ID PLMN_HUMAN Reviewed; 810 AA. AC P00747; Q15146; Q5TEH4; Q6PA00; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1989, sequence version 2. DT 13-FEB-2019, entry version 238. DE RecName: Full=Plasminogen; DE EC=3.4.21.7; DE Contains: DE RecName: Full=Plasmin heavy chain A; DE Contains: DE RecName: Full=Activation peptide; DE Contains: DE RecName: Full=Angiostatin; DE Contains: DE RecName: Full=Plasmin heavy chain A, short form; DE Contains: DE RecName: Full=Plasmin light chain B; DE Flags: Precursor; GN Name=PLG; 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 [GENOMIC DNA], AND VARIANT ASN-472. RX PubMed=2318848; RA Petersen T.E., Martzen M.R., Ichinose A., Davie E.W.; RT "Characterization of the gene for human plasminogen, a key proenzyme RT in the fibrinolytic system."; RL J. Biol. Chem. 265:6104-6111(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3030813; DOI=10.1016/0014-5793(87)81501-6; RA Forsgren M., Raden B., Israelsson M., Larsson K., Heden L.-O.; RT "Molecular cloning and characterization of a full-length cDNA clone RT for human plasminogen."; RL FEBS Lett. 213:254-260(1987). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Liver; RA Browne M.J., Chapman C.G., Dodd I., Carey J.E., Lawrence G.M.P., RA Mitchell D., Robinson J.H.; RT "Expression of recombinant human plasminogen and aglycoplasminogen in RT HeLa cells."; RL Submitted (OCT-1991) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LYS-57; GLN-133; RP HIS-261; TRP-408; ASN-472; VAL-494 AND TRP-523. RG SeattleSNPs variation discovery resource; RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S., RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., RA Frankland J., French L., Garner P., Garnett J., Ghori M.J., RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASP-676. RC TISSUE=Kidney; 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 [7] RP PROTEIN SEQUENCE OF 20-810, AND VARIANT ASN-472. RA Sottrup-Jensen L., Petersen T.E., Magnusson S.; RL Submitted (JUL-1977) to the PIR data bank. RN [8] RP PROTEIN SEQUENCE OF 20-100. RX PubMed=122932; DOI=10.1111/j.1432-1033.1975.tb09887.x; RA Wiman B., Wallen P.; RT "Structural relationship between 'glutamic acid' and 'lysine' forms of RT human plasminogen and their interaction with the NH2-terminal RT activation peptide as studied by affinity chromatography."; RL Eur. J. Biochem. 50:489-494(1975). RN [9] RP PROTEIN SEQUENCE OF 95-580; 581-626; 657-700 AND 732-810, AND VARIANT RP ASN-472. RA Sottrup-Jensen L., Claeys H., Zajdel M., Petersen T.E., Magnusson S.; RT "The primary structure of human plasminogen."; RL (In) Davidson J.F., Rowan R.M., Samama M.M., Desnoyers P.C. (eds.); RL Progress in chemical fibrinolysis and thrombolysis, pp.3:191-209, RL Raven Press, New York (1978). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 292-810. RX PubMed=6148961; DOI=10.1021/bi00313a035; RA Malinowski D.P., Sadler J.E., Davie E.W.; RT "Characterization of a complementary deoxyribonucleic acid coding for RT human and bovine plasminogen."; RL Biochemistry 23:4243-4250(1984). RN [11] RP PROTEIN SEQUENCE OF 483-604. RX PubMed=126863; DOI=10.1111/j.1432-1033.1975.tb02403.x; RA Wiman B., Wallen P.; RT "Amino-acid sequence of the cyanogen-bromide fragment from human RT plasminogen that forms the linkage between the plasmin chains."; RL Eur. J. Biochem. 58:539-547(1975). RN [12] RP PROTEIN SEQUENCE OF 581-810. RX PubMed=142009; DOI=10.1111/j.1432-1033.1977.tb11578.x; RA Wiman B.; RT "Primary structure of the B-chain of human plasmin."; RL Eur. J. Biochem. 76:129-137(1977). RN [13] RP ACTIVE SITE. RX PubMed=4694729; RA Robbins K.C., Bernabe P., Arzadon L., Summaria L.; RT "The primary structure of human plasminogen. II. The histidine loop of RT human plasmin: light (B) chain active center histidine sequence."; RL J. Biol. Chem. 248:1631-1633(1973). RN [14] RP ACTIVE SITE. RX PubMed=4240117; RA Groskopf W.R., Summaria L., Robbins K.C.; RT "Studies on the active center of human plasmin. Partial amino acid RT sequence of a peptide containing the active center serine residue."; RL J. Biol. Chem. 244:3590-3597(1969). RN [15] RP OMEGA-AMINOCARBOXYLIC ACID-BINDING SITES. RX PubMed=6919539; RA Trexler M., Vali Z., Patthy L.; RT "Structure of the omega-aminocarboxylic acid-binding sites of human RT plasminogen. Arginine 70 and aspartic acid 56 are essential for RT binding of ligand by kringle 4."; RL J. Biol. Chem. 257:7401-7406(1982). RN [16] RP FIBRIN AND OMEGA-AMINOCARBOXYLIC ACID BINDING SITES. RX PubMed=6094526; RA Vali Z., Patthy L.; RT "The fibrin-binding site of human plasminogen. Arginines 32 and 34 are RT essential for fibrin affinity of the kringle 1 domain."; RL J. Biol. Chem. 259:13690-13694(1984). RN [17] RP PHOSPHORYLATION AT SER-597. RX PubMed=9201958; DOI=10.1021/bi970328d; RA Wang H., Prorok M., Bretthauer R.K., Castellino F.J.; RT "Serine-578 is a major phosphorylation locus in human plasma RT plasminogen."; RL Biochemistry 36:8100-8106(1997). RN [18] RP GLYCOSYLATION AT SER-268; ASN-308 AND THR-365, AND STRUCTURE OF RP CARBOHYDRATES. RX PubMed=3356193; DOI=10.1111/j.1432-1033.1988.tb13966.x; RA Marti T., Schaller J., Rickli E.E., Schmid K., Kamerling J.P., RA Gerwig G.J., van Halbeek H., Vliegenthart J.F.G.; RT "The N- and O-linked carbohydrate chains of human, bovine and porcine RT plasminogen. Species specificity in relation to sialylation and RT fucosylation patterns."; RL Eur. J. Biochem. 173:57-63(1988). RN [19] RP INTERACTION WITH HRG. RX PubMed=9102401; DOI=10.1074/jbc.272.9.5718; RA Borza D.B., Morgan W.T.; RT "Acceleration of plasminogen activation by tissue plasminogen RT activator on surface-bound histidine-proline-rich glycoprotein."; RL J. Biol. Chem. 272:5718-5726(1997). RN [20] RP GLYCOSYLATION AT SER-268. RX PubMed=9054441; DOI=10.1074/jbc.272.11.7408; RA Pirie-Shepherd S.R., Stevens R.D., Andon N.L., Enghild J.J., RA Pizzo S.V.; RT "Evidence for a novel O-linked sialylated trisaccharide on Ser-248 of RT human plasminogen 2."; RL J. Biol. Chem. 272:7408-7411(1997). RN [21] RP CHARACTERIZATION OF ANGIOSTATIN, AND PARTIAL PROTEIN SEQUENCE. RX PubMed=7525077; DOI=10.1016/0092-8674(94)90200-3; RA O'Reilly M.S., Holmgren L., Shing Y., Chen C., Rosenthal R.A., RA Moses M., Lane W.S., Cao Y., Sage E.H., Folkman J.; RT "Angiostatin: a novel angiogenesis inhibitor that mediates the RT suppression of metastases by a Lewis lung carcinoma."; RL Cell 79:315-328(1994). RN [22] RP CHARACTERIZATION OF ANGIOSTATIN. RX PubMed=9102221; RA Sim B.K., O'Reilly M.S., Liang H., Fortier A.H., He W., Madsen J.W., RA Lapcevich R., Nacy C.A.; RT "A recombinant human angiostatin protein inhibits experimental primary RT and metastatic cancer."; RL Cancer Res. 57:1329-1334(1997). RN [23] RP PROTEOLYTIC CLEAVAGE. RX PubMed=9548733; DOI=10.1021/bi9731798; RA Lijnen H.R., Ugwu F., Bini A., Collen D.; RT "Generation of an angiostatin-like fragment from plasminogen by RT stromelysin-1 (MMP-3)."; RL Biochemistry 37:4699-4702(1998). RN [24] RP INTERACTION WITH ATP5F1A, AND SUBCELLULAR LOCATION. RX PubMed=10077593; DOI=10.1073/pnas.96.6.2811; RA Moser T.L., Stack M.S., Asplin I., Enghild J.J., Hojrup P., RA Everitt L., Hubchak S., Schnaper H.W., Pizzo S.V.; RT "Angiostatin binds ATP synthase on the surface of human endothelial RT cells."; RL Proc. Natl. Acad. Sci. U.S.A. 96:2811-2816(1999). RN [25] RP INTERACTION WITH CSPG4, AND DOMAIN. RX PubMed=10889192; DOI=10.1074/jbc.M002290200; RA Goretzki L., Lombardo C.R., Stallcup W.B.; RT "Binding of the NG2 proteoglycan to kringle domains modulates the RT functional properties of angiostatin and plasmin(ogen)."; RL J. Biol. Chem. 275:28625-28633(2000). RN [26] RP PROTEOLYTIC PROCESSING, ACTIVITY REGULATION, SUBCELLULAR LOCATION, RP FUNCTION OF PLASMIN, AND MUTAGENESIS OF SER-741. RX PubMed=14699093; DOI=10.1074/jbc.M310964200; RA Rossignol P., Ho-Tin-Noe B., Vranckx R., Bouton M.C., Meilhac O., RA Lijnen H.R., Guillin M.C., Michel J.B., Angles-Cano E.; RT "Protease nexin-1 inhibits plasminogen activation-induced apoptosis of RT adherent cells."; RL J. Biol. Chem. 279:10346-10356(2004). RN [27] RP INTERACTION WITH ADA. RX PubMed=15016824; DOI=10.1074/jbc.M401023200; RA Gonzalez-Gronow M., Hershfield M.S., Arredondo-Vega F.X., Pizzo S.V.; RT "Cell surface adenosine deaminase binds and stimulates plasminogen RT activation on 1-LN human prostate cancer cells."; RL J. Biol. Chem. 279:20993-20998(2004). RN [28] RP INTERACTION WITH AMOT. RX PubMed=16043488; DOI=10.1074/jbc.M503915200; RA Bratt A., Birot O., Sinha I., Veitonmaeki N., Aase K., Ernkvist M., RA Holmgren L.; RT "Angiomotin regulates endothelial cell-cell junctions and cell RT motility."; RL J. Biol. Chem. 280:34859-34869(2005). RN [29] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-308. RC TISSUE=Milk; RX PubMed=18780401; DOI=10.1002/pmic.200701057; RA Picariello G., Ferranti P., Mamone G., Roepstorff P., Addeo F.; RT "Identification of N-linked glycoproteins in human milk by hydrophilic RT interaction liquid chromatography and mass spectrometry."; RL Proteomics 8:3833-3847(2008). RN [30] RP CATALYTIC ACTIVITY. RX PubMed=2143188; RA Kirschbaum N.E., Budzynski A.Z.; RT "A unique proteolytic fragment of human fibrinogen containing the A RT alpha COOH-terminal domain of the native molecule."; RL J. Biol. Chem. 265:13669-13676(1990). RN [31] RP INTERACTION WITH HRG. RX PubMed=19712047; DOI=10.1042/BJ20090794; RA Poon I.K., Olsson A.K., Hulett M.D., Parish C.R.; RT "Regulation of histidine-rich glycoprotein (HRG) function via plasmin- RT mediated proteolytic cleavage."; RL Biochem. J. 424:27-37(2009). RN [32] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-688, AND IDENTIFICATION RP BY 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [33] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 374-461. RX PubMed=1657148; DOI=10.1021/bi00107a029; RA Mulichak A.M., Tulinsky A., Ravichandran K.G.; RT "Crystal and molecular structure of human plasminogen kringle 4 RT refined at 1.9-A resolution."; RL Biochemistry 30:10576-10588(1991). RN [34] RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 374-461. RX PubMed=1657149; DOI=10.1021/bi00107a030; RA Wu T.-P., Padmanabhan K., Tulinsky A., Mulichak A.M.; RT "The refined structure of the epsilon-aminocaproic acid complex of RT human plasminogen kringle 4."; RL Biochemistry 30:10589-10594(1991). RN [35] RP X-RAY CRYSTALLOGRAPHY (2.48 ANGSTROMS) OF 101-181. RX PubMed=8054447; RA Wu T.-P., Padmanabhan K.P., Tulinsky A.; RT "The structure of recombinant plasminogen kringle 1 and the fibrin RT binding site."; RL Blood Coagul. Fibrinolysis 5:157-166(1994). RN [36] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 102-181. RX PubMed=8611560; DOI=10.1021/bi9521351; RA Mathews I.I., Vanderhoff-Hanaver P., Castellino F.J., Tulinsky A.; RT "Crystal structures of the recombinant kringle 1 domain of human RT plasminogen in complexes with the ligands epsilon-aminocaproic acid RT and trans-4-(aminomethyl)cyclohexane-1-carboxylic Acid."; RL Biochemistry 35:2567-2576(1996). RN [37] RP X-RAY CRYSTALLOGRAPHY (1.67 ANGSTROMS) OF 376-454. RX PubMed=15299951; DOI=10.1107/S0907444996012267; RA Stec B., Yamano A., Whitlow M., Teeter M.M.; RT "Structure of human plasminogen kringle 4 at 1.68 Angstrom and 277 K. RT A possible structural role of disordered residues."; RL Acta Crystallogr. D 53:169-178(1997). RN [38] RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 561-810, AND DISULFIDE RP BONDS. RX PubMed=9783753; DOI=10.1038/2359; RA Parry M.A., Fernandez-Catalan C., Bergner A., Huber R., Hopfner K.P., RA Schlott B., Guehrs K.H., Bode W.; RT "The ternary microplasmin-staphylokinase-microplasmin complex is a RT proteinase-cofactor-substrate complex in action."; RL Nat. Struct. Biol. 5:917-923(1998). RN [39] RP X-RAY CRYSTALLOGRAPHY (1.66 ANGSTROMS) OF 480-563. RX PubMed=9521645; DOI=10.1021/bi972284e; RA Chang Y., Mochalkin I., McCance S.G., Cheng B., Tulinsky A., RA Castellino F.J.; RT "Structure and ligand binding determinants of the recombinant kringle RT 5 domain of human plasminogen."; RL Biochemistry 37:3258-3271(1998). RN [40] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 564-810, AND DISULFIDE BONDS. RX PubMed=10656799; DOI=10.1006/jmbi.1999.3397; RA Wang X., Terzyan S., Tang J., Loy J.A., Lin X., Zhang X.C.; RT "Human plasminogen catalytic domain undergoes an unusual RT conformational change upon activation."; RL J. Mol. Biol. 295:903-914(2000). RN [41] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 183-262. RX PubMed=11350170; DOI=10.1006/jmbi.2001.4646; RA Rios-Steiner J.L., Schenone M., Mochalkin I., Tulinsky A., RA Castellino F.J.; RT "Structure and binding determinants of the recombinant kringle-2 RT domain of human plasminogen to an internal peptide from a group A RT Streptococcal surface protein."; RL J. Mol. Biol. 308:705-719(2001). RN [42] RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 100-352, AND DISULFIDE RP BONDS. RX PubMed=12054798; DOI=10.1016/S0022-2836(02)00211-5; RA Abad M.C., Arni R.K., Grella D.K., Castellino F.J., Tulinsky A., RA Geiger J.H.; RT "The X-ray crystallographic structure of the angiogenesis inhibitor RT angiostatin."; RL J. Mol. Biol. 318:1009-1017(2002). RN [43] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 562-810. RX PubMed=12456874; DOI=10.1093/protein/15.9.753; RA Wakeham N., Terzyan S., Zhai P., Loy J.A., Tang J., Zhang X.C.; RT "Effects of deletion of streptokinase residues 48-59 on plasminogen RT activation."; RL Protein Eng. 15:753-761(2002). RN [44] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 564-810. RX PubMed=15211511; DOI=10.1002/prot.20070; RA Terzyan S., Wakeham N., Zhai P., Rodgers K., Zhang X.C.; RT "Characterization of Lys-698-to-Met substitution in human plasminogen RT catalytic domain."; RL Proteins 56:277-284(2004). RN [45] RP X-RAY CRYSTALLOGRAPHY (2.78 ANGSTROMS) OF 564-810 IN COMPLEX WITH THE RP SNAKE VENOM PROTEASE INHIBITOR TEXTILININ-1, AND DISULFIDE BOND. RX PubMed=23335990; DOI=10.1371/journal.pone.0054104; RA Millers E.K., Johnson L.A., Birrell G.W., Masci P.P., Lavin M.F., RA de Jersey J., Guddat L.W.; RT "The structure of human microplasmin in complex with textilinin-1, an RT aprotinin-like inhibitor from the Australian brown snake."; RL PLoS ONE 8:E54104-E54104(2013). RN [46] RP STRUCTURE BY NMR OF 374-461. RX PubMed=2157850; DOI=10.1016/0022-2836(90)90330-O; RA Atkinson R.A., Williams R.J.P.; RT "Solution structure of the kringle 4 domain from human plasminogen by RT 1H nuclear magnetic resonance spectroscopy and distance geometry."; RL J. Mol. Biol. 212:541-552(1990). RN [47] RP STRUCTURE BY NMR OF 96-184. RX PubMed=8181475; DOI=10.1111/j.1432-1033.1994.tb18808.x; RA Rejante M.R., Llinas M.; RT "1H-NMR assignments and secondary structure of human plasminogen RT kringle 1."; RL Eur. J. Biochem. 221:927-937(1994). RN [48] RP STRUCTURE BY NMR OF 96-184. RX PubMed=8181476; DOI=10.1111/j.1432-1033.1994.tb18809.x; RA Rejante M.R., Llinas M.; RT "Solution structure of the epsilon-aminohexanoic acid complex of human RT plasminogen kringle 1."; RL Eur. J. Biochem. 221:939-949(1994). RN [49] RP STRUCTURE BY NMR OF 183-354. RX PubMed=8652577; DOI=10.1021/bi9520949; RA Soehndel S., Hu C.-K., Marti D., Affolter M., Schaller J., Llinas M., RA Rickli E.E.; RT "Recombinant gene expression and 1H NMR characteristics of the kringle RT (2 + 3) supermodule: spectroscopic/functional individuality of RT plasminogen kringle domains."; RL Biochemistry 35:2357-2364(1996). RN [50] RP STRUCTURE BY NMR OF 183-263. RX PubMed=9305949; DOI=10.1021/bi971316v; RA Marti D.N., Hu C.K., An S.S., von Haller P., Schaller J., Llinas M.; RT "Ligand preferences of kringle 2 and homologous domains of human RT plasminogen: canvassing weak, intermediate, and high-affinity binding RT sites by 1H-NMR."; RL Biochemistry 36:11591-11604(1997). RN [51] RP VARIANTS PLGD PHE-374 AND THR-620. RX PubMed=1986355; DOI=10.1073/pnas.88.1.115; RA Ichinose A., Espling E.S., Takamatsu J., Saito H., Shinmyozu K., RA Maruyama I., Petersen T.E., Davie E.W.; RT "Two types of abnormal genes for plasminogen in families with a RT predisposition for thrombosis."; RL Proc. Natl. Acad. Sci. U.S.A. 88:115-119(1991). RN [52] RP ERRATUM. RA Ichinose A., Espling E.S., Takamatsu J., Saito H., Shinmyozu K., RA Maruyama I., Petersen T.E., Davie E.W.; RL Proc. Natl. Acad. Sci. U.S.A. 88:2067-2067(1991). RN [53] RP VARIANT PLGD PRO-591. RX PubMed=8392398; RA Azuma H., Uno Y., Shigekiyo T., Saito S.; RT "Congenital plasminogen deficiency caused by a Ser-572 to Pro RT mutation."; RL Blood 82:475-480(1993). RN [54] RP VARIANT PLGD THR-620. RX PubMed=6216475; DOI=10.1073/pnas.79.20.6132; RA Miyata T., Iwanaga S., Sakata Y., Aoki N.; RT "Plasminogen Tochigi: inactive plasmin resulting from replacement of RT alanine-600 by threonine in the active site."; RL Proc. Natl. Acad. Sci. U.S.A. 79:6132-6136(1982). RN [55] RP VARIANT PLGD THR-620. RX PubMed=6238949; RA Miyata T., Iwanaga S., Sakata Y., Aoki N., Takamatsu J., Kamiya T.; RT "Plasminogens Tochigi II and Nagoya: two additional molecular defects RT with Ala-600-->Thr replacement found in plasmin light chain RT variants."; RL J. Biochem. 96:277-287(1984). RN [56] RP VARIANT PLGD THR-620. RX PubMed=1427790; DOI=10.1007/BF00210737; RA Kikuchi S., Yamanouchi Y., Li L., Kobayashi K., Ijima H., Miyazaki R., RA Tsuchiya S., Hamaguchi H.; RT "Plasminogen with type-I mutation is polymorphic in the Japanese RT population."; RL Hum. Genet. 90:7-11(1992). RN [57] RP VARIANT PLGD HIS-235. RX PubMed=9242524; RA Schuster V., Mingers A.-M., Seidenspinner S., Nuessgens Z., Pukrop T., RA Kreth H.W.; RT "Homozygous mutations in the plasminogen gene of two unrelated girls RT with ligneous conjunctivitis."; RL Blood 90:958-966(1997). RN [58] RP VARIANT PLGD ARG-751. RX PubMed=9858247; DOI=10.1046/j.1365-2141.1998.01074.x; RA Higuchi Y., Furihata K., Ueno I., Ishikawa S., Okumura N., Tozuka M., RA Sakurai N.; RT "Plasminogen Kanagawa-I, a novel missense mutation, is caused by the RT amino acid substitution G732R."; RL Br. J. Haematol. 103:867-870(1998). RN [59] RP VARIANTS PLGD GLU-38; PRO-147 AND HIS-532. RX PubMed=10233898; RA Schuster V., Seidenspinner S., Zeitler P., Escher C., Pleyer U., RA Bernauer W., Stiehm E.R., Isenberg S., Seregard S., Olsson T., RA Mingers A.-M., Schambeck C., Kreth H.W.; RT "Compound-heterozygous mutations in the plasminogen gene predispose to RT the development of ligneous conjunctivitis."; RL Blood 93:3457-3466(1999). CC -!- FUNCTION: Plasmin dissolves the fibrin of blood clots and acts as CC a proteolytic factor in a variety of other processes including CC embryonic development, tissue remodeling, tumor invasion, and CC inflammation. In ovulation, weakens the walls of the Graafian CC follicle. It activates the urokinase-type plasminogen activator, CC collagenases and several complement zymogens, such as C1 and C5. CC Cleavage of fibronectin and laminin leads to cell detachment and CC apoptosis. Also cleaves fibrin, thrombospondin and von Willebrand CC factor. Its role in tissue remodeling and tumor invasion may be CC modulated by CSPG4. Binds to cells. {ECO:0000269|PubMed:14699093}. CC -!- FUNCTION: Angiostatin is an angiogenesis inhibitor that blocks CC neovascularization and growth of experimental primary and CC metastatic tumors in vivo. {ECO:0000269|PubMed:14699093}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Preferential cleavage: Lys-|-Xaa > Arg-|-Xaa, higher CC selectivity than trypsin. Converts fibrin into soluble CC products.; EC=3.4.21.7; Evidence={ECO:0000269|PubMed:2143188}; CC -!- ACTIVITY REGULATION: Converted into plasmin by plasminogen CC activators, both plasminogen and its activator being bound to CC fibrin. Activated with catalytic amounts of streptokinase. Plasmin CC activity inhibited by SERPINE2. {ECO:0000269|PubMed:14699093}. CC -!- SUBUNIT: Interacts (both mature PLG and the angiostatin peptide) CC with CSPG4 and AMOT (PubMed:10889192, PubMed:16043488). Interacts CC (via the Kringle domains) with HRG; the interaction tethers PLG to CC the cell surface and enhances its activation (PubMed:9102401, CC PubMed:19712047). Interacts (via Kringle 4 domain) with ADA; the CC interaction stimulates PLG activation when in complex with DPP4 CC (PubMed:15016824). Angiostatin: Interacts with ATP5F1A; the CC interaction inhibits most of the angiogenic effects of angiostatin CC (PubMed:10077593). {ECO:0000269|PubMed:10077593, CC ECO:0000269|PubMed:10889192, ECO:0000269|PubMed:15016824, CC ECO:0000269|PubMed:16043488, ECO:0000269|PubMed:19712047, CC ECO:0000269|PubMed:9102401}. CC -!- INTERACTION: CC Q6V4L1:- (xeno); NbExp=2; IntAct=EBI-999394, EBI-984250; CC Q6V4L4:- (xeno); NbExp=2; IntAct=EBI-999394, EBI-984286; CC Q6V4L5:- (xeno); NbExp=2; IntAct=EBI-999394, EBI-984118; CC Q6V4L9:- (xeno); NbExp=2; IntAct=EBI-999394, EBI-984197; CC P02749:APOH; NbExp=2; IntAct=EBI-999394, EBI-2114682; CC P28300:LOX; NbExp=2; IntAct=EBI-999394, EBI-20724846; CC Q8N4S9:MARVELD2; NbExp=2; IntAct=EBI-999394, EBI-6875061; CC P75390:pdhA (xeno); NbExp=5; IntAct=EBI-999394, EBI-2259629; CC P75391:pdhB (xeno); NbExp=11; IntAct=EBI-999394, EBI-2259621; CC P75392:pdhC (xeno); NbExp=5; IntAct=EBI-999394, EBI-2259593; CC P75393:pdhD (xeno); NbExp=3; IntAct=EBI-999394, EBI-2259617; CC Q99SU7:sak (xeno); NbExp=7; IntAct=EBI-999394, EBI-7689378; CC P00779:skc (xeno); NbExp=2; IntAct=EBI-999394, EBI-1035089; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10077593, CC ECO:0000269|PubMed:14699093}. Note=Locates to the cell surface CC where it is proteolytically cleaved to produce the active plasmin. CC Interaction with HRG tethers it to the cell surface. CC -!- TISSUE SPECIFICITY: Present in plasma and many other extracellular CC fluids. It is synthesized in the liver. CC -!- DOMAIN: Kringle domains mediate interaction with CSPG4. CC {ECO:0000269|PubMed:10889192}. CC -!- PTM: N-linked glycan contains N-acetyllactosamine and sialic acid. CC O-linked glycans consist of Gal-GalNAc disaccharide modified with CC up to 2 sialic acid residues (microheterogeneity). CC {ECO:0000269|PubMed:18780401, ECO:0000269|PubMed:3356193, CC ECO:0000269|PubMed:9054441}. CC -!- PTM: In the presence of the inhibitor, the activation involves CC only cleavage after Arg-580, yielding two chains held together by CC two disulfide bonds. In the absence of the inhibitor, the CC activation involves additionally the removal of the activation CC peptide. {ECO:0000269|PubMed:14699093, CC ECO:0000269|PubMed:9548733}. CC -!- DISEASE: Plasminogen deficiency (PLGD) [MIM:217090]: A disorder CC characterized by decreased serum plasminogen activity. Two forms CC of the disorder are distinguished: type 1 deficiency is CC additionally characterized by decreased plasminogen antigen levels CC and clinical symptoms, whereas type 2 deficiency, also known as CC dysplasminogenemia, is characterized by normal, or slightly CC reduced antigen levels, and absence of clinical manifestations. CC Plasminogen deficiency type 1 results in markedly impaired CC extracellular fibrinolysis and chronic mucosal pseudomembranous CC lesions due to subepithelial fibrin deposition and inflammation. CC The most common clinical manifestation of type 1 deficiency is CC ligneous conjunctivitis in which pseudomembranes formation on the CC palpebral surfaces of the eye progresses to white, yellow-white, CC or red thick masses with a wood-like consistency that replace the CC normal mucosa. {ECO:0000269|PubMed:10233898, CC ECO:0000269|PubMed:1427790, ECO:0000269|PubMed:1986355, CC ECO:0000269|PubMed:6216475, ECO:0000269|PubMed:6238949, CC ECO:0000269|PubMed:8392398, ECO:0000269|PubMed:9242524, CC ECO:0000269|PubMed:9858247}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Plasmin is inactivated by alpha-2-antiplasmin CC immediately after dissociation from the clot. CC -!- SIMILARITY: Belongs to the peptidase S1 family. Plasminogen CC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00274}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Plasmin entry; CC URL="https://en.wikipedia.org/wiki/Plasmin"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/plg/"; 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; M34276; AAA60113.1; -; Genomic_DNA. DR EMBL; M33272; AAA60113.1; JOINED; Genomic_DNA. DR EMBL; M33274; AAA60113.1; JOINED; Genomic_DNA. DR EMBL; M33275; AAA60113.1; JOINED; Genomic_DNA. DR EMBL; M33278; AAA60113.1; JOINED; Genomic_DNA. DR EMBL; M33279; AAA60113.1; JOINED; Genomic_DNA. DR EMBL; M33280; AAA60113.1; JOINED; Genomic_DNA. DR EMBL; M33282; AAA60113.1; JOINED; Genomic_DNA. DR EMBL; M33283; AAA60113.1; JOINED; Genomic_DNA. DR EMBL; M33284; AAA60113.1; JOINED; Genomic_DNA. DR EMBL; M33285; AAA60113.1; JOINED; Genomic_DNA. DR EMBL; M33286; AAA60113.1; JOINED; Genomic_DNA. DR EMBL; M33287; AAA60113.1; JOINED; Genomic_DNA. DR EMBL; M33288; AAA60113.1; JOINED; Genomic_DNA. DR EMBL; M33289; AAA60113.1; JOINED; Genomic_DNA. DR EMBL; M33290; AAA60113.1; JOINED; Genomic_DNA. DR EMBL; M34272; AAA60113.1; JOINED; Genomic_DNA. DR EMBL; M34273; AAA60113.1; JOINED; Genomic_DNA. DR EMBL; M34275; AAA60113.1; JOINED; Genomic_DNA. DR EMBL; X05199; CAA28831.1; -; mRNA. DR EMBL; M74220; AAA36451.1; -; mRNA. DR EMBL; AY192161; AAN85555.1; -; Genomic_DNA. DR EMBL; AL109933; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC060513; AAH60513.1; -; mRNA. DR EMBL; K02922; AAA60124.1; -; mRNA. DR CCDS; CCDS5279.1; -. DR PIR; A35229; PLHU. DR RefSeq; NP_000292.1; NM_000301.3. DR UniGene; Hs.143436; -. DR PDB; 1B2I; NMR; -; A=181-263. DR PDB; 1BML; X-ray; 2.90 A; A/B=561-810. DR PDB; 1BUI; X-ray; 2.65 A; A/B=561-810. DR PDB; 1CEA; X-ray; 2.06 A; A/B=100-187. DR PDB; 1CEB; X-ray; 2.07 A; A/B=100-187. DR PDB; 1DDJ; X-ray; 2.00 A; A/B/C/D=564-810. DR PDB; 1HPJ; NMR; -; A=103-181. DR PDB; 1HPK; NMR; -; A=103-181. DR PDB; 1I5K; X-ray; 2.70 A; A/B=184-262. DR PDB; 1KI0; X-ray; 1.75 A; A=100-352. DR PDB; 1KRN; X-ray; 1.67 A; A=374-461. DR PDB; 1L4D; X-ray; 2.30 A; A=562-810. DR PDB; 1L4Z; X-ray; 2.80 A; A=563-810. DR PDB; 1PK4; X-ray; 1.90 A; A=376-454. DR PDB; 1PKR; X-ray; 2.48 A; A=101-181. DR PDB; 1PMK; X-ray; 2.25 A; A/B=374-461. DR PDB; 1QRZ; X-ray; 2.00 A; A/B/C/D=565-810. DR PDB; 1RJX; X-ray; 2.30 A; B=564-810. DR PDB; 2DOH; X-ray; 2.30 A; X=100-333. DR PDB; 2DOI; X-ray; 3.10 A; A/X=100-333. DR PDB; 2KNF; NMR; -; A=480-562. DR PDB; 2L0S; NMR; -; A=272-354. DR PDB; 2PK4; X-ray; 2.25 A; A=375-454. DR PDB; 3UIR; X-ray; 2.78 A; A/B=564-810. DR PDB; 4A5T; X-ray; 3.49 A; S=20-810. DR PDB; 4CIK; X-ray; 1.78 A; A=101-181. DR PDB; 4DCB; X-ray; 2.03 A; F=576-585. DR PDB; 4DUR; X-ray; 2.45 A; A/B=20-810. DR PDB; 4DUU; X-ray; 5.20 A; A=20-810. DR PDB; 5HPG; X-ray; 1.66 A; A/B=480-563. DR PDB; 5UGD; X-ray; 1.38 A; A=562-810. DR PDB; 5UGG; X-ray; 1.20 A; A=562-810. DR PDBsum; 1B2I; -. DR PDBsum; 1BML; -. DR PDBsum; 1BUI; -. DR PDBsum; 1CEA; -. DR PDBsum; 1CEB; -. DR PDBsum; 1DDJ; -. DR PDBsum; 1HPJ; -. DR PDBsum; 1HPK; -. DR PDBsum; 1I5K; -. DR PDBsum; 1KI0; -. DR PDBsum; 1KRN; -. DR PDBsum; 1L4D; -. DR PDBsum; 1L4Z; -. DR PDBsum; 1PK4; -. DR PDBsum; 1PKR; -. DR PDBsum; 1PMK; -. DR PDBsum; 1QRZ; -. DR PDBsum; 1RJX; -. DR PDBsum; 2DOH; -. DR PDBsum; 2DOI; -. DR PDBsum; 2KNF; -. DR PDBsum; 2L0S; -. DR PDBsum; 2PK4; -. DR PDBsum; 3UIR; -. DR PDBsum; 4A5T; -. DR PDBsum; 4CIK; -. DR PDBsum; 4DCB; -. DR PDBsum; 4DUR; -. DR PDBsum; 4DUU; -. DR PDBsum; 5HPG; -. DR PDBsum; 5UGD; -. DR PDBsum; 5UGG; -. DR DisProt; DP00191; -. DR ProteinModelPortal; P00747; -. DR SMR; P00747; -. DR BioGrid; 111356; 38. DR CORUM; P00747; -. DR IntAct; P00747; 46. DR MINT; P00747; -. DR STRING; 9606.ENSP00000308938; -. DR BindingDB; P00747; -. DR ChEMBL; CHEMBL1801; -. DR DrugBank; DB00009; Alteplase. DR DrugBank; DB00513; Aminocaproic Acid. DR DrugBank; DB00029; Anistreplase. DR DrugBank; DB06692; Aprotinin. DR DrugBank; DB03709; Bicine. DR DrugBank; DB04925; Desmoteplase. DR DrugBank; DB00015; Reteplase. DR DrugBank; DB00086; Streptokinase. DR DrugBank; DB00031; Tenecteplase. DR DrugBank; DB00302; Tranexamic Acid. DR DrugBank; DB00013; Urokinase. DR GuidetoPHARMACOLOGY; 2394; -. DR MEROPS; S01.233; -. DR GlyConnect; 502; -. DR iPTMnet; P00747; -. DR PhosphoSitePlus; P00747; -. DR UniCarbKB; P00747; -. DR BioMuta; PLG; -. DR DMDM; 130316; -. DR SWISS-2DPAGE; P00747; -. DR jPOST; P00747; -. DR MaxQB; P00747; -. DR PaxDb; P00747; -. DR PeptideAtlas; P00747; -. DR PRIDE; P00747; -. DR ProteomicsDB; 51277; -. DR Ensembl; ENST00000308192; ENSP00000308938; ENSG00000122194. DR GeneID; 5340; -. DR KEGG; hsa:5340; -. DR UCSC; uc003qtm.5; human. DR CTD; 5340; -. DR DisGeNET; 5340; -. DR EuPathDB; HostDB:ENSG00000122194.18; -. DR GeneCards; PLG; -. DR HGNC; HGNC:9071; PLG. DR HPA; CAB000668; -. DR HPA; CAB016678; -. DR HPA; HPA021602; -. DR HPA; HPA048823; -. DR HPA; HPA053770; -. DR MalaCards; PLG; -. DR MIM; 173350; gene. DR MIM; 217090; phenotype. DR neXtProt; NX_P00747; -. DR OpenTargets; ENSG00000122194; -. DR Orphanet; 722; Hypoplasminogenemia. DR Orphanet; 97231; Ligneous conjunctivitis. DR PharmGKB; PA33405; -. DR eggNOG; ENOG410IDXR; Eukaryota. DR eggNOG; COG5640; LUCA. DR GeneTree; ENSGT00940000155208; -. DR HOGENOM; HOG000112892; -. DR HOVERGEN; HBG004381; -. DR InParanoid; P00747; -. DR KO; K01315; -. DR OMA; SGHTCQR; -. DR OrthoDB; 1058295at2759; -. DR PhylomeDB; P00747; -. DR TreeFam; TF329901; -. DR BioCyc; MetaCyc:HS04553-MONOMER; -. DR BRENDA; 3.4.21.7; 2681. DR Reactome; R-HSA-114608; Platelet degranulation. DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix. DR Reactome; R-HSA-1592389; Activation of Matrix Metalloproteinases. DR Reactome; R-HSA-186797; Signaling by PDGF. 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-75205; Dissolution of Fibrin Clot. DR SABIO-RK; P00747; -. DR SIGNOR; P00747; -. DR ChiTaRS; PLG; human. DR EvolutionaryTrace; P00747; -. DR GeneWiki; Plasmin; -. DR GeneWiki; Plasminogen_activator; -. DR GenomeRNAi; 5340; -. DR PMAP-CutDB; P00747; -. DR PRO; PR:P00747; -. DR Proteomes; UP000005640; Chromosome 6. DR Bgee; ENSG00000122194; Expressed in 101 organ(s), highest expression level in right lobe of liver. DR ExpressionAtlas; P00747; baseline and differential. DR Genevisible; P00747; HS. DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB. DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL. DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA: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; IDA:CAFA. DR GO; GO:0031232; C:extrinsic component of external side of plasma membrane; IDA:BHF-UCL. DR GO; GO:0044218; C:other organism cell membrane; IDA:CAFA. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome. DR GO; GO:0034185; F:apolipoprotein binding; IPI:BHF-UCL. DR GO; GO:0051087; F:chaperone binding; IPI:CAFA. DR GO; GO:0004175; F:endopeptidase activity; IDA:CAFA. DR GO; GO:0019899; F:enzyme binding; IPI:CAFA. DR GO; GO:0019900; F:kinase binding; IPI:CAFA. DR GO; GO:1904854; F:proteasome core complex binding; IPI:CAFA. DR GO; GO:1990405; F:protein antigen binding; IPI:CAFA. DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB. DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:CAFA. DR GO; GO:0008236; F:serine-type peptidase activity; TAS:AgBase. DR GO; GO:0005102; F:signaling receptor binding; IPI:AgBase. DR GO; GO:0007596; P:blood coagulation; IMP:HGNC. DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome. DR GO; GO:0022617; P:extracellular matrix disassembly; IDA:BHF-UCL. DR GO; GO:0042730; P:fibrinolysis; IDA:CAFA. DR GO; GO:0051702; P:interaction with symbiont; IDA:CAFA. DR GO; GO:0052213; P:interaction with symbiont via secreted substance involved in symbiotic interaction; IDA:CAFA. DR GO; GO:0052182; P:modification by host of symbiont morphology or physiology via secreted substance; IDA:CAFA. DR GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:ProtInc. DR GO; GO:2000048; P:negative regulation of cell-cell adhesion mediated by cadherin; TAS:BHF-UCL. DR GO; GO:0010812; P:negative regulation of cell-substrate adhesion; IDA:BHF-UCL. DR GO; GO:0051918; P:negative regulation of fibrinolysis; IDA:BHF-UCL. DR GO; GO:0002576; P:platelet degranulation; TAS:Reactome. DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IGI:CAFA. DR GO; GO:0051919; P:positive regulation of fibrinolysis; IDA:AgBase. DR GO; GO:0006508; P:proteolysis; IDA:CAFA. DR GO; GO:0048771; P:tissue remodeling; IEA:UniProtKB-KW. DR CDD; cd00108; KR; 5. DR CDD; cd00190; Tryp_SPc; 1. DR Gene3D; 2.40.20.10; -; 4. DR InterPro; IPR000001; Kringle. DR InterPro; IPR013806; Kringle-like. DR InterPro; IPR018056; Kringle_CS. DR InterPro; IPR038178; Kringle_sf. DR InterPro; IPR003609; Pan_app. DR InterPro; IPR023317; Pept_S1A_plasmin. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; IPR001314; Peptidase_S1A. DR InterPro; IPR001254; Trypsin_dom. DR InterPro; IPR018114; TRYPSIN_HIS. DR InterPro; IPR033116; TRYPSIN_SER. DR Pfam; PF00051; Kringle; 5. DR Pfam; PF00024; PAN_1; 1. DR Pfam; PF00089; Trypsin; 1. DR PIRSF; PIRSF001150; Plasmin; 1. DR PRINTS; PR00722; CHYMOTRYPSIN. DR SMART; SM00130; KR; 5. DR SMART; SM00473; PAN_AP; 1. DR SMART; SM00020; Tryp_SPc; 1. DR SUPFAM; SSF50494; SSF50494; 1. DR SUPFAM; SSF57440; SSF57440; 5. DR PROSITE; PS00021; KRINGLE_1; 5. DR PROSITE; PS50070; KRINGLE_2; 5. DR PROSITE; PS50948; PAN; 1. 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; Blood coagulation; Cleavage on pair of basic residues; KW Complete proteome; Direct protein sequencing; Disease mutation; KW Disulfide bond; Fibrinolysis; Glycoprotein; Hemostasis; Hydrolase; KW Kringle; Phosphoprotein; Polymorphism; Protease; Reference proteome; KW Repeat; Secreted; Serine protease; Signal; Thrombophilia; KW Tissue remodeling; Zymogen. FT SIGNAL 1 19 {ECO:0000269|PubMed:122932, FT ECO:0000269|Ref.7}. FT CHAIN 20 810 Plasminogen. FT /FTId=PRO_0000028053. FT CHAIN 20 580 Plasmin heavy chain A. FT /FTId=PRO_0000028054. FT PEPTIDE 20 97 Activation peptide. FT /FTId=PRO_0000028055. FT CHAIN 79 466 Angiostatin. FT /FTId=PRO_0000028057. FT CHAIN 98 580 Plasmin heavy chain A, short form. FT /FTId=PRO_0000028056. FT CHAIN 581 810 Plasmin light chain B. FT /FTId=PRO_0000028058. FT DOMAIN 20 98 PAN. {ECO:0000255|PROSITE- FT ProRule:PRU00315}. FT DOMAIN 103 181 Kringle 1. {ECO:0000255|PROSITE- FT ProRule:PRU00121}. FT DOMAIN 184 262 Kringle 2. {ECO:0000255|PROSITE- FT ProRule:PRU00121}. FT DOMAIN 275 352 Kringle 3. {ECO:0000255|PROSITE- FT ProRule:PRU00121}. FT DOMAIN 377 454 Kringle 4. {ECO:0000255|PROSITE- FT ProRule:PRU00121}. FT DOMAIN 481 560 Kringle 5. {ECO:0000255|PROSITE- FT ProRule:PRU00121}. FT DOMAIN 581 808 Peptidase S1. {ECO:0000255|PROSITE- FT ProRule:PRU00274}. FT ACT_SITE 622 622 Charge relay system. FT ACT_SITE 665 665 Charge relay system. FT ACT_SITE 760 760 Charge relay system. FT BINDING 134 134 Fibrin. FT BINDING 136 136 Fibrin. FT BINDING 136 136 Omega-aminocarboxylic acids. FT BINDING 158 158 Omega-aminocarboxylic acids. FT BINDING 172 172 Omega-aminocarboxylic acids. FT BINDING 432 432 Omega-aminocarboxylic acids. FT BINDING 445 445 Omega-aminocarboxylic acids. FT SITE 78 79 Cleavage; by stromelysin-1. FT SITE 466 467 Cleavage; by stromelysin-19. FT SITE 580 581 Cleavage; by plasminogen activator. FT MOD_RES 597 597 Phosphoserine. FT {ECO:0000269|PubMed:9201958}. FT MOD_RES 688 688 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT CARBOHYD 268 268 O-linked (GalNAc...) serine. FT {ECO:0000269|PubMed:3356193, FT ECO:0000269|PubMed:9054441}. FT /FTId=CAR_000016. FT CARBOHYD 308 308 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:18780401, FT ECO:0000269|PubMed:3356193}. FT /FTId=CAR_000017. FT CARBOHYD 365 365 O-linked (GalNAc...) threonine. FT {ECO:0000269|PubMed:3356193}. FT /FTId=CAR_000018. FT DISULFID 49 73 FT DISULFID 53 61 FT DISULFID 103 181 FT DISULFID 124 164 FT DISULFID 152 176 FT DISULFID 185 262 FT DISULFID 188 316 FT DISULFID 206 245 FT DISULFID 234 257 FT DISULFID 275 352 FT DISULFID 296 335 FT DISULFID 324 347 FT DISULFID 377 454 FT DISULFID 398 437 FT DISULFID 426 449 FT DISULFID 481 560 FT DISULFID 502 543 FT DISULFID 531 555 FT DISULFID 567 685 Interchain (between A and B chains). FT DISULFID 577 585 Interchain (between A and B chains). FT DISULFID 607 623 FT DISULFID 699 766 FT DISULFID 729 745 FT DISULFID 756 784 FT VARIANT 38 38 K -> E (in PLGD; common mutation; FT dbSNP:rs73015965). FT {ECO:0000269|PubMed:10233898}. FT /FTId=VAR_018657. FT VARIANT 46 46 I -> R (in dbSNP:rs1049573). FT /FTId=VAR_011779. FT VARIANT 57 57 E -> K (in dbSNP:rs4252070). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_016287. FT VARIANT 133 133 H -> Q (in dbSNP:rs4252186). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_016288. FT VARIANT 147 147 L -> P (in PLGD; dbSNP:rs770198253). FT {ECO:0000269|PubMed:10233898}. FT /FTId=VAR_018658. FT VARIANT 235 235 R -> H (in PLGD; severe type 1 FT deficiency; dbSNP:rs121918030). FT {ECO:0000269|PubMed:9242524}. FT /FTId=VAR_018659. FT VARIANT 261 261 R -> H (in dbSNP:rs4252187). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_016289. FT VARIANT 374 374 V -> F (in PLGD; Nagoya-1; FT dbSNP:rs121918028). FT {ECO:0000269|PubMed:1986355}. FT /FTId=VAR_006627. FT VARIANT 408 408 R -> W (in dbSNP:rs4252119). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_016290. FT VARIANT 453 453 K -> I (in dbSNP:rs1804181). FT /FTId=VAR_011780. FT VARIANT 472 472 D -> N (in dbSNP:rs4252125). FT {ECO:0000269|PubMed:2318848, FT ECO:0000269|Ref.4, ECO:0000269|Ref.7, FT ECO:0000269|Ref.9}. FT /FTId=VAR_016291. FT VARIANT 494 494 A -> V (in dbSNP:rs4252128). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_016292. FT VARIANT 523 523 R -> W (in dbSNP:rs4252129). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_016293. FT VARIANT 532 532 R -> H (in PLGD). FT {ECO:0000269|PubMed:10233898}. FT /FTId=VAR_018660. FT VARIANT 591 591 S -> P (in PLGD; may be associated with FT susceptibility to thrombosis; FT dbSNP:rs121918029). FT {ECO:0000269|PubMed:8392398}. FT /FTId=VAR_006628. FT VARIANT 620 620 A -> T (in PLGD; type 2 plasminogen FT deficiency; decreased activity; Nagoya-2/ FT Tochigi/Kagoshima; may be associated with FT susceptibility to thrombosis; FT dbSNP:rs121918027). FT {ECO:0000269|PubMed:1427790, FT ECO:0000269|PubMed:1986355, FT ECO:0000269|PubMed:6216475, FT ECO:0000269|PubMed:6238949}. FT /FTId=VAR_006629. FT VARIANT 676 676 V -> D (in dbSNP:rs17857492). FT {ECO:0000269|PubMed:15489334}. FT /FTId=VAR_031213. FT VARIANT 751 751 G -> R (in PLGD; Kanagawa-1; 50% FT activity; dbSNP:rs121918033). FT {ECO:0000269|PubMed:9858247}. FT /FTId=VAR_006630. FT MUTAGEN 741 741 S->A: Proteolytically cleaved, but FT abolishes plasmin activity and cell FT detachment. FT {ECO:0000269|PubMed:14699093}. FT CONFLICT 50 50 A -> AQ (in Ref. 8; AA sequence). FT {ECO:0000305}. FT CONFLICT 72 72 Q -> E (in Ref. 7; AA sequence and 8; AA FT sequence). {ECO:0000305}. FT CONFLICT 86 86 Missing (in Ref. 7; AA sequence and 8; AA FT sequence). {ECO:0000305}. FT CONFLICT 361 361 Q -> E (in Ref. 7; AA sequence and 9; AA FT sequence). {ECO:0000305}. FT CONFLICT 701 701 I -> V (in Ref. 3; AAA36451). FT {ECO:0000305}. FT STRAND 25 33 {ECO:0000244|PDB:4DUR}. FT STRAND 36 42 {ECO:0000244|PDB:4DUR}. FT HELIX 46 55 {ECO:0000244|PDB:4DUR}. FT STRAND 57 59 {ECO:0000244|PDB:4DUR}. FT STRAND 63 67 {ECO:0000244|PDB:4DUR}. FT TURN 68 71 {ECO:0000244|PDB:4DUR}. FT STRAND 72 77 {ECO:0000244|PDB:4DUR}. FT TURN 80 82 {ECO:0000244|PDB:4DUR}. FT STRAND 85 96 {ECO:0000244|PDB:4DUR}. FT HELIX 97 99 {ECO:0000244|PDB:4DUR}. FT STRAND 102 104 {ECO:0000244|PDB:1KI0}. FT STRAND 105 110 {ECO:0000244|PDB:1HPJ}. FT HELIX 113 115 {ECO:0000244|PDB:1HPJ}. FT TURN 119 121 {ECO:0000244|PDB:1HPJ}. FT STRAND 131 133 {ECO:0000244|PDB:1KI0}. FT TURN 139 141 {ECO:0000244|PDB:1KI0}. FT TURN 143 146 {ECO:0000244|PDB:4CIK}. FT STRAND 148 150 {ECO:0000244|PDB:1HPJ}. FT STRAND 155 157 {ECO:0000244|PDB:1HPK}. FT STRAND 163 167 {ECO:0000244|PDB:1KI0}. FT STRAND 172 175 {ECO:0000244|PDB:1KI0}. FT STRAND 180 182 {ECO:0000244|PDB:2DOH}. FT STRAND 184 186 {ECO:0000244|PDB:1KI0}. FT STRAND 205 207 {ECO:0000244|PDB:1I5K}. FT STRAND 209 211 {ECO:0000244|PDB:1B2I}. FT STRAND 213 215 {ECO:0000244|PDB:1KI0}. FT TURN 221 223 {ECO:0000244|PDB:1KI0}. FT HELIX 225 227 {ECO:0000244|PDB:2DOH}. FT STRAND 237 239 {ECO:0000244|PDB:1KI0}. FT STRAND 244 248 {ECO:0000244|PDB:1KI0}. FT STRAND 253 256 {ECO:0000244|PDB:1KI0}. FT STRAND 273 276 {ECO:0000244|PDB:1KI0}. FT STRAND 281 283 {ECO:0000244|PDB:2L0S}. FT STRAND 291 293 {ECO:0000244|PDB:2L0S}. FT STRAND 295 297 {ECO:0000244|PDB:4DUR}. FT STRAND 303 305 {ECO:0000244|PDB:2L0S}. FT TURN 311 313 {ECO:0000244|PDB:1KI0}. FT HELIX 315 317 {ECO:0000244|PDB:1KI0}. FT STRAND 334 339 {ECO:0000244|PDB:1KI0}. FT STRAND 343 346 {ECO:0000244|PDB:1KI0}. FT STRAND 377 379 {ECO:0000244|PDB:4DUR}. FT STRAND 382 384 {ECO:0000244|PDB:4DUR}. FT STRAND 405 407 {ECO:0000244|PDB:1PK4}. FT TURN 413 415 {ECO:0000244|PDB:1KRN}. FT TURN 417 419 {ECO:0000244|PDB:2PK4}. FT STRAND 429 431 {ECO:0000244|PDB:1PMK}. FT STRAND 436 441 {ECO:0000244|PDB:1KRN}. FT STRAND 446 450 {ECO:0000244|PDB:1KRN}. FT STRAND 460 462 {ECO:0000244|PDB:4DUR}. FT STRAND 481 483 {ECO:0000244|PDB:2KNF}. FT STRAND 487 489 {ECO:0000244|PDB:4DUR}. FT STRAND 509 511 {ECO:0000244|PDB:5HPG}. FT STRAND 514 516 {ECO:0000244|PDB:5HPG}. FT TURN 518 520 {ECO:0000244|PDB:5HPG}. FT TURN 522 525 {ECO:0000244|PDB:4DUR}. FT STRAND 542 546 {ECO:0000244|PDB:5HPG}. FT STRAND 552 554 {ECO:0000244|PDB:5HPG}. FT STRAND 582 586 {ECO:0000244|PDB:5UGG}. FT STRAND 595 600 {ECO:0000244|PDB:5UGG}. FT STRAND 605 613 {ECO:0000244|PDB:5UGG}. FT STRAND 616 619 {ECO:0000244|PDB:5UGG}. FT HELIX 621 623 {ECO:0000244|PDB:5UGG}. FT TURN 624 626 {ECO:0000244|PDB:5UGG}. FT HELIX 630 632 {ECO:0000244|PDB:5UGG}. FT STRAND 633 638 {ECO:0000244|PDB:5UGG}. FT STRAND 640 644 {ECO:0000244|PDB:5UGG}. FT STRAND 650 659 {ECO:0000244|PDB:5UGG}. FT TURN 661 663 {ECO:0000244|PDB:1QRZ}. FT STRAND 667 673 {ECO:0000244|PDB:5UGG}. FT STRAND 698 704 {ECO:0000244|PDB:5UGG}. FT STRAND 708 710 {ECO:0000244|PDB:1DDJ}. FT TURN 711 714 {ECO:0000244|PDB:1DDJ}. FT STRAND 717 724 {ECO:0000244|PDB:5UGG}. FT HELIX 726 729 {ECO:0000244|PDB:5UGG}. FT TURN 732 737 {ECO:0000244|PDB:5UGG}. FT STRAND 743 746 {ECO:0000244|PDB:5UGG}. FT STRAND 749 751 {ECO:0000244|PDB:1DDJ}. FT STRAND 752 754 {ECO:0000244|PDB:1BML}. FT STRAND 763 768 {ECO:0000244|PDB:5UGG}. FT STRAND 771 780 {ECO:0000244|PDB:5UGG}. FT STRAND 782 785 {ECO:0000244|PDB:5UGG}. FT STRAND 791 795 {ECO:0000244|PDB:5UGG}. FT HELIX 796 799 {ECO:0000244|PDB:5UGG}. FT HELIX 800 809 {ECO:0000244|PDB:5UGG}. SQ SEQUENCE 810 AA; 90569 MW; 8B31CB877CCB3AB6 CRC64; MEHKEVVLLL LLFLKSGQGE PLDDYVNTQG ASLFSVTKKQ LGAGSIEECA AKCEEDEEFT CRAFQYHSKE QQCVIMAENR KSSIIIRMRD VVLFEKKVYL SECKTGNGKN YRGTMSKTKN GITCQKWSST SPHRPRFSPA THPSEGLEEN YCRNPDNDPQ GPWCYTTDPE KRYDYCDILE CEEECMHCSG ENYDGKISKT MSGLECQAWD SQSPHAHGYI PSKFPNKNLK KNYCRNPDRE LRPWCFTTDP NKRWELCDIP RCTTPPPSSG PTYQCLKGTG ENYRGNVAVT VSGHTCQHWS AQTPHTHNRT PENFPCKNLD ENYCRNPDGK RAPWCHTTNS QVRWEYCKIP SCDSSPVSTE QLAPTAPPEL TPVVQDCYHG DGQSYRGTSS TTTTGKKCQS WSSMTPHRHQ KTPENYPNAG LTMNYCRNPD ADKGPWCFTT DPSVRWEYCN LKKCSGTEAS VVAPPPVVLL PDVETPSEED CMFGNGKGYR GKRATTVTGT PCQDWAAQEP HRHSIFTPET NPRAGLEKNY CRNPDGDVGG PWCYTTNPRK LYDYCDVPQC AAPSFDCGKP QVEPKKCPGR VVGGCVAHPH SWPWQVSLRT RFGMHFCGGT LISPEWVLTA AHCLEKSPRP SSYKVILGAH QEVNLEPHVQ EIEVSRLFLE PTRKDIALLK LSSPAVITDK VIPACLPSPN YVVADRTECF ITGWGETQGT FGAGLLKEAQ LPVIENKVCN RYEFLNGRVQ STELCAGHLA GGTDSCQGDS GGPLVCFEKD KYILQGVTSW GLGCARPNKP GVYVRVSRFV TWIEGVMRNN //