RBCC

Full text data of PLG

PLG [Confidence: low (only semi-automatic identification from reviews)]
Plasminogen; 3.4.21.7; Plasmin heavy chain A; Activation peptide; Angiostatin; Plasmin heavy chain A, short form; Plasmin light chain B; Flags: Precursor
Note: presumably soluble (membrane word is not in UniProt keywords or features)

UniProt P00747
ID PLMN_HUMAN Reviewed; 810 AA.
AC P00747; Q15146; Q5TEH4; Q6PA00;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUL-1989, sequence version 2.
DT 22-JAN-2014, entry version 186.
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 ATP5A1, 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, ENZYME 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 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 [28]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-308, AND MASS
RP SPECTROMETRY.
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 [29]
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 [30]
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 [31]
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 [32]
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 [33]
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 [34]
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 [35]
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 [36]
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 [37]
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 [38]
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 [39]
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 [40]
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 [41]
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 [42]
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 [43]
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 [44]
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 [45]
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 [46]
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 [47]
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 [48]
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 [49]
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 [50]
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 [51]
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 [52]
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 [53]
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 [54]
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 [55]
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 [56]
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.
CC -!- FUNCTION: Angiostatin is an angiogenesis inhibitor that blocks
CC neovascularization and growth of experimental primary and
CC metastatic tumors in vivo.
CC -!- CATALYTIC ACTIVITY: Preferential cleavage: Lys-|-Xaa > Arg-|-Xaa;
CC higher selectivity than trypsin. Converts fibrin into soluble
CC products.
CC -!- ENZYME 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.
CC -!- SUBUNIT: Interacts (both mature PLG and the angiostatin peptide)
CC with CSPG4 and AMOT. Interacts (via the Kringle domains) with HRG;
CC the interaction tethers PLG to the cell surface and enhances its
CC activation (By similarity).
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 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. 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 -!- 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 -!- 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.
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. Note=The disease is caused by mutations affecting
CC 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.
CC -!- SIMILARITY: Contains 5 kringle domains.
CC -!- SIMILARITY: Contains 1 PAN domain.
CC -!- SIMILARITY: Contains 1 peptidase S1 domain.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Plasmin entry;
CC URL="http://en.wikipedia.org/wiki/Plasmin";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/plg/";
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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; CAI22908.1; -; Genomic_DNA.
DR EMBL; BC060513; AAH60513.1; -; mRNA.
DR EMBL; K02922; AAA60124.1; -; mRNA.
DR PIR; A35229; PLHU.
DR RefSeq; NP_000292.1; NM_000301.3.
DR UniGene; Hs.143436; -.
DR PDB; 1B2I; NMR; -; A=183-263.
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=183-262.
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; 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 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; 4DCB; -.
DR PDBsum; 4DUR; -.
DR PDBsum; 4DUU; -.
DR PDBsum; 5HPG; -.
DR DisProt; DP00191; -.
DR ProteinModelPortal; P00747; -.
DR SMR; P00747; 20-810.
DR IntAct; P00747; 28.
DR STRING; 9606.ENSP00000308938; -.
DR BindingDB; P00747; -.
DR ChEMBL; CHEMBL1801; -.
DR DrugBank; DB00513; Aminocaproic Acid.
DR DrugBank; DB00086; Streptokinase.
DR DrugBank; DB00302; Tranexamic Acid.
DR DrugBank; DB00013; Urokinase.
DR GuidetoPHARMACOLOGY; 2394; -.
DR MEROPS; S01.233; -.
DR PhosphoSite; P00747; -.
DR UniCarbKB; P00747; -.
DR DMDM; 130316; -.
DR SWISS-2DPAGE; P00747; -.
DR PeptideAtlas; P00747; -.
DR PRIDE; P00747; -.
DR Ensembl; ENST00000308192; ENSP00000308938; ENSG00000122194.
DR GeneID; 5340; -.
DR KEGG; hsa:5340; -.
DR UCSC; uc003qtm.4; human.
DR CTD; 5340; -.
DR GeneCards; GC06P161123; -.
DR HGNC; HGNC:9071; PLG.
DR HPA; CAB000668; -.
DR HPA; CAB016678; -.
DR HPA; HPA021602; -.
DR MIM; 173350; gene.
DR MIM; 217090; phenotype.
DR neXtProt; NX_P00747; -.
DR Orphanet; 722; Hypoplasminogenemia.
DR Orphanet; 97231; Ligneous conjunctivitis.
DR PharmGKB; PA33405; -.
DR HOGENOM; HOG000112892; -.
DR HOVERGEN; HBG004381; -.
DR InParanoid; P00747; -.
DR KO; K01315; -.
DR OMA; EGLEENY; -.
DR OrthoDB; EOG75B84T; -.
DR PhylomeDB; P00747; -.
DR BioCyc; MetaCyc:HS04553-MONOMER; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_604; Hemostasis.
DR SABIO-RK; P00747; -.
DR EvolutionaryTrace; P00747; -.
DR GeneWiki; Plasmin; -.
DR GeneWiki; Plasminogen_activator; -.
DR GenomeRNAi; 5340; -.
DR NextBio; 20698; -.
DR PMAP-CutDB; P00747; -.
DR PRO; PR:P00747; -.
DR ArrayExpress; P00747; -.
DR Bgee; P00747; -.
DR CleanEx; HS_PLG; -.
DR Genevestigator; P00747; -.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0031232; C:extrinsic to external side of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:BHF-UCL.
DR GO; GO:0006915; P:apoptotic process; IEA:Ensembl.
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; TAS:Reactome.
DR GO; GO:0060716; P:labyrinthine layer blood vessel development; IEA:Ensembl.
DR GO; GO:0071674; P:mononuclear cell migration; IEA:Ensembl.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; IEA:Ensembl.
DR GO; GO:0045445; P:myoblast differentiation; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell 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:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0002576; P:platelet degranulation; TAS:Reactome.
DR GO; GO:0051919; P:positive regulation of fibrinolysis; IDA:BHF-UCL.
DR GO; GO:0051603; P:proteolysis involved in cellular protein catabolic process; IEA:Ensembl.
DR GO; GO:0042246; P:tissue regeneration; IEA:Ensembl.
DR GO; GO:0048771; P:tissue remodeling; IEA:UniProtKB-KW.
DR GO; GO:0060707; P:trophoblast giant cell differentiation; IEA:Ensembl.
DR Gene3D; 2.40.20.10; -; 5.
DR InterPro; IPR000001; Kringle.
DR InterPro; IPR013806; Kringle-like.
DR InterPro; IPR018056; Kringle_CS.
DR InterPro; IPR003014; PAN-1_domain.
DR InterPro; IPR003609; Pan_app.
DR InterPro; IPR023317; Pept_S1A_plasmin.
DR InterPro; IPR001254; Peptidase_S1.
DR InterPro; IPR018114; Peptidase_S1_AS.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR009003; Trypsin-like_Pept_dom.
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
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.
FT DOMAIN 103 181 Kringle 1.
FT DOMAIN 184 262 Kringle 2.
FT DOMAIN 275 352 Kringle 3.
FT DOMAIN 377 454 Kringle 4.
FT DOMAIN 481 560 Kringle 5.
FT DOMAIN 581 808 Peptidase S1.
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 CARBOHYD 268 268 O-linked (GalNAc...).
FT /FTId=CAR_000016.
FT CARBOHYD 308 308 N-linked (GlcNAc...).
FT /FTId=CAR_000017.
FT CARBOHYD 365 365 O-linked (GalNAc...).
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 /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 /FTId=VAR_016287.
FT VARIANT 133 133 H -> Q (in dbSNP:rs4252186).
FT /FTId=VAR_016288.
FT VARIANT 134 134 R -> K (in dbSNP:rs2817).
FT /FTId=VAR_033653.
FT VARIANT 147 147 L -> P (in PLGD).
FT /FTId=VAR_018658.
FT VARIANT 235 235 R -> H (in PLGD; severe type 1
FT deficiency).
FT /FTId=VAR_018659.
FT VARIANT 261 261 R -> H (in dbSNP:rs4252187).
FT /FTId=VAR_016289.
FT VARIANT 374 374 V -> F (in PLGD; Nagoya-1;
FT dbSNP:rs121918028).
FT /FTId=VAR_006627.
FT VARIANT 408 408 R -> W (in dbSNP:rs4252119).
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 /FTId=VAR_016291.
FT VARIANT 494 494 A -> V (in dbSNP:rs4252128).
FT /FTId=VAR_016292.
FT VARIANT 523 523 R -> W (in dbSNP:rs4252129).
FT /FTId=VAR_016293.
FT VARIANT 532 532 R -> H (in PLGD).
FT /FTId=VAR_018660.
FT VARIANT 591 591 S -> P (in PLGD; may be associated with
FT susceptibility to thrombosis).
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 /FTId=VAR_006629.
FT VARIANT 676 676 V -> D (in dbSNP:rs17857492).
FT /FTId=VAR_031213.
FT VARIANT 751 751 G -> R (in PLGD; Kanagawa-1; 50%
FT activity).
FT /FTId=VAR_006630.
FT MUTAGEN 741 741 S->A: Proteolytically cleaved, but
FT abolishes plasmin activity and cell
FT detachment.
FT CONFLICT 50 50 A -> AQ (in Ref. 8; AA sequence).
FT CONFLICT 72 72 Q -> E (in Ref. 7; AA sequence and 8; AA
FT sequence).
FT CONFLICT 86 86 Missing (in Ref. 7; AA sequence and 8; AA
FT sequence).
FT CONFLICT 361 361 Q -> E (in Ref. 7; AA sequence and 9; AA
FT sequence).
FT CONFLICT 701 701 I -> V (in Ref. 3; AAA36451).
FT STRAND 25 33
FT STRAND 36 42
FT HELIX 46 55
FT STRAND 57 59
FT STRAND 63 67
FT TURN 68 71
FT STRAND 72 77
FT TURN 80 82
FT STRAND 85 96
FT HELIX 97 99
FT STRAND 102 104
FT STRAND 105 110
FT HELIX 113 115
FT TURN 119 121
FT STRAND 131 133
FT TURN 139 141
FT HELIX 143 145
FT STRAND 148 150
FT STRAND 155 157
FT STRAND 163 167
FT STRAND 172 175
FT STRAND 180 182
FT STRAND 184 186
FT STRAND 205 207
FT STRAND 209 211
FT STRAND 213 215
FT TURN 221 223
FT HELIX 225 227
FT STRAND 237 239
FT STRAND 244 248
FT STRAND 253 256
FT STRAND 273 276
FT STRAND 281 283
FT STRAND 291 293
FT STRAND 295 297
FT STRAND 303 305
FT TURN 311 313
FT HELIX 315 317
FT STRAND 334 339
FT STRAND 343 346
FT STRAND 377 379
FT STRAND 382 384
FT STRAND 405 407
FT TURN 413 415
FT TURN 417 419
FT STRAND 429 431
FT STRAND 436 441
FT STRAND 446 450
FT STRAND 481 483
FT STRAND 487 489
FT STRAND 509 511
FT STRAND 514 516
FT TURN 518 520
FT TURN 522 525
FT STRAND 542 546
FT STRAND 552 554
FT STRAND 582 586
FT STRAND 595 599
FT STRAND 605 613
FT STRAND 616 619
FT HELIX 621 624
FT HELIX 630 632
FT STRAND 634 638
FT STRAND 640 644
FT STRAND 650 659
FT TURN 661 663
FT STRAND 667 673
FT STRAND 698 703
FT STRAND 708 710
FT TURN 711 714
FT STRAND 717 724
FT HELIX 726 729
FT TURN 732 737
FT STRAND 743 747
FT STRAND 749 751
FT STRAND 752 754
FT STRAND 763 767
FT STRAND 769 778
FT HELIX 780 782
FT STRAND 791 795
FT HELIX 796 798
FT HELIX 800 808
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
//

MIM 173350
*RECORD*
*FIELD* NO
173350
*FIELD* TI
*173350 PLASMINOGEN; PLG
ANGIOSTATIN, INCLUDED;;
MICROPLASMIN, INCLUDED
*FIELD* TX
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DESCRIPTION

Plasminogen (PLG) is a circulating zymogen that is converted to the
active enzyme plasmin by cleavage of the peptide bond between arg560 and
val561, which is mediated by urokinase (PLAU; 191840) and tissue
plasminogen activator (PLAT; 173370). The main function of plasmin is to
dissolve fibrin (see, e.g., FGA, 134820) clots. Plasmin, like trypsin,
belongs to the family of serine proteinases (Miyata et al., 1982;
Forsgren et al., 1987).

CLONING

Forsgren et al. (1987) isolated a full-length cDNA corresponding to the
PLG gene from a human liver cDNA library. The deduced 791-residue
nonglycosylated protein has a calculated molecular mass of 88.4 kD.
After conversion, active plasmin consists of a heavy (A) and light (B)
chain that have molecular masses of 63.2 and 25.2 kD, respectively. The
N terminus of plasminogen corresponds to the heavy chain and contains 5
tandem repeats called kringles, which may mediate fibrin binding. The
proteolytic active center of plasmin is located within the C-terminal
light chain.

McLean et al. (1987) found that the human apolipoprotein(a) gene (LPA;
152200) shows striking similarities to the human PLG gene. In addition,
both genes are located on chromosome 6q27.

Degen et al. (1990) isolated cDNA for the mouse Plg gene.

- Angiostatin

O'Reilly et al. (1994) isolated a novel angiogenesis inhibitor, termed
'angiostatin,' from the urine and plasma of mice with lung carcinoma. It
was found to be a 38-kD internal fragment of mouse plasminogen that
contains the first 4 kringle structures. The circulating protein
mediated the suppression of remote tumor metastases in mice by
inhibiting the growth of capillary endothelial cells. Human angiostatin
had the same effect on mouse tumors. Cao et al. (1996) demonstrated that
recombinant fragments of angiostatin had inhibitory activity on
capillary endothelial cell proliferation in vitro.

Gately et al. (1996) showed that angiostatin is produced by the
proteolytic cleavage of plasminogen by a serine protease produced by
several human prostate carcinoma cell lines.

- Microplasmin

Wu et al. (1987) described the preparation and purification of a fully
functional human microplasmin derived from native plasmin. Microplasmin
is formed from the autolytic cleavage of plasmin in an alkaline
solution. Microplasmin consists mainly of the light chain of native
human plasmin and has a molecular mass of approximately 29 kD.

Wu et al. (1987) determined that microplasmin consists of 2 polypeptides
connected by disulfide bonds. One polypeptide is the 230-residue light
chain of plasmin and the other is a 31-residue fragment from the C
terminal portion of the heavy chain. The calculated molecular mass is
28.6 kD.

GENE STRUCTURE

Petersen et al. (1990) reported that the human plasminogen gene spans
about 52.5 kb of DNA and contains 19 exons. They concluded that there is
at least one other plasminogen-related gene in the human genome in
addition to LPA.

Kida et al. (1997) characterized the 5-prime flanking region of the
human plasminogen gene and found 3 TATA boxes 550 to 600 bp upstream of
the transcription initiation site, a TATA-like sequence (TGTAA) at
position -16, and putative binding sites for several transcription
factors. The 1.1-kb 5-prime flanking sequence directed basal
liver-specific expression in HepG2 cells, and deletion analysis
identified 2 negative elements in the PLG promoter.

MAPPING

Eiberg et al. (1984) found a lod score of 7.37 at theta = 0.12 in males
for linkage of FUCA2 (136820) and PLG. By somatic cell hybridization,
Murray et al. (1985) mapped the PLG gene to chromosome 6. Using DNA
probes for in situ mapping, Swisshelm et al. (1985) localized the gene
to 6q25-q27. Murray et al. (1987) mapped the PLG locus to 6q26-q27 by
study of somatic cell hybrids and by in situ hybridization. By
fluorescence in situ hybridization, Rao et al. (1994) mapped the gene to
6q26.

Magnaghi et al. (1995) illustrated the orientation and relative position
of the LPA and PLG genes and the apo(a)-like and plasminogen-like genes.
The PLG and LPA genes are transcribed in opposite directions.

Degen et al. (1990) localized the mouse Plg gene to chromosome 17.
Segregation of 2 allelic forms in 3 sets of recombinant inbred strains
allowed localization within the t-complex. The gene was found to be
deleted in the semidominant deletion mutant 'hairpintail.'

- Mapping History

Hobart (1978,1979) identified a diallelic polymorphism of plasminogen
with gene frequencies about 0.7 and 0.3. Recombinants were found with
HLA, C3, C6 and ABO.

Bissbort et al. (1983) found no linkage between PLG and 35 other marker
genes. Although for the PLG:GC (138200) linkage, positive lod scores (up
to 1.52 at theta = 0.20) were found in females, negative lod scores in
males suggested caution in acceptance of this linkage as true. GC is
located on chromosome 4q. The results were based on 18 families. Several
studies gave negative evidence on the possible chromosome 4 localization
of the PLG locus or, at best, weakly positive evidence (Falk and Huss,
1985; Buetow et al., 1985; Marazita et al., 1985).

GENE FUNCTION

Fischer et al. (2000) identified plasminogen, a proprotease implicated
in neuronal excitotoxicity, as a PrPsc (176640)-binding protein. Binding
is abolished if the conformation of the PrPsc is disrupted by 6-molar
urea or guanidine. The isolated lysine-binding site-1 of plasminogen
(kringles I-III) retains this binding activity, and binding can be
competed for with lysine. Plasminogen does not bind to PrPc; thus
plasminogen represents the first endogenous factor discriminating
between normal and pathologic prion protein. Fischer et al. (2000)
suggested that this unexpected property may be exploited for diagnostic
purposes.

Nguyen et al. (2007) stated that kringle-5 (K5) of plasminogen is an
inhibitor of angiogenesis and found that it induces autophagy and
apoptosis in endothelial cells. They showed that exposure of human cell
lines to recombinant K5 resulted in upregulated beclin-1 (604378) levels
within a few hours, and progressively increasing amounts of
antiapoptotic BCL2 (151430) became complexed with beclin-1. Prolonged
exposure to K5 ultimately led to apoptosis via mitochondrial membrane
depolarization and caspase activation (see CASP1, 147678) in endothelial
cells. Knockdown of beclin-1 by RNA interference decreased K5-induced
autophagy, but accelerated K5-induced apoptosis.

By immunoprecipitation and immunoblot analyses, Kunert et al. (2007)
found that factor H (CFH; 134370) and factor H-related protein-1 (CFHR1;
134371) bound to surface-expressed Pseudomonas aeruginosa elongation
factor Tuf and also to recombinant Tuf. Factor H and plasminogen bound
simultaneously to Tuf, and plasminogen was proteolytically activated.
Plasma without factor H did not support P. aeruginosa survival, and
survival increased in a factor H dose-dependent manner. Kunert et al.
(2007) proposed that Tuf acts as a virulence factor by acquiring host
proteins to the pathogen surface, controlling complement, and possibly
facilitating tissue invasion.

MOLECULAR GENETICS

Data on gene frequencies of allelic variants of plasminogen were
tabulated by Roychoudhury and Nei (1988).

- Type I Plasminogen Deficiency

In 2 unrelated Turkish girls with type I plasminogen deficiency (217090)
manifest as ligneous conjunctivitis, Schuster et al. (1997) identified 2
different homozygous mutations in the PLG gene, respectively
(173350.0004; 173350.0005).

In 2 sibs with plasminogen deficiency originally reported by Bateman et
al. (1986), Schuster et al. (1999) identified compound heterozygosity
for 2 mutations in the PLG gene (173350.0008; 173350.0009).

Tefs et al. (2006) identified compound heterozygous or homozygous
mutations in the PLG gene in 31 of 50 patients with type I plasminogen
deficiency. In 7 patients, only a heterozygous mutation could be
detected. No mutations in the PLG gene were identified in 12 patients of
Turkish origin, but 9 of these cases had a homozygous combination of 3
common PLG polymorphisms suggestive of a founder effect. The most common
mutation was K19E (173350.0010), which was present in 17 (34%) of 50
patients. Functional expression studies of 9 different type I mutant PLG
variants in COS-7 cells showed decreased plasmin antigen levels,
increased instability and degradation of the mutant protein, and
impaired cellular secretion.

- Heterozygous Mutations in the PLG Gene

Initial studies suggested that heterozygous changes in the PLG gene
resulting in dysfunctional plasminogen with decreased activity
('dysplasminogenemia') may predispose to thrombotic events (Aoki et al.,
1978; Dolan et al., 1988). However, further studies (Shigekiyo et al.,
1992; Tait et al., 1996) suggested that heterozygotes do not experience
excess thrombotic events.

Dysfunctional plasminogen variants were described by Wohl et al. (1982),
Miyata et al. (1984), Kazama et al. (1981), and Soria et al. (1983).
Although the plasminogen variant was associated with thrombosis in the
proband in most cases, family members who were also found to be
heterozygous did not experience thrombotic events.

Aoki et al. (1978) reported a Japanese man with recurrent thrombosis who
had decreased plasminogen activity with normal levels of immunoreactive
plasminogen. Miyata et al. (1982) found that this patient was
heterozygous for the Tochigi plasminogen variant (173350.0001). Multiple
other family members with the variant did not have thrombotic events.
Hach-Wunderle et al. (1988) found moderate plasminogen deficiency in a
53-year-old woman who developed deep venous thrombosis of the left thigh
and calf following an injury to the leg. A similar deficiency of
plasminogen was found in the patient's mother and sister who had no
thrombotic episodes. This patient was the only example of plasminogen
deficiency among 435 German individuals with a history of
thromboembolism. Dolan et al. (1988) reported 3 unrelated individuals
with decreased plasminogen activity and antigen associated with
thrombosis. Investigation of family members showed other relatives with
low levels of plasminogen who were asymptomatic. In 1 woman, Dolan et
al. (1988) observed that plasminogen levels rose to within normal limits
during pregnancy and returned to low levels after delivery. In a total
of 8 pregnancies, no thrombotic events occurred.

Shigekiyo et al. (1992) studied the frequency of thrombosis in 21
heterozygotes for plasminogen deficiency in 2 unrelated families. Only 3
of the 21 individuals had thromboses. Analysis by the Kaplan-Meier
method suggested no difference in frequency of thrombotic events from
controls.

Patrassi et al. (1993) reported a 17-year-old man with thrombotic-like
retinopathy associated with heterozygous plasminogen deficiency. Five of
13 paternal relatives had the same decrease, 2 of whom had a history of
recurrent phlebites of the legs. However, another family member with
normal plasminogen also had superficial phlebites. No other family
members showed retinal abnormality.

Magnaghi et al. (1995) reported a 37-year-old Italian man who developed
a deep venous thrombosis and pulmonary embolism following a hip fracture
in a car accident. He had decreased plasminogen activity and antigen
(63% and 65%, respectively). Analysis of the family identified a
haplotype associated with the abnormal plasminogen, which was inherited
in an autosomal dominant pattern. A brother who carried the same
haplotype had a lethal ischemic stroke at age 41 years. However, another
family member without plasminogen deficiency died of posttraumatic
pulmonary embolism at age 39, and there were multiple family members
without thrombotic events who were heterozygous and even homozygous for
the abnormal plasminogen haplotype.

Iijima et al. (1998) reported a 49-year-old woman with unilateral
central retinal vein occlusion and ipsilateral cilioretinal artery
occlusion who showed familial dysplasminogenemia associated with
elevated lipoprotein(a). Decreased plasminogen activity without
reduction of plasminogen antigen was found in the patient, her 2 sibs,
and her 2 children.

ANIMAL MODEL

Bugge et al. (1995) reported that Plg-deficient mice completed embryonic
development, survived to adulthood, and were capable of reproduction.
However, the mice developed multiple spontaneous thrombotic lesions
leading to severe organ damage and high morbidity or mortality at an
early age. Urine levels of urokinase-type plasminogen activator were
normal.

Romer et al. (1995) analyzed skin wound repair in Plg knockout mice and
demonstrated that Plg is required for normal repair of skin wounds.

Ploplis et al. (1995) found that Plg-null mice developed spontaneous
fibrin deposition due to impaired thrombolysis and exhibited retarded
growth and reduced fertility and survival compared to wildtype mice.

Drew et al. (1998) and Kao et al. (1998) found that mice with targeted
disruption of the plasminogen gene developed ligneous conjunctivitis
characterized by the formation of the fibrin-rich viscous or membranous
material.

A number of studies have shown that gram-negative and gram-positive
bacteria can interact with the host plasminogen activation system to
increase their invasiveness and enhance their ability to cross tissue
barriers (Boyle and Lottenberg, 1997). Gebbia et al. (1999) studied the
role of the plasminogen activation system during the course of infection
of relapsing fever caused by a species of Borrelia in plasminogen
knockout mice (Plg -/-). Subcutaneous inoculation of spirochetes
achieved a similar peak spirochetemia in control and deficient mice,
indicating that the plasminogen activation system had no effect on the
development of this phase of the infection. Anemia, thrombocytopenia,
hepatitis, carditis, and splenomegaly were noted in all mice during and
immediately after peak spirochetemia. Fibrin deposition in organs was
noted in Plg -/- mice but not in controls. Significantly greater
spirochetal DNA burdens were consistently observed in the hearts and
brains of control mice 28 to 30 days after infection. Furthermore, the
decreased spirochetal load in brains of Plg -/- mice was associated with
a significant decrease in the degree of inflammation of the
leptomeninges in these mice. These findings indicated a role for the
plasminogen activation system in heart and brain invasion by relapsing
fever Borrelia, resulting in organ injury.

Swaisgood et al. (2002) evaluated the in vivo effect of plasma
carboxypeptidase B (CPB2; 603101) on plasminogen function.
Cpb2-deficient mice, generated by homologous recombination, were healthy
and did not exhibit the poor health characteristics of Plg-deficient
mice. In a pulmonary clot lysis model, fibrinolysis was significantly
increased in mice with partial (Cpb2 +/-) or total (Cpb2 -/-) absence of
Cpb2 compared with their wildtype counterparts (Cpb2 +/+). In a
thioglycollate model of peritoneal inflammation, leukocyte migration at
72 hours increased significantly in Plg +/-/Cpb2 +/- and Plg +/-/Cpb2
-/- compared with their wildtype counterparts. The studies demonstrated
that Cpb2 regulates primary functions of Plg in fibrinolysis and cell
migration in vivo.

Gong et al. (2008) found that Plg -/- mice displayed diminished
macrophage trans-extracellular matrix (ECM) migration and decreased Mmp9
(120361) activation following induction of peritonitis. Injection of
active Mmp9 rescued macrophage migration in Plg -/- mice. Macrophage
migration and aneurysm formation were also reduced in Plg -/- mice
induced to undergo abdominal aortic aneurysm (AAA). Administration of
active Mmp9 to Plg -/- mice promoted macrophage infiltration and
development of AAA. Gong et al. (2008) concluded that PLG regulates
macrophage migration in inflammation via activation of MMP9, which in
turn regulates the ability of macrophages to migrate across ECM.

- Angiostatin

Cao et al. (1998) demonstrated that gene transfer of a cDNA coding for
mouse angiostatin into murine T241 fibrosarcoma cells suppressed primary
and metastatic tumor growth in vivo. Implementation of stable clones
expressing mouse angiostatin in C57B16/J mice inhibited primary tumor
growth by an average of 77%. After removal of primary tumors, the
pulmonary micrometastases in approximately 70% of mice remained in a
microscopic dormant and avascular state for 2 to 5 months. The tumor
cells in the dormant micrometastases exhibited a high rate of apoptosis
balanced by a high proliferation rate. These studies showed the
diminished growth of lung metastases after removal of the primary tumor,
suggesting that metastases are self-inhibitory by halting angiogenesis.
The angiostatin-induced long-term dormancy of lung metastases was
equivalent to 14 to 15 human years (when 1 mouse day is equivalent to
approximately 35 human days).

Drixler et al. (2001) examined the biologic effects of angiostatin on
pathologic and physiologic retinal angiogenesis as well as its effects
on growth and development in newborn mice. They found that angiostatin
successfully inhibited oxygen-induced intravitreal pathologic
angiogenesis without affecting the development of physiologic retinal
vascularization, development, and growth.

Lund et al. (2006) observed that wound healing in Plat-null or Plau-null
mice was similar to that in wildtype mice, but wound healing in mice
deficient for both Plat and Plau was significantly delayed. These
findings suggested functional overlap between the 2 plasminogen
activators. However, wound healing in the Plat/Plau-deficient mice was
not as impaired as in plasminogen-null mice, suggesting the presence of
an additional plasminogen activator. Pharmacologic inhibition of
kallikrein (KLK1; 147910) in Plat/Plau-null mice resulted in delayed
wound healing similar that in Plg-null mice. Lund et al. (2006)
concluded that kallikrein may play a role in plasmin generation.

*FIELD* AV
.0001
DYSPLASMINOGENEMIA
PLG, ALA601THR

Miyata et al. (1982) identified a variant of plasminogen with an
ALA600THR (A600T) substitution, caused by a G-to-A transition in exon 15
of the PLG gene, in the active site of the enzyme. (Ala600 is the
equivalent of ala55 in the chymotrypsin numbering system.) The authors
referred to this variant as plasminogen Tochigi. The A600T substitution
was identified in a 31-year-old Japanese man with a 15-year history of
recurrent thromboses originally reported by Aoki et al. (1978). Serum
plasminogen activity was decreased by about 50%, but plasminogen antigen
levels were normal; see 217090. Detailed family studies reported by Aoki
et al. (1978) identified 12 additional members with half-normal
plasminogen activity, presumably heterozygotes, and 1 young girl with no
plasminogen activity, presumably a homozygote. None of the family
members had thrombotic episodes. Gel electrofocusing of the purified
plasminogen confirmed the abnormality in this family. Aoki et al. (1978)
noted that the low level of plasminogen activity in this patient could
not be the sole cause of thrombosis because none of the other affected
family members had a thrombotic event. Miyata et al. (1982) suggested
that the A600T substitution may perturb the protein such that proton
transfers associated with the normal catalytic process cannot occur in
the abnormal enzyme. Miyata et al. (1984) found that plasminogen Tochigi
II and Nagoya, both of which showed decreased enzyme activity, were also
due to the A600T substitution.

Ichinose et al. (1991) described the same variation, which they referred
to as ala601-to-thr.

By isoelectric focusing electrophoresis, several workers identified a
functionally inactive PLG variant designated plasminogen M5, present in
2 to 4% of Japanese subjects (review by Kikuchi et al., 1992). Kikuchi
et al. (1992) demonstrated that plasminogen Tochigi and plasminogen
Nagoya II are identical to PLG M5. The plasma levels of immunoreactive
plasminogen associated with the A601T substitution are normal, but
activity is reduced. Despite the report of Aoki et al. (1978), the role
of the A601T substitution in thrombotic events was unclear; many
heterozygous and even homozygous individuals did not have a history of
thrombosis. Kikuchi et al. (1992) estimated the allele frequency to be
0.011 to 0.023 in the Japanese population.

Murata et al. (1997) studied 3 patients with retinochoroidal vascular
disorders and found that each carried the A601T mutation. They suggested
that this defect may play a role in the pathogenesis of circulatory
disorders in small local vessels because of reduced fibrinolytic
activity due to decreased functional plasminogen levels.

This variant has also been called plasminogen Kagoshima.

.0002
DYSPLASMINOGENEMIA
PLG, VAL355PHE

Ichinose et al. (1991) described a G-to-T transversion in exon 10 of the
PLG gene, resulting in a val355-to-phe (V355F) substitution just prior
to the first disulfide bond in kringle 4. The V355F substitution was
associated with decreased plasminogen activity and antigen levels (see
217090). This mutation was demonstrated by digestion with AvaII
endonuclease, which recognized the normal GGTCC but not GTTCC.

This variant has been called plasminogen Nagoya I.

.0003
DYSPLASMINOGENEMIA
PLG, SER572PRO

In a 43-year-old Japanese woman with late-onset epilepsy as a result of
cerebral infarction, Azuma et al. (1993) identified a heterozygous
T-to-C transition in exon 14 of the PLG gene, resulting in a
ser572-to-pro (S572P) substitution. Biochemical analysis showed
decreased PLG antigen levels and activity to about 50% of normal,
consistent with dysplasminogenemia (see 217090). The patient's mother
and daughter, who both carried the mutation, had similarly decreased PLG
antigen and activity. The mother had an episode of arterial thrombosis
of the femur at age 56 years.

.0004
PLASMINOGEN DEFICIENCY, TYPE I
PLG, ARG216HIS

In a Turkish girl with severe plasminogen deficiency (217090) manifest
as ligneous conjunctivitis and occlusive hydrocephalus, Schuster et al.
(1997) identified a homozygous 780G-A transition in exon 7 of the PLG
gene, resulting in an arg216-to-his (R216H) substitution. The mutation
was identified using PCR, SSCP analysis, and DNA sequencing. The
patient's unaffected parents and sister were heterozygous for the
mutation.

In a previously healthy 71-year-old woman who had first developed
unilateral ligneous conjunctivitis at the age of 69 years, Schuster et
al. (1999) identified compound heterozygosity for 2 mutations in the PLG
gene: R216H and K19E (173350.0010).

.0005
PLASMINOGEN DEFICIENCY, TYPE I
PLG, TRP597TER

In a Turkish girl with severe plasminogen deficiency (217090) manifest
as ligneous conjunctivitis and occlusive hydrocephalus, Schuster et al.
(1997) identified a homozygous 1924G-A transition in exon 15 of the PLG
gene, resulting in a trp597-to-ter (W597X) substitution. The healthy
parents were heterozygous for the mutation.

.0006
PLASMINOGEN DEFICIENCY, TYPE I
PLG, GLU460TER

In a child of a consanguineous Turkish couple with plasminogen
deficiency (217090) manifest as ligneous conjunctivitis and occlusive
hydrocephalus, Schott et al. (1998) identified a homozygous 1511G-T
transversion, resulting in a glu460-to-ter (E460X) substitution. The
mutation abolished the catalytic domain of plasmin. A healthy brother
and the unaffected parents were heterozygous for the mutation.

.0007
DYSPLASMINOGENEMIA
PLG, GLY732ARG

Higuchi et al. (1998) identified a new dysplasminogen, plasminogen
Kanagawa-I, in a healthy 20-year-old male with no past history of
thrombosis or bleeding. He was found to have dysplasminogenemia (see
217090) following voluntary blood donation for teaching purposes. His
plasma plasminogen activity was approximately 50% of that of normal
pooled plasma. Nucleotide sequencing revealed a heterozygous G-to-A
transition in exon 18, which resulted in a gly732-to-arg (G732R)
substitution. Both the proband's father and paternal grandfather were
heterozygous for this mutation. The grandfather was a compound
heterozygote for plasminogen Kanagawa-I and Tochigi (173350.0001); his
plasminogen activity and antigen levels were 7.7% and 87.2% of that of
normal pooled plasma, respectively. He had never had significant
thrombosis.

.0008
PLASMINOGEN DEFICIENCY, TYPE I
PLG, LYS212DEL

In a brother and sister with plasminogen deficiency (217090), Schuster
et al. (1999) identified compound heterozygosity for 2 mutations in the
PLG gene: a deletion of lys212 inherited from the mother, and a 1-bp
deletion in the first nucleotide of intron Q following exon 17
(173350.0009) inherited from the father. Both sibs had plasminogen
antigen and functional activity levels below the limit of detection. The
sibs were originally reported by Bateman et al. (1986).

.0009
PLASMINOGEN DEFICIENCY, TYPE I
PLG, 1-BP DEL, IVS17, G, +1

See 173350.0008 and Schuster et al. (1999).

.0010
PLASMINOGEN DEFICIENCY, TYPE I
PLG, LYS19GLU

In 3 unrelated individuals with plasminogen deficiency (217090),
Schuster et al. (1999) identified a 118A-G transition in exon 2 of the
PLG gene resulting in a lys19-to-glu (K19E) substitution. All patients
were compound heterozygous for K19E and another pathogenic PLG mutation
(see, e.g., 173350.0004).

Schuster and Seregard (2003) stated that the K19E mutation was the most
common PLG mutation identified in patients with plasminogen deficiency.

Tefs et al. (2006) identified the K19E mutation in 17 (34%) of 50
patients with plasminogen deficiency. Six patients who were homozygous
for the mutation had a milder clinical course and higher residual PLG
antigen and activity compared to patients with other PLG mutations.

*FIELD* SA
Cohen (1990); Dayhoff (1972); Ikemoto et al. (1982); Mannucci et
al. (1986); Nakamura and Abe (1982); Nishigaki and Omoto (1982); Raum
et al. (1980); Sakata and Aoki (1980); Scharrer et al. (1986)
*FIELD* RF
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a hereditary molecular abnormality found in a patient with recurrent
thrombosis. J. Clin. Invest. 61: 1186-1195, 1978.

2. Azuma, H.; Uno, Y.; Shigekiyo, T.; Saito, S.: Congenital plasminogen
deficiency caused by a ser572-to-pro mutation. Blood 82: 475-480,
1993.

3. Bateman, J. B.; Pettit, T. H.; Isenberg, S. J.; Simons, K. B.:
Ligneous conjunctivitis: an autosomal recessive disorder. J. Pediat.
Ophthal. Strabismus 23: 137-140, 1986.

4. Bissbort, S.; Bender, K.; Mayerova, A.; Wienker, T. F.; Mauff,
G.: Genetic linkage relations of the human plasminogen gene. Hum.
Genet. 63: 126-131, 1983.

5. Boyle, M. D. P.; Lottenberg, R.: Plasminogen activation by invasive
human pathogens. Thromb. Haemost. 77: 1-10, 1997.

6. Buetow, K. H.; Murray, J. C.; Ferrell, R. E.: Linkage relationship
of PLG, GC and ALB. (Abstract) Cytogenet. Cell Genet. 40: 595-596,
1985.

7. Bugge, T. H.; Flick, M. J.; Daugherty, C. C.; Degen, J. L.: Plasminogen
deficiency causes severe thrombosis but is compatible with development
and reproduction. Genes Dev. 9: 794-807, 1995.

8. Cao, Y.; Ji, R. W.; Davidson, D.; Schaller, J.; Marti, D.; Sohndel,
S.; McCance, S. G.; O'Reilly, M. S.; Llinas, M.; Folkman, J.: Kringle
domains of human angiostatin: characterization of the anti-proliferative
activity on endothelial cells. J. Biol. Chem. 271: 29461-29467,
1996.

9. Cao, Y.; O'Reilly, M. S.; Marshall, B.; Flynn, E.; Ji, R.-W.; Folkman,
J.: Expression of angiostatin cDNA in a murine fibrosarcoma suppresses
primary tumor growth and produces long-term dormancy of metastases. J.
Clin. Invest. 101: 1055-1063, 1998. Note: Erratum: J. Clin. Invest.
102: 2031 only, 1998.

10. Cohen, S. R.: Ligneous conjunctivitis: an ophthalmic disease
with potentially fatal tracheobronchial obstruction. Laryngeal and
tracheobronchial features. Ann. Otol. Rhinol. Laryng. 99: 509-512,
1990.

11. Dayhoff, M. O.: Atlas of Protein Sequence and Structure. Thrombin
and plasmin. Washington: National Biomedical Research Foundation
(pub.) 5: 1972. Pp. D100-D101 and D110.

12. Degen, S. J. F.; Bell, S. M.; Schaefer, L. A.; Elliott, R. W.
: Characterization of the cDNA coding for mouse plasminogen and localization
of the gene to mouse chromosome 17. Genomics 8: 49-61, 1990.

13. Dolan, G.; Greaves, M.; Cooper, P.; Preston, F. E.: Thrombovascular
disease and familial plasminogen deficiency: a report of three kindreds. Brit.
J. Haemat. 70: 417-421, 1988.

14. Drew, A. F.; Kaufman, A. H.; Kombrinck, K. W.; Danton, M. J.;
Daugherty, C. C.; Degen, J. L.; Bugge, T. H.: Ligneous conjunctivitis
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15. Drixler, T. A.; Borel Rinkes, I. H. M.; Ritchie, E. D.; Treffers,
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1987.

*FIELD* CN
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MIM 217090
*RECORD*
*FIELD* NO
217090
*FIELD* TI
#217090 PLASMINOGEN DEFICIENCY, TYPE I
LIGNEOUS CONJUNCTIVITIS, INCLUDED;;
DYSPLASMINOGENEMIA, INCLUDED
read more*FIELD* TX
A number sign (#) is used with this entry because type I plasminogen
deficiency is caused by mutation in the gene encoding plasminogen (PLG;
173350). Ligneous conjunctivitis is usually the initial and most common
manifestation of type I congenital plasminogen deficiency.

DESCRIPTION

Congenital plasminogen deficiency is a rare autosomal recessive disorder
characterized clinically by chronic muscosal pseudomembranous lesions
consisting of subepithelial fibrin deposition and inflammation. The most
common clinical manifestation is ligneous ('wood-like') conjunctivitis,
a redness and subsequent formation of pseudomembranes mostly on the
palpebral surfaces of the eye that progress to white, yellow-white, or
red thick masses with a wood-like consistency that replace the normal
mucosa. The lesions may be triggered by local injury and/or infection
and often recur after local excision. Pseudomembranous lesions of other
mucous membranes often occur in the mouth, nasopharynx, trachea, and
female genital tract. Some affected children also have congenital
occlusive hydrocephalus. A slightly increased female:male ratio has been
observed (1.4:1 to 2:1) (Schuster and Seregard, 2003; Tefs et al.,
2006).

Type I plasminogen deficiency is characterized by decreased serum
plasminogen activity, decreased plasminogen antigen levels, and clinical
symptoms, whereas type II plasminogen deficiency, also known as
'dysplasminogenemia,' is characterized by decreased plasminogen activity
with normal or slightly reduced antigen levels. Patients with type II
deficiency are usually asymptomatic. Ligneous conjunctivitis and
pseudomembranous formation has only been associated with type I
plasminogen deficiency. Presumably, normal amounts of plasminogen
antigen with decreased activity, as seen in type II, is sufficient for
normal wound healing (Schuster and Seregard, 2003).

CLINICAL FEATURES

Bateman et al. (1986) reported a brother and sister with ligneous
conjunctivitis. The authors found reports of 9 other sets of affected
sibs, suggesting autosomal recessive inheritance, although no parental
consanguinity was observed. In 1 of the patients reported by Bateman et
al. (1986), Cohen (1990) observed laryngeal and tracheobronchial
involvement resulting in voice change and obstructive pulmonary disease.

Mingers et al. (1997) described 3 unrelated females with ligneous
conjunctivitis and additional pseudomembranous lesions of other mucous
membranes associated with plasminogen deficiency. The disease was
characterized by massive fibrin deposition within mucous membranes due
to the absence of clearance by plasmin. Infusion of plasminogen in 2 of
the patients resulted in normal plasminogen activity, confirming the
causative defect, although there was no significant clinical
improvement.

Schuster et al. (1997) reported 2 unrelated girls of Turkish extraction
who had ligneous conjunctivitis and occlusive hydrocephalus. One patient
first developed chronic bilateral conjunctivitis at the age of 4 months.
Enlargement of the head was noted at 2 years of age. At the age of 25
months, the child suddenly became comatose and exhibited generalized
hypotonia. She was found to have occlusive internal hydrocephalus; a
ventriculoatrial shunt was placed. Pseudomembranous lesions of both
conjunctivae and gingival hyperplasia were present at that time. At 3
years of age and on several occasions thereafter, pseudomembranes were
surgically removed from both eyes. At age 8, local treatment with
hyaluronidase-containing eyedrops was highly beneficial. Genetic
analysis revealed that both girls had a homozygous mutation in the
plasminogen gene (see 173350.0004 and 173350.0005).

Schott et al. (1998) reported a child, born of consanguineous Turkish
parents, with plasminogen deficiency. Prenatal ultrasound examination
demonstrated progressive internal hydrocephalus, and the child was
delivered by elective cesarean section at 35 weeks' gestation. Bulging
fontanel and macrocephalus were the only findings at that time. Three
days after birth, she developed bilateral inflammation of the palpebral
portion of the conjunctiva, with hypersecretion and formation of
pseudomembranes. Within 2 weeks, a thick, yellowish-white, fibrous,
woody pseudomembranous layer of conjunctival proliferation had
developed, spreading from the inner side of the upper and lower eyelids
and completely closing both eyes. The pseudomembranes were removed
surgically several times but regrew rapidly. Imaging studies
demonstrated Dandy-Walker malformation, hypoplasia of the cerebellum,
and hypoplastic corpus callosum. There was also hyperviscosity of
tracheobronchial and nasopharyngeal secretions and impaired wound
healing. Replacement therapy with lysine-conjugated plasminogen led to
rapid regression of the pseudomembranes and normalization of respiratory
tract secretions and wound healing. Molecular analysis identified a
homozygous mutation in the PLG gene (173350.0006). A healthy brother and
the unaffected parents were heterozygous for the mutation.

Schuster et al. (1999) provided follow-up of the sibs reported by
Bateman et al. (1986). The 19-year-old sister first developed
conjunctivitis at 3 weeks of age. At 3 years of age, she developed
bilateral conjunctival pseudomembranes and was diagnosed with ligneous
conjunctivitis. These membranes recurred repeatedly, necessitating
surgical removal on 18 different occasions. The rate of conjunctival
membrane formation had decreased in recent years. At 5 years of age, she
developed hoarseness and was noted to have a ligneous membrane in the
vocal cords. She also showed asthma-like symptoms. At the age of 8
years, she developed pneumomediastinum and had her first of 20
bronchoscopies to remove thickened membranes from her
laryngotracheobronchial tree. At 16 years of age, she developed an
abscess of the left lung, necessitating bronchoscopic drainage. Other
features included gingival membranes and nodular, calcified masses in
the renal collecting system, demonstrable by ultrasound and pyelography.
Treatment with multiple eyedrops, corticosteroids, local heparin, and
multiple courses of various antibiotics had been ineffective. The
14-year-old brother had developed conjunctivitis at 9 months of age,
which became severe at 4 years of age. He had required surgery for
ligneous conjunctival membranes on 15 occasions, beginning at the age of
5 years. He also had had gingival membranes associated with intermittent
bleeding, geographic tongue, and sinusitis, as well as membrane
formation in the pharynx and in the renal collecting system. Duodenal
ulceration and an eosinophilic gastric infiltration were also observed.

Tefs et al. (2006) reported 50 patients from 44 families with severe
congenital plasminogen deficiency. The parents were consanguineous in 21
cases. The median age of first clinical manifestation was 9.75 months,
but ranged up to 61 years. The most common manifestation was ligneous
conjunctivitis (80% of patients), followed by ligneous gingivitis (34%),
and involvement of the upper and lower respiratory tract (30%),
including the ears, sinus, larynx, bronchi, and lungs. Other less
commonly involved areas included the female genital tract (8%),
gastrointestinal tract, and skin. Four patients had congenital occlusive
hydrocephalus and 2 had Dandy-Walker malformation with cerebellar
hypoplasia. Venous thrombosis did not occur in 45 patients; the
thrombosis history was unknown in 5 patients.

CLINICAL MANAGEMENT

Results of treatment of ligneous conjunctivitis with hyaluronidase eye
drops, corticosteroids, cyclosporine, and antiviral agents have been
generally disappointing. Surgical treatment often causes accelerated
recurrence of pseudomembranes. Schott et al. (1998) reported dramatic
results with purified plasminogen concentrate in an infant with ligneous
conjunctivitis and homozygous plasminogen deficiency.

Among 50 patients, Tefs et al. (2006) reported variable success of
treatment of ligneous conjunctivitis with topical solutions containing
corticosteroids, heparin, fresh frozen plasma, plasminogen, and
immunosuppression. Surgical excision of pseudomembranes was often
followed by relapse. Gingivectomy in patients with ligneous gingivitis
was unsuccessful and followed by loss of teeth in at least 2 patients.

MOLECULAR GENETICS

In 2 unrelated Turkish girls with plasminogen deficiency, Schuster et
al. (1997) identified 2 different homozygous mutations in the PLG gene
(173350.0004; 173350.0005).

In 2 sibs with plasminogen deficiency originally reported by Bateman et
al. (1986), Schuster et al. (1999) identified compound heterozygosity
for 2 mutations in the PLG gene (173350.0008; 173350.0009).

PATHOGENESIS

Plasminogen activators released by the cornea in the tear fluid of the
normal eye (Mirshahi et al., 1996) convert plasminogen into the
fibrinolytic enzyme plasmin, which rapidly clears the cornea of fibrin
deposits. The absence of plasmin activity in patients with plasminogen
deficiency results in the formation of fibrin-rich viscous or membranous
material in ligneous conjunctivitis and in mice with targeted disruption
of the plasminogen gene (Drew et al., 1998; Kao et al., 1998). An
inflammatory reaction combined with activation of inflammatory cells in
fibroblasts, with a drying out of the fibrin, results in the wood-like
appearance of the conjunctival lesions. A similar reaction occurs in
other affected areas of the body. Tracheobronchial fibrin deposits
impair the ciliary system of the tracheobronchial tree and support
bacterial growth, predisposing patients to multiple sinobronchial
infections. Involvement of the ear (Marcus et al., 1990) is attributable
to fibrin deposition in the middle ear. The pathophysiologic mechanism
of occlusive hydrocephalus may be fibrin deposition in the cerebral
ventricular system, causing impaired circulation of the fluid in the
aqueduct region (Schott et al., 1998).

Schuster et al. (1997) and Schuster and Seregard (2003) noted that
patients with ligneous conjuncitivis and congenital plasminogen
deficiency do not experience intravascular thromboembolic episodes
despite a severe deficiency of the key zymogen of the fibrinolytic
system. In addition, heterozygous plasminogen deficiency does not appear
to be a risk factor for thrombosis (Tait et al., 1996; Shigekiyo et al.,
1992), despite several earlier reports to the contrary (Aoki et al.,
1978; Dolan et al., 1988).

HISTORY

Schuster and Seregard (2003) provided a detailed history of ligneous
conjunctivitis and plasminogen deficiency. The authors stated that
ligneous conjunctivitis was first described in a 46-year-old man by
Bouisson (1847). Borel (1934) was the first to describe the familial
occurrence of the disorder, which he termed 'ligneous conjunctivitis.'

ANIMAL MODEL

Ligneous conjunctivitis has been described in different animal species,
including Doberman pinschers (Ramsey et al., 1996).

*FIELD* SA
Nussgens and Roggenkamper (1993)
*FIELD* RF
1. Aoki, N.; Morio, M.; Sakata, Y.; Yoshida, N.: Abnormal plasminogen:
a hereditary molecular abnormality found in a patient with recurrent
thrombosis. J. Clin. Invest. 61: 1186-1195, 1978.

2. Bateman, J. B.; Pettit, T. H.; Isenberg, S. J.; Simons, K. B.:
Ligneous conjunctivitis: an autosomal recessive disorder. J. Pediat.
Ophthal. Strabismus 23: 137-140, 1986.

3. Borel, G.: Un nouveau syndrome oculo-palpebral. Ann. Oculist. 171:
207-222, 1934.

4. Bouisson, M.: Ophthalmie sur-aigue avec formation de pseudomembranes
a la surface de la conjonctive. Ann. Oculist. 17: 100-104, 1847.

5. Cohen, S. R.: Ligneous conjunctivitis: an ophthalmic disease with
potentially fatal tracheobronchial obstruction. Laryngeal and tracheobronchial
features. Ann. Otol. Rhinol. Laryng. 99: 509-512, 1990.

6. Dolan, G.; Greaves, M.; Cooper, P.; Preston, F. E.: Thrombovascular
disease and familial plasminogen deficiency: a report of three kindreds. Brit.
J. Haemat. 70: 417-421, 1988.

7. Drew, A. F.; Kaufman, A. H.; Kombrinck, K. W.; Danton, M. J.; Daugherty,
C. C.; Degen, J. L.; Bugge, T. H.: Ligneous conjunctivitis in plasminogen-deficient
mice. Blood 91: 1616-1624, 1998.

8. Kao, W. W.; Kao, C. W.; Kaufman, A. H.; Kombrinck, K. W.; Converse,
R. L.; Good, W. V.; Bugge, T. H.; Degen, J. L.: Healing of corneal
epithelial defects in plasminogen- and fibrinogen-deficient mice. Invest.
Ophthal. Vis. Sci. 39: 502-508, 1998.

9. Marcus, D. M.; Walton, D.; Donshik, P.; Choo, L.; Newman, R. A.;
Albert, D. M.: Ligneous conjunctivitis with ear involvement. Arch.
Ophthal. 108: 514-519, 1990.

10. Mingers, A.-M.; Heimburger, N.; Zeitler, P.; Kreth, H. W.; Schuster,
V.: Homozygous type I plasminogen deficiency. Semin. Thromb. Hemost. 23:
259-269, 1997.

11. Mirshahi, S.; Soria, J.; Nelles, L.; Soria, C.; Faure, J. P.;
Pouliguen, Y.; Mirshahi, M.: Plasminogen activators in human corneal
fibroblasts: secretion, cellular localization, and regulation. Fibrinolysis 10:
255-262, 1996.

12. Nussgens, Z.; Roggenkamper, P.: Ligneous conjunctivitis: ten
years follow-up. Ophthalmic Paediat. Genet. 14: 137-140, 1993.

13. Ramsey, D. T.; Ketring, K. L.; Glaze, M. B.; Knight, B.; Render,
J. A.: Ligneous conjunctivitis in four Doberman pinschers. J. Am.
Animal Hosp. Assoc. 32: 439-447, 1996.

14. Schott, D.; Dempfle, C.-E.; Beck, P.; Liermann, A.; Mohr-Pennert,
A.; Goldner, M.; Mehlem, P.; Azuma, H.; Schuster, V.; Mingers, A.-M.;
Schwarz, H. P.; Kramer, M. D.: Therapy with a purified plasminogen
concentrate in an infant with ligneous conjunctivitis and homozygous
plasminogen deficiency. New Eng. J. Med. 339: 1679-1686, 1998.

15. Schuster, V.; Mingers, A.-M.; Seidenspinner, S.; Nussgens, Z.;
Pukrop, T.; Kreth, H. W.: Homozygous mutations in the plasminogen
gene of two unrelated girls with ligneous conjunctivitis. Blood 90:
958-966, 1997.

16. Schuster, V.; Seidenspinner, S.; Zeitler, P.; Escher, C.; Pleyer,
U.; Bernauer, W.; Stiehm, E. R.; Isenberg, S.; Seregard, S.; Olsson,
T.; Mingers, A.-M.; Schambeck, C.; Kreth, H. W.: Compound-heterozygous
mutations in the plasminogen gene predispose to the development of
ligneous conjunctivitis. Blood 93: 3457-3466, 1999.

17. Schuster, V.; Seregard, S.: Ligneous conjunctivitis. Surv. Ophthalmol.
48: 369-388, 2003.

18. Shigekiyo, T.; Uno, Y.; Tomonari, A.; Satoh, K.; Hondo, H.; Ueda,
S.; Saito, S.: Type I congenital plasminogen deficiency is not a
risk factor for thrombosis. Thromb. Haemost. 67: 189-192, 1992.

19. Tait, R. C.; Walker, I. D.; Conkie, J. A.; Islam, S. I.; McCall,
F.: Isolated familial plasminogen deficiency may not be a risk factor
for thrombosis. Thromb. Haemost. 76: 1004-1008, 1996.

20. Tefs, K.; Gueorguieva, M.; Klammt, J.; Allen, C. M.; Aktas, D.;
Anlar, F. Y.; Aydogdu, S. D.; Brown, D.; Ciftci, E.; Contarini, P.;
Dempfle, C.-E.; Dostalek, M.; and 21 others: Molecular and clinical
spectrum of type I plasminogen deficiency: a series of 50 patients. Blood 108:
3021-3026, 2006.

*FIELD* CS
INHERITANCE:
Autosomal recessive

HEAD AND NECK:
[Head];
Macrocephaly;
[Ears];
Pseudomembranous inflammation of the middle ear;
[Eyes];
Ligneous conjunctivitis;
Chronic tearing;
Redness of the conjunctivae;
Formation of mucosal pseudomembranes that progress to plaques;
Visual impairment;
Blindness;
[Mouth];
Ligneous gingivitis;
Gingival hyperplasia;
Pseudomembranous inflammation of the oral mucosa;
Periodontitis;
[Teeth];
Tooth loss;
Gingivitis, severe

CARDIOVASCULAR:
[Vascular];
No increased risk of thrombotic vascular events

RESPIRATORY:
Upper respiratory tract infections;
Pseudomembranous inflammation of the sinuses;
[Nasopharynx];
Pseudomembranous inflammation of the nasopharynx;
[Larynx];
Pseudomembranous inflammation of the larynx;
[Airways];
Pseudomembranous inflammation of the bronchi;
Airway obstruction;
[Lung];
Pseudomembranous inflammation of the lung

ABDOMEN:
[Gastrointestinal];
Pseudomembranous inflammation of the gastrointestinal mucosa;
Duodenal ulcer

GENITOURINARY:
[Internal genitalia, female];
Pseudomembranous inflammation of the vaginal mucosa or cervix;
[Kidneys];
Pseudomembranous, calcified plaques in the renal collecting system
(rare);
Renal calculi (rare);
Acute nephritis (rare)

SKIN, NAILS, HAIR:
[Skin];
Juvenile colloid milium;
Small papules on sun-exposed areas

NEUROLOGIC:
[Central nervous system];
Occlusive hydrocephalus, congenital;
Dandy-Walker malformation;
Cerebellar hypoplasia

LABORATORY ABNORMALITIES:
Decreased plasminogen antigen;
Decreased plasminogen activity;
Subepithelial fibrin deposition with inflammation (pseudomembranous
inflammation) of mucosal tissues

MISCELLANEOUS:
Onset usually in infancy or early childhood;
Adult onset of symptoms has been reported;
Slightly increased female:male ratio (1.4:1 to 2:1);
Pseudomembrane formation triggered by injury, infection, irritation,
surgery;
Estimated prevalence of 1.6 in 1,000,000 individuals in the U.K.;
Increased prevalence in individuals of Turkish descent

MOLECULAR BASIS:
Caused by mutation in the plasminogen gene (PLG, 173350.0001)

*FIELD* CN
Cassandra L. Kniffin - revised: 6/5/2007

*FIELD* CD
John. F. Jackson: 6/15/1995

*FIELD* ED
joanna: 03/19/2008
ckniffin: 6/5/2007

*FIELD* CN
Cassandra L. Kniffin - reorganized: 6/13/2007
Cassandra L. Kniffin - updated: 6/5/2007
Victor A. McKusick - updated: 7/6/1999
Victor A. McKusick - updated: 12/4/1998
Victor A. McKusick - updated: 9/5/1997

*FIELD* CD
Victor A. McKusick: 6/3/1986

*FIELD* ED
terry: 03/10/2011
terry: 3/10/2011
terry: 6/6/2008
carol: 6/13/2007
ckniffin: 6/5/2007
carol: 7/23/1999
jlewis: 7/21/1999
terry: 7/6/1999
carol: 1/5/1999
carol: 12/8/1998
terry: 12/4/1998
dholmes: 9/30/1997
terry: 9/12/1997
terry: 9/5/1997
mimadm: 2/19/1994
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/26/1989
marie: 3/25/1988
root: 6/15/1987

RBCC Red Blood Cell Collection

Full text data of PLG