A1AT_HUMAN
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 03-AUG-2022, entry version 274.
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-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 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 Z-WREXHAM LEU-4 AND Q0-NEWPORT 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 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-Malton
RT (Phe51-->deletion) and PiI (Arg39-->Cys).";
RL Hum. Genet. 84:55-58(1989).
RN [72]
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, with
RT altered tertiary structure.";
RL J. Clin. Invest. 86:1878-1884(1990).
RN [73]
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-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; 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 ---------------------------------------------------------------------------
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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; 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; 9API; -.
DR AlphaFoldDB; P01009; -.
DR BMRB; P01009; -.
DR PCDDB; P01009; -.
DR SMR; P01009; -.
DR BioGRID; 111283; 154.
DR CORUM; P01009; -.
DR DIP; DIP-35493N; -.
DR IntAct; P01009; 44.
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 GlyGen; P01009; 11 sites, 112 N-linked glycans (5 sites), 5 O-linked glycans (6 sites).
DR iPTMnet; P01009; -.
DR MetOSite; P01009; -.
DR PhosphoSitePlus; 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 CPTAC; CPTAC-651; -.
DR CPTAC; non-CPTAC-1063; -.
DR EPD; P01009; -.
DR jPOST; P01009; -.
DR MassIVE; P01009; -.
DR MaxQB; P01009; -.
DR PaxDb; P01009; -.
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; 1729 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 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; MEAIPMS; -.
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; 9 hits in 1081 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 94 other tissues.
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: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:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central.
DR Gene3D; 2.30.39.10; -; 1.
DR Gene3D; 3.30.497.10; -; 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; 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 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 N-
FT 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 /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
