 DEL; THR-84; THR-112; ARG-172; TRP-172; RP GLU-180; PHE-354; ASN-365 AND 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-antitrypsin RT variants, including two PI*Q0 alleles and one deficient PI*M allele."; RL Am. J. Hum. Genet. 55:1113-1121(1994). RN [74] RP VARIANT Z-BRISTOL MET-109. RX PubMed=9459000; DOI=10.1046/j.1469-1809.1997.6150385.x; 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) associated RT with novel electrophoretic properties."; RL Ann. Hum. Genet. 61:385-391(1997). RN [75] 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 Pro391His)."; RL Hum. Mutat. 12:213-213(1998). RN [76] 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 sample RT from Sao Tome e Principe (Gulf of Guinea, West Africa)."; RL Hum. Mutat. 13:414-414(1999). RN [77] 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 sample RT from the Basque country."; RL Hum. Mutat. 15:121-122(2000). RN [78] RP VARIANTS Z ALA-237 AND LYS-366, VARIANT S VAL-288, SUBCELLULAR LOCATION, RP TISSUE SPECIFICITY, GLYCOSYLATION, AND INTERACTION WITH CANX 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 [79] 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 coagulation RT 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 thrombin. CC Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. CC The aberrant form inhibits insulin-induced NO synthesis in platelets, CC decreases coagulation time and has proteolytic activity against insulin CC and plasmin. CC -!- FUNCTION: [Short peptide from AAT]: Reversible chymotrypsin inhibitor. CC It also inhibits elastase, but not trypsin. Its major physiological CC function is the protection of the lower respiratory tract against CC proteolytic destruction by human leukocyte elastase (HLE). CC -!- SUBUNIT: Interacts with CELA2A (PubMed:31358993). Interacts with ERGIC3 CC and LMAN1/ERGIC53 (PubMed:31142615). Interacts with PRSS1/trypsin CC (PubMed:11057674). Interacts with PRSS1/Trypsin (PubMed:11057674). The CC variants S and Z interact with CANX and PDIA3 (PubMed:23826168). CC {ECO:0000269|PubMed:11057674, ECO:0000269|PubMed:23826168, CC ECO:0000269|PubMed:31142615, ECO:0000269|PubMed:31358993}. CC -!- INTERACTION: CC P01009; Q9Y282: ERGIC3; NbExp=2; IntAct=EBI-986224, EBI-781551; CC P01009; Q8N7X4: MAGEB6; NbExp=3; IntAct=EBI-986224, EBI-6447163; CC P01009; P01009: SERPINA1; NbExp=7; IntAct=EBI-986224, EBI-986224; CC P01009; P43307: SSR1; NbExp=4; IntAct=EBI-986224, EBI-714168; CC P01009; O15393: TMPRSS2; NbExp=2; IntAct=EBI-986224, EBI-12549863; CC P01009; P00772: CELA1; Xeno; NbExp=2; IntAct=EBI-986224, EBI-986248; CC P01009; P71213: espB; Xeno; NbExp=3; IntAct=EBI-986224, EBI-2615322; CC P01009; P00760: PRSS1; Xeno; NbExp=5; IntAct=EBI-986224, EBI-986385; CC -!- SUBCELLULAR LOCATION: Secreted. Endoplasmic reticulum. Note=The S and Z CC allele are not secreted effectively and accumulate intracellularly in CC the endoplasmic reticulum. CC -!- SUBCELLULAR LOCATION: [Short peptide from AAT]: Secreted, extracellular CC 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 Name=3; CC IsoId=P01009-3; Sequence=VSP_028890; CC -!- TISSUE SPECIFICITY: Ubiquitous. Expressed in leukocytes and plasma. CC {ECO:0000269|PubMed:23826168}. CC -!- DOMAIN: The reactive center loop (RCL) extends out from the body of the CC protein and directs binding to the target protease. The protease CC cleaves the serpin at the reactive site within the RCL, establishing a CC covalent linkage between the carboxyl group of the serpin reactive site CC and the serine hydroxyl of the protease. The resulting inactive serpin- CC protease complex is highly stable. CC -!- PTM: N-glycosylated. Differential glycosylation produces a number of CC isoforms. N-linked glycan at Asn-107 is alternatively di-antennary, CC tri-antennary or tetra-antennary. The glycan at Asn-70 is di-antennary CC with trace amounts of tri-antennary. Glycan at Asn-271 is exclusively CC di-antennary. Structure of glycans at Asn-70 and Asn-271 is CC Hex5HexNAc4. The structure of the antennae is Neu5Ac(alpha1- CC 6)Gal(beta1-4)GlcNAc attached to the core structure Man(alpha1- CC 6)[Man(alpha1-3)]Man(beta1-4)GlcNAc(beta1-4)GlcNAc. Some antennae are CC 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 ranges CC from Asp-30 to Lys-418. CC -!- PTM: (Microbial infection) Proteolytically processed by Staphylococcus CC aureus seryl, cysteinyl, and metallo-proteases. CC {ECO:0000269|PubMed:3533918}. CC -!- POLYMORPHISM: The sequence shown is that of the M1V allele which is the CC most common form of PI (44 to 49%). Other frequent alleles are: M1A 20 CC to 23%; M2 10 to 11%; M3 14 to 19%. {ECO:0000269|PubMed:2901226}. CC -!- DISEASE: Alpha-1-antitrypsin deficiency (A1ATD) [MIM:613490]: A CC disorder whose most common manifestation is emphysema, which becomes CC evident by the third to fourth decade. A less common manifestation of CC the deficiency is liver disease, which occurs in children and adults, CC and may result in cirrhosis and liver failure. Environmental factors, CC particularly cigarette smoking, greatly increase the risk of emphysema CC at an earlier age. {ECO:0000269|PubMed:1905728, CC ECO:0000269|PubMed:2227940, ECO:0000269|PubMed:2390072}. Note=The CC disease is caused by variants affecting the gene represented in this CC 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 found CC ten years after smoking has ceased. CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA CC decay. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the serpin family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAD62334.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAD62585.1; Type=Erroneous initiation; Note=Extended N-terminus.; 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 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; 6HX4; X-ray; 2.95 A; A/B=24-418. DR PDB; 6I4V; X-ray; 1.78 A; A=26-418. DR PDB; 6I7U; X-ray; 1.55 A; A=26-418. DR PDB; 6IAY; X-ray; 1.90 A; A=26-418. DR PDB; 6ROD; X-ray; 1.85 A; A=26-418. DR PDB; 7AEL; X-ray; 1.76 A; AAA=26-418. DR PDB; 7API; X-ray; 3.00 A; A=36-382, B=383-418. DR PDB; 7NPK; X-ray; 1.83 A; A=26-417. DR PDB; 7NPL; X-ray; 1.82 A; A=26-418. DR PDB; 8API; X-ray; 3.10 A; A=36-382, B=383-418. DR PDB; 8PI2; X-ray; 1.48 A; A=26-418. 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; 6HX4; -. DR PDBsum; 6I4V; -. DR PDBsum; 6I7U; -. DR PDBsum; 6IAY; -. DR PDBsum; 6ROD; -. DR PDBsum; 7AEL; -. DR PDBsum; 7API; -. DR PDBsum; 7NPK; -. DR PDBsum; 7NPL; -. DR PDBsum; 8API; -. DR PDBsum; 8PI2; -. DR PDBsum; 9API; -. DR AlphaFoldDB; P01009; -. DR BMRB; P01009; -. DR EMDB; EMD-4620; -. DR EMDB; EMD-4631; -. DR EMDB; EMD-4632; -. DR PCDDB; P01009; -. DR SMR; P01009; -. DR BioGRID; 111283; 165. DR CORUM; P01009; -. DR DIP; DIP-35493N; -. DR IntAct; P01009; 46. DR MINT; P01009; -. DR STRING; 9606.ENSP00000416066; -. DR DrugBank; DB01998; 2-[3,4-Dihydroxy-2-Hydroxymethyl-5-(2-Hydroxy-Nonyl)-Tetrahydro-Furan-2-Yloxy]-6-Hydroxymethyl-Tetra Hydro-Pyran-3,4,5-Triol. DR DrugBank; DB09130; Copper. DR DrugBank; DB00080; Daptomycin. DR DrugBank; DB03345; Mercaptoethanol. DR DrugBank; DB14007; Pentetic acid. DR DrugBank; DB05961; PPL-100. DR DrugBank; DB05481; Recombinant alpha 1-antitrypsin. DR DrugBank; DB01593; Zinc. DR DrugBank; DB14487; Zinc acetate. DR DrugBank; DB14533; Zinc chloride. DR DrugBank; DB14548; Zinc sulfate, unspecified form. DR MEROPS; I04.001; -. DR CarbonylDB; P01009; -. DR GlyConnect; 20; 101 N-Linked glycans (4 sites), 3 O-Linked glycans (2 sites). DR GlyCosmos; P01009; 10 sites, 101 glycans. DR GlyGen; P01009; 11 sites, 120 N-linked glycans (5 sites), 5 O-linked glycans (6 sites). DR iPTMnet; P01009; -. DR MetOSite; P01009; -. DR PhosphoSitePlus; P01009; -. DR SwissPalm; P01009; -. DR BioMuta; SERPINA1; -. DR DMDM; 1703025; -. DR DOSAC-COBS-2DPAGE; P01009; -. DR OGP; P01009; -. DR REPRODUCTION-2DPAGE; IPI00553177; -. DR REPRODUCTION-2DPAGE; P01009; -. DR CPTAC; CPTAC-651; -. DR CPTAC; non-CPTAC-1063; -. DR EPD; P01009; -. DR jPOST; P01009; -. DR MassIVE; P01009; -. DR MaxQB; P01009; -. DR PaxDb; 9606-ENSP00000416066; -. DR PeptideAtlas; P01009; -. DR PRIDE; P01009; -. DR ProteomicsDB; 51300; -. [P01009-1] DR ProteomicsDB; 51301; -. [P01009-2] DR ProteomicsDB; 51302; -. [P01009-3] DR ABCD; P01009; 3 sequenced antibodies. DR Antibodypedia; 767; 1882 antibodies from 49 providers. DR CPTC; P01009; 1 antibody. DR DNASU; 5265; -. DR Ensembl; ENST00000355814.8; ENSP00000348068.4; ENSG00000197249.14. [P01009-1] DR Ensembl; ENST00000393087.9; ENSP00000376802.4; ENSG00000197249.14. [P01009-1] DR Ensembl; ENST00000393088.8; ENSP00000376803.4; ENSG00000197249.14. [P01009-1] DR Ensembl; ENST00000402629.1; ENSP00000386094.1; ENSG00000197249.14. [P01009-2] DR Ensembl; ENST00000404814.8; ENSP00000385960.4; ENSG00000197249.14. [P01009-1] DR Ensembl; ENST00000437397.5; ENSP00000408474.1; ENSG00000197249.14. [P01009-1] DR Ensembl; ENST00000440909.5; ENSP00000390299.1; ENSG00000197249.14. [P01009-1] DR Ensembl; ENST00000448921.5; ENSP00000416066.1; ENSG00000197249.14. [P01009-1] DR Ensembl; ENST00000449399.7; ENSP00000416354.3; ENSG00000197249.14. [P01009-1] DR Ensembl; ENST00000489769.1; ENSP00000451525.1; ENSG00000197249.14. [P01009-3] DR Ensembl; ENST00000636712.1; ENSP00000490054.1; ENSG00000197249.14. [P01009-1] DR GeneID; 5265; -. DR KEGG; hsa:5265; -. DR MANE-Select; ENST00000393087.9; ENSP00000376802.4; NM_000295.5; NP_000286.3. DR UCSC; uc001ycx.5; human. [P01009-1] DR AGR; HGNC:8941; -. DR CTD; 5265; -. DR DisGeNET; 5265; -. DR GeneCards; SERPINA1; -. DR GeneReviews; SERPINA1; -. DR HGNC; HGNC:8941; SERPINA1. DR HPA; ENSG00000197249; Tissue enriched (liver). 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; 586; Cystic fibrosis. DR Orphanet; 178396; Hemorrhagic disease due to alpha-1-antitrypsin Pittsburgh mutation. DR PharmGKB; PA35509; -. DR VEuPathDB; HostDB:ENSG00000197249; -. DR eggNOG; KOG2392; Eukaryota. DR GeneTree; ENSGT00940000154493; -. DR HOGENOM; CLU_023330_2_1_1; -. DR InParanoid; P01009; -. DR OMA; MEIMPMS; -. DR OrthoDB; 3218836at2759; -. DR PhylomeDB; P01009; -. DR TreeFam; TF343201; -. DR PathwayCommons; P01009; -. 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 SignaLink; P01009; -. DR SIGNOR; P01009; -. DR BioGRID-ORCS; 5265; 12 hits in 1171 CRISPR screens. DR ChiTaRS; SERPINA1; human. DR EvolutionaryTrace; P01009; -. DR GeneWiki; Alpha_1-antitrypsin; -. DR GenomeRNAi; 5265; -. DR Pharos; P01009; Tbio. DR PRO; PR:P01009; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; P01009; Protein. DR Bgee; ENSG00000197249; Expressed in right lobe of liver and 96 other cell types or tissues. DR ExpressionAtlas; P01009; baseline and differential. 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: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 CDD; cd02056; serpinA1_A1AT; 1. DR Gene3D; 2.30.39.10; Alpha-1-antitrypsin, domain 1; 1. DR Gene3D; 3.30.497.10; Antithrombin, subunit I, domain 2; 1. DR Gene3D; 2.10.310.10; Serpins superfamily; 1. DR InterPro; IPR023795; Serpin_CS. DR InterPro; IPR023796; Serpin_dom. DR InterPro; IPR000215; Serpin_fam. DR InterPro; IPR036186; Serpin_sf. DR InterPro; IPR042178; Serpin_sf_1. DR InterPro; IPR042185; Serpin_sf_2. DR PANTHER; PTHR11461:SF165; ALPHA-1-ANTITRYPSIN; 1. DR PANTHER; PTHR11461; SERINE PROTEASE INHIBITOR, SERPIN; 1. DR Pfam; PF00079; Serpin; 1. DR SMART; SM00093; SERPIN; 1. DR SUPFAM; SSF56574; Serpins; 1. DR PROSITE; PS00284; SERPIN; 1. DR SWISS-2DPAGE; P01009; -. DR UCD-2DPAGE; P01009; -. DR Genevisible; P01009; HS. PE 1: Evidence at protein level; KW 3D-structure; Acute phase; Alternative splicing; Blood coagulation; KW Direct protein sequencing; Endoplasmic reticulum; Extracellular matrix; KW Glycoprotein; Hemostasis; Phosphoprotein; Protease inhibitor; KW Reference proteome; Secreted; Serine protease inhibitor; Signal. FT SIGNAL 1..24 FT /evidence="ECO:0000269|PubMed:1906855" FT CHAIN 25..418 FT /note="Alpha-1-antitrypsin" FT /evidence="ECO:0000269|PubMed:6093867" FT /id="PRO_0000032377" FT PEPTIDE 375..418 FT /note="Short peptide from AAT" FT /id="PRO_0000364030" FT REGION 368..392 FT /note="RCL" FT SITE 352..353 FT /note="(Microbial infection) Cleavage; by Staphylococcus FT aureus aureolysin/Aur" FT /evidence="ECO:0000269|PubMed:3533918" FT SITE 354..355 FT /note="(Microbial infection) Cleavage; by Staphylococcus FT aureus serine and cysteine proteinases" FT /evidence="ECO:0000269|PubMed:3533918" FT SITE 382..383 FT /note="Reactive bond" FT MOD_RES 38 FT /note="Phosphoserine; by FAM20C" FT /evidence="ECO:0000269|PubMed:26091039" FT MOD_RES 256 FT /note="S-cysteinyl cysteine" FT MOD_RES 383 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT CARBOHYD 70 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:12754519, FT ECO:0000269|PubMed:14760718, ECO:0000269|PubMed:15084671, FT ECO:0000269|PubMed:16263699, ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:16622833, ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:22171320" FT CARBOHYD 107 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:16622833, ECO:0000269|PubMed:19139490, FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19838169" FT CARBOHYD 271 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:12754519, FT ECO:0000269|PubMed:14760718, ECO:0000269|PubMed:15084671, FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:16622833, FT ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:22171320" FT VAR_SEQ 307..418 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|Ref.10" FT /id="VSP_028890" FT VAR_SEQ 356..418 FT /note="AVHKAVLTIDEKGTEAAGAMFLEAIPMSIPPEVKFNKPFVFLMIEQNTKSPL FT FMGKVVNPTQK -> VRSP (in isoform 2)" FT /evidence="ECO:0000303|Ref.10" FT /id="VSP_028889" FT VARIANT 4 FT /note="S -> L (in Z-Wrexham)" FT /evidence="ECO:0000269|PubMed:2227940" FT /id="VAR_006978" FT VARIANT 26 FT /note="D -> A (in V-Munich; dbSNP:rs199422212)" FT /evidence="ECO:0000269|PubMed:2316526" FT /id="VAR_006979" FT VARIANT 37 FT /note="T -> A (in dbSNP:rs11558262)" FT /id="VAR_051938" FT VARIANT 58 FT /note="A -> T (in M5-Karlsruhe; dbSNP:rs149319176)" FT /evidence="ECO:0000269|PubMed:7977369" FT /id="VAR_006980" FT VARIANT 63 FT /note="R -> C (in I; dbSNP:rs28931570)" FT /evidence="ECO:0000269|PubMed:2606478" FT /id="VAR_006981" FT VARIANT 65 FT /note="L -> P (in M-Procida; dbSNP:rs28931569)" FT /evidence="ECO:0000269|PubMed:3262617" FT /id="VAR_006982" FT VARIANT 69 FT /note="S -> F (in M6-Bonn; dbSNP:rs199687431)" FT /evidence="ECO:0000269|PubMed:7977369" FT /id="VAR_006983" FT VARIANT 75 FT /note="Missing (in M-Malton, M-Nichinan and M-Palermo; FT associated with very low serum levels of AAT; homozygosity FT for allele M-Malton may be associated with a risk for FT chronic emphysema or infantile liver cirrhosis)" FT /evidence="ECO:0000269|PubMed:2309708, FT ECO:0000269|PubMed:2606478, ECO:0000269|PubMed:2786335, FT ECO:0000269|PubMed:7977369" FT /id="VAR_006984" FT VARIANT 77 FT /note="S -> F (in S-Iiyama; dbSNP:rs55819880)" FT /evidence="ECO:0000269|PubMed:1905728" FT /id="VAR_006985" FT VARIANT 84 FT /note="A -> T (in M6-Passau; dbSNP:rs111850950)" FT /evidence="ECO:0000269|PubMed:7977369" FT /id="VAR_006986" FT VARIANT 91 FT /note="G -> E (in M-Mineral springs; causes reduced AAT FT secretion; dbSNP:rs28931568)" FT /evidence="ECO:0000269|PubMed:1967187" FT /id="VAR_006987" FT VARIANT 92 FT /note="T -> I (in QO-Lisbon; deficient AAT with very low FT serum levels; dbSNP:rs1490133295)" FT /id="VAR_006988" FT VARIANT 109 FT /note="T -> M (in Z-Bristol; deficient AA; disrupts the FT N-glycosylation site N-107; dbSNP:rs199422213)" FT /evidence="ECO:0000269|PubMed:9459000" FT /id="VAR_011620" FT VARIANT 112 FT /note="P -> T (in M5-Berlin; dbSNP:rs886044322)" FT /evidence="ECO:0000269|PubMed:7977369" FT /id="VAR_006989" FT VARIANT 116 FT /note="I -> N (in QO-Ludwigshafen; dbSNP:rs28931572)" FT /evidence="ECO:0000269|PubMed:2254451" FT /id="VAR_006990" FT VARIANT 125 FT /note="R -> H (in M2; associated with D-400; FT dbSNP:rs709932)" FT /id="VAR_006991" FT VARIANT 139 FT /note="G -> S (in QO-Newport; dbSNP:rs11558261)" FT /evidence="ECO:0000269|PubMed:2227940" FT /id="VAR_006992" FT VARIANT 172 FT /note="G -> R (in V and M-Nichinan; dbSNP:rs112030253)" FT /evidence="ECO:0000269|PubMed:7977369" FT /id="VAR_006993" FT VARIANT 172 FT /note="G -> W (in M2-Obernburg; dbSNP:rs112030253)" FT /evidence="ECO:0000269|PubMed:7977369, ECO:0000269|Ref.8" FT /id="VAR_006994" FT VARIANT 180 FT /note="Q -> E (in L-Frankfurt; dbSNP:rs864622051)" FT /evidence="ECO:0000269|PubMed:7977369" FT /id="VAR_006995" FT VARIANT 190..198 FT /note="QGKIVDLVK -> GFQNAILVR (in Aberrant form)" FT /evidence="ECO:0000269|Ref.17" FT /id="VAR_036746" FT VARIANT 228 FT /note="E -> K (in X; dbSNP:rs199422208)" FT /id="VAR_006996" FT VARIANT 237 FT /note="V -> A (in M1A and Z; associated with K-366 in Z; FT dbSNP:rs6647)" FT /evidence="ECO:0000269|PubMed:17650587, FT ECO:0000269|PubMed:23826168, ECO:0000269|Ref.12, FT ECO:0000269|Ref.8" FT /id="VAR_006997" FT VARIANT 247 FT /note="R -> C (in F; dbSNP:rs28929470)" FT /evidence="ECO:0000269|PubMed:2035534" FT /id="VAR_006998" FT VARIANT 280 FT /note="D -> V (in P-Duarte/P-Cardiff/P-Lowell; associated FT with H-415 in Y-Barcelona; dbSNP:rs121912714)" FT /evidence="ECO:0000269|PubMed:10651487, FT ECO:0000269|PubMed:2606478, ECO:0000269|PubMed:8364590" FT /id="VAR_006999" FT VARIANT 288 FT /note="E -> V (in S and T; dbSNP:rs17580)" FT /evidence="ECO:0000269|PubMed:23826168, ECO:0000269|Ref.17" FT /id="VAR_007000" FT VARIANT 305 FT /note="Missing (in Basque)" FT /evidence="ECO:0000269|PubMed:10612848" FT /id="VAR_009216" FT VARIANT 354 FT /note="S -> F (in S-Munich; dbSNP:rs201788603)" FT /evidence="ECO:0000269|PubMed:7977369" FT /id="VAR_007001" FT VARIANT 360 FT /note="A -> T (in W-Bethesda; dbSNP:rs1802959)" FT /evidence="ECO:0000269|PubMed:2390072" FT /id="VAR_007002" FT VARIANT 365 FT /note="D -> N (in P-St.Albans/P-Donauwoerth; FT dbSNP:rs143370956)" FT /evidence="ECO:0000269|PubMed:7977369" FT /id="VAR_007003" FT VARIANT 366 FT /note="E -> K (in Z/Z-Augsburg/Z-Tun; associated with A-237 FT in Z; dbSNP:rs28929474)" FT /evidence="ECO:0000269|PubMed:2339709, FT ECO:0000269|PubMed:23826168, ECO:0000269|Ref.8" FT /id="VAR_007004" FT VARIANT 382 FT /note="M -> R (in Pittsburgh; has antithrombin activity; FT inhibits factor VIIa activity; causes fatal bleeding FT diathesis; dbSNP:rs121912713)" FT /evidence="ECO:0000269|PubMed:12860985, FT ECO:0000269|PubMed:26797521, ECO:0000269|PubMed:6604220" FT /id="VAR_007005" FT VARIANT 386 FT /note="P -> H (in Sao Tome; dbSNP:rs569384943)" FT /evidence="ECO:0000269|Ref.76" FT /id="VAR_007006" FT VARIANT 386 FT /note="P -> T (in L-Offenbach; dbSNP:rs12233)" FT /evidence="ECO:0000269|PubMed:7977369" FT /id="VAR_007007" FT VARIANT 387 FT /note="E -> K (in Christchurch; dbSNP:rs121912712)" FT /id="VAR_007008" FT VARIANT 393 FT /note="P -> L (in M-Heerlen; dbSNP:rs199422209)" FT /evidence="ECO:0000269|PubMed:2784123" FT /id="VAR_007009" FT VARIANT 400 FT /note="E -> D (in M2 and M3; associated with H-125 in M2; FT dbSNP:rs1303)" FT /evidence="ECO:0000269|PubMed:17650587, FT ECO:0000269|PubMed:2394452" FT /id="VAR_007010" FT VARIANT 415 FT /note="P -> H (in Y-Barcelona; associated with V-280)" FT /evidence="ECO:0000269|PubMed:10651487" FT /id="VAR_007011" FT MUTAGEN 382 FT /note="M->V: Oxidation-resistant inhibitor of therapeutic FT importance." FT /evidence="ECO:0000269|PubMed:6387509" FT CONFLICT 12 FT /note="Missing (in Ref. 4; AAA51546)" FT /evidence="ECO:0000305" FT CONFLICT 23 FT /note="L -> P (in Ref. 11; BAG38005)" FT /evidence="ECO:0000305" FT CONFLICT 26 FT /note="D -> H (in Ref. 18; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 39 FT /note="H -> L (in Ref. 18; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 61 FT /note="L -> P (in Ref. 9; AAF29581)" FT /evidence="ECO:0000305" FT CONFLICT 96 FT /note="T -> A (in Ref. 7; ABG73380)" FT /evidence="ECO:0000305" FT CONFLICT 139..140 FT /note="GN -> DG (in Ref. 1; AAB59375)" FT /evidence="ECO:0000305" FT CONFLICT 174 FT /note="T -> H (in Ref. 4; AAA51546)" FT /evidence="ECO:0000305" FT CONFLICT 229 FT /note="E -> D (in Ref. 4; AAA51546)" FT /evidence="ECO:0000305" FT CONFLICT 273 FT /note="T -> N (in Ref. 1; AAB59375)" FT /evidence="ECO:0000305" FT CONFLICT 280 FT /note="D -> G (in Ref. 7; ABG73380)" FT /evidence="ECO:0000305" FT CONFLICT 326 FT /note="V -> I (in Ref. 3; CAA25838)" FT /evidence="ECO:0000305" FT CONFLICT 410 FT /note="G -> L (in Ref. 24; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 414 FT /note="N -> S (in Ref. 24; AA sequence)" FT /evidence="ECO:0000305" FT TURN 48..50 FT /evidence="ECO:0007829|PDB:1HP7" FT HELIX 51..68 FT /evidence="ECO:0007829|PDB:3NDD" FT STRAND 70..72 FT /evidence="ECO:0007829|PDB:6I7U" FT STRAND 74..76 FT /evidence="ECO:0007829|PDB:3NDD" FT HELIX 78..89 FT /evidence="ECO:0007829|PDB:3NDD" FT HELIX 94..103 FT /evidence="ECO:0007829|PDB:3NDD" FT TURN 108..110 FT /evidence="ECO:0007829|PDB:3NDD" FT HELIX 113..127 FT /evidence="ECO:0007829|PDB:3NDD" FT HELIX 130..133 FT /evidence="ECO:0007829|PDB:7NPL" FT STRAND 135..145 FT /evidence="ECO:0007829|PDB:3NDD" FT STRAND 146..148 FT /evidence="ECO:0007829|PDB:1ATU" FT HELIX 152..162 FT /evidence="ECO:0007829|PDB:3NDD" FT STRAND 164..169 FT /evidence="ECO:0007829|PDB:3NDD" FT STRAND 171..173 FT /evidence="ECO:0007829|PDB:1ATU" FT HELIX 174..188 FT /evidence="ECO:0007829|PDB:3NDD" FT TURN 189..191 FT /evidence="ECO:0007829|PDB:3NDD" FT STRAND 206..220 FT /evidence="ECO:0007829|PDB:3NDD" FT HELIX 224..226 FT /evidence="ECO:0007829|PDB:3NDD" FT STRAND 228..235 FT /evidence="ECO:0007829|PDB:3NDD" FT STRAND 238..256 FT /evidence="ECO:0007829|PDB:3NDD" FT TURN 257..260 FT /evidence="ECO:0007829|PDB:3NDD" FT STRAND 261..279 FT /evidence="ECO:0007829|PDB:3NDD" FT STRAND 280..282 FT /evidence="ECO:0007829|PDB:1ATU" FT HELIX 284..290 FT /evidence="ECO:0007829|PDB:3NDD" FT HELIX 293..301 FT /evidence="ECO:0007829|PDB:3NDD" FT STRAND 306..313 FT /evidence="ECO:0007829|PDB:3NDD" FT STRAND 315..322 FT /evidence="ECO:0007829|PDB:3NDD" FT HELIX 324..329 FT /evidence="ECO:0007829|PDB:3NDD" FT HELIX 334..336 FT /evidence="ECO:0007829|PDB:3NDD" FT TURN 337..339 FT /evidence="ECO:0007829|PDB:1QMB" FT TURN 343..345 FT /evidence="ECO:0007829|PDB:3NDD" FT STRAND 347..349 FT /evidence="ECO:0007829|PDB:3NDD" FT STRAND 351..364 FT /evidence="ECO:0007829|PDB:3NDD" FT STRAND 366..381 FT /evidence="ECO:0007829|PDB:3NDD" FT STRAND 387..389 FT /evidence="ECO:0007829|PDB:3NDD" FT STRAND 394..400 FT /evidence="ECO:0007829|PDB:3NDD" FT TURN 401..403 FT /evidence="ECO:0007829|PDB:3NDD" FT STRAND 406..414 FT /evidence="ECO:0007829|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 //