ID TPA_HUMAN Reviewed; 562 AA. AC P00750; Q15103; Q7Z7N2; Q86YK8; Q9BU99; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 28-NOV-2006, entry version 109. DE Tissue-type plasminogen activator precursor (EC 3.4.21.68) (tPA) (t- DE PA) (t-plasminogen activator) (Alteplase) (Reteplase) [Contains: DE Tissue-type plasminogen activator chain A; Tissue-type plasminogen DE activator chain B]. GN Name=PLAT; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Melanoma; RX MEDLINE=83115262; PubMed=6337343; DOI=10.1038/301214a0; RA Pennica D., Holmes W.E., Kohr W.J., Harkins R.N., Vehar G.A., RA Ward C.A., Bennett W.F., Yelverton E., Seeburg P.H., Heyneker H.L., RA Goeddel D.V., Collen D.; RT "Cloning and expression of human tissue-type plasminogen activator RT cDNA in E. coli."; RL Nature 301:214-221(1983). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX MEDLINE=84298137; PubMed=6089198; 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 [MRNA] (ISOFORM 1). RX MEDLINE=86284200; PubMed=3090401; RA Harris T.J., Patel T., Marston F.A., Little S., Emtage J.S., RA Opdenakker G., Volckaert G., Rombauts W., Billiau A., Somer P.; RT "Cloning of cDNA coding for human tissue-type plasminogen activator RT and its expression in Escherichia coli."; RL Mol. Biol. Med. 3:279-292(1986). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX MEDLINE=86196143; PubMed=3009482; 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 [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX MEDLINE=88054470; PubMed=2824147; 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 RT mouse cells using BPV vectors."; RL DNA 6:461-472(1987). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Fetal lung; RX MEDLINE=88262579; PubMed=3133640; RA Sasaki H., Saito Y., Hayashi M., Otsuka K., Niwa M.; RT "Nucleotide sequence of the tissue-type plasminogen activator cDNA RT from 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 MEDLINE=90192129; PubMed=2107528; RA Siebert P.D., Fong K.; RT "Variant tissue-type plasminogen activator (PLAT) cDNA obtained from RT human endothelial cells."; RL Nucleic Acids Res. 18:1086-1086(1990). RN [8] 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 [9] 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 RT vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Rieder M.J., Carrington D.P., da Ponte S.H., Hastings N.C., RA Ahearn M.O., Kuldanek S.A., Rajkumar N., Toth E.J., Yi Q., RA Nickerson D.A.; RT "SeattleSNPs. NHLBI HL66682 program for genomic applications, UW- RT FHCRC, Seattle, WA (URL: http://pga.gs.washington.edu)."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Brain, 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [12] RP NUCLEOTIDE SEQUENCE [MRNA] OF 212-361. RX MEDLINE=83169656; PubMed=6572897; 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 RT plasminogen activator."; RL Proc. Natl. Acad. Sci. U.S.A. 80:349-352(1983). RN [13] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-36. RX MEDLINE=85289338; PubMed=3161893; 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 [14] RP NUCLEOTIDE SEQUENCE [MRNA] OF 31-562. RX MEDLINE=91291340; PubMed=1368681; RA Itagaki Y., Yasuda H., Morinaga T., Mitsuda S., Higashio K.; RT "Purification and characterization of tissue plasminogen activator RT secreted by human embryonic lung diploid fibroblasts, IMR-90 cells."; RL Agric. Biol. Chem. 55:1225-1232(1991). RN [15] RP PROTEIN SEQUENCE OF 36-562. RC TISSUE=Melanoma; RX MEDLINE=85000468; 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 [16] RP PROTEIN SEQUENCE OF 33-52 AND 311-330. RC TISSUE=Melanoma; RX MEDLINE=83209620; PubMed=6682760; 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 [17] RP STRUCTURE OF CARBOHYDRATES. RX MEDLINE=90092112; PubMed=2513186; RA Pfeiffer G., Schmidt M., Strube K.-H., Geyer R.; RT "Carbohydrate structure of recombinant human uterine tissue RT plasminogen activator expressed in mouse epithelial cells."; RL Eur. J. Biochem. 186:273-286(1989). RN [18] RP GLYCOSYLATION AT THR-96. RX MEDLINE=91159408; 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 RT threonine-61 in the epidermal growth factor domain."; RL Biochemistry 30:2311-2314(1991). RN [19] RP DISULFIDE BONDS IN KRINGLE 2. RX MEDLINE=91244765; PubMed=1645336; 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 [20] 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:RESEARCH008.1-RESEARCH008.16(2004). RN [21] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF CATALYTIC DOMAIN. RX MEDLINE=96200985; PubMed=8613982; DOI=10.1006/jmbi.1996.0238; RA Lamba D., Bauer M., Huber R., Fischer S., Rudolph R., Kohnert U., RA Bode W.; RT "The 2.3 A crystal structure of the catalytic domain of recombinant RT two-chain human tissue-type plasminogen activator."; RL J. Mol. Biol. 258:117-135(1996). RN [22] RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF CATALYTIC DOMAIN. RX MEDLINE=97449126; 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 RT crystal structure of single-chain human tPA."; RL EMBO J. 16:4797-4805(1997). RN [23] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF KRINGLE 2. RX MEDLINE=92118803; 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 RT activator at 2.4-A resolution."; RL Biochemistry 31:270-279(1992). RN [24] RP STRUCTURE BY NMR OF KRINGLE 2. RX MEDLINE=90122799; 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 RT from human tissue-type plasminogen activator."; RL Biochemistry 28:9350-9360(1989). RN [25] RP STRUCTURE BY NMR OF KRINGLE 2. RX MEDLINE=91200042; PubMed=1901789; 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 [26] RP STRUCTURE BY NMR OF KRINGLE 2. RX MEDLINE=92106329; PubMed=1762144; 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 [27] RP STRUCTURE BY NMR OF 38-85. RX MEDLINE=92292163; PubMed=1602484; 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 [28] RP STRUCTURE BY NMR OF 36-126. RX MEDLINE=96027104; 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 RT I and epidermal growth factor-like pair of modules of tissue-type RT plasminogen activator."; RL Structure 3:823-833(1995). RN [29] RP INTERACTION WITH LRP1B. RX MEDLINE=21369943; 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 RT density lipoprotein (LDL) receptor family, exhibits both overlapping RT and distinct properties with the LDL receptor-related protein."; RL J. Biol. Chem. 276:28889-28896(2001). CC -!- FUNCTION: Converts the abundant, but inactive, zymogen plasminogen CC to plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By CC controlling plasmin-mediated proteolysis, it plays an important CC role in tissue remodeling and degradation, in cell migration and CC many other physiopathological events. Play a direct role in CC facilitating neuronal migration. CC -!- CATALYTIC ACTIVITY: Specific cleavage of Arg-|-Val bond in CC plasminogen to form plasmin. CC -!- SUBUNIT: Heterodimer of chain A and chain B held by a disulfide CC bond. Binds to fibrin with high affinity. This interaction leads CC to an increase in the catalytic efficiency of the enzyme between CC 100-fold and 1000-fold, due to an increase in affinity for CC plasminogen. Similarly, binding to heparin increases the CC activation of plasminogen. Binding to laminin and fibronectin has CC also been demonstrated. Binds to mannose receptor and the low- CC density lipoprotein receptor-related protein (LRP1). These CC proteins are involved in TPA clearance. Also binds to annexin II CC and to cytokeratin 8. 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 CC VSMC reduces TPA inhibition by PAI-1 by 30-fold. Binds LRP1B; CC binding is followed by internalization and degradation. CC -!- SUBCELLULAR LOCATION: Secreted protein; extracellular space. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; 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 Note=May be produced at very low levels due to a premature stop CC codon in the mRNA, leading to nonsense-mediated mRNA decay; CC Name=3; CC IsoId=P00750-3; Sequence=VSP_015957; CC Note=No experimental confirmation available; CC -!- TISSUE SPECIFICITY: Synthesized in numerous tissues (including CC tumors) and secreted into most extracellular body fluids, such as CC plasma, uterine fluid, saliva, gingival crevicular fluid, tears, CC seminal fluid, 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 II. 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 CC Arg-310 catalyzed by plasmin, tissue kallikrein or factor Xa. CC -!- PTM: Differential cell-specific N-linked glycosylation gives rise CC to two variants: type I and type II. The single chain type I CC variant is less readily converted into the two-chain form by CC plasmin and the two-chain type I variant has a lower activity than CC the two-chain type II in the presence of fibrin. CC -!- PTM: N-glycosylation of Asn-152; the bound oligomannosidic glycan CC is involved in the interaction with the mannose receptor. CC -!- PTM: Characterization of O-linked glycan was studied in Bowes CC melanoma cell line. CC -!- DISEASE: Increased activity of TPA causes hyperfibrinolysis, with CC excessive bleeding as a consequence. CC -!- DISEASE: Defective release of TPA causes hypofibrinolysis, leading CC to thrombosis or embolism. 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 CC BM 06.022]. Used in Acute Myocardial Infarction (AMI), in Acute CC Ischemic Stroke (AIS) and Pulmonary Embolism (PE) to initiate CC fibrinolysis. CC -!- SIMILARITY: Belongs to the peptidase S1 family. CC -!- SIMILARITY: Contains 1 EGF-like domain. CC -!- SIMILARITY: Contains 1 fibronectin type-I domain. CC -!- SIMILARITY: Contains 2 kringle domains. CC -!- SIMILARITY: Contains 1 peptidase S1 domain. CC -!- WEB RESOURCE: NAME=Activase; NOTE=Clinical information on Activase; CC URL="http://www.gene.com/gene/products/information/cardiovascular/activase/index.jsp". CC -!- WEB RESOURCE: NAME=Retavase; NOTE=Clinical information on Retavase; CC URL="http://www.retavase.com/RETLibrary/RETLib008/dld/Retavase_PI.pdf". CC -!- WEB RESOURCE: NAME=SHMPD; CC NOTE=The Singapore human mutation and polymorphism database; CC URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=PLAT". CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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; M15518; AAA60111.1; -; mRNA. DR EMBL; K03021; AAA98809.1; -; Genomic_DNA. DR EMBL; M18182; AAA36800.1; -; mRNA. DR EMBL; X07393; CAA30302.1; -; mRNA. DR EMBL; X13097; CAA31489.1; -; mRNA. DR EMBL; AY221101; AAO34406.1; -; mRNA. DR EMBL; BT007060; AAP35709.1; -; mRNA. DR EMBL; AY291060; AAP34246.1; -; Genomic_DNA. DR EMBL; BC002795; AAH02795.2; ALT_INIT; mRNA. DR EMBL; BC007231; AAH07231.1; -; mRNA. DR EMBL; V00570; CAA23833.1; -; mRNA. DR EMBL; M11890; AAA61213.1; -; Genomic_DNA. DR EMBL; M11889; AAA61213.1; JOINED; Genomic_DNA. DR EMBL; D01096; BAA00881.1; -; mRNA. DR EMBL; A07197; CAA00642.1; -; Unassigned_RNA. DR EMBL; A01465; CAA00166.1; -; Unassigned_DNA. DR PIR; A94004; UKHUT. DR UniGene; Hs.491582; -. DR PDB; 1A5H; X-ray; A/B=311-562, C/D=298-304. DR PDB; 1BDA; X-ray; A/B=298-562. DR PDB; 1PK2; NMR; @=209-298. DR PDB; 1PML; X-ray; A/B/C=213-298. DR PDB; 1RTF; X-ray; B=311-562. DR PDB; 1TPG; NMR; @=36-126. DR PDB; 1TPK; X-ray; A/B/C=211-298. DR PDB; 1TPM; NMR; @=36-85. DR PDB; 1TPN; NMR; @=36-85. DR MEROPS; S01.232; -. DR GlycoSuiteDB; P00750; -. DR Ensembl; ENSG00000104368; Homo sapiens. DR KEGG; hsa:5327; -. DR H-InvDB; HIX0007476; -. DR HGNC; HGNC:9051; PLAT. DR MIM; 173370; gene+phenotype. DR Reactome; P00750; -. DR LinkHub; P00750; -. DR ArrayExpress; P00750; -. DR RZPD-ProtExp; F0362; -. DR RZPD-ProtExp; IOH29603; -. DR RZPD-ProtExp; RZPDo839F0170; -. DR RZPD-ProtExp; Z0341; -. DR GO; GO:0007596; P:blood coagulation; TAS:ProtInc. DR GO; GO:0006464; P:protein modification; TAS:ProtInc. DR GO; GO:0006508; P:proteolysis; TAS:ProtInc. DR InterPro; IPR006210; EGF. DR InterPro; IPR000742; EGF_3. DR InterPro; IPR006209; EGF_like. DR InterPro; IPR013032; EGF_like_reg. DR InterPro; IPR000083; Fibrnctn1. DR InterPro; IPR000001; Kringle. DR InterPro; IPR013806; Kringle-like. DR InterPro; IPR011357; Pept_S1A_tPA. DR InterPro; IPR009003; Pept_Ser_Cys. DR InterPro; IPR001254; Peptidase_S1_S6. DR InterPro; IPR001314; Peptidase_S1A. DR Gene3D; G3DSA:2.40.20.10; Kringle; 2. 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 PRINTS; PR00018; KRINGLE. DR ProDom; PD000395; Kringle; 2. DR SMART; SM00181; EGF; 1. DR SMART; SM00058; FN1; 1. DR SMART; SM00130; KR; 2. DR SMART; SM00020; Tryp_SPc; 1. 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. KW 3D-structure; Alternative splicing; Direct protein sequencing; KW EGF-like domain; Glycoprotein; Hydrolase; Kringle; Pharmaceutical; KW Plasminogen activation; Polymorphism; Protease; Repeat; KW Serine protease; Signal. FT SIGNAL 1 23 Potential. FT PROPEP 24 32 FT /FTId=PRO_0000028348. FT PROPEP 33 35 Removed by plasmin. FT /FTId=PRO_0000028349. FT CHAIN 36 562 Tissue-type plasminogen activator. FT /FTId=PRO_0000028350. FT CHAIN 36 310 Tissue-type plasminogen activator chain FT A. FT /FTId=PRO_0000028351. FT CHAIN 311 562 Tissue-type plasminogen activator chain FT B. FT /FTId=PRO_0000028352. FT DOMAIN 39 81 Fibronectin type-I. FT DOMAIN 82 120 EGF-like. FT DOMAIN 127 208 Kringle 1. FT DOMAIN 215 296 Kringle 2. FT DOMAIN 311 561 Peptidase S1. FT REGION 42 52 Important for binding to annexin II. FT ACT_SITE 357 357 Charge relay system. FT ACT_SITE 406 406 Charge relay system. FT ACT_SITE 513 513 Charge relay system. FT SITE 102 102 Important for binding to LRP1. FT SITE 464 464 Important for single-chain activity. FT SITE 512 512 Important for single-chain activity. FT CARBOHYD 96 96 O-linked (Fuc). FT /FTId=CAR_000029. FT CARBOHYD 152 152 N-linked (GlcNAc...); in type I and II FT variants. FT CARBOHYD 219 219 N-linked (GlcNAc...); in type I variant FT only. FT /FTId=CAR_000030. FT CARBOHYD 483 483 N-linked (GlcNAc...); in type I and II FT variants. FT /FTId=CAR_000031. FT DISULFID 41 71 FT DISULFID 69 78 FT DISULFID 86 97 FT DISULFID 91 108 FT DISULFID 110 119 FT DISULFID 127 208 By similarity. FT DISULFID 148 190 By similarity. FT DISULFID 179 203 By similarity. FT DISULFID 215 296 FT DISULFID 236 278 FT DISULFID 267 291 FT DISULFID 299 430 Interchain (between A and B chains). FT DISULFID 342 358 By similarity. FT DISULFID 350 419 By similarity. FT DISULFID 444 519 By similarity. FT DISULFID 476 492 By similarity. FT DISULFID 509 537 By similarity. FT VAR_SEQ 39 85 VICRDEKTQMIYQQHQSWLRPVLRSNRVEYCWCNSGRAQCH FT SVPVKS -> G (in isoform 3). FT /FTId=VSP_015957. FT VAR_SEQ 269 291 NPDGDAKPWCHVLKNRRLTWEYC -> TGRSVSSPATASMR FT PCPLSIRSG (in isoform 2). FT /FTId=VSP_005411. FT VAR_SEQ 292 562 Missing (in isoform 2). FT /FTId=VSP_005412. FT VARIANT 34 34 A -> D (in dbSNP:rs8178733). FT /FTId=VAR_020181. FT VARIANT 164 164 R -> W (in dbSNP:rs2020921). FT /FTId=VAR_011783. FT CONFLICT 93 93 N -> T (in Ref. 2). FT CONFLICT 159 160 KP -> NA (in Ref. 7). FT CONFLICT 247 247 K -> N (in Ref. 8). FT STRAND 44 46 FT STRAND 55 59 FT STRAND 61 64 FT STRAND 66 70 FT STRAND 72 74 FT STRAND 83 85 FT TURN 93 94 FT STRAND 96 104 FT STRAND 106 109 FT TURN 112 113 FT STRAND 115 118 FT TURN 210 211 FT TURN 218 219 FT TURN 221 222 FT TURN 231 232 FT TURN 239 240 FT HELIX 242 244 FT TURN 245 246 FT STRAND 248 250 FT TURN 251 252 FT TURN 254 255 FT HELIX 256 259 FT TURN 260 260 FT STRAND 262 264 FT STRAND 277 282 FT TURN 283 284 FT STRAND 285 291 FT TURN 296 297 FT TURN 299 300 FT STRAND 309 311 FT STRAND 312 316 FT HELIX 319 321 FT TURN 323 324 FT STRAND 325 331 FT STRAND 338 346 FT STRAND 348 354 FT HELIX 356 359 FT TURN 360 361 FT HELIX 365 367 FT STRAND 368 373 FT STRAND 375 379 FT TURN 382 383 FT STRAND 385 394 FT TURN 396 397 FT TURN 400 402 FT TURN 404 405 FT STRAND 408 412 FT STRAND 415 417 FT TURN 424 425 FT TURN 434 435 FT TURN 440 441 FT STRAND 443 449 FT TURN 454 455 FT STRAND 464 470 FT HELIX 473 475 FT TURN 478 483 FT TURN 488 489 FT STRAND 490 494 FT TURN 510 511 FT TURN 513 514 FT STRAND 516 521 FT TURN 522 523 FT STRAND 524 533 FT STRAND 535 538 FT TURN 540 541 FT STRAND 544 548 FT HELIX 549 552 FT HELIX 553 559 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 //