TPA_HUMAN
ID TPA_HUMAN Reviewed; 562 AA.
AC P00750; A8K022; B2R8E8; Q15103; Q503B0; Q6PJA5; Q7Z7N2; Q86YK8; Q9BU99;
AC Q9BZW1;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 264.
DE RecName: Full=Tissue-type plasminogen activator {ECO:0000305};
DE Short=t-PA;
DE Short=t-plasminogen activator;
DE Short=tPA;
DE EC=3.4.21.68;
DE AltName: INN=Alteplase;
DE AltName: INN=Reteplase;
DE Contains:
DE RecName: Full=Tissue-type plasminogen activator chain A;
DE Contains:
DE RecName: Full=Tissue-type plasminogen activator chain B;
DE Flags: Precursor;
GN Name=PLAT {ECO:0000312|HGNC:HGNC:9051};
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).
RC TISSUE=Melanoma;
RX PubMed=6337343; DOI=10.1038/301214a0;
RA Pennica D., Holmes W.E., Kohr W.J., Harkins R.N., Vehar G.A., Ward C.A.,
RA Bennett W.F., Yelverton E., Seeburg P.H., Heyneker H.L., Goeddel D.V.,
RA Collen D.;
RT "Cloning and expression of human tissue-type plasminogen activator cDNA in
RT E. coli.";
RL Nature 301:214-221(1983).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6089198; DOI=10.1073/pnas.81.17.5355;
RA Ny T., Elgh F., Lund B.;
RT "The structure of the human tissue-type plasminogen activator gene:
RT correlation of intron and exon structures to functional and structural
RT domains.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:5355-5359(1984).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3009482; DOI=10.1016/s0021-9258(19)62711-0;
RA Friezner Degen S.J., Rajput B., Reich E.;
RT "The human tissue plasminogen activator gene.";
RL J. Biol. Chem. 261:6972-6985(1986).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=3090401;
RA Harris T.J., Patel T., Marston F.A., Little S., Emtage J.S., Opdenakker G.,
RA Volckaert G., Rombauts W., Billiau A., Somer P.;
RT "Cloning of cDNA coding for human tissue-type plasminogen activator and its
RT expression in Escherichia coli.";
RL Mol. Biol. Med. 3:279-292(1986).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2824147; DOI=10.1089/dna.1987.6.461;
RA Reddy V.B., Garramone A.J., Sasak H., Wei C.-M., Watkins P., Galli J.,
RA Hsiung N.;
RT "Expression of human uterine tissue-type plasminogen activator in mouse
RT cells using BPV vectors.";
RL DNA 6:461-472(1987).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Fetal lung;
RX PubMed=3133640; DOI=10.1093/nar/16.12.5695;
RA Sasaki H., Saito Y., Hayashi M., Otsuka K., Niwa M.;
RT "Nucleotide sequence of the tissue-type plasminogen activator cDNA from
RT human fetal lung cells.";
RL Nucleic Acids Res. 16:5695-5695(1988).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Umbilical vein;
RX PubMed=2107528; DOI=10.1093/nar/18.4.1086;
RA Siebert P.D., Fong K.;
RT "Variant tissue-type plasminogen activator (PLAT) cDNA obtained from human
RT endothelial cells.";
RL Nucleic Acids Res. 18:1086-1086(1990).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RA Dou D.;
RT "A brain-type plasminogen activator.";
RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Liu Y., Xu L., Zeng Y., He X.;
RT "cDNA of tissue plasminogen activator.";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Testis;
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 [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ASP-34; SER-136; THR-146
RP AND TRP-164.
RG SeattleSNPs variation discovery resource;
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [13]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Brain, Placenta, and Skin;
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 [15]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-36.
RX PubMed=3161893; DOI=10.1016/s0021-9258(17)39169-x;
RA Fisher R., Waller E.K., Grossi G., Thompson D., Tizard R.,
RA Schleuning W.-D.;
RT "Isolation and characterization of the human tissue-type plasminogen
RT activator structural gene including its 5' flanking region.";
RL J. Biol. Chem. 260:11223-11230(1985).
RN [16]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 31-562.
RX PubMed=1368681; DOI=10.1271/bbb1961.55.1225;
RA Itagaki Y., Yasuda H., Morinaga T., Mitsuda S., Higashio K.;
RT "Purification and characterization of tissue plasminogen activator secreted
RT by human embryonic lung diploid fibroblasts, IMR-90 cells.";
RL Agric. Biol. Chem. 55:1225-1232(1991).
RN [17]
RP PROTEIN SEQUENCE OF 33-52 AND 311-330.
RC TISSUE=Melanoma;
RX PubMed=6682760; DOI=10.1111/j.1432-1033.1983.tb07418.x;
RA Wallen P., Pohl G., Bergsdorf N., Raanby M., Ny T., Joernvall H.;
RT "Purification and characterization of a melanoma cell plasminogen
RT activator.";
RL Eur. J. Biochem. 132:681-686(1983).
RN [18]
RP PROTEIN SEQUENCE OF 36-562.
RC TISSUE=Melanoma;
RX PubMed=6433976; DOI=10.1021/bi00311a020;
RA Pohl G., Kaellstroem M., Bergsdorf N., Wallen P., Joernvall H.;
RT "Tissue plasminogen activator: peptide analyses confirm an indirectly
RT derived amino acid sequence, identify the active site serine residue,
RT establish glycosylation sites, and localize variant differences.";
RL Biochemistry 23:3701-3707(1984).
RN [19]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 251-358.
RX PubMed=6572897; DOI=10.1073/pnas.80.2.349;
RA Edlund T., Ny T., Raanby M., Heden L.-O., Palm G., Holmgren E.,
RA Josephson S.;
RT "Isolation of cDNA sequences coding for a part of human tissue plasminogen
RT activator.";
RL Proc. Natl. Acad. Sci. U.S.A. 80:349-352(1983).
RN [20]
RP PARTIAL PROTEIN SEQUENCE, AND SIGNAL SEQUENCE CLEAVAGE SITE.
RA Jalah R., Pavlakis G.N., Felber B.J.;
RL Submitted (JUL-2007) to UniProtKB.
RN [21]
RP GLYCOSYLATION AT ASN-152; ASN-219 AND ASN-483, AND STRUCTURE OF
RP CARBOHYDRATES.
RX PubMed=2513186; DOI=10.1111/j.1432-1033.1989.tb15206.x;
RA Pfeiffer G., Schmidt M., Strube K.-H., Geyer R.;
RT "Carbohydrate structure of recombinant human uterine tissue plasminogen
RT activator expressed in mouse epithelial cells.";
RL Eur. J. Biochem. 186:273-286(1989).
RN [22]
RP GLYCOSYLATION AT THR-96.
RX PubMed=1900431; DOI=10.1021/bi00223a004;
RA Harris R.J., Leonard C.K., Guzzetta A.W., Spellman M.W.;
RT "Tissue plasminogen activator has an O-linked fucose attached to threonine-
RT 61 in the epidermal growth factor domain.";
RL Biochemistry 30:2311-2314(1991).
RN [23]
RP DISULFIDE BONDS IN KRINGLE 2 DOMAIN.
RX PubMed=1645336; DOI=10.1016/s0021-9258(18)99190-8;
RA Vlahos C.J., Wilhelm O.G., Hassell T., Jaskunas S.R., Bang N.U.;
RT "Disulfide pairing of the recombinant kringle-2 domain of tissue
RT plasminogen activator produced in Escherichia coli.";
RL J. Biol. Chem. 266:10070-10072(1991).
RN [24]
RP ACTIVITY REGULATION, AND HETERODIMER WITH SERPINA5.
RX PubMed=10340997; DOI=10.1093/molehr/5.6.513;
RA He S., Lin Y.L., Liu Y.X.;
RT "Functionally inactive protein C inhibitor in seminal plasma may be
RT associated with infertility.";
RL Mol. Hum. Reprod. 5:513-519(1999).
RN [25]
RP INTERACTION WITH LRP1B.
RX PubMed=11384978; DOI=10.1074/jbc.m102727200;
RA Liu C.-X., Li Y., Obermoeller-McCormick L.M., Schwartz A.L., Bu G.;
RT "The putative tumor suppressor LRP1B, a novel member of the low density
RT lipoprotein (LDL) receptor family, exhibits both overlapping and distinct
RT properties with the LDL receptor-related protein.";
RL J. Biol. Chem. 276:28889-28896(2001).
RN [26]
RP INTERACTION WITH SERPINE1 AND SORL1.
RX PubMed=15053742; DOI=10.1042/bj20040149;
RA Gliemann J., Hermey G., Nykjaer A., Petersen C.M., Jacobsen C.,
RA Andreasen P.A.;
RT "The mosaic receptor sorLA/LR11 binds components of the plasminogen-
RT activating system and platelet-derived growth factor-BB similarly to LRP1
RT (low-density lipoprotein receptor-related protein), but mediates slow
RT internalization of bound ligand.";
RL Biochem. J. 381:203-212(2004).
RN [27]
RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA Hillman R.T., Green R.E., Brenner S.E.;
RT "An unappreciated role for RNA surveillance.";
RL Genome Biol. 5:R8.1-R8.16(2004).
RN [28]
RP STRUCTURE BY NMR OF KRINGLE 2.
RX PubMed=2558718; DOI=10.1021/bi00450a016;
RA Byeon I.-J.L., Kelley R.F., Llinas M.;
RT "1H NMR structural characterization of a recombinant kringle 2 domain from
RT human tissue-type plasminogen activator.";
RL Biochemistry 28:9350-9360(1989).
RN [29]
RP STRUCTURE BY NMR OF KRINGLE 2.
RX PubMed=1901789; DOI=10.1111/j.1432-1033.1991.tb15894.x;
RA Byeon I.-J.L., Kelley R.F., Llinas M.;
RT "Kringle-2 domain of the tissue-type plasminogen activator. 1H-NMR
RT assignments and secondary structure.";
RL Eur. J. Biochem. 197:155-165(1991).
RN [30]
RP STRUCTURE BY NMR OF KRINGLE 2.
RX PubMed=1762144; DOI=10.1016/0022-2836(91)90592-t;
RA Byeon I.-J.L., Llinas M.;
RT "Solution structure of the tissue-type plasminogen activator kringle 2
RT domain complexed to 6-aminohexanoic acid an antifibrinolytic drug.";
RL J. Mol. Biol. 222:1035-1051(1991).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF KRINGLE 2.
RX PubMed=1310033; DOI=10.1021/bi00116a037;
RA de Vos A., Ultsch M.H., Kelley R.F., Padmanabhan K., Tulinskly A.,
RA Westbrook M.L., Kossiakof A.A.;
RT "Crystal structure of the kringle 2 domain of tissue plasminogen activator
RT at 2.4-A resolution.";
RL Biochemistry 31:270-279(1992).
RN [32]
RP STRUCTURE BY NMR OF 38-85.
RX PubMed=1602484; DOI=10.1016/0022-2836(92)90403-7;
RA Downing A.K., Driscoll P.C., Harvey T.S., Dudgeon T.J., Smith B.O.,
RA Baron M., Campbell I.D.;
RT "Solution structure of the fibrin binding finger domain of tissue-type
RT plasminogen activator determined by 1H nuclear magnetic resonance.";
RL J. Mol. Biol. 225:821-833(1992).
RN [33]
RP STRUCTURE BY NMR OF 36-126.
RX PubMed=7582899; DOI=10.1016/s0969-2126(01)00217-9;
RA Smith B.O., Downing A.K., Driscoll P.C., Dudgeon T.J., Campbell I.D.;
RT "The solution structure and backbone dynamics of the fibronectin type I and
RT epidermal growth factor-like pair of modules of tissue-type plasminogen
RT activator.";
RL Structure 3:823-833(1995).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF CATALYTIC DOMAIN.
RX PubMed=8613982; DOI=10.1006/jmbi.1996.0238;
RA Lamba D., Bauer M., Huber R., Fischer S., Rudolph R., Kohnert U., Bode W.;
RT "The 2.3 A crystal structure of the catalytic domain of recombinant two-
RT chain human tissue-type plasminogen activator.";
RL J. Mol. Biol. 258:117-135(1996).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF CATALYTIC DOMAIN.
RX PubMed=9305622; DOI=10.1093/emboj/16.16.4797;
RA Renatus M., Engh R.A., Stubbs M.T., Huber R., Fischer S., Kohnert U.,
RA Bode W.;
RT "Lysine 156 promotes the anomalous proenzyme activity of tPA: X-ray crystal
RT structure of single-chain human tPA.";
RL EMBO J. 16:4797-4805(1997).
CC -!- FUNCTION: Converts the abundant, but inactive, zymogen plasminogen to
CC plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By
CC controlling plasmin-mediated proteolysis, it plays an important role in
CC tissue remodeling and degradation, in cell migration and many other
CC physiopathological events. During oocyte activation, plays a role in
CC cortical granule reaction in the zona reaction, which contributes to
CC the block to polyspermy (By similarity).
CC {ECO:0000250|UniProtKB:P19637}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Specific cleavage of Arg-|-Val bond in plasminogen to form
CC plasmin.; EC=3.4.21.68;
CC -!- ACTIVITY REGULATION: Inhibited by SERPINA5.
CC {ECO:0000269|PubMed:10340997}.
CC -!- SUBUNIT: Heterodimer of chain A and chain B held by a disulfide bond.
CC Forms a heterodimer with SERPINA5. Binds to fibrin with high affinity.
CC This interaction leads to an increase in the catalytic efficiency of
CC the enzyme between 100-fold and 1000-fold, due to an increase in
CC affinity for plasminogen. Similarly, binding to heparin increases the
CC activation of plasminogen. Binds to annexin A2, cytokeratin-8,
CC fibronectin and laminin. Binds to mannose receptor and the low-density
CC lipoprotein receptor-related protein (LRP1); these proteins are
CC involved in TPA clearance. Yet unidentified interactions on endothelial
CC cells and vascular smooth muscle cells (VSMC) lead to a 100-fold
CC stimulation of plasminogen activation. In addition, binding to VSMC
CC reduces TPA inhibition by PAI-1 by 30-fold. Binds LRP1B; binding is
CC followed by internalization and degradation. In complex with SERPINE1,
CC interacts with SORL1 (PubMed:15053742). {ECO:0000269|PubMed:15053742}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Long;
CC IsoId=P00750-1; Sequence=Displayed;
CC Name=2; Synonyms=Short;
CC IsoId=P00750-2; Sequence=VSP_005411, VSP_005412;
CC Name=3;
CC IsoId=P00750-3; Sequence=VSP_015957;
CC Name=4; Synonyms=Neonatal;
CC IsoId=P00750-4; Sequence=VSP_028029, VSP_028030;
CC -!- TISSUE SPECIFICITY: Synthesized in numerous tissues (including tumors)
CC and secreted into most extracellular body fluids, such as plasma,
CC uterine fluid, saliva, gingival crevicular fluid, tears, seminal fluid,
CC and milk.
CC -!- DOMAIN: Both FN1 and one of the kringle domains are required for
CC binding to fibrin.
CC -!- DOMAIN: Both FN1 and EGF-like domains are important for binding to
CC LRP1.
CC -!- DOMAIN: The FN1 domain mediates binding to annexin A2.
CC -!- DOMAIN: The second kringle domain is implicated in binding to
CC cytokeratin-8 and to the endothelial cell surface binding site.
CC -!- PTM: The single chain, almost fully active enzyme, can be further
CC processed into a two-chain fully active form by a cleavage after Arg-
CC 310 catalyzed by plasmin, tissue kallikrein or factor Xa.
CC -!- PTM: Differential cell-specific N-linked glycosylation gives rise to
CC two glycoforms, type I (glycosylated at Asn-219) and type II (not
CC glycosylated at Asn-219). The single chain type I glycoform is less
CC readily converted into the two-chain form by plasmin, and the two-chain
CC type I glycoform has a lower activity than the two-chain type II
CC glycoform in the presence of fibrin. {ECO:0000269|PubMed:1900431}.
CC -!- PTM: N-glycosylation of Asn-152; the bound oligomannosidic glycan is
CC involved in the interaction with the mannose receptor.
CC {ECO:0000269|PubMed:1900431}.
CC -!- PTM: Characterization of O-linked glycan was studied in Bowes melanoma
CC cell line. {ECO:0000269|PubMed:1900431}.
CC -!- DISEASE: Note=Increased activity of TPA results in increased
CC fibrinolysis of fibrin blood clots that is associated with excessive
CC bleeding. Defective release of TPA results in hypofibrinolysis that can
CC lead to thrombosis or embolism. {ECO:0000269|PubMed:1762144}.
CC -!- PHARMACEUTICAL: Available under the names Activase (Genentech) and
CC Retavase (Centocor and Roche) [Retavase is a fragment of TPA that
CC contains kringle 2 and the protease domain; it was also known as BM
CC 06.022]. Used in Acute Myocardial Infarction (AMI), in Acute Ischemic
CC Stroke (AIS) and Pulmonary Embolism (PE) to initiate fibrinolysis.
CC -!- MISCELLANEOUS: [Isoform 2]: 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 peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Tissue plasminogen activator entry;
CC URL="https://en.wikipedia.org/wiki/Tissue_plasminogen_Activator";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/plat/";
CC -!- WEB RESOURCE: Name=Activase; Note=Clinical information on Activase;
CC URL="https://www.activase.com/";
CC -!- WEB RESOURCE: Name=Chiesi; Note=Clinical information on Retavase;
CC URL="https://chiesiusa.com/products/retavase-2/";
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DR EMBL; L00153; AAB59510.1; -; Genomic_DNA.
DR EMBL; L00141; AAB59510.1; JOINED; Genomic_DNA.
DR EMBL; L00142; AAB59510.1; JOINED; Genomic_DNA.
DR EMBL; L00143; AAB59510.1; JOINED; Genomic_DNA.
DR EMBL; L00144; AAB59510.1; JOINED; Genomic_DNA.
DR EMBL; L00145; AAB59510.1; JOINED; Genomic_DNA.
DR EMBL; L00146; AAB59510.1; JOINED; Genomic_DNA.
DR EMBL; L00147; AAB59510.1; JOINED; Genomic_DNA.
DR EMBL; L00148; AAB59510.1; JOINED; Genomic_DNA.
DR EMBL; L00149; AAB59510.1; JOINED; Genomic_DNA.
DR EMBL; L00150; AAB59510.1; JOINED; Genomic_DNA.
DR EMBL; L00151; AAB59510.1; JOINED; Genomic_DNA.
DR EMBL; K03021; AAA98809.1; -; Genomic_DNA.
DR EMBL; M15518; AAA60111.1; -; mRNA.
DR EMBL; M18182; AAA36800.1; -; mRNA.
DR EMBL; X07393; CAA30302.1; -; mRNA.
DR EMBL; X13097; CAA31489.1; -; mRNA.
DR EMBL; AF260825; AAK11956.1; -; mRNA.
DR EMBL; AY221101; AAO34406.1; -; mRNA.
DR EMBL; AK289387; BAF82076.1; -; mRNA.
DR EMBL; AK290575; BAF83264.1; -; mRNA.
DR EMBL; AK313342; BAG36145.1; -; mRNA.
DR EMBL; BT007060; AAP35709.1; -; mRNA.
DR EMBL; AY291060; AAP34246.1; -; Genomic_DNA.
DR EMBL; CH471080; EAW63235.1; -; Genomic_DNA.
DR EMBL; CH471080; EAW63233.1; -; Genomic_DNA.
DR EMBL; BC002795; AAH02795.3; -; mRNA.
DR EMBL; BC007231; AAH07231.1; -; mRNA.
DR EMBL; BC013968; AAH13968.3; -; mRNA.
DR EMBL; BC018636; AAH18636.3; -; mRNA.
DR EMBL; BC095403; AAH95403.1; -; mRNA.
DR EMBL; M11890; AAA61213.1; -; Genomic_DNA.
DR EMBL; M11889; AAA61213.1; JOINED; Genomic_DNA.
DR EMBL; D01096; BAA00881.1; -; mRNA.
DR EMBL; V00570; CAA23833.1; -; mRNA.
DR CCDS; CCDS6126.1; -. [P00750-1]
DR CCDS; CCDS6127.1; -. [P00750-3]
DR PIR; A94004; UKHUT.
DR PIR; I38098; I38098.
DR RefSeq; NP_000921.1; NM_000930.4. [P00750-1]
DR RefSeq; NP_001306118.1; NM_001319189.1.
DR RefSeq; NP_127509.1; NM_033011.3. [P00750-3]
DR PDB; 1A5H; X-ray; 2.90 A; A/B=311-562, C/D=298-304.
DR PDB; 1BDA; X-ray; 3.35 A; A/B=298-562.
DR PDB; 1PK2; NMR; -; A=209-298.
DR PDB; 1PML; X-ray; 2.38 A; A/B/C=213-298.
DR PDB; 1RTF; X-ray; 2.30 A; B=311-562.
DR PDB; 1TPG; NMR; -; A=36-126.
DR PDB; 1TPK; X-ray; 2.40 A; A/B/C=211-298.
DR PDB; 1TPM; NMR; -; A=36-85.
DR PDB; 1TPN; NMR; -; A=36-85.
DR PDB; 5BRR; X-ray; 3.16 A; E=311-562.
DR PDB; 5ZLZ; X-ray; 3.58 A; E=311-561.
DR PDBsum; 1A5H; -.
DR PDBsum; 1BDA; -.
DR PDBsum; 1PK2; -.
DR PDBsum; 1PML; -.
DR PDBsum; 1RTF; -.
DR PDBsum; 1TPG; -.
DR PDBsum; 1TPK; -.
DR PDBsum; 1TPM; -.
DR PDBsum; 1TPN; -.
DR PDBsum; 5BRR; -.
DR PDBsum; 5ZLZ; -.
DR AlphaFoldDB; P00750; -.
DR SMR; P00750; -.
DR BioGRID; 111343; 51.
DR ComplexPortal; CPX-494; tPA-PAI-1 complex.
DR ELM; P00750; -.
DR IntAct; P00750; 14.
DR MINT; P00750; -.
DR STRING; 9606.ENSP00000220809; -.
DR BindingDB; P00750; -.
DR ChEMBL; CHEMBL1873; -.
DR DrugBank; DB07684; 5-(DIMETHYLAMINO)-2-NAPHTHALENESULFONIC ACID.
DR DrugBank; DB00513; Aminocaproic acid.
DR DrugBank; DB09228; Conestat alfa.
DR DrugBank; DB09213; Dexibuprofen.
DR DrugBank; DB06404; Human C1-esterase inhibitor.
DR DrugBank; DB01088; Iloprost.
DR DrugBank; DB16701; Plasminogen.
DR DrugCentral; P00750; -.
DR GuidetoPHARMACOLOGY; 2392; -.
DR MEROPS; S01.232; -.
DR GlyConnect; 603; 43 N-Linked glycans (3 sites), 1 O-Linked glycan (1 site).
DR GlyConnect; 86; 16 N-Linked glycans (1 site).
DR GlyGen; P00750; 6 sites, 103 N-linked glycans (4 sites), 1 O-linked glycan (1 site).
DR iPTMnet; P00750; -.
DR PhosphoSitePlus; P00750; -.
DR BioMuta; PLAT; -.
DR DMDM; 137119; -.
DR CPTAC; non-CPTAC-1164; -.
DR EPD; P00750; -.
DR jPOST; P00750; -.
DR MassIVE; P00750; -.
DR MaxQB; P00750; -.
DR PaxDb; P00750; -.
DR PeptideAtlas; P00750; -.
DR PRIDE; P00750; -.
DR ProteomicsDB; 51281; -. [P00750-1]
DR ProteomicsDB; 51282; -. [P00750-2]
DR ProteomicsDB; 51283; -. [P00750-3]
DR ProteomicsDB; 51284; -. [P00750-4]
DR Antibodypedia; 998; 804 antibodies from 39 providers.
DR DNASU; 5327; -.
DR Ensembl; ENST00000220809.9; ENSP00000220809.4; ENSG00000104368.19. [P00750-1]
DR Ensembl; ENST00000352041.7; ENSP00000270188.6; ENSG00000104368.19. [P00750-3]
DR Ensembl; ENST00000429089.6; ENSP00000392045.2; ENSG00000104368.19. [P00750-1]
DR Ensembl; ENST00000679151.1; ENSP00000504311.1; ENSG00000104368.19. [P00750-1]
DR GeneID; 5327; -.
DR KEGG; hsa:5327; -.
DR MANE-Select; ENST00000220809.9; ENSP00000220809.4; NM_000930.5; NP_000921.1.
DR UCSC; uc003xos.3; human. [P00750-1]
DR CTD; 5327; -.
DR DisGeNET; 5327; -.
DR GeneCards; PLAT; -.
DR HGNC; HGNC:9051; PLAT.
DR HPA; ENSG00000104368; Tissue enhanced (parathyroid gland, urinary bladder).
DR MalaCards; PLAT; -.
DR MIM; 173370; gene.
DR neXtProt; NX_P00750; -.
DR OpenTargets; ENSG00000104368; -.
DR Orphanet; 480528; Lethal hydranencephaly-diaphragmatic hernia syndrome.
DR Orphanet; 64738; NON RARE IN EUROPE: Non rare thrombophilia.
DR PharmGKB; PA33381; -.
DR VEuPathDB; HostDB:ENSG00000104368; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000158930; -.
DR HOGENOM; CLU_006842_18_4_1; -.
DR InParanoid; P00750; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; P00750; -.
DR TreeFam; TF329901; -.
DR BRENDA; 3.4.21.68; 2681.
DR PathwayCommons; P00750; -.
DR Reactome; R-HSA-186797; Signaling by PDGF.
DR Reactome; R-HSA-75205; Dissolution of Fibrin Clot.
DR SignaLink; P00750; -.
DR SIGNOR; P00750; -.
DR BioGRID-ORCS; 5327; 11 hits in 1078 CRISPR screens.
DR ChiTaRS; PLAT; human.
DR EvolutionaryTrace; P00750; -.
DR GeneWiki; Tissue_plasminogen_activator; -.
DR GenomeRNAi; 5327; -.
DR Pharos; P00750; Tclin.
DR PRO; PR:P00750; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P00750; protein.
DR Bgee; ENSG00000104368; Expressed in stromal cell of endometrium and 189 other tissues.
DR ExpressionAtlas; P00750; baseline and differential.
DR Genevisible; P00750; HS.
DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl.
DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
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; IBA:GO_Central.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0098992; C:neuronal dense core vesicle; IEA:Ensembl.
DR GO; GO:0099544; C:perisynaptic space; IEA:Ensembl.
DR GO; GO:0098794; C:postsynapse; IEA:Ensembl.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IEA:Ensembl.
DR GO; GO:0097180; C:serine protease inhibitor complex; IPI:ComplexPortal.
DR GO; GO:0051219; F:phosphoprotein binding; IPI:AgBase.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:BHF-UCL.
DR GO; GO:0005102; F:signaling receptor binding; IPI:AgBase.
DR GO; GO:0007596; P:blood coagulation; TAS:ProtInc.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IEA:Ensembl.
DR GO; GO:0071373; P:cellular response to luteinizing hormone stimulus; IEA:Ensembl.
DR GO; GO:0042730; P:fibrinolysis; TAS:Reactome.
DR GO; GO:0051918; P:negative regulation of fibrinolysis; IC:ComplexPortal.
DR GO; GO:0010757; P:negative regulation of plasminogen activation; IC:ComplexPortal.
DR GO; GO:0045861; P:negative regulation of proteolysis; IDA:BHF-UCL.
DR GO; GO:0031639; P:plasminogen activation; IDA:UniProtKB.
DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0060279; P:positive regulation of ovulation; IEA:Ensembl.
DR GO; GO:0060468; P:prevention of polyspermy; ISS:UniProtKB.
DR GO; GO:0036211; P:protein modification process; TAS:ProtInc.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR GO; GO:0048167; P:regulation of synaptic plasticity; IEA:Ensembl.
DR GO; GO:0051591; P:response to cAMP; IEA:Ensembl.
DR GO; GO:0070542; P:response to fatty acid; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0014909; P:smooth muscle cell migration; IBA:GO_Central.
DR GO; GO:0035249; P:synaptic transmission, glutamatergic; IEA:Ensembl.
DR GO; GO:0099183; P:trans-synaptic signaling by BDNF, modulating synaptic transmission; IEA:Ensembl.
DR CDD; cd00061; FN1; 1.
DR CDD; cd00108; KR; 2.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR Gene3D; 2.40.20.10; -; 2.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000083; Fibronectin_type1.
DR InterPro; IPR000001; Kringle.
DR InterPro; IPR013806; Kringle-like.
DR InterPro; IPR018056; Kringle_CS.
DR InterPro; IPR038178; Kringle_sf.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR026280; Tissue_plasm_act.
DR InterPro; IPR034811; tPA.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR PANTHER; PTHR24264:SF42; PTHR24264:SF42; 3.
DR Pfam; PF00008; EGF; 1.
DR Pfam; PF00039; fn1; 1.
DR Pfam; PF00051; Kringle; 2.
DR Pfam; PF00089; Trypsin; 1.
DR PIRSF; PIRSF001145; Tissue_plasm_act; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00058; FN1; 1.
DR SMART; SM00130; KR; 2.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF57440; SSF57440; 2.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS50026; EGF_3; 1.
DR PROSITE; PS01253; FN1_1; 1.
DR PROSITE; PS51091; FN1_2; 1.
DR PROSITE; PS00021; KRINGLE_1; 2.
DR PROSITE; PS50070; KRINGLE_2; 2.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disulfide bond; EGF-like domain; Glycoprotein;
KW Hydrolase; Kringle; Pharmaceutical; Plasminogen activation; Protease;
KW Reference proteome; Repeat; Secreted; Serine protease; Signal; Zymogen.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|Ref.20"
FT PROPEP 23..32
FT /evidence="ECO:0000269|PubMed:6682760"
FT /id="PRO_0000028348"
FT PROPEP 33..35
FT /note="Removed by plasmin"
FT /evidence="ECO:0000269|PubMed:6433976"
FT /id="PRO_0000028349"
FT CHAIN 36..562
FT /note="Tissue-type plasminogen activator"
FT /id="PRO_0000028350"
FT CHAIN 36..310
FT /note="Tissue-type plasminogen activator chain A"
FT /id="PRO_0000028351"
FT CHAIN 311..562
FT /note="Tissue-type plasminogen activator chain B"
FT /id="PRO_0000028352"
FT DOMAIN 39..81
FT /note="Fibronectin type-I"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00478"
FT DOMAIN 82..120
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 127..208
FT /note="Kringle 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 215..296
FT /note="Kringle 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 311..561
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT REGION 42..52
FT /note="Important for binding to annexin A2"
FT ACT_SITE 357
FT /note="Charge relay system"
FT /evidence="ECO:0000305|PubMed:8613982"
FT ACT_SITE 406
FT /note="Charge relay system"
FT /evidence="ECO:0000305|PubMed:8613982"
FT ACT_SITE 513
FT /note="Charge relay system"
FT /evidence="ECO:0000305|PubMed:8613982"
FT SITE 102
FT /note="Important for binding to LRP1"
FT SITE 253
FT /note="Not glycosylated"
FT SITE 464
FT /note="Important for single-chain activity"
FT SITE 512
FT /note="Important for single-chain activity"
FT CARBOHYD 96
FT /note="O-linked (Fuc) threonine"
FT /evidence="ECO:0000269|PubMed:1900431"
FT /id="CAR_000029"
FT CARBOHYD 152
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:2513186"
FT CARBOHYD 219
FT /note="N-linked (GlcNAc...) asparagine; partial"
FT /evidence="ECO:0000269|PubMed:2513186"
FT /id="CAR_000030"
FT CARBOHYD 483
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:2513186"
FT /id="CAR_000031"
FT DISULFID 41..71
FT /evidence="ECO:0000269|PubMed:1645336"
FT DISULFID 69..78
FT /evidence="ECO:0000269|PubMed:1645336"
FT DISULFID 86..97
FT /evidence="ECO:0000269|PubMed:1645336"
FT DISULFID 91..108
FT /evidence="ECO:0000269|PubMed:1645336"
FT DISULFID 110..119
FT /evidence="ECO:0000269|PubMed:1645336"
FT DISULFID 127..208
FT /evidence="ECO:0000250"
FT DISULFID 148..190
FT /evidence="ECO:0000250"
FT DISULFID 179..203
FT /evidence="ECO:0000250"
FT DISULFID 215..296
FT /evidence="ECO:0000269|PubMed:1645336"
FT DISULFID 236..278
FT /evidence="ECO:0000269|PubMed:1645336"
FT DISULFID 267..291
FT /evidence="ECO:0000269|PubMed:1645336"
FT DISULFID 299..430
FT /note="Interchain (between A and B chains)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000255|PROSITE-ProRule:PRU00121, ECO:0000255|PROSITE-
FT ProRule:PRU00274, ECO:0000255|PROSITE-ProRule:PRU00478,
FT ECO:0000269|PubMed:1645336"
FT DISULFID 342..358
FT /evidence="ECO:0000250"
FT DISULFID 350..419
FT /evidence="ECO:0000250"
FT DISULFID 444..519
FT /evidence="ECO:0000250"
FT DISULFID 476..492
FT /evidence="ECO:0000250"
FT DISULFID 509..537
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..40
FT /note="MDAMKRGLCCVLLLCGAVFVSPSQEIHARFRRGARSYQVI -> MAS (in
FT isoform 4)"
FT /evidence="ECO:0000303|Ref.8"
FT /id="VSP_028029"
FT VAR_SEQ 39..85
FT /note="VICRDEKTQMIYQQHQSWLRPVLRSNRVEYCWCNSGRAQCHSVPVKS -> G
FT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_015957"
FT VAR_SEQ 79..208
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.8"
FT /id="VSP_028030"
FT VAR_SEQ 269..291
FT /note="NPDGDAKPWCHVLKNRRLTWEYC -> TGRSVSSPATASMRPCPLSIRSG
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:2107528"
FT /id="VSP_005411"
FT VAR_SEQ 292..562
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:2107528"
FT /id="VSP_005412"
FT VARIANT 34
FT /note="A -> D (in dbSNP:rs8178733)"
FT /evidence="ECO:0000269|Ref.12"
FT /id="VAR_020181"
FT VARIANT 136
FT /note="R -> S (in dbSNP:rs8178747)"
FT /evidence="ECO:0000269|Ref.12"
FT /id="VAR_038732"
FT VARIANT 146
FT /note="A -> T (in dbSNP:rs8178748)"
FT /evidence="ECO:0000269|Ref.12"
FT /id="VAR_038733"
FT VARIANT 164
FT /note="R -> W (in dbSNP:rs2020921)"
FT /evidence="ECO:0000269|Ref.12"
FT /id="VAR_011783"
FT CONFLICT 93
FT /note="N -> T (in Ref. 2; AAB59510)"
FT /evidence="ECO:0000305"
FT CONFLICT 159..160
FT /note="KP -> NA (in Ref. 7; CAA31489)"
FT /evidence="ECO:0000305"
FT CONFLICT 247
FT /note="K -> N (in Ref. 9; AAO34406)"
FT /evidence="ECO:0000305"
FT CONFLICT 283
FT /note="N -> S (in Ref. 14; AAH95403)"
FT /evidence="ECO:0000305"
FT CONFLICT 333..334
FT /note="RR -> EE (in Ref. 8; AAK11956)"
FT /evidence="ECO:0000305"
FT CONFLICT 389
FT /note="V -> C (in Ref. 8; AAK11956)"
FT /evidence="ECO:0000305"
FT STRAND 41..43
FT /evidence="ECO:0007829|PDB:1TPM"
FT STRAND 44..46
FT /evidence="ECO:0007829|PDB:1TPG"
FT STRAND 48..50
FT /evidence="ECO:0007829|PDB:1TPM"
FT STRAND 55..59
FT /evidence="ECO:0007829|PDB:1TPG"
FT STRAND 61..64
FT /evidence="ECO:0007829|PDB:1TPG"
FT STRAND 66..70
FT /evidence="ECO:0007829|PDB:1TPG"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:1TPG"
FT STRAND 77..81
FT /evidence="ECO:0007829|PDB:1TPM"
FT STRAND 83..85
FT /evidence="ECO:0007829|PDB:1TPG"
FT STRAND 96..104
FT /evidence="ECO:0007829|PDB:1TPG"
FT STRAND 106..109
FT /evidence="ECO:0007829|PDB:1TPG"
FT STRAND 115..118
FT /evidence="ECO:0007829|PDB:1TPG"
FT STRAND 221..223
FT /evidence="ECO:0007829|PDB:1PK2"
FT STRAND 229..233
FT /evidence="ECO:0007829|PDB:1PK2"
FT HELIX 242..244
FT /evidence="ECO:0007829|PDB:1PML"
FT STRAND 248..250
FT /evidence="ECO:0007829|PDB:1PML"
FT STRAND 251..253
FT /evidence="ECO:0007829|PDB:1PK2"
FT HELIX 256..259
FT /evidence="ECO:0007829|PDB:1PML"
FT STRAND 262..264
FT /evidence="ECO:0007829|PDB:1PML"
FT STRAND 277..282
FT /evidence="ECO:0007829|PDB:1PML"
FT STRAND 285..291
FT /evidence="ECO:0007829|PDB:1PML"
FT STRAND 309..311
FT /evidence="ECO:0007829|PDB:1BDA"
FT STRAND 312..316
FT /evidence="ECO:0007829|PDB:1RTF"
FT HELIX 319..321
FT /evidence="ECO:0007829|PDB:1RTF"
FT STRAND 325..331
FT /evidence="ECO:0007829|PDB:1RTF"
FT STRAND 338..346
FT /evidence="ECO:0007829|PDB:1RTF"
FT STRAND 348..354
FT /evidence="ECO:0007829|PDB:1RTF"
FT HELIX 356..359
FT /evidence="ECO:0007829|PDB:1RTF"
FT HELIX 365..367
FT /evidence="ECO:0007829|PDB:1RTF"
FT STRAND 368..373
FT /evidence="ECO:0007829|PDB:1RTF"
FT STRAND 375..379
FT /evidence="ECO:0007829|PDB:1RTF"
FT STRAND 385..394
FT /evidence="ECO:0007829|PDB:1RTF"
FT TURN 400..402
FT /evidence="ECO:0007829|PDB:1RTF"
FT STRAND 408..412
FT /evidence="ECO:0007829|PDB:1RTF"
FT STRAND 415..417
FT /evidence="ECO:0007829|PDB:1RTF"
FT STRAND 423..425
FT /evidence="ECO:0007829|PDB:5BRR"
FT STRAND 443..449
FT /evidence="ECO:0007829|PDB:1RTF"
FT STRAND 451..453
FT /evidence="ECO:0007829|PDB:1BDA"
FT STRAND 464..470
FT /evidence="ECO:0007829|PDB:1RTF"
FT HELIX 473..475
FT /evidence="ECO:0007829|PDB:1RTF"
FT TURN 478..483
FT /evidence="ECO:0007829|PDB:1RTF"
FT STRAND 490..494
FT /evidence="ECO:0007829|PDB:1RTF"
FT STRAND 499..501
FT /evidence="ECO:0007829|PDB:1A5H"
FT STRAND 516..521
FT /evidence="ECO:0007829|PDB:1RTF"
FT STRAND 524..533
FT /evidence="ECO:0007829|PDB:1RTF"
FT STRAND 535..538
FT /evidence="ECO:0007829|PDB:1RTF"
FT STRAND 544..548
FT /evidence="ECO:0007829|PDB:1RTF"
FT HELIX 549..552
FT /evidence="ECO:0007829|PDB:1RTF"
FT HELIX 553..559
FT /evidence="ECO:0007829|PDB:1RTF"
SQ SEQUENCE 562 AA; 62917 MW; B7EC9B1A5E3FDC4D CRC64;
MDAMKRGLCC VLLLCGAVFV SPSQEIHARF RRGARSYQVI CRDEKTQMIY QQHQSWLRPV
LRSNRVEYCW CNSGRAQCHS VPVKSCSEPR CFNGGTCQQA LYFSDFVCQC PEGFAGKCCE
IDTRATCYED QGISYRGTWS TAESGAECTN WNSSALAQKP YSGRRPDAIR LGLGNHNYCR
NPDRDSKPWC YVFKAGKYSS EFCSTPACSE GNSDCYFGNG SAYRGTHSLT ESGASCLPWN
SMILIGKVYT AQNPSAQALG LGKHNYCRNP DGDAKPWCHV LKNRRLTWEY CDVPSCSTCG
LRQYSQPQFR IKGGLFADIA SHPWQAAIFA KHRRSPGERF LCGGILISSC WILSAAHCFQ
ERFPPHHLTV ILGRTYRVVP GEEEQKFEVE KYIVHKEFDD DTYDNDIALL QLKSDSSRCA
QESSVVRTVC LPPADLQLPD WTECELSGYG KHEALSPFYS ERLKEAHVRL YPSSRCTSQH
LLNRTVTDNM LCAGDTRSGG PQANLHDACQ GDSGGPLVCL NDGRMTLVGI ISWGLGCGQK
DVPGVYTKVT NYLDWIRDNM RP
