ANT3_HUMAN
ID ANT3_HUMAN Reviewed; 464 AA.
AC P01008; B2R6P0; P78439; P78447; Q13815; Q5TC78; Q7KZ43; Q7KZ97; Q9UC78;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 257.
DE RecName: Full=Antithrombin-III;
DE Short=ATIII;
DE AltName: Full=Serpin C1;
DE Flags: Precursor;
GN Name=SERPINC1; Synonyms=AT3; ORFNames=PRO0309;
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 [GENOMIC DNA].
RX PubMed=6298709; DOI=10.1093/nar/10.24.8113;
RA Bock S.C., Wion K.L., Vehar G.A., Lawn R.M.;
RT "Cloning and expression of the cDNA for human antithrombin III.";
RL Nucleic Acids Res. 10:8113-8125(1982).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=6572945; DOI=10.1073/pnas.80.7.1845;
RA Chandra T., Stackhouse R., Kidd V.J., Woo S.L.C.;
RT "Isolation and sequence characterization of a cDNA clone of human
RT antithrombin III.";
RL Proc. Natl. Acad. Sci. U.S.A. 80:1845-1848(1983).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT AT3D MET-438.
RA Tsuji H., Takada O., Nakagawa M., Tanaka S., Hashimoto-Gotoh T.;
RT "Hereditary antithrombin III deficiency: identification of an arginine-406
RT to methionine point mutation near protease reactive site.";
RL (In) Yoshida T.O., Wilson J.M. (eds.);
RL Molecular approaches to the study and treatment of Human diseases,
RL pp.51-55, Elsevier, Amsterdam (1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8476848; DOI=10.1021/bi00067a008;
RA Olds R.J., Lane D.A., Chowdhury V., de Stefano V., Leone G., Thein S.L.;
RT "Complete nucleotide sequence of the antithrombin gene: evidence for
RT homologous recombination causing thrombophilia.";
RL Biochemistry 32:4216-4224(1993).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Fetal liver;
RA Zhang C., Yu Y., Zhang S., Wei H., Bi J., Zhou G., Dong C., Zai Y., Xu W.,
RA Gao F., Liu M., He F.;
RT "Functional prediction of the coding sequences of 75 new genes deduced by
RT analysis of cDNA clones from human fetal liver.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
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 [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLU-30 AND ALA-147.
RG SeattleSNPs variation discovery resource;
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP PROTEIN SEQUENCE OF 33-464, GLYCOSYLATION AT ASN-128; ASN-167; ASN-187 AND
RP ASN-224, AND DISULFIDE BONDS.
RA Petersen T.E., Dudek-Wojciechowska G., Sottrup-Jensen L., Magnusson S.;
RT "Primary structure of antithrombin-III (heparin cofactor). Partial homology
RT between alpha-1-antitrypsin and antithrombin-III.";
RL (In) Collen D., Wiman B., Verstraete M. (eds.);
RL The physiological inhibitors of blood coagulation and fibrinolysis,
RL pp.43-54, Elsevier, Amsterdam (1979).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 42-464.
RX PubMed=6305982; DOI=10.1016/s0021-9258(20)82077-8;
RA Prochownik E.V., Markham A.F., Orkin S.H.;
RT "Isolation of a cDNA clone for human antithrombin III.";
RL J. Biol. Chem. 258:8389-8394(1983).
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 137-208, AND VARIANT AT3D LEU-439.
RX PubMed=3191114; DOI=10.1021/bi00416a052;
RA Bock S.C., Marrinan J.A., Radziejewska E.;
RT "Antithrombin III Utah: proline-407 to leucine mutation in a highly
RT conserved region near the inhibitor reactive site.";
RL Biochemistry 27:6171-6178(1988).
RN [13]
RP PROTEIN SEQUENCE OF 371-425, MASS SPECTROMETRY, AND VARIANT AT3D THR-414.
RC TISSUE=Plasma;
RX PubMed=7734359; DOI=10.1111/j.1365-2141.1995.tb08368.x;
RA Lindo V.S., Kakkar V.V., Learmonth M., Melissari E., Zappacosta F.,
RA Panico M., Morris H.R.;
RT "Antithrombin-TRI (Ala382 to Thr) causing severe thromboembolic tendency
RT undergoes the S-to-R transition and is associated with a plasma-inactive
RT high-molecular-weight complex of aggregated antithrombin.";
RL Br. J. Haematol. 89:589-601(1995).
RN [14]
RP REACTIVE SITE.
RX PubMed=7238875; DOI=10.1016/0014-5793(81)80255-4;
RA Bjoerk I., Danielsson A., Fenton J.W. II, Joernvall H.;
RT "The site in human antithrombin for functional proteolytic cleavage by
RT human thrombin.";
RL FEBS Lett. 126:257-260(1981).
RN [15]
RP HEPARIN-BINDING SITE.
RX PubMed=6693405; DOI=10.1016/s0021-9258(17)43548-4;
RA Blackburn M.N., Smith R.L., Carson J., Sibley C.C.;
RT "The heparin-binding site of antithrombin III. Identification of a critical
RT tryptophan in the amino acid sequence.";
RL J. Biol. Chem. 259:939-941(1984).
RN [16]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-187.
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 [17]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-128 AND ASN-187.
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 [18]
RP FUNCTION IN MEMBRANE-ANCHORED SERINE PROTEASE TMPRSS7 INHIBITION, AND
RP HETERODIMER WITH TMPRSS7.
RX PubMed=15853774; DOI=10.1042/bj20050299;
RA Szabo R., Netzel-Arnett S., Hobson J.P., Antalis T.M., Bugge T.H.;
RT "Matriptase-3 is a novel phylogenetically preserved membrane-anchored
RT serine protease with broad serpin reactivity.";
RL Biochem. J. 390:231-242(2005).
RN [19]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-128; ASN-187 AND ASN-224.
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 [20]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-224.
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 [21]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-128 AND ASN-187.
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 [22]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-187, AND STRUCTURE OF
RP 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 [23]
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 [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-68, 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 [25]
RP PHOSPHORYLATION AT THR-63 AND SER-68.
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 [26]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
RX PubMed=8087553; DOI=10.1016/s0969-2126(00)00028-9;
RA Carrell R.W., Stein P.E., Fermi G., Wardell M.R.;
RT "Biological implications of a 3 A structure of dimeric antithrombin.";
RL Structure 2:257-270(1994).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS).
RX PubMed=7656006; DOI=10.1038/nsb0194-48;
RA Schreuder H.A., de Boer B., Dijkema R., Mulders J., Theunissen H.J.M.,
RA Grootenhuis P.D.J., Hol W.G.J.;
RT "The intact and cleaved human antithrombin III complex as a model for
RT serpin-proteinase interactions.";
RL Nat. Struct. Biol. 1:48-54(1994).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
RX PubMed=9067613; DOI=10.1006/jmbi.1996.0798;
RA Skinner R., Abrahams J.P., Whisstock J.C., Lesk A.M., Carrel R.W.,
RA Wardell M.R.;
RT "The 2.6 A structure of antithrombin indicates a conformational change at
RT the heparin binding site.";
RL J. Mol. Biol. 266:601-609(1997).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
RX PubMed=9761669; DOI=10.1006/jmbi.1998.2083;
RA Skinner R., Chang W.-S.W., Jin L., Pei X.Y., Huntington J.A.,
RA Abrahams J.P., Carrell R.W., Lomas D.A.;
RT "Implications for function and therapy of a 2.9 A structure of binary-
RT complexed antithrombin.";
RL J. Mol. Biol. 283:9-14(1998).
RN [30]
RP REVIEW.
RX PubMed=2126464; DOI=10.1016/0300-9084(90)90123-x;
RA Mourey L., Samama J.-P., Delarue M., Choay J., Lormeau J.C., Petitou M.,
RA Moras D.;
RT "Antithrombin III: structural and functional aspects.";
RL Biochimie 72:599-608(1990).
RN [31]
RP REVIEW ON VARIANTS.
RX PubMed=8236149;
RA Lane D.A., Olds R.J., Boisclair M., Chowdhury V., Thein S.L., Cooper D.N.,
RA Blajchman M., Perry D., Emmerich J., Aiach M.;
RT "Antithrombin III mutation database: first update. For the Thrombin and its
RT Inhibitors Subcommittee of the Scientific and Standardization Committee of
RT the International Society on Thrombosis and Haemostasis.";
RL Thromb. Haemost. 70:361-369(1993).
RN [32]
RP REVIEW ON VARIANTS.
RX PubMed=7749926; DOI=10.1038/nsb0295-96;
RA Stein P.E., Carrell R.W.;
RT "What do dysfunctional serpins tell us about molecular mobility and
RT disease?";
RL Nat. Struct. Biol. 2:96-113(1995).
RN [33]
RP REVIEW ON VARIANTS.
RX PubMed=8664906;
RX DOI=10.1002/(sici)1098-1004(1996)7:1<7::aid-humu2>3.0.co;2-b;
RA Perry D.J., Carrell R.W.;
RT "Molecular genetics of human antithrombin deficiency.";
RL Hum. Mutat. 7:7-22(1996).
RN [34]
RP VARIANTS AT3D SER-17; PRO-23; ASN-39; CYS-56; LEU-73; CYS-79; HIS-79;
RP SER-79; ASN-87 DEL; CYS-89; LEU-90; CYS-95; SER-95; PRO-98; THR-112;
RP PHE-131; VAL-131; LYS-133; PHE-138-139-LYS DEL; PRO-148; PRO-150; PRO-158;
RP TYR-160; GLN-161; CYS-198; HIS-198; ILE-218 DEL; ASP-219; LYS-219; ARG-257;
RP LYS-269; ILE-283; ASN-316; LYS-334; ARG-412; THR-414; PRO-416; SER-416;
RP VAL-419; ASP-424; CYS-425; HIS-425; PRO-425; LEU-426; CYS-434; LEU-434;
RP SER-434; THR-436; LYS-437; GLY-438; MET-438; LEU-439; THR-439; THR-453;
RP ARG-456; THR-457; ASP-459; LEU-461 AND PHE-462, AND VARIANTS GLU-30; THR-52
RP AND CYS-190.
RX PubMed=9031473;
RG The plasma coagulation inhibitors subcommittee of the scientific and standardization committee of the international society on thrombosis and haemostasis;
RA Lane D.A., Bayston T., Olds R.J., Fitches A.C., Cooper D.N., Millar D.S.,
RA Jochmans K., Perry D.J., Okajima K., Thein S.L., Emmerich J.;
RT "Antithrombin mutation database: 2nd (1997) update.";
RL Thromb. Haemost. 77:197-211(1997).
RN [35]
RP VARIANT AT3D CYS-79.
RX PubMed=6582486; DOI=10.1073/pnas.81.2.289;
RA Koide T., Odani S., Takahashi K., Ono T., Sakuragawa N.;
RT "Antithrombin III Toyama: replacement of arginine-47 by cysteine in
RT hereditary abnormal antithrombin III that lacks heparin-binding ability.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:289-293(1984).
RN [36]
RP VARIANT AT3D LEU-73, AND CHARACTERIZATION OF VARIANT AT3D LEU-73.
RX PubMed=3080419; DOI=10.1016/s0021-9258(17)36071-4;
RA Chang J.Y., Tran T.H.;
RT "Antithrombin III Basel. Identification of a Pro-Leu substitution in a
RT hereditary abnormal antithrombin with impaired heparin cofactor activity.";
RL J. Biol. Chem. 261:1174-1176(1986).
RN [37]
RP VARIANT AT3D LEU-426.
RX PubMed=3805013; DOI=10.1016/s0021-9258(19)75747-0;
RA Stephens A.W., Thalley B.S., Hirs C.H.W.;
RT "Antithrombin-III Denver, a reactive site variant.";
RL J. Biol. Chem. 262:1044-1048(1987).
RN [38]
RP VARIANT AT3D THR-414.
RX PubMed=3179438;
RA Devrak-Kizuk R., Chui D.H.K., Prochownik E.V., Carter C.J., Ofosu F.A.,
RA Blajchman M.A.;
RT "Antithrombin-III-Hamilton: a gene with a point mutation (guanine to
RT adenine) in codon 382 causing impaired serine protease reactivity.";
RL Blood 72:1518-1523(1988).
RN [39]
RP VARIANTS AT3D CYS-425 AND HIS-425.
RX PubMed=3162733; DOI=10.1016/s0021-9258(18)60605-2;
RA Erdjument H., Laned D.A., Panico M., di Marzo V., Morris H.R.;
RT "Single amino acid substitutions in the reactive site of antithrombin
RT leading to thrombosis. Congenital substitution of arginine 393 to cysteine
RT in antithrombin Northwick Park and to histidine in antithrombin Glasgow.";
RL J. Biol. Chem. 263:5589-5593(1988).
RN [40]
RP VARIANT AT3D HIS-425.
RX PubMed=2781509; DOI=10.1016/0049-3848(89)90127-8;
RA Erdjument H., Lane D.A., Panico M., di Marzo V., Morris H.R., Bauer K.,
RA Rosenberg R.D.;
RT "Antithrombin Chicago, amino acid substitution of arginine 393 to
RT histidine.";
RL Thromb. Res. 54:613-619(1989).
RN [41]
RP VARIANT AT3D CYS-56.
RX PubMed=2365065; DOI=10.1016/0014-5793(90)81530-2;
RA Borg J.Y., Brennan S.O., Carrell R.W., George P., Perry D.J., Shaw J.;
RT "Antithrombin Rouen-IV 24 Arg-->Cys. The amino-terminal contribution to
RT heparin binding.";
RL FEBS Lett. 266:163-166(1990).
RN [42]
RP VARIANT GLU-30.
RX PubMed=1977621; DOI=10.1016/0014-5793(90)81057-u;
RA Daly M., Bruce D., Perry D.J., Price J., Harper P.L., O'Meara A.,
RA Carrell R.W.;
RT "Antithrombin Dublin (-3 Val-->Glu): an N-terminal variant which has an
RT aberrant signal peptidase cleavage site.";
RL FEBS Lett. 273:87-90(1990).
RN [43]
RP VARIANT AT3D GLN-161.
RX PubMed=2229057; DOI=10.1016/s0021-9258(17)30614-2;
RA Gandrille S., Aiach M., Lane D.A., Vidaud D., Molho-Sabatier P., Caso R.,
RA de Moerloose P., Fiessinger J.-N., Clauser E.;
RT "Important role of arginine 129 in heparin-binding site of antithrombin
RT III. Identification of a novel mutation arginine 129 to glutamine.";
RL J. Biol. Chem. 265:18997-19001(1990).
RN [44]
RP CHARACTERIZATION OF VARIANT AT3D THR-414, AND MUTAGENESIS OF ALA-414.
RX PubMed=2013320; DOI=10.1016/0014-5793(91)80305-m;
RA Austin R.C., Rachubinski R.A., Blachjman M.A.;
RT "Site-directed mutagenesis of alanine-382 of human antithrombin III.";
RL FEBS Lett. 280:254-258(1991).
RN [45]
RP VARIANT AT3D SER-416.
RX PubMed=1906811; DOI=10.1016/0014-5793(91)80809-h;
RA Perry D.J., Daly M., Harper P.L., Tait R.C., Price J., Walker I.D.,
RA Carrell R.W.;
RT "Antithrombin Cambridge II, 384 Ala to Ser. Further evidence of the role of
RT the reactive centre loop in the inhibitory function of the serpins.";
RL FEBS Lett. 285:248-250(1991).
RN [46]
RP VARIANT AT3D PHE-131.
RX PubMed=1555650; DOI=10.1016/0014-5793(92)80854-a;
RA Olds R.J., Lane D.A., Boisclair M., Sas G., Bock S.C., Thein S.L.;
RT "Antithrombin Budapest 3. An antithrombin variant with reduced heparin
RT affinity resulting from the substitution L99F.";
RL FEBS Lett. 300:241-246(1992).
RN [47]
RP VARIANT AT3D ASP-424.
RX PubMed=1547341;
RA Blajchman M.A., Fernandez-Rachubinski F., Sheffield W.P., Austin R.C.,
RA Schulman S.;
RT "Antithrombin-III Stockholm: a codon 392 (Gly-->Asp) mutation with normal
RT heparin binding and impaired serine protease reactivity.";
RL Blood 79:1428-1434(1992).
RN [48]
RP VARIANT AT3D PRO-148.
RX PubMed=8443391;
RA Okajima K., Abe H., Maeda S., Motomura M., Tsujihata M., Nagataki S.,
RA Okabe H., Takatsuki K.;
RT "Antithrombin III Nagasaki (Ser116-Pro): a heterozygous variant with
RT defective heparin binding associated with thrombosis.";
RL Blood 81:1300-1305(1993).
RN [49]
RP VARIANT AT3D 138-PHE-LYS-139 DEL.
RX PubMed=8486379; DOI=10.1006/geno.1993.1184;
RA Olds R.J., Lane D.A., Beresford C.H., Abildgaard U., Hughes P.M.,
RA Thein S.L.;
RT "A recurrent deletion in the antithrombin gene, AT106-108(-6 bp),
RT identified by DNA heteroduplex detection.";
RL Genomics 16:298-299(1993).
RN [50]
RP VARIANTS AT3D HIS-79 AND TYR-160.
RX PubMed=7981186; DOI=10.1161/01.atv.14.12.1958;
RA Emmerich J., Vidaud D., Alhenc-Gelas M., Chadeuf G., Gouault-Heilmann M.,
RA Aillaud M.-F., Aiach M.;
RT "Three novel mutations of antithrombin inducing high-molecular-mass
RT compounds.";
RL Arterioscler. Thromb. 14:1958-1965(1994).
RN [51]
RP VARIANTS AT3D THR-112; TYR-152 AND ILE-283, AND VARIANT CYS-190.
RX PubMed=7959685; DOI=10.1007/bf00211016;
RA Millar D.S., Wacey A.I., Ribando J., Melissari E., Laursen B., Woods P.,
RA Kakkar V.V., Cooper D.N.;
RT "Three novel missense mutations in the antithrombin III (AT3) gene causing
RT recurrent venous thrombosis.";
RL Hum. Genet. 94:509-512(1994).
RN [52]
RP VARIANT AT3D ARG-456.
RX PubMed=8274732;
RA Jochmans K., Lissens W., Vervoort R., Peeters S., de Waelwe M.,
RA Liebaers I.;
RT "Antithrombin-Gly 424 Arg: a novel point mutation responsible for type 1
RT antithrombin deficiency and neonatal thrombosis.";
RL Blood 83:146-151(1994).
RN [53]
RP VARIANTS AT3D SER-95; THR-453 AND PHE-462.
RX PubMed=7994035;
RA van Boven H.H., Olds R.J., Thein S.L., Reitsma P.H., Lane D.A., Briet E.,
RA Vandenbroucke J.P., Rosendaal F.R.;
RT "Hereditary antithrombin deficiency: heterogeneity of the molecular basis
RT and mortality in Dutch families.";
RL Blood 84:4209-4213(1994).
RN [54]
RP VARIANT AT3D ASP-219.
RX PubMed=7989582; DOI=10.1172/jci117589;
RA Bruce D., Perry D.J., Borg J.-Y., Carrell R.W., Wardell M.R.;
RT "Thromboembolic disease due to thermolabile conformational changes of
RT antithrombin Rouen-VI (187 Asn-->Asp).";
RL J. Clin. Invest. 94:2265-2274(1994).
RN [55]
RP VARIANTS AT3D VAL-131 AND PRO-150.
RA Chowdhury V., Olds R.J., Lane D.A., Mille B., Pabinger I., Thein S.L.;
RT "Two novel antithrombin variants (L99V and Q118P) which alter the heparin
RT binding domain.";
RL Nouv. Rev. Fr. Hematol. 86:268-268(1994).
RN [56]
RP VARIANT AT3D 273-LYS--LYS-307 DEL.
RX PubMed=7878627;
RA Emmerich J., Chadeuf G., Alhenc-Gelas M., Gouault-Heilman M., Toulon P.,
RA Fiessinger J.-N., Aiach M.;
RT "Molecular basis of antithrombin type I deficiency: the first large in-
RT frame deletion and two novel mutations in exon 6.";
RL Thromb. Haemost. 72:534-539(1994).
RN [57]
RP VARIANT AT3D HIS-425.
RX PubMed=7832187; DOI=10.1002/ajh.2830480104;
RA Okajima K., Abe H., Wagatsuma M., Okabe H., Takatsuki K.;
RT "Antithrombin III Kumamoto II; a single mutation at Arg393-His increased
RT the affinity of antithrombin III for heparin.";
RL Am. J. Hematol. 48:12-18(1995).
RN [58]
RP VARIANT AT3D ARG-127.
RX PubMed=9157604;
RA Ozawa T., Takikawa Y., Niiya K., Fujiwara T., Suzuki K., Sato S.,
RA Sakuragawa N.;
RT "Antithrombin Morioka (Cys 95-Arg): a novel missense mutation causing type
RT I antithrombin deficiency.";
RL Thromb. Haemost. 77:403-403(1997).
RN [59]
RP VARIANT AT3D PRO-23.
RX PubMed=9845533;
RA Fitches A.C., Appleby R., Lane D.A., De Stefano V., Leone G., Olds R.J.;
RT "Impaired cotranslational processing as a mechanism for type I antithrombin
RT deficiency.";
RL Blood 92:4671-4676(1998).
RN [60]
RP VARIANTS AT3D ARG-32; LEU-73; CYS-79; HIS-198; ARG-257 AND ARG-412.
RX PubMed=9759613;
RA Jochmans K., Lissens W., Seneca S., Capel P., Chatelain B., Meeus P.,
RA Osselaer J.C., Peerlinck K., Seghers J., Slacmeulder M., Stibbe J.,
RA van de Loo J., Vermylen J., Liebaers I., De Waele M.;
RT "The molecular basis of antithrombin deficiency in Belgian and Dutch
RT families.";
RL Thromb. Haemost. 80:376-381(1998).
RN [61]
RP VARIANT THR-167.
RX PubMed=10361121;
RA Bayston T.A., Tripodi A., Mannucci P.M., Thompson E., Ireland H.,
RA Fitches A.C., Hananeia L., Olds R.J., Lane D.A.;
RT "Familial overexpression of beta-antithrombin caused by an Asn135-to-Thr
RT substitution.";
RL Blood 93:4242-4247(1999).
RN [62]
RP VARIANTS AT3D PHE-214; PRO-223; ILE-243; THR-251; VAL-283 AND PRO-397.
RX PubMed=10997988; DOI=10.1046/j.1365-2141.2000.02245.x;
RA Picard V., Bura A., Emmerich J., Alhenc-Gelas M., Biron C.,
RA Houbouyan-Reveillard L.L., Molho P., Labatide-Alanore A., Sie P.,
RA Toulon P., Verdy E., Aiach M.;
RT "Molecular bases of antithrombin deficiency in French families:
RT identification of seven novel mutations in the antithrombin gene.";
RL Br. J. Haematol. 110:731-734(2000).
RN [63]
RP VARIANT AT3D 152-HIS--PHE-154 DEL.
RX PubMed=11794707; DOI=10.1007/bf02982095;
RA Niiya K., Kiguchi T., Dansako H., Fujimura K., Fujimoto T., Iijima K.,
RA Tanimoto M., Harada M.;
RT "Two novel gene mutations in type I antithrombin deficiency.";
RL Int. J. Hematol. 74:469-472(2001).
RN [64]
RP VARIANT AT3D PRO-223.
RX PubMed=11713457; DOI=10.1067/mpd.2001.118191;
RA Baud O., Picard V., Durand P., Duchemin J., Proulle V., Alhenc-Gelas M.,
RA Devictor D., Dreyfus M.;
RT "Intracerebral hemorrhage associated with a novel antithrombin gene
RT mutation in a neonate.";
RL J. Pediatr. 139:741-743(2001).
RN [65]
RP VARIANT AT3D GLU-146.
RX PubMed=12353073; DOI=10.1267/THRO88030436;
RA Mushunje A., Zhou A., Huntington J.A., Conard J., Carrell R.W.;
RT "Antithrombin 'DREUX' (Lys 114Glu): a variant with complete loss of heparin
RT affinity.";
RL Thromb. Haemost. 88:436-443(2002).
RN [66]
RP VARIANT AT3D LEU-261.
RX PubMed=12595305; DOI=10.1182/blood-2002-11-3391;
RA Picard V., Dautzenberg M.-D., Villoutreix B.O., Orliaguet G.,
RA Alhenc-Gelas M., Aiach M.;
RT "Antithrombin Phe229Leu: a new homozygous variant leading to spontaneous
RT antithrombin polymerization in vivo associated with severe childhood
RT thrombosis.";
RL Blood 102:919-925(2003).
RN [67]
RP VARIANTS AT3D LYS-121; HIS-178; CYS-425; HIS-425 AND PRO-441.
RX PubMed=12894857; DOI=10.1007/bf02983246;
RA Nagaizumi K., Inaba H., Amano K., Suzuki M., Arai M., Fukutake K.;
RT "Five novel and four recurrent point mutations in the antithrombin gene
RT causing venous thrombosis.";
RL Int. J. Hematol. 78:79-83(2003).
RN [68]
RP VARIANTS AT3D LEU-179; CYS-425 AND LEU-426.
RX PubMed=15164384; DOI=10.1002/ajh.20067;
RA David D., Ribeiro S., Ferrao L., Gago T., Crespo F.;
RT "Molecular basis of inherited antithrombin deficiency in Portuguese
RT families: identification of genetic alterations and screening for
RT additional thrombotic risk factors.";
RL Am. J. Hematol. 76:163-171(2004).
RN [69]
RP VARIANTS AT3D SER-112 AND ARG-456, CHARACTERIZATION OF VARIANTS AT3D
RP SER-112 AND ARG-456, AND FUNCTION.
RX PubMed=15140129; DOI=10.1111/j.1538-7836.2004.00749.x;
RA Corral J., Huntington J.A., Gonzalez-Conejero R., Mushunje A., Navarro M.,
RA Marco P., Vicente V., Carrell R.W.;
RT "Mutations in the shutter region of antithrombin result in formation of
RT disulfide-linked dimers and severe venous thrombosis.";
RL J. Thromb. Haemost. 2:931-939(2004).
RN [70]
RP VARIANT AT3D HIS-398.
RX PubMed=16908819; DOI=10.1001/archopht.124.8.1165;
RA Kuhli C., Jochmans K., Scharrer I., Luechtenberg M., Hattenbach L.-O.;
RT "Retinal vein occlusion associated with antithrombin deficiency secondary
RT to a novel G9840C missense mutation.";
RL Arch. Ophthalmol. 124:1165-1169(2006).
RN [71]
RP VARIANT AT3D 241-GLU-LEU-242 DELINS
RP VAL-LEU-VAL-LEU-VAL-ASN-THR-ARG-THR-SER, AND CHARACTERIZATION OF VARIANT
RP AT3D 241-GLU-LEU-242 DELINS VAL-LEU-VAL-LEU-VAL-ASN-THR-ARG-THR-SER.
RX PubMed=22758787; DOI=10.1111/j.1538-7836.2012.04839.x;
RA Martinez-Martinez I., Johnson D.J., Yamasaki M., Navarro-Fernandez J.,
RA Ordonez A., Vicente V., Huntington J.A., Corral J.;
RT "Type II antithrombin deficiency caused by a large in-frame insertion:
RT structural, functional and pathological relevance.";
RL J. Thromb. Haemost. 10:1859-1866(2012).
RN [72]
RP VARIANTS AT3D PHE-53; LEU-73; ASP-125; PRO-170; ASN-218; GLY-248; PRO-293;
RP ARG-401; CYS-425; GLY-438 AND ALA-439, AND VARIANT GLU-30.
RX PubMed=23910795; DOI=10.1111/jth.12364;
RA Puurunen M., Salo P., Engelbarth S., Javela K., Perola M.;
RT "Type II antithrombin deficiency caused by a founder mutation Pro73Leu in
RT the Finnish population: clinical picture.";
RL J. Thromb. Haemost. 11:1844-1849(2013).
RN [73]
RP VARIANT AT3D VAL-PHE-LEU-PRO-384 INS.
RX PubMed=30046692; DOI=10.1002/rth2.12025;
RA de la Morena-Barrio M.E., Lopez-Galvez R., Martinez-Martinez I., Asenjo S.,
RA Sevivas T.S., Lopez M.F., Wypasek E., Entrena L., Vicente V., Corral J.;
RT "Defects of splicing in antithrombin deficiency.";
RL Res. Pract. Thromb. Haemost. 1:216-222(2017).
CC -!- FUNCTION: Most important serine protease inhibitor in plasma that
CC regulates the blood coagulation cascade (PubMed:15853774,
CC PubMed:15140129). AT-III inhibits thrombin, matriptase-3/TMPRSS7, as
CC well as factors IXa, Xa and XIa (PubMed:15140129). Its inhibitory
CC activity is greatly enhanced in the presence of heparin.
CC {ECO:0000269|PubMed:15140129, ECO:0000269|PubMed:15853774}.
CC -!- SUBUNIT: Forms protease inhibiting heterodimer with TMPRSS7.
CC -!- INTERACTION:
CC P01008; Q8IXL6: FAM20C; NbExp=2; IntAct=EBI-1039832, EBI-7147442;
CC P01008; P01008: SERPINC1; NbExp=2; IntAct=EBI-1039832, EBI-1039832;
CC PRO_0000032489; PRO_0000028160 [P00734]: F2; NbExp=2; IntAct=EBI-26959093, EBI-26959170;
CC PRO_0000032489; PRO_0000032489 [P01008]: SERPINC1; NbExp=2; IntAct=EBI-26959093, EBI-26959093;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space.
CC -!- TISSUE SPECIFICITY: Found in plasma.
CC -!- PTM: Phosphorylated by FAM20C in the extracellular medium.
CC {ECO:0000269|PubMed:26091039}.
CC -!- MASS SPECTROMETRY: Mass=57863; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:7734359};
CC -!- MASS SPECTROMETRY: Mass=57911; Method=Electrospray; Note=Variant Thr-
CC 414.; Evidence={ECO:0000269|PubMed:7734359};
CC -!- DISEASE: Antithrombin III deficiency (AT3D) [MIM:613118]: An important
CC risk factor for hereditary thrombophilia, a hemostatic disorder
CC characterized by a tendency to recurrent thrombosis. Antithrombin-III
CC deficiency is classified into 4 types. Type I: characterized by a 50%
CC decrease in antigenic and functional levels. Type II: has defects
CC affecting the thrombin-binding domain. Type III: alteration of the
CC heparin-binding domain. Plasma AT-III antigen levels are normal in type
CC II and III. Type IV: consists of miscellaneous group of unclassifiable
CC mutations. {ECO:0000269|PubMed:10997988, ECO:0000269|PubMed:11713457,
CC ECO:0000269|PubMed:11794707, ECO:0000269|PubMed:12353073,
CC ECO:0000269|PubMed:12595305, ECO:0000269|PubMed:12894857,
CC ECO:0000269|PubMed:15140129, ECO:0000269|PubMed:15164384,
CC ECO:0000269|PubMed:1547341, ECO:0000269|PubMed:1555650,
CC ECO:0000269|PubMed:16908819, ECO:0000269|PubMed:1906811,
CC ECO:0000269|PubMed:2013320, ECO:0000269|PubMed:2229057,
CC ECO:0000269|PubMed:22758787, ECO:0000269|PubMed:2365065,
CC ECO:0000269|PubMed:23910795, ECO:0000269|PubMed:2781509,
CC ECO:0000269|PubMed:30046692, ECO:0000269|PubMed:3080419,
CC ECO:0000269|PubMed:3162733, ECO:0000269|PubMed:3179438,
CC ECO:0000269|PubMed:3191114, ECO:0000269|PubMed:3805013,
CC ECO:0000269|PubMed:6582486, ECO:0000269|PubMed:7734359,
CC ECO:0000269|PubMed:7832187, ECO:0000269|PubMed:7878627,
CC ECO:0000269|PubMed:7959685, ECO:0000269|PubMed:7981186,
CC ECO:0000269|PubMed:7989582, ECO:0000269|PubMed:7994035,
CC ECO:0000269|PubMed:8274732, ECO:0000269|PubMed:8443391,
CC ECO:0000269|PubMed:8486379, ECO:0000269|PubMed:9031473,
CC ECO:0000269|PubMed:9157604, ECO:0000269|PubMed:9759613,
CC ECO:0000269|PubMed:9845533, ECO:0000269|Ref.3, ECO:0000269|Ref.55}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the serpin family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Antithrombin entry;
CC URL="https://en.wikipedia.org/wiki/Antithrombin";
CC -!- WEB RESOURCE: Name=Antithrombin mutation database;
CC URL="https://www1.imperial.ac.uk/departmentofmedicine/divisions/experimentalmedicine/haematology/coag/antithrombin/";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/serpinc1/";
CC ---------------------------------------------------------------------------
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DR EMBL; L00185; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L00186; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L00190; AAB40025.1; -; Genomic_DNA.
DR EMBL; D29832; BAA06212.1; -; mRNA.
DR EMBL; X68793; CAA48690.1; -; Genomic_DNA.
DR EMBL; AF130100; AAG35525.1; -; mRNA.
DR EMBL; AK312654; BAG35537.1; -; mRNA.
DR EMBL; AF386078; AAK60337.1; -; Genomic_DNA.
DR EMBL; AL136170; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471067; EAW90969.1; -; Genomic_DNA.
DR EMBL; M21643; AAA51793.1; -; Genomic_DNA.
DR EMBL; M21644; AAA51794.1; -; Genomic_DNA.
DR EMBL; M21643; AAA51794.1; JOINED; Genomic_DNA.
DR EMBL; M21642; AAA51796.1; -; Genomic_DNA.
DR EMBL; M21636; AAA51796.1; JOINED; Genomic_DNA.
DR EMBL; M21637; AAA51796.1; JOINED; Genomic_DNA.
DR EMBL; M21638; AAA51796.1; JOINED; Genomic_DNA.
DR EMBL; M21640; AAA51796.1; JOINED; Genomic_DNA.
DR EMBL; M21641; AAA51796.1; JOINED; Genomic_DNA.
DR CCDS; CCDS1313.1; -.
DR PIR; A49494; XHHU3.
DR RefSeq; NP_000479.1; NM_000488.3.
DR PDB; 1ANT; X-ray; 3.00 A; I/L=33-464.
DR PDB; 1ATH; X-ray; 3.20 A; A/B=33-464.
DR PDB; 1AZX; X-ray; 2.90 A; I/L=33-464.
DR PDB; 1BR8; X-ray; 2.90 A; I/L=33-464.
DR PDB; 1DZG; X-ray; 2.80 A; I/L=33-464.
DR PDB; 1DZH; X-ray; 2.85 A; I/L=33-464.
DR PDB; 1E03; X-ray; 2.90 A; I/L=33-464.
DR PDB; 1E04; X-ray; 2.60 A; I/L=33-464.
DR PDB; 1E05; X-ray; 2.62 A; I/L=33-464.
DR PDB; 1JVQ; X-ray; 2.60 A; I/L=33-464.
DR PDB; 1LK6; X-ray; 2.80 A; I/L=33-464.
DR PDB; 1NQ9; X-ray; 2.60 A; I/L=33-464.
DR PDB; 1OYH; X-ray; 2.62 A; I/L=33-464.
DR PDB; 1R1L; X-ray; 2.70 A; I/L=33-464.
DR PDB; 1SR5; X-ray; 3.10 A; A=33-464.
DR PDB; 1T1F; X-ray; 2.75 A; A/B/C=33-464.
DR PDB; 1TB6; X-ray; 2.50 A; I=33-464.
DR PDB; 2ANT; X-ray; 2.60 A; I/L=33-464.
DR PDB; 2B4X; X-ray; 2.80 A; I/L=37-463.
DR PDB; 2B5T; X-ray; 2.10 A; I=33-464.
DR PDB; 2BEH; X-ray; 2.70 A; I/L=33-464.
DR PDB; 2GD4; X-ray; 3.30 A; C/I=22-464.
DR PDB; 2HIJ; X-ray; 2.90 A; I/L=33-464.
DR PDB; 2ZNH; X-ray; 2.80 A; A/B=33-464.
DR PDB; 3EVJ; X-ray; 3.00 A; I/L=33-464.
DR PDB; 3KCG; X-ray; 1.70 A; I=33-464.
DR PDB; 4EB1; X-ray; 2.80 A; I/L=33-464.
DR PDBsum; 1ANT; -.
DR PDBsum; 1ATH; -.
DR PDBsum; 1AZX; -.
DR PDBsum; 1BR8; -.
DR PDBsum; 1DZG; -.
DR PDBsum; 1DZH; -.
DR PDBsum; 1E03; -.
DR PDBsum; 1E04; -.
DR PDBsum; 1E05; -.
DR PDBsum; 1JVQ; -.
DR PDBsum; 1LK6; -.
DR PDBsum; 1NQ9; -.
DR PDBsum; 1OYH; -.
DR PDBsum; 1R1L; -.
DR PDBsum; 1SR5; -.
DR PDBsum; 1T1F; -.
DR PDBsum; 1TB6; -.
DR PDBsum; 2ANT; -.
DR PDBsum; 2B4X; -.
DR PDBsum; 2B5T; -.
DR PDBsum; 2BEH; -.
DR PDBsum; 2GD4; -.
DR PDBsum; 2HIJ; -.
DR PDBsum; 2ZNH; -.
DR PDBsum; 3EVJ; -.
DR PDBsum; 3KCG; -.
DR PDBsum; 4EB1; -.
DR AlphaFoldDB; P01008; -.
DR PCDDB; P01008; -.
DR SMR; P01008; -.
DR BioGRID; 106953; 35.
DR DIP; DIP-38009N; -.
DR IntAct; P01008; 19.
DR MINT; P01008; -.
DR STRING; 9606.ENSP00000356671; -.
DR BindingDB; P01008; -.
DR ChEMBL; CHEMBL1950; -.
DR DrugBank; DB11598; Antithrombin III human.
DR DrugBank; DB00407; Ardeparin.
DR DrugBank; DB09258; Bemiparin.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB06779; Dalteparin.
DR DrugBank; DB06754; Danaparoid.
DR DrugBank; DB01225; Enoxaparin.
DR DrugBank; DB00569; Fondaparinux.
DR DrugBank; DB01109; Heparin.
DR DrugBank; DB04464; N-Formylmethionine.
DR DrugBank; DB08813; Nadroparin.
DR DrugBank; DB09141; Protamine sulfate.
DR DrugBank; DB05361; SR-123781A.
DR DrugBank; DB06271; Sulodexide.
DR DrugBank; DB06822; Tinzaparin.
DR DrugCentral; P01008; -.
DR GuidetoPHARMACOLOGY; 2632; -.
DR MEROPS; I04.018; -.
DR CarbonylDB; P01008; -.
DR GlyConnect; 766; 21 N-Linked glycans (4 sites).
DR GlyGen; P01008; 7 sites, 24 N-linked glycans (4 sites), 2 O-linked glycans (1 site).
DR iPTMnet; P01008; -.
DR PhosphoSitePlus; P01008; -.
DR BioMuta; SERPINC1; -.
DR DMDM; 113936; -.
DR DOSAC-COBS-2DPAGE; P01008; -.
DR REPRODUCTION-2DPAGE; P01008; -.
DR SWISS-2DPAGE; P01008; -.
DR CPTAC; non-CPTAC-1070; -.
DR CPTAC; non-CPTAC-1071; -.
DR CPTAC; non-CPTAC-1072; -.
DR EPD; P01008; -.
DR jPOST; P01008; -.
DR MassIVE; P01008; -.
DR MaxQB; P01008; -.
DR PaxDb; P01008; -.
DR PeptideAtlas; P01008; -.
DR PRIDE; P01008; -.
DR ProteomicsDB; 51299; -.
DR Antibodypedia; 793; 861 antibodies from 42 providers.
DR DNASU; 462; -.
DR Ensembl; ENST00000367698.4; ENSP00000356671.3; ENSG00000117601.15.
DR GeneID; 462; -.
DR KEGG; hsa:462; -.
DR MANE-Select; ENST00000367698.4; ENSP00000356671.3; NM_000488.4; NP_000479.1.
DR UCSC; uc001gjt.4; human.
DR CTD; 462; -.
DR DisGeNET; 462; -.
DR GeneCards; SERPINC1; -.
DR HGNC; HGNC:775; SERPINC1.
DR HPA; ENSG00000117601; Tissue enriched (liver).
DR MalaCards; SERPINC1; -.
DR MIM; 107300; gene.
DR MIM; 613118; phenotype.
DR neXtProt; NX_P01008; -.
DR OpenTargets; ENSG00000117601; -.
DR Orphanet; 82; Hereditary thrombophilia due to congenital antithrombin deficiency.
DR PharmGKB; PA35026; -.
DR VEuPathDB; HostDB:ENSG00000117601; -.
DR eggNOG; KOG2392; Eukaryota.
DR GeneTree; ENSGT00940000157967; -.
DR HOGENOM; CLU_023330_0_2_1; -.
DR InParanoid; P01008; -.
DR OMA; PICIYRN; -.
DR OrthoDB; 1124079at2759; -.
DR PhylomeDB; P01008; -.
DR TreeFam; TF343094; -.
DR PathwayCommons; P01008; -.
DR Reactome; R-HSA-140837; Intrinsic Pathway of Fibrin Clot Formation.
DR Reactome; R-HSA-140875; Common Pathway of Fibrin Clot Formation.
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-8957275; Post-translational protein phosphorylation.
DR SignaLink; P01008; -.
DR SIGNOR; P01008; -.
DR BioGRID-ORCS; 462; 13 hits in 1070 CRISPR screens.
DR ChiTaRS; SERPINC1; human.
DR EvolutionaryTrace; P01008; -.
DR GeneWiki; Antithrombin; -.
DR GenomeRNAi; 462; -.
DR Pharos; P01008; Tclin.
DR PRO; PR:P01008; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P01008; protein.
DR Bgee; ENSG00000117601; Expressed in right lobe of liver and 99 other tissues.
DR ExpressionAtlas; P01008; baseline and differential.
DR Genevisible; P01008; HS.
DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; 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:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
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; IBA:GO_Central.
DR GO; GO:0007596; P:blood coagulation; IEA:UniProtKB-KW.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central.
DR GO; GO:2000266; P:regulation of blood coagulation, intrinsic pathway; IEA:InterPro.
DR CDD; cd02045; serpinC1_AT3; 1.
DR Gene3D; 2.30.39.10; -; 1.
DR Gene3D; 3.30.497.10; -; 1.
DR InterPro; IPR033829; Antithrombin_3_serpin_domain.
DR InterPro; IPR015555; AT-III.
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 PANTHER; PTHR11461:SF53; PTHR11461:SF53; 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; Blood coagulation; Direct protein sequencing;
KW Disease variant; Disulfide bond; Glycoprotein; Hemostasis; Heparin-binding;
KW Phosphoprotein; Protease inhibitor; Reference proteome; Secreted;
KW Serine protease inhibitor; Signal; Thrombophilia.
FT SIGNAL 1..32
FT /evidence="ECO:0000269|Ref.10"
FT CHAIN 33..464
FT /note="Antithrombin-III"
FT /id="PRO_0000032489"
FT BINDING 81
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT BINDING 161
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT BINDING 177
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT SITE 425..426
FT /note="Reactive bond"
FT /evidence="ECO:0000269|PubMed:7238875"
FT MOD_RES 63
FT /note="Phosphothreonine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 68
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039,
FT ECO:0007744|PubMed:24275569"
FT CARBOHYD 128
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:14760718,
FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218,
FT ECO:0000269|Ref.10"
FT CARBOHYD 167
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|Ref.10"
FT CARBOHYD 187
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:14760718,
FT ECO:0000269|PubMed:15084671, ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19838169,
FT ECO:0000269|Ref.10"
FT CARBOHYD 224
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16263699,
FT ECO:0000269|PubMed:16335952, ECO:0000269|Ref.10"
FT DISULFID 40..160
FT /evidence="ECO:0000269|Ref.10"
FT DISULFID 53..127
FT /evidence="ECO:0000269|Ref.10"
FT DISULFID 279..462
FT /evidence="ECO:0000269|Ref.10"
FT VARIANT 17
FT /note="Y -> S (in AT3D; type-I)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_027450"
FT VARIANT 23
FT /note="L -> P (in AT3D; type-I; does not undergo post-
FT translational glycosylation; dbSNP:rs387906575)"
FT /evidence="ECO:0000269|PubMed:9031473,
FT ECO:0000269|PubMed:9845533"
FT /id="VAR_012748"
FT VARIANT 30
FT /note="V -> E (in Dublin; dbSNP:rs2227624)"
FT /evidence="ECO:0000269|PubMed:1977621,
FT ECO:0000269|PubMed:23910795, ECO:0000269|PubMed:9031473,
FT ECO:0000269|Ref.7"
FT /id="VAR_007032"
FT VARIANT 32
FT /note="C -> R (in AT3D; type-I)"
FT /evidence="ECO:0000269|PubMed:9759613"
FT /id="VAR_027451"
FT VARIANT 39
FT /note="I -> N (in AT3D; type-II; Rouen-3; lack of heparin-
FT binding properties; dbSNP:rs121909558)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_007033"
FT VARIANT 52
FT /note="M -> T (previously Whitechapel; dbSNP:rs892712171)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_007034"
FT VARIANT 53
FT /note="C -> F (in AT3D)"
FT /evidence="ECO:0000269|PubMed:23910795"
FT /id="VAR_071199"
FT VARIANT 56
FT /note="R -> C (in AT3D; type-II; Rouen-4; lack of heparin-
FT binding properties; dbSNP:rs28929469)"
FT /evidence="ECO:0000269|PubMed:2365065,
FT ECO:0000269|PubMed:9031473"
FT /id="VAR_007035"
FT VARIANT 73
FT /note="P -> L (in AT3D; type-II; lacks heparin-binding
FT ability; dbSNP:rs121909551)"
FT /evidence="ECO:0000269|PubMed:23910795,
FT ECO:0000269|PubMed:3080419, ECO:0000269|PubMed:9031473,
FT ECO:0000269|PubMed:9759613"
FT /id="VAR_007036"
FT VARIANT 79
FT /note="R -> C (in AT3D; Tours/Alger/Amiens/Toyama/Paris-1/
FT Paris-2/Padua-2/Barcelona-2/Kumamoto/Omura/Sasebo; lacks
FT heparin-binding ability; dbSNP:rs121909547)"
FT /evidence="ECO:0000269|PubMed:6582486,
FT ECO:0000269|PubMed:9031473, ECO:0000269|PubMed:9759613"
FT /id="VAR_007037"
FT VARIANT 79
FT /note="R -> H (in AT3D; type-II; Rouen-1/Padua-1/Bligny/
FT Budapest-2; lack of heparin-binding properties;
FT dbSNP:rs121909552)"
FT /evidence="ECO:0000269|PubMed:7981186,
FT ECO:0000269|PubMed:9031473"
FT /id="VAR_007038"
FT VARIANT 79
FT /note="R -> S (in AT3D; type-II; Rouen-2; lack of heparin-
FT binding properties; dbSNP:rs121909547)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_007039"
FT VARIANT 87
FT /note="Missing (in AT3D; type-I)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_007040"
FT VARIANT 89
FT /note="R -> C (in AT3D; type-I; dbSNP:rs147266200)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_007041"
FT VARIANT 90
FT /note="F -> L (in AT3D; type-I; Budapest-6)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_007042"
FT VARIANT 95
FT /note="Y -> C (in AT3D; type-I; dbSNP:rs907768931)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_027452"
FT VARIANT 95
FT /note="Y -> S (in AT3D; type-I)"
FT /evidence="ECO:0000269|PubMed:7994035,
FT ECO:0000269|PubMed:9031473"
FT /id="VAR_012316"
FT VARIANT 98
FT /note="L -> P (in AT3D; type-I)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_027453"
FT VARIANT 108..109
FT /note="Missing (in AT3D; type-I)"
FT /id="VAR_007043"
FT VARIANT 112
FT /note="P -> S (in AT3D; severely decreased antithrombin
FT activity)"
FT /evidence="ECO:0000269|PubMed:15140129"
FT /id="VAR_086227"
FT VARIANT 112
FT /note="P -> T (in AT3D; type-I)"
FT /evidence="ECO:0000269|PubMed:7959685,
FT ECO:0000269|PubMed:9031473"
FT /id="VAR_007044"
FT VARIANT 121
FT /note="M -> K (in AT3D; type-I)"
FT /evidence="ECO:0000269|PubMed:12894857"
FT /id="VAR_027454"
FT VARIANT 125
FT /note="G -> D (in AT3D)"
FT /evidence="ECO:0000269|PubMed:23910795"
FT /id="VAR_071200"
FT VARIANT 127
FT /note="C -> R (in AT3D; type-I; dbSNP:rs121909573)"
FT /evidence="ECO:0000269|PubMed:9157604"
FT /id="VAR_027455"
FT VARIANT 131
FT /note="L -> F (in AT3D; type-II; Budapest-3/Budapest-7;
FT dbSNP:rs121909567)"
FT /evidence="ECO:0000269|PubMed:1555650,
FT ECO:0000269|PubMed:9031473"
FT /id="VAR_007045"
FT VARIANT 131
FT /note="L -> V (in AT3D; type-II; Southport)"
FT /evidence="ECO:0000269|PubMed:9031473, ECO:0000269|Ref.55"
FT /id="VAR_007046"
FT VARIANT 133
FT /note="Q -> K (in AT3D; type I; dbSNP:rs1411331203)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_007047"
FT VARIANT 138..139
FT /note="Missing (in AT3D; type-I)"
FT /evidence="ECO:0000269|PubMed:8486379"
FT /id="VAR_007048"
FT VARIANT 146
FT /note="K -> E (in AT3D; Dreux; complete loss af heparin
FT binding; dbSNP:rs1170430756)"
FT /evidence="ECO:0000269|PubMed:12353073"
FT /id="VAR_027456"
FT VARIANT 147
FT /note="T -> A (in dbSNP:rs2227606)"
FT /evidence="ECO:0000269|Ref.7"
FT /id="VAR_013085"
FT VARIANT 148
FT /note="S -> P (in AT3D; type-II; Nagasaki; defective
FT heparin binding associated with thrombosis;
FT dbSNP:rs121909569)"
FT /evidence="ECO:0000269|PubMed:8443391,
FT ECO:0000269|PubMed:9031473"
FT /id="VAR_007049"
FT VARIANT 150
FT /note="Q -> P (in AT3D; type-II; Vienna;
FT dbSNP:rs765445413)"
FT /evidence="ECO:0000269|PubMed:9031473, ECO:0000269|Ref.55"
FT /id="VAR_007050"
FT VARIANT 152..154
FT /note="Missing (in AT3D; type-I)"
FT /evidence="ECO:0000269|PubMed:11794707"
FT /id="VAR_012749"
FT VARIANT 152
FT /note="H -> Y (in AT3D; type-I)"
FT /evidence="ECO:0000269|PubMed:7959685"
FT /id="VAR_007051"
FT VARIANT 153
FT /note="Missing (in AT3D; type-I)"
FT /id="VAR_007052"
FT VARIANT 158
FT /note="L -> P (in AT3D; type-I)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_007053"
FT VARIANT 160
FT /note="C -> Y (in AT3D; type-I)"
FT /evidence="ECO:0000269|PubMed:7981186,
FT ECO:0000269|PubMed:9031473"
FT /id="VAR_027457"
FT VARIANT 161
FT /note="R -> Q (in AT3D; type-II; Geneva;
FT dbSNP:rs121909563)"
FT /evidence="ECO:0000269|PubMed:2229057,
FT ECO:0000269|PubMed:9031473"
FT /id="VAR_007054"
FT VARIANT 167
FT /note="N -> T (in dbSNP:rs121909570)"
FT /evidence="ECO:0000269|PubMed:10361121"
FT /id="VAR_012750"
FT VARIANT 170
FT /note="S -> P (in AT3D)"
FT /evidence="ECO:0000269|PubMed:23910795"
FT /id="VAR_071201"
FT VARIANT 178
FT /note="L -> H (in AT3D; type-I)"
FT /evidence="ECO:0000269|PubMed:12894857"
FT /id="VAR_027458"
FT VARIANT 179
FT /note="F -> L (in AT3D; type-I)"
FT /evidence="ECO:0000269|PubMed:15164384"
FT /id="VAR_027459"
FT VARIANT 190
FT /note="Y -> C (variant of uncertain significance)"
FT /evidence="ECO:0000269|PubMed:7959685,
FT ECO:0000269|PubMed:9031473"
FT /id="VAR_007055"
FT VARIANT 198
FT /note="Y -> C (in AT3D; type-I and -II; Whitechapel;
FT dbSNP:rs1425532034)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_007056"
FT VARIANT 198
FT /note="Y -> H (in AT3D; type-I; dbSNP:rs1572090114)"
FT /evidence="ECO:0000269|PubMed:9031473,
FT ECO:0000269|PubMed:9759613"
FT /id="VAR_027460"
FT VARIANT 214
FT /note="S -> F (in AT3D; type-I)"
FT /evidence="ECO:0000269|PubMed:10997988"
FT /id="VAR_027461"
FT VARIANT 214
FT /note="S -> Y (in AT3D; type-I; dbSNP:rs483352854)"
FT /id="VAR_007057"
FT VARIANT 218
FT /note="I -> N (in AT3D)"
FT /evidence="ECO:0000269|PubMed:23910795"
FT /id="VAR_071202"
FT VARIANT 218
FT /note="Missing (in AT3D; type-I)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_027462"
FT VARIANT 219
FT /note="N -> D (in AT3D; type-II; Rouen-6; increases
FT affinity for heparin; dbSNP:rs121909571)"
FT /evidence="ECO:0000269|PubMed:7989582,
FT ECO:0000269|PubMed:9031473"
FT /id="VAR_007059"
FT VARIANT 219
FT /note="N -> K (in AT3D; type-II; Glasgow-3)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_007058"
FT VARIANT 223
FT /note="S -> P (in AT3D; type-I; dbSNP:rs121909572)"
FT /evidence="ECO:0000269|PubMed:10997988,
FT ECO:0000269|PubMed:11713457"
FT /id="VAR_027463"
FT VARIANT 241..242
FT /note="EL -> VLVLVNTRTS (in AT3D; severely decreased
FT antithrombin activity; low affinity for heparin)"
FT /evidence="ECO:0000269|PubMed:22758787"
FT /id="VAR_086197"
FT VARIANT 243
FT /note="T -> I (in AT3D; type-I)"
FT /evidence="ECO:0000269|PubMed:10997988"
FT /id="VAR_027464"
FT VARIANT 248
FT /note="V -> G (in AT3D)"
FT /evidence="ECO:0000269|PubMed:23910795"
FT /id="VAR_071203"
FT VARIANT 251
FT /note="I -> T (in AT3D; type-I; dbSNP:rs1423630663)"
FT /evidence="ECO:0000269|PubMed:10997988"
FT /id="VAR_027465"
FT VARIANT 257
FT /note="W -> R (in AT3D; type-I)"
FT /evidence="ECO:0000269|PubMed:9031473,
FT ECO:0000269|PubMed:9759613"
FT /id="VAR_027466"
FT VARIANT 261
FT /note="F -> L (in AT3D)"
FT /evidence="ECO:0000269|PubMed:12595305"
FT /id="VAR_027467"
FT VARIANT 269
FT /note="E -> K (in AT3D; type-II; Truro; increases affinity
FT for heparin; dbSNP:rs758087836)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_007060"
FT VARIANT 273..307
FT /note="Missing (in AT3D; type-I)"
FT /evidence="ECO:0000269|PubMed:7878627"
FT /id="VAR_007061"
FT VARIANT 283
FT /note="M -> I (in AT3D; type-II)"
FT /evidence="ECO:0000269|PubMed:7959685,
FT ECO:0000269|PubMed:9031473"
FT /id="VAR_007062"
FT VARIANT 283
FT /note="M -> V (in AT3D; type-II)"
FT /evidence="ECO:0000269|PubMed:10997988"
FT /id="VAR_027468"
FT VARIANT 293
FT /note="R -> P (in AT3D)"
FT /evidence="ECO:0000269|PubMed:23910795"
FT /id="VAR_071204"
FT VARIANT 302
FT /note="L -> P (in AT3D; type-I)"
FT /id="VAR_007063"
FT VARIANT 316
FT /note="I -> N (in AT3D; type-II; Haslar/Whitechapel)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_007064"
FT VARIANT 323
FT /note="S -> P (in AT3D)"
FT /id="VAR_027469"
FT VARIANT 334
FT /note="E -> K (in AT3D; type-II)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_007065"
FT VARIANT 344
FT /note="Missing (in AT3D; type-I)"
FT /id="VAR_007066"
FT VARIANT 381
FT /note="S -> P (in AT3D; type-I; dbSNP:rs121909565)"
FT /id="VAR_007067"
FT VARIANT 384
FT /note="P -> PVFLP (in AT3D)"
FT /evidence="ECO:0000269|PubMed:30046692"
FT /id="VAR_086198"
FT VARIANT 391
FT /note="R -> Q (in dbSNP:rs201541724)"
FT /id="VAR_007068"
FT VARIANT 397
FT /note="S -> P (in AT3D; type-I)"
FT /evidence="ECO:0000269|PubMed:10997988"
FT /id="VAR_027470"
FT VARIANT 398
FT /note="D -> H (in AT3D; type-I)"
FT /evidence="ECO:0000269|PubMed:16908819"
FT /id="VAR_027471"
FT VARIANT 401
FT /note="H -> R (in AT3D)"
FT /evidence="ECO:0000269|PubMed:23910795"
FT /id="VAR_071205"
FT VARIANT 412
FT /note="S -> R (in AT3D; type-I)"
FT /evidence="ECO:0000269|PubMed:9031473,
FT ECO:0000269|PubMed:9759613"
FT /id="VAR_027472"
FT VARIANT 414
FT /note="A -> T (in AT3D; type-II; Hamilton/Glasgow-2;
FT reduces interaction with thrombin by 90%;
FT dbSNP:rs121909557)"
FT /evidence="ECO:0000269|PubMed:2013320,
FT ECO:0000269|PubMed:3179438, ECO:0000269|PubMed:7734359,
FT ECO:0000269|PubMed:9031473"
FT /id="VAR_007069"
FT VARIANT 416
FT /note="A -> P (in AT3D; type-II; Charleville/Sudbury/
FT Vicenza/Cambridge-1; dbSNP:rs121909548)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_007070"
FT VARIANT 416
FT /note="A -> S (in AT3D; type-II; Cambridge-2;
FT dbSNP:rs121909548)"
FT /evidence="ECO:0000269|PubMed:1906811,
FT ECO:0000269|PubMed:9031473"
FT /id="VAR_007071"
FT VARIANT 419
FT /note="A -> V (in AT3D; type-I; dbSNP:rs121909568)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_007072"
FT VARIANT 424
FT /note="G -> D (in AT3D; type-II; Stockholm;
FT dbSNP:rs121909566)"
FT /evidence="ECO:0000269|PubMed:1547341,
FT ECO:0000269|PubMed:9031473"
FT /id="VAR_007073"
FT VARIANT 425
FT /note="R -> C (in AT3D; type-II; dbSNP:rs121909554)"
FT /evidence="ECO:0000269|PubMed:12894857,
FT ECO:0000269|PubMed:15164384, ECO:0000269|PubMed:23910795,
FT ECO:0000269|PubMed:3162733, ECO:0000269|PubMed:9031473"
FT /id="VAR_007075"
FT VARIANT 425
FT /note="R -> H (in AT3D; type-II; Glasgow/Sheffield/Chicago/
FT Avranches/Kumamoto-2; increases affinity for heparin;
FT deprived of inhibitory activity; dbSNP:rs121909549)"
FT /evidence="ECO:0000269|PubMed:12894857,
FT ECO:0000269|PubMed:2781509, ECO:0000269|PubMed:3162733,
FT ECO:0000269|PubMed:7832187, ECO:0000269|PubMed:9031473"
FT /id="VAR_007074"
FT VARIANT 425
FT /note="R -> P (in AT3D; type-II; Pescara; deprived of
FT inhibitory of activity; dbSNP:rs121909549)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_007076"
FT VARIANT 426
FT /note="S -> L (in AT3D; type-II; Denver/Milano-2; deprived
FT of inhibitory activity; dbSNP:rs121909550)"
FT /evidence="ECO:0000269|PubMed:15164384,
FT ECO:0000269|PubMed:3805013, ECO:0000269|PubMed:9031473"
FT /id="VAR_007077"
FT VARIANT 434
FT /note="F -> C (in AT3D; type-II; Rosny;
FT dbSNP:rs1572084546)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_007078"
FT VARIANT 434
FT /note="F -> L (in AT3D; type-II; Maisons-Laffite)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_007080"
FT VARIANT 434
FT /note="F -> S (in AT3D; type-II; Torino)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_007079"
FT VARIANT 436
FT /note="A -> T (in AT3D; type-II; Oslo/Paris-3;
FT dbSNP:rs121909546)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_007081"
FT VARIANT 437
FT /note="N -> K (in AT3D; type-II; La Rochelle;
FT dbSNP:rs1301351856)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_007082"
FT VARIANT 438
FT /note="R -> G (in AT3D; type I and type-II)"
FT /evidence="ECO:0000269|PubMed:23910795,
FT ECO:0000269|PubMed:9031473"
FT /id="VAR_009258"
FT VARIANT 438
FT /note="R -> M (in AT3D; type-II; Kyoto)"
FT /evidence="ECO:0000269|PubMed:9031473, ECO:0000269|Ref.3"
FT /id="VAR_007083"
FT VARIANT 439
FT /note="P -> A (in AT3D)"
FT /evidence="ECO:0000269|PubMed:23910795"
FT /id="VAR_071206"
FT VARIANT 439
FT /note="P -> L (in AT3D; type-II; Utah; deprived of
FT inhibitory activity; dbSNP:rs121909555)"
FT /evidence="ECO:0000269|PubMed:3191114,
FT ECO:0000269|PubMed:9031473"
FT /id="VAR_007084"
FT VARIANT 439
FT /note="P -> T (in AT3D; type-II; Budapest-5;
FT dbSNP:rs1487411568)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_007085"
FT VARIANT 441
FT /note="L -> P (in AT3D; type-II; dbSNP:rs1188571702)"
FT /evidence="ECO:0000269|PubMed:12894857"
FT /id="VAR_027473"
FT VARIANT 453
FT /note="I -> T (in AT3D; type-I)"
FT /evidence="ECO:0000269|PubMed:7994035,
FT ECO:0000269|PubMed:9031473"
FT /id="VAR_007086"
FT VARIANT 456
FT /note="G -> R (in AT3D; type-I; severely decreased
FT antithrombin activity)"
FT /evidence="ECO:0000269|PubMed:15140129,
FT ECO:0000269|PubMed:8274732, ECO:0000269|PubMed:9031473"
FT /id="VAR_007087"
FT VARIANT 457
FT /note="R -> T (in AT3D; type-II)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_007088"
FT VARIANT 459..461
FT /note="Missing (in AT3D; type-I)"
FT /id="VAR_007089"
FT VARIANT 459
FT /note="A -> D (in AT3D; type-I; dbSNP:rs1572084448)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_007090"
FT VARIANT 461
FT /note="P -> L (in AT3D; type-II; Budapest;
FT dbSNP:rs121909564)"
FT /evidence="ECO:0000269|PubMed:9031473"
FT /id="VAR_007091"
FT VARIANT 462
FT /note="C -> F (in AT3D; type-I)"
FT /evidence="ECO:0000269|PubMed:7994035,
FT ECO:0000269|PubMed:9031473"
FT /id="VAR_007092"
FT MUTAGEN 414
FT /note="A->K: Reduces interaction with thrombin by 99%."
FT /evidence="ECO:0000269|PubMed:2013320"
FT MUTAGEN 414
FT /note="A->Q: Reduces interaction with thrombin by 80%."
FT /evidence="ECO:0000269|PubMed:2013320"
FT CONFLICT 69..70
FT /note="EQ -> QE (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 77
FT /note="N -> NN (in Ref. 3; BAA06212)"
FT /evidence="ECO:0000305"
FT CONFLICT 97
FT /note="H -> R (in Ref. 5; AAG35525)"
FT /evidence="ECO:0000305"
FT CONFLICT 120
FT /note="A -> T (in Ref. 6; BAG35537)"
FT /evidence="ECO:0000305"
FT CONFLICT 226
FT /note="T -> A (in Ref. 6; BAG35537)"
FT /evidence="ECO:0000305"
FT CONFLICT 247..249
FT /note="Missing (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 388
FT /note="Missing (in Ref. 13; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 395
FT /note="Y -> YA (in Ref. 13; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 39..41
FT /evidence="ECO:0007829|PDB:3KCG"
FT TURN 44..46
FT /evidence="ECO:0007829|PDB:3KCG"
FT STRAND 51..53
FT /evidence="ECO:0007829|PDB:1OYH"
FT HELIX 78..101
FT /evidence="ECO:0007829|PDB:3KCG"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:1DZG"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:3KCG"
FT HELIX 112..123
FT /evidence="ECO:0007829|PDB:3KCG"
FT HELIX 128..137
FT /evidence="ECO:0007829|PDB:3KCG"
FT HELIX 140..142
FT /evidence="ECO:0007829|PDB:2B5T"
FT HELIX 145..149
FT /evidence="ECO:0007829|PDB:3KCG"
FT HELIX 151..166
FT /evidence="ECO:0007829|PDB:3KCG"
FT TURN 167..169
FT /evidence="ECO:0007829|PDB:3KCG"
FT STRAND 170..181
FT /evidence="ECO:0007829|PDB:3KCG"
FT STRAND 184..186
FT /evidence="ECO:0007829|PDB:1E04"
FT HELIX 188..198
FT /evidence="ECO:0007829|PDB:3KCG"
FT STRAND 203..205
FT /evidence="ECO:0007829|PDB:3KCG"
FT HELIX 207..225
FT /evidence="ECO:0007829|PDB:3KCG"
FT TURN 226..228
FT /evidence="ECO:0007829|PDB:3KCG"
FT STRAND 236..239
FT /evidence="ECO:0007829|PDB:2B4X"
FT STRAND 240..242
FT /evidence="ECO:0007829|PDB:1DZG"
FT STRAND 245..255
FT /evidence="ECO:0007829|PDB:3KCG"
FT STRAND 257..259
FT /evidence="ECO:0007829|PDB:3KCG"
FT HELIX 263..265
FT /evidence="ECO:0007829|PDB:3KCG"
FT STRAND 267..272
FT /evidence="ECO:0007829|PDB:3KCG"
FT STRAND 274..276
FT /evidence="ECO:0007829|PDB:2B5T"
FT STRAND 278..294
FT /evidence="ECO:0007829|PDB:3KCG"
FT HELIX 296..298
FT /evidence="ECO:0007829|PDB:3KCG"
FT STRAND 300..306
FT /evidence="ECO:0007829|PDB:3KCG"
FT STRAND 309..317
FT /evidence="ECO:0007829|PDB:3KCG"
FT STRAND 320..322
FT /evidence="ECO:0007829|PDB:2B5T"
FT HELIX 324..329
FT /evidence="ECO:0007829|PDB:3KCG"
FT HELIX 333..342
FT /evidence="ECO:0007829|PDB:3KCG"
FT STRAND 344..353
FT /evidence="ECO:0007829|PDB:3KCG"
FT STRAND 355..362
FT /evidence="ECO:0007829|PDB:3KCG"
FT HELIX 364..369
FT /evidence="ECO:0007829|PDB:3KCG"
FT HELIX 374..376
FT /evidence="ECO:0007829|PDB:3KCG"
FT TURN 378..380
FT /evidence="ECO:0007829|PDB:3KCG"
FT TURN 384..386
FT /evidence="ECO:0007829|PDB:3KCG"
FT STRAND 389..392
FT /evidence="ECO:0007829|PDB:3KCG"
FT STRAND 398..407
FT /evidence="ECO:0007829|PDB:3KCG"
FT STRAND 409..413
FT /evidence="ECO:0007829|PDB:2B5T"
FT STRAND 419..422
FT /evidence="ECO:0007829|PDB:1E04"
FT STRAND 423..426
FT /evidence="ECO:0007829|PDB:3KCG"
FT STRAND 432..435
FT /evidence="ECO:0007829|PDB:3KCG"
FT STRAND 440..446
FT /evidence="ECO:0007829|PDB:3KCG"
FT TURN 447..450
FT /evidence="ECO:0007829|PDB:3KCG"
FT STRAND 451..459
FT /evidence="ECO:0007829|PDB:3KCG"
SQ SEQUENCE 464 AA; 52602 MW; 9A4E324F00683D9D CRC64;
MYSNVIGTVT SGKRKVYLLS LLLIGFWDCV TCHGSPVDIC TAKPRDIPMN PMCIYRSPEK
KATEDEGSEQ KIPEATNRRV WELSKANSRF ATTFYQHLAD SKNDNDNIFL SPLSISTAFA
MTKLGACNDT LQQLMEVFKF DTISEKTSDQ IHFFFAKLNC RLYRKANKSS KLVSANRLFG
DKSLTFNETY QDISELVYGA KLQPLDFKEN AEQSRAAINK WVSNKTEGRI TDVIPSEAIN
ELTVLVLVNT IYFKGLWKSK FSPENTRKEL FYKADGESCS ASMMYQEGKF RYRRVAEGTQ
VLELPFKGDD ITMVLILPKP EKSLAKVEKE LTPEVLQEWL DELEEMMLVV HMPRFRIEDG
FSLKEQLQDM GLVDLFSPEK SKLPGIVAEG RDDLYVSDAF HKAFLEVNEE GSEAAASTAV
VIAGRSLNPN RVTFKANRPF LVFIREVPLN TIIFMGRVAN PCVK
