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UniProtKB/Swiss-Prot entry P00747


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Entry information
Entry name PLMN_HUMAN
Primary accession number P00747
Secondary accession numbers Q15146 Q5TEH4 Q6PA00
Integrated into Swiss-Prot on July 21, 1986
Sequence was last modified on July 1, 1989 (Sequence version 2)
Annotations were last modified on    October 14, 2008 (Entry version 130)
Name and origin of the protein
Protein name Plasminogen [Precursor]
Synonym EC 3.4.21.7
Contains Plasmin heavy chain A
Activation peptide
Angiostatin
Plasmin heavy chain A, short form
Plasmin light chain B
Gene name
Name: PLG
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASN-472.
PubMed=2318848 [NCBI, ExPASy, EBI, Israel, Japan]
Petersen T.E., Martzen M.R., Ichinose A., Davie E.W.;
"Characterization of the gene for human plasminogen, a key proenzyme in the fibrinolytic system.";
J. Biol. Chem. 265:6104-6111(1990).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
DOI=10.1016/0014-5793(87)81501-6; PubMed=3030813 [NCBI, ExPASy, EBI, Israel, Japan]
Forsgren M., Raden B., Israelsson M., Larsson K., Heden L.-O.;
"Molecular cloning and characterization of a full-length cDNA clone for human plasminogen.";
FEBS Lett. 213:254-260(1987).
[3]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Liver;
Browne M.J., Chapman C.G., Dodd I., Carey J.E., Lawrence G.M.P., Mitchell D., Robinson J.H.;
"Expression of recombinant human plasminogen and aglycoplasminogen in HeLa cells.";
Submitted (OCT-1991) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LYS-57; GLN-133; HIS-261; TRP-408; ASN-472; VAL-494 AND TRP-523.
SeattleSNPs program for genomic applications;
Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature02055; PubMed=14574404 [NCBI, ExPASy, EBI, Israel, Japan]
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
"The DNA sequence and analysis of human chromosome 6.";
Nature 425:805-811(2003).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASP-676.
TISSUE=Kidney;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
PROTEIN SEQUENCE OF 20-810, AND VARIANT ASN-472.
Sottrup-Jensen L., Petersen T.E., Magnusson S.;
Submitted (JUL-1977) to the PIR data bank.
[8]
PROTEIN SEQUENCE OF 20-100.
PubMed=122932 [NCBI, ExPASy, EBI, Israel, Japan]
Wiman B., Wallen P.;
"Structural relationship between 'glutamic acid' and 'lysine' forms of human plasminogen and their interaction with the NH2-terminal activation peptide as studied by affinity chromatography.";
Eur. J. Biochem. 50:489-494(1975).
[9]
PROTEIN SEQUENCE OF 95-580; 581-626; 657-700 AND 732-810, AND VARIANT ASN-472.
Sottrup-Jensen L., Claeys H., Zajdel M., Petersen T.E., Magnusson S.;
"The primary structure of human plasminogen.";
(In) Davidson J.F., Rowan R.M., Samama M.M., Desnoyers P.C. (eds.); Progress in chemical fibrinolysis and thrombolysis, pp.3:191-209, Raven Press, New York (1978).
[10]
NUCLEOTIDE SEQUENCE [MRNA] OF 292-810.
DOI=10.1021/bi00313a035; PubMed=6148961 [NCBI, ExPASy, EBI, Israel, Japan]
Malinowski D.P., Sadler J.E., Davie E.W.;
"Characterization of a complementary deoxyribonucleic acid coding for human and bovine plasminogen.";
Biochemistry 23:4243-4250(1984).
[11]
PROTEIN SEQUENCE OF 483-604.
PubMed=126863 [NCBI, ExPASy, EBI, Israel, Japan]
Wiman B., Wallen P.;
"Amino-acid sequence of the cyanogen-bromide fragment from human plasminogen that forms the linkage between the plasmin chains.";
Eur. J. Biochem. 58:539-547(1975).
[12]
PROTEIN SEQUENCE OF 581-810.
PubMed=142009 [NCBI, ExPASy, EBI, Israel, Japan]
Wiman B.;
"Primary structure of the B-chain of human plasmin.";
Eur. J. Biochem. 76:129-137(1977).
[13]
ACTIVE SITE.
PubMed=4694729 [NCBI, ExPASy, EBI, Israel, Japan]
Robbins K.C., Bernabe P., Arzadon L., Summaria L.;
"The primary structure of human plasminogen. II. The histidine loop of human plasmin: light (B) chain active center histidine sequence.";
J. Biol. Chem. 248:1631-1633(1973).
[14]
ACTIVE SITE.
PubMed=4240117 [NCBI, ExPASy, EBI, Israel, Japan]
Groskopf W.R., Summaria L., Robbins K.C.;
"Studies on the active center of human plasmin. Partial amino acid sequence of a peptide containing the active center serine residue.";
J. Biol. Chem. 244:3590-3597(1969).
[15]
OMEGA-AMINOCARBOXYLIC ACID-BINDING SITES.
PubMed=6919539 [NCBI, ExPASy, EBI, Israel, Japan]
Trexler M., Vali Z., Patthy L.;
"Structure of the omega-aminocarboxylic acid-binding sites of human plasminogen. Arginine 70 and aspartic acid 56 are essential for binding of ligand by kringle 4.";
J. Biol. Chem. 257:7401-7406(1982).
[16]
FIBRIN AND OMEGA-AMINOCARBOXYLIC ACID BINDING SITES.
PubMed=6094526 [NCBI, ExPASy, EBI, Israel, Japan]
Vali Z., Patthy L.;
"The fibrin-binding site of human plasminogen. Arginines 32 and 34 are essential for fibrin affinity of the kringle 1 domain.";
J. Biol. Chem. 259:13690-13694(1984).
[17]
PHOSPHORYLATION AT SER-597.
DOI=10.1021/bi970328d; PubMed=9201958 [NCBI, ExPASy, EBI, Israel, Japan]
Wang H., Prorok M., Bretthauer R.K., Castellino F.J.;
"Serine-578 is a major phosphorylation locus in human plasma plasminogen.";
Biochemistry 36:8100-8106(1997).
[18]
STRUCTURE OF CARBOHYDRATES.
PubMed=3356193 [NCBI, ExPASy, EBI, Israel, Japan]
Marti T., Schaller J., Rickli E.E., Schmid K., Kamerling J.P., Gerwig G.J., van Halbeek H., Vliegenthart J.F.;
"The N- and O-linked carbohydrate chains of human, bovine and porcine plasminogen. Species specificity in relation to sialylation and fucosylation patterns.";
Eur. J. Biochem. 173:57-63(1988).
[19]
GLYCOSYLATION AT SER-268.
DOI=10.1074/jbc.272.11.7408; PubMed=9054441 [NCBI, ExPASy, EBI, Israel, Japan]
Pirie-Shepherd S.R., Stevens R.D., Andon N.L., Enghild J.J., Pizzo S.V.;
"Evidence for a novel O-linked sialylated trisaccharide on Ser-248 of human plasminogen 2.";
J. Biol. Chem. 272:7408-7411(1997).
[20]
CHARACTERIZATION OF ANGIOSTATIN, AND PARTIAL PROTEIN SEQUENCE.
DOI=10.1016/0092-8674(94)90200-3; PubMed=7525077 [NCBI, ExPASy, EBI, Israel, Japan]
O'Reilly M.S., Holmgren L., Shing Y., Chen C., Rosenthal R.A., Moses M., Lane W.S., Cao Y., Sage E.H., Folkman J.;
"Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma.";
Cell 79:315-328(1994).
[21]
CHARACTERIZATION OF ANGIOSTATIN.
PubMed=9102221 [NCBI, ExPASy, EBI, Israel, Japan]
Sim B.K., O'Reilly M.S., Liang H., Fortier A.H., He W., Madsen J.W., Lapcevich R., Nacy C.A.;
"A recombinant human angiostatin protein inhibits experimental primary and metastatic cancer.";
Cancer Res. 57:1329-1334(1997).
[22]
PROTEOLYTIC CLEAVAGE.
DOI=10.1021/bi9731798; PubMed=9548733 [NCBI, ExPASy, EBI, Israel, Japan]
Lijnen H.R., Ugwu F., Bini A., Collen D.;
"Generation of an angiostatin-like fragment from plasminogen by stromelysin-1 (MMP-3).";
Biochemistry 37:4699-4702(1998).
[23]
INTERACTION WITH CSPG4, AND DOMAIN.
DOI=10.1074/jbc.M002290200; PubMed=10889192 [NCBI, ExPASy, EBI, Israel, Japan]
Goretzki L., Lombardo C.R., Stallcup W.B.;
"Binding of the NG2 proteoglycan to kringle domains modulates the functional properties of angiostatin and plasmin(ogen).";
J. Biol. Chem. 275:28625-28633(2000).
[24]
INTERACTION WITH AMOT.
DOI=10.1074/jbc.M503915200; PubMed=16043488 [NCBI, ExPASy, EBI, Israel, Japan]
Bratt A., Birot O., Sinha I., Veitonmaeki N., Aase K., Ernkvist M., Holmgren L.;
"Angiomotin regulates endothelial cell-cell junctions and cell motility.";
J. Biol. Chem. 280:34859-34869(2005).
[25]
X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 374-461.
DOI=10.1021/bi00107a029; PubMed=1657148 [NCBI, ExPASy, EBI, Israel, Japan]
Mulichak A.M., Tulinsky A., Ravichandran K.G.;
"Crystal and molecular structure of human plasminogen kringle 4 refined at 1.9-A resolution.";
Biochemistry 30:10576-10588(1991).
[26]
X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 374-461.
DOI=10.1021/bi00107a030; PubMed=1657149 [NCBI, ExPASy, EBI, Israel, Japan]
Wu T.-P., Padmanabhan K., Tulinsky A., Mulichak A.M.;
"The refined structure of the epsilon-aminocaproic acid complex of human plasminogen kringle 4.";
Biochemistry 30:10589-10594(1991).
[27]
X-RAY CRYSTALLOGRAPHY (2.48 ANGSTROMS) OF 101-181.
PubMed=8054447 [NCBI, ExPASy, EBI, Israel, Japan]
Wu T.-P., Padmanabhan K.P., Tulinsky A.;
"The structure of recombinant plasminogen kringle 1 and the fibrin binding site.";
Blood Coagul. Fibrinolysis 5:157-166(1994).
[28]
X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 102-181.
DOI=10.1021/bi9521351; PubMed=8611560 [NCBI, ExPASy, EBI, Israel, Japan]
Mathews I.I., Vanderhoff-Hanaver P., Castellino F.J., Tulinsky A.;
"Crystal structures of the recombinant kringle 1 domain of human plasminogen in complexes with the ligands epsilon-aminocaproic acid and trans-4-(aminomethyl)cyclohexane-1-carboxylic Acid.";
Biochemistry 35:2567-2576(1996).
[29]
X-RAY CRYSTALLOGRAPHY (1.67 ANGSTROMS) OF 376-454.
DOI=10.1107/S0907444996012267; PubMed=15299951 [NCBI, ExPASy, EBI, Israel, Japan]
Stec B., Yamano A., Whitlow M., Teeter M.M.;
"Structure of human plasminogen kringle 4 at 1.68 Angstrom and 277 K. A possible structural role of disordered residues.";
Acta Crystallogr. D 53:169-178(1997).
[30]
X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 561-810, AND DISULFIDE BONDS.
DOI=10.1038/2359; PubMed=9783753 [NCBI, ExPASy, EBI, Israel, Japan]
Parry M.A., Fernandez-Catalan C., Bergner A., Huber R., Hopfner K.P., Schlott B., Guehrs K.H., Bode W.;
"The ternary microplasmin-staphylokinase-microplasmin complex is a proteinase-cofactor-substrate complex in action.";
Nat. Struct. Biol. 5:917-923(1998).
[31]
X-RAY CRYSTALLOGRAPHY (1.66 ANGSTROMS) OF 480-563.
DOI=10.1021/bi972284e; PubMed=9521645 [NCBI, ExPASy, EBI, Israel, Japan]
Chang Y., Mochalkin I., McCance S.G., Cheng B., Tulinsky A., Castellino F.J.;
"Structure and ligand binding determinants of the recombinant kringle 5 domain of human plasminogen.";
Biochemistry 37:3258-3271(1998).
[32]
X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 564-810, AND DISULFIDE BONDS.
DOI=10.1006/jmbi.1999.3397; PubMed=10656799 [NCBI, ExPASy, EBI, Israel, Japan]
Wang X., Terzyan S., Tang J., Loy J.A., Lin X., Zhang X.C.;
"Human plasminogen catalytic domain undergoes an unusual conformational change upon activation.";
J. Mol. Biol. 295:903-914(2000).
[33]
X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 183-262.
DOI=10.1006/jmbi.2001.4646; PubMed=11350170 [NCBI, ExPASy, EBI, Israel, Japan]
Rios-Steiner J.L., Schenone M., Mochalkin I., Tulinsky A., Castellino F.J.;
"Structure and binding determinants of the recombinant kringle-2 domain of human plasminogen to an internal peptide from a group A Streptococcal surface protein.";
J. Mol. Biol. 308:705-719(2001).
[34]
X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 100-352, AND DISULFIDE BONDS.
DOI=10.1016/S0022-2836(02)00211-5; PubMed=12054798 [NCBI, ExPASy, EBI, Israel, Japan]
Abad M.C., Arni R.K., Grella D.K., Castellino F.J., Tulinsky A., Geiger J.H.;
"The X-ray crystallographic structure of the angiogenesis inhibitor angiostatin.";
J. Mol. Biol. 318:1009-1017(2002).
[35]
X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 562-810.
DOI=10.1093/protein/15.9.753; PubMed=12456874 [NCBI, ExPASy, EBI, Israel, Japan]
Wakeham N., Terzyan S., Zhai P., Loy J.A., Tang J., Zhang X.C.;
"Effects of deletion of streptokinase residues 48-59 on plasminogen activation.";
Protein Eng. 15:753-761(2002).
[36]
X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 564-810.
DOI=10.1002/prot.20070; PubMed=15211511 [NCBI, ExPASy, EBI, Israel, Japan]
Terzyan S., Wakeham N., Zhai P., Rodgers K., Zhang X.C.;
"Characterization of Lys-698-to-Met substitution in human plasminogen catalytic domain.";
Proteins 56:277-284(2004).
[37]
STRUCTURE BY NMR OF 374-461.
DOI=10.1016/0022-2836(90)90330-O; PubMed=2157850 [NCBI, ExPASy, EBI, Israel, Japan]
Atkinson R.A., Williams R.J.P.;
"Solution structure of the kringle 4 domain from human plasminogen by 1H nuclear magnetic resonance spectroscopy and distance geometry.";
J. Mol. Biol. 212:541-552(1990).
[38]
STRUCTURE BY NMR OF 96-184.
PubMed=8181475 [NCBI, ExPASy, EBI, Israel, Japan]
Rejante M.R., Llinas M.;
"1H-NMR assignments and secondary structure of human plasminogen kringle 1.";
Eur. J. Biochem. 221:927-937(1994).
[39]
STRUCTURE BY NMR OF 96-184.
PubMed=8181476 [NCBI, ExPASy, EBI, Israel, Japan]
Rejante M.R., Llinas M.;
"Solution structure of the epsilon-aminohexanoic acid complex of human plasminogen kringle 1.";
Eur. J. Biochem. 221:939-949(1994).
[40]
STRUCTURE BY NMR OF 183-354.
DOI=10.1021/bi9520949; PubMed=8652577 [NCBI, ExPASy, EBI, Israel, Japan]
Soehndel S., Hu C.-K., Marti D., Affolter M., Schaller J., Llinas M., Rickli E.E.;
"Recombinant gene expression and 1H NMR characteristics of the kringle (2 + 3) supermodule: spectroscopic/functional individuality of plasminogen kringle domains.";
Biochemistry 35:2357-2364(1996).
[41]
STRUCTURE BY NMR OF 183-263.
DOI=10.1021/bi971316v; PubMed=9305949 [NCBI, ExPASy, EBI, Israel, Japan]
Marti D.N., Hu C.K., An S.S., von Haller P., Schaller J., Llinas M.;
"Ligand preferences of kringle 2 and homologous domains of human plasminogen: canvassing weak, intermediate, and high-affinity binding sites by 1H-NMR.";
Biochemistry 36:11591-11604(1997).
[42]
VARIANTS THROMBOPHILIA PHE-374 AND THR-620.
PubMed=1986355 [NCBI, ExPASy, EBI, Israel, Japan]
Ichinose A., Espling E.S., Takamatsu J., Saito H., Shinmyozu K., Maruyama I., Petersen T.E., Davie E.W.;
"Two types of abnormal genes for plasminogen in families with a predisposition for thrombosis.";
Proc. Natl. Acad. Sci. U.S.A. 88:115-119(1991).
[43]
ERRATUM.
Ichinose A., Espling E.S., Takamatsu J., Saito H., Shinmyozu K., Maruyama I., Petersen T.E., Davie E.W.;
Proc. Natl. Acad. Sci. U.S.A. 88:2067-2067(1991).
[44]
VARIANT THROMBOPHILIA PRO-591.
PubMed=8392398 [NCBI, ExPASy, EBI, Israel, Japan]
Azuma H., Uno Y., Shigekiyo T., Saito S.;
"Congenital plasminogen deficiency caused by a Ser-572 to Pro mutation.";
Blood 82:475-480(1993).
[45]
VARIANT THROMBOPHILIA THR-620.
PubMed=6216475 [NCBI, ExPASy, EBI, Israel, Japan]
Miyata T., Iwanaga S., Sakata Y., Aoki N.;
"Plasminogen Tochigi: inactive plasmin resulting from replacement of alanine-600 by threonine in the active site.";
Proc. Natl. Acad. Sci. U.S.A. 79:6132-6136(1982).
[46]
VARIANT THROMBOPHILIA THR-620.
PubMed=6238949 [NCBI, ExPASy, EBI, Israel, Japan]
Miyata T., Iwanaga S., Sakata Y., Aoki N., Takamatsu J., Kamiya T.;
"Plasminogens Tochigi II and Nagoya: two additional molecular defects with Ala-600-->Thr replacement found in plasmin light chain variants.";
J. Biochem. 96:277-287(1984).
[47]
VARIANT THROMBOPHILIA THR-620.
DOI=10.1007/BF00210737; PubMed=1427790 [NCBI, ExPASy, EBI, Israel, Japan]
Kikuchi S., Yamanouchi Y., Li L., Kobayashi K., Ijima H., Miyazaki R., Tsuchiya S., Hamaguchi H.;
"Plasminogen with type-I mutation is polymorphic in the Japanese population.";
Hum. Genet. 90:7-11(1992).
[48]
VARIANT LIGNEOUS CONJUNCTIVITIS HIS-235.
PubMed=9242524 [NCBI, ExPASy, EBI, Israel, Japan]
Schuster V., Mingers A.-M., Seidenspinner S., Nuessgens Z., Pukrop T., Kreth H.W.;
"Homozygous mutations in the plasminogen gene of two unrelated girls with ligneous conjunctivitis.";
Blood 90:958-966(1997).
[49]
VARIANT KANAGAWA-1 ARG-751.
DOI=10.1046/j.1365-2141.1998.01074.x; PubMed=9858247 [NCBI, ExPASy, EBI, Israel, Japan]
Higuchi Y., Furihata K., Ueno I., Ishikawa S., Okumura N., Tozuka M., Sakurai N.;
"Plasminogen Kanagawa-I, a novel missense mutation, is caused by the amino acid substitution G732R.";
Br. J. Haematol. 103:867-870(1998).
[50]
VARIANTS LIGNEOUS CONJONCTIVITIS GLU-38; PRO-147 AND HIS-532.
PubMed=10233898 [NCBI, ExPASy, EBI, Israel, Japan]
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).
Comments
  • FUNCTION: Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation; in ovulation it weakens the walls of the Graafian follicle. It activates the urokinase-type plasminogen activator, collagenases and several complement zymogens, such as C1 and C5. It cleaves fibrin, fibronectin, thrombospondin, laminin and von Willebrand factor. Its role in tissue remodeling and tumor invasion may be modulated by CSPG4.
  • FUNCTION: Angiostatin is an angiogenesis inhibitor that blocks neovascularization and growth of experimental primary and metastatic tumors in vivo.
  • CATALYTIC ACTIVITY: Preferential cleavage: Lys-|-Xaa > Arg-|-Xaa; higher selectivity than trypsin. Converts fibrin into soluble products.
  • ENZYME REGULATION: Converted into plasmin by plasminogen activators, both plasminogen and its activator being bound to fibrin. Activated with catalytic amounts of streptokinase.
  • SUBUNIT: Interacts with AMOT and CSPG4 (also true for angiostatin).
  • INTERACTION:
    Q6V4K9:- (xeno); NbExp=1; IntAct=EBI-999394, EBI-984399;
    Q6V4L1:- (xeno); NbExp=2; IntAct=EBI-999394, EBI-984250;
    Q6V4L4:- (xeno); NbExp=2; IntAct=EBI-999394, EBI-984286;
    Q6V4L5:- (xeno); NbExp=2; IntAct=EBI-999394, EBI-984118;
    Q6V4L9:- (xeno); NbExp=2; IntAct=EBI-999394, EBI-984197;
    P00779:skc (xeno); NbExp=1; IntAct=EBI-999394, EBI-1035089;
  • SUBCELLULAR LOCATION: Secreted.
  • TISSUE SPECIFICITY: Present in plasma and many other extracellular fluids. It is synthesized in the kidney.
  • DOMAIN: Kringle domains mediate interaction with CSPG4.
  • PTM: N-linked glycan contains N-acetyllactosamine and sialic acid. O-linked glycans consist of Gal-GalNAc disaccharide modified with up to 2 sialic acid residues (microheterogeneity).
  • PTM: In the presence of the inhibitor, the activation involves only cleavage after Arg-580, yielding two chains held together by two disulfide bonds. In the absence of the inhibitor, the activation involves additionally the removal of the activation peptide.
  • DISEASE: Defects in PLG are a cause of thrombophilia [MIM:188050]; a form of recurrent thrombosis.
  • DISEASE: Defects in PLG may be associated with ligneous conjunctivitis [MIM:217090]. Ligneous conjunctivitis is an unusual and rare form of chronic conjunctivitis, characterized by chronic tearing and redness of the conjunctivae. Initially, pseudomembranes form on the palpebral surfaces which then progress to thick nodular masses that replace the normal mucosa. Because the pseudomembranes have a woodlike consistency, the disease is termed "ligneous" conjunctivitis. The disease may be associated with pseudomembranous lesions of other mucous membranes in the mouth, nasopharynx, trachea, and female genital tract.
  • MISCELLANEOUS: Plasmin is inactivated by alpha-2-antiplasmin immediately after dissociation from the clot.
  • SIMILARITY: Belongs to the peptidase S1 family. Plasminogen subfamily [view classification].
  • SIMILARITY: Contains 5 kringle domains.
  • SIMILARITY: Contains 1 PAN domain.
  • SIMILARITY: Contains 1 peptidase S1 domain [view classification].
  • WEB RESOURCE: Name=Wikipedia; Note=Plasmin entry; URL="http://en.wikipedia.org/wiki/Plasmin";.
  • WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/plg/";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
M34276; AAA60113.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M33272; AAA60113.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M33274; AAA60113.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M33275; AAA60113.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M33278; AAA60113.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M33279; AAA60113.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M33280; AAA60113.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M33282; AAA60113.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M33283; AAA60113.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M33284; AAA60113.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M33285; AAA60113.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M33286; AAA60113.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M33287; AAA60113.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M33288; AAA60113.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M33289; AAA60113.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M33290; AAA60113.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M34272; AAA60113.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M34273; AAA60113.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M34275; AAA60113.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X05199; CAA28831.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M74220; AAA36451.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AY192161; AAN85555.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL109933; CAI22908.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC060513; AAH60513.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
K02922; AAA60124.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A35229; PLHU.
RefSeq NP_000292.1; -.
UniGene Hs.143436
3D structure databases
PDB
1B2I; NMR; -; A=183-263.[ExPASy / RCSB / EBI]
1BML; X-ray; 2.90 A; A/B=561-810.[ExPASy / RCSB / EBI]
1BUI; X-ray; 2.65 A; A/B=561-810.[ExPASy / RCSB / EBI]
1CEA; X-ray; 2.06 A; A/B=100-187.[ExPASy / RCSB / EBI]
1CEB; X-ray; 2.07 A; A/B=100-187.[ExPASy / RCSB / EBI]
1DDJ; X-ray; 2.00 A; A/B/C/D=564-810.[ExPASy / RCSB / EBI]
1HPJ; NMR; -; A=103-181.[ExPASy / RCSB / EBI]
1HPK; NMR; -; A=103-181.[ExPASy / RCSB / EBI]
1I5K; X-ray; 2.70 A; A/B=183-262.[ExPASy / RCSB / EBI]
1KI0; X-ray; 1.75 A; A=100-352.[ExPASy / RCSB / EBI]
1KRN; X-ray; 1.67 A; A=374-461.[ExPASy / RCSB / EBI]
1L4D; X-ray; 2.30 A; A=562-810.[ExPASy / RCSB / EBI]
1L4Z; X-ray; 2.80 A; A=563-810.[ExPASy / RCSB / EBI]
1PK4; X-ray; 1.90 A; A=376-454.[ExPASy / RCSB / EBI]
1PKR; X-ray; 2.48 A; A=101-181.[ExPASy / RCSB / EBI]
1PMK; X-ray; 2.25 A; A/B=374-461.[ExPASy / RCSB / EBI]
1QRZ; X-ray; 2.00 A; A/B/C/D=565-810.[ExPASy / RCSB / EBI]
1RJX; X-ray; 2.30 A; B=564-810.[ExPASy / RCSB / EBI]
2DOH; X-ray; 2.30 A; X=100-333.[ExPASy / RCSB / EBI]
2DOI; X-ray; 3.10 A; A/X=100-333.[ExPASy / RCSB / EBI]
2PK4; X-ray; 2.25 A; A=375-454.[ExPASy / RCSB / EBI]
5HPG; X-ray; 1.66 A; A/B=480-563.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1B2I; -.
1BML; -.
1BUI; -.
1CEA; -.
1CEB; -.
1DDJ; -.
1HPJ; -.
1HPK; -.
1I5K; -.
1KI0; -.
1KRN; -.
1L4D; -.
1L4Z; -.
1PK4; -.
1PKR; -.
1PMK; -.
1QRZ; -.
1RJX; -.
2DOH; -.
2DOI; -.
2PK4; -.
5HPG; -.
DisProt DP00191; -.
ModBase P00747.
Protein-protein interaction databases
IntAct P00747; -.
Protein family/group databases
MEROPS S01.233; -.
PTM databases
GlycoSuiteDB P00747; -.
PhosphoSite P00747; -.
Enzyme and pathway databases
BioCyc MetaCyc:MON-12950; -.
Reactome REACT_604; Hemostasis.
2D gel databases
SWISS-2DPAGE P00747; -.
Organism-specific databases
H-InvDB HIX0032909; -.
HGNC HGNC:9071; PLG.
GenAtlas PLG.
HPA CAB000668; -.
CAB016678; -.
MIM 173350; gene+phenotype. [NCBI / EBI]
188050; phenotype. [NCBI / EBI]
217090; phenotype. [NCBI / EBI]
Orphanet 722; Hypoplasminogenemia.
PharmGKB PA33405; -.
GeneCards P00747.
Gene expression databases
ArrayExpress P00747; -.
CleanEx HS_PLG; -.
GermOnline ENSG00000122194; Homo sapiens.
Ontologies
GO
GO:0005615; Cellular component: extracellular space (inferred from direct assay from HGNC).
GO:0034185; Molecular function: apolipoprotein binding (inferred from physical interaction from UniProtKB).
GO:0004283; Molecular function: plasmin activity (traceable author statement from ProtInc).
GO:0006917; Biological process: induction of apoptosis (traceable author statement from HGNC).
GO:0016525; Biological process: negative regulation of angiogenesis (traceable author statement from HGNC).
GO:0043537; Biological process: negative regulation of blood vessel endothelial cell migration (traceable author statement from HGNC).
GO:0008285; Biological process: negative regulation of cell proliferation (traceable author statement from ProtInc).
GO:0051918; Biological process: negative regulation of fibrinolysis (inferred from direct assay from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR000001; Kringle.
IPR003014; PAN.
IPR003609; Pan_app.
IPR011358; Pept_S1A_Plasmin.
IPR001254; Peptidase_S1_S6.
IPR001314; Peptidase_S1A.
IPR003966; Peptidase_S1A_prothrombin.
Graphical view of domain structure.
Gene3D G3DSA:2.40.20.10; Kringle; 5.
Pfam PF00051; Kringle; 5.
PF00024; PAN_1; 1.
PF00089; Trypsin; 1.
Pfam graphical view of domain structure.
PIRSF PIRSF001150; Plasmin; 1.
PRINTS PR00722; CHYMOTRYPSIN.
PR00018; KRINGLE.
PR01505; PROTHROMBIN.
ProDom PD000395; Kringle; 5.
[Domain structure / List of seq. sharing at least 1 domain]
SMART SM00130; KR; 5.
SM00473; PAN_AP; 1.
SM00020; Tryp_SPc; 1.
SMART graphical view of domain structure.
PROSITE PS00021; KRINGLE_1; 5.
PS50070; KRINGLE_2; 5.
PS50948; PAN; 1.
PS50240; TRYPSIN_DOM; 1.
PS00134; TRYPSIN_HIS; 1.
PS00135; TRYPSIN_SER; 1.
PROSITE graphical view of domain structure (profiles).
BLOCKS</