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Plasminogen

ID 234
Name Plasminogen
Synonyms
  • EC 3.4.21.7
  • Plasminogen precursor
Gene Name PLG
Protein Sequence
>Plasminogen precursor
MEHKEVVLLLLLFLKSGQGEPLDDYVNTQGASLFSVTKKQLGAGSIEECAAKCEEDEEFT
CRAFQYHSKEQQCVIMAENRKSSIIIRMRDVVLFEKKVYLSECKTGNGKNYRGTMSKTKN
GITCQKWSSTSPHRPRFSPATHPSEGLEENYCRNPDNDPQGPWCYTTDPEKRYDYCDILE
CEEECMHCSGENYDGKISKTMSGLECQAWDSQSPHAHGYIPSKFPNKNLKKNYCRNPDRE
LRPWCFTTDPNKRWELCDIPRCTTPPPSSGPTYQCLKGTGENYRGNVAVTVSGHTCQHWS
AQTPHTHNRTPENFPCKNLDENYCRNPDGKRAPWCHTTNSQVRWEYCKIPSCDSSPVSTE
QLAPTAPPELTPVVQDCYHGDGQSYRGTSSTTTTGKKCQSWSSMTPHRHQKTPENYPNAG
LTMNYCRNPDADKGPWCFTTDPSVRWEYCNLKKCSGTEASVVAPPPVVLLPDVETPSEED
CMFGNGKGYRGKRATTVTGTPCQDWAAQEPHRHSIFTPETNPRAGLEKNYCRNPDGDVGG
PWCYTTNPRKLYDYCDVPQCAAPSFDCGKPQVEPKKCPGRVVGGCVAHPHSWPWQVSLRT
RFGMHFCGGTLISPEWVLTAAHCLEKSPRPSSYKVILGAHQEVNLEPHVQEIEVSRLFLE
PTRKDIALLKLSSPAVITDKVIPACLPSPNYVVADRTECFITGWGETQGTFGAGLLKEAQ
LPVIENKVCNRYEFLNGRVQSTELCAGHLAGGTDSCQGDSGGPLVCFEKDKYILQGVTSW
GLGCARPNKPGVYVRVSRFVTWIEGVMRNN
Number of Residues 810
Molecular Weight 90569
Theoretical pI 7.25
GO Classification
Function
binding
calcium ion binding
catalytic activity
peptidase activity
ion binding
endopeptidase activity
cation binding
serine-type endopeptidase activity
hydrolase activity
plasmin activity
Process
organismal physiological process
regulation of body fluids
hemostasis
blood coagulation
physiological process
metabolism
proteolysis
macromolecule metabolism
protein metabolism
cellular protein metabolism
General Function Involved in plasmin activity
Specific Function Angiostatin is an angiogenesis inhibitor that blocks neovascularization and growth of experimental primary and metastatic tumors in vivo
Pathways
Name SMPDB Link KEGG Link
Warfarin Pathway SMP00268
Acenocoumarol Pathway SMP00269
Dicumarol Pathway SMP00270
Phenprocoumon Pathway SMP00271
Enoxaparin Pathway SMP00272
Fondaparinux Pathway SMP00273
Heparin Pathway SMP00274
Ardeparin Pathway SMP00275
Argatroban Pathway SMP00276
Bivalirudin Pathway SMP00277
Lepirudin Pathway SMP00278
Ximelagatran Pathway SMP00279
Alteplase Pathway SMP00280
Anistreplase Pathway SMP00281
Streptokinase Pathway SMP00282
Tenecteplase Pathway SMP00283
Urokinase Pathway SMP00284
Reteplase Pathway SMP00285
Aminocaproic Acid Pathway SMP00286
Tranexamic Acid Pathway SMP00287
Aprotinin Pathway SMP00288
Reactions
  • Preferential cleavage: Lys! > Arg!
  • higher selectivity than trypsin. Converts fibrin into soluble products
Pfam Domain Function
Signals 1-19
Transmembrane Regions None
Essentiality Non-Essential
GenBank Protein ID 387026 Link_out
UniProtKB ID P00747 Link_out
UniProtKB Entry Name PLMN_HUMAN Link_out
PDB ID 1KI0 Link_out
PDB File show
3D Structure View 3D Structure
Cellular Location Secreted protein
Gene Sequence
>2433 bp
ATGGAACATAAGGAAGTGGTTCTTCTACTTCTTTTATTTCTGAAATCAGGTCAAGGAGAG
CCTCTGGATGACTATGTGAATACCCAGGGGGCTTCACTGTTCAGTGTCACTAAGAAGCAG
CTGGGAGCAGGAAGTATAGAAGAATGTGCAGCAAAATGTGAGGAGGACGAAGAATTCACC
TGCAGGGCATTCCAATATCACAGTAAAGAGCAACAATGTGTGATAATGGCTGAAAACAGG
AAGTCCTCCATAATCATTAGGATGAGAGATGTAGTTTTATTTGAAAAGAAAGTGTATCTC
TCAGAGTGCAAGACTGGGAATGGAAAGAATTACAGAGGGACGATGTCCAAAACAAAAAAT
GGCATCACCTGTCAAAAATGGAGTTCCACTTCTCCCCACAGACCTAGATTCTCACCTGCT
ACACACCCCTCAGAGGGACTGGAGGAGAACTACTGCAGGAATCCAGACAACGATCCGCAG
GGGCCCTGGTGCTATACTACTGATCCAGAAAAGAGATATGACTACTGCGACATTCTTGAG
TGTGAAGAGGAATGTATGCATTGCAGTGGAGAAAACTATGACGGCAAAATTTCCAAGACC
ATGTCTGGACTGGAATGCCAGGCCTGGGACTCTCAGAGCCCACACGCTCATGGATACATT
CCTTCCAAATTTCCAAACAAGAACCTGAAGAAGAATTACTGTCGTAACCCCGATAGGGAG
CTGCGGCCTTGGTGTTTCACCACCGACCCCAACAAGCGCTGGGAACTTTGCGACATCCCC
CGCTGCACAACACCTCCACCATCTTCTGGTCCCACCTACCAGTGTCTGAAGGGAACAGGT
GAAAACTATCGCGGGAATGTGGCTGTTACCGTGTCCGGGCACACCTGTCAGCACTGGAGT
GCACAGACCCCTCACACACATAACAGGACACCAGAAAACTTTCCCTGCAAAAATTTGGAT
GAAAACTACTGCCGCAATCCTGACGGAAAAAGGGCCCCATGGTGCCATACAACCAACAGC
CAAGTGCGGTGGGAGTACTGTAAGATACCGTCCTGTGACTCCTCCCCAGTATCCACGGAA
CAATTGGCTCCCACAGCACCACCTGAGCTAACCCCTGTGGTCCAGGACTGCTACCATGGT
GATGGACAGAGCTACCGAGGCACATCCTCCACCACCACCACAGGAAAGAAGTGTCAGTCT
TGGTCATCTATGACACCACACCGGCACCAGAAGACCCCAGAAAACTACCCAAATGCTGGC
CTGACAATGAACTACTGCAGGAATCCAGATGCCGATAAAGGCCCCTGGTGTTTTACCACA
GACCCCAGCGTCAGGTGGGAGTACTGCAACCTGAAAAAATGCTCAGGAACAGAAGCGAGT
GTTGTAGCACCTCCGCCTGTTGTCCTGCTTCCAAATGTAGAGACTCCTTCCGAAGAAGAC
TGTATGTTTGGGAATGGGAAAGGATACCGAGGCAAGAGGGCGACCACTGTTACTGGGACG
CCATGCCAGGACTGGGCTGCCCAGGAGCCCCATAGACACAGCATTTTCACTCCAGAGACA
AATCCACGGGCGGGTCTGGAAAAAAATTACTGCCGTAACCCTGATGGTGATGTAGGTGGT
CCCTGGTGCTACACGACAAATCCAAGAAAACTTTACGACTACTGTGATGTCCCTCAGTGT
GCGGCCCCTTCATTTGATTGTGGGAAGCCTCAAGTGGAGCCGAAGAAATGTCCTGGAAGG
GTTGTAGGGGGGTGTGTGGCCCACCCACATTCCTGGCCCTGGCAAGTCAGTCTTAGAACA
AGGTTTGGAATGCACTTCTGTGGAGGCACCTTGATATCCCCAGAGTGGGTGTTGACTGCT
GCCCACTGCTTGGAGAAGTCCCCAAGGCCTTCATCCTACAAGGTCATCCTGGGTGCACAC
CAAGAAGTGAATCTCGAACCGCATGTTCAGGAAATAGAAGTGTCTAGGCTGTTCTTGGAG
CCCACACGAAAAGATATTGCCTTGCTAAAGCTAAGCAGTCCTGCCGTCATCACTGACAAA
GTAATCCCAGCTTGTCTGCCATCCCCAAATTATGTGGTCGCTGACCGGACCGAATGTTTC
ATCACTGGCTGGGGAGAAACCCAAGGTACTTTTGGAGCTGGCCTTCTCAAGGAAGCCCAG
CTCCCTGTGATTGAGAATAAAGTGTGCAATCGCTATGAGTTTCTGAATGGAAGAGTCCAA
TCCACCGAACTCTGTGCTGGGCATTTGGCCGGAGGCACTGACAGTTGCCAGGGTGACAGT
GGAGGGCCTCTGGTTTGCTTCGAGAAGGACAAATACATTTTACAAGGAGTCACTTCTTGG
GGTCTTGGCTGTGCACGCCCCAATAAGCCTGGTGTCTATGTTCGTGTTTCAAGGTTTGTT
ACTTGGATTGAGGGAGTGATGAGAAATAATTAA
GenBank Gene ID X05199 Link_out
GeneCard ID PLG Link_out
GenAtlas ID PLG Link_out
HGNC ID HGNC:9071 Link_out
HPRD ID 01417
IUPHAR ID Not Available
Guide to Pharmacology ID Not Available
Chromosome Location Not Available
Locus 6q26
SNPs PLG Link_out
General References
  1. Petersen TE, Martzen MR, Ichinose A, Davie EW: Characterization of the gene for human plasminogen, a key proenzyme in the fibrinolytic system. J Biol Chem. 1990 Apr 15;265(11):6104-11. Pubmed
  2. Forsgren M, Raden B, Israelsson M, Larsson K, Heden LO: Molecular cloning and characterization of a full-length cDNA clone for human plasminogen. FEBS Lett. 1987 Mar 23;213(2):254-60. Pubmed
  3. Malinowski DP, Sadler JE, Davie EW: Characterization of a complementary deoxyribonucleic acid coding for human and bovine plasminogen. Biochemistry. 1984 Aug 28;23(18):4243-50. Pubmed
  4. 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. 1975 Jan 15;50(3):489-94. Pubmed
  5. 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. 1975 Oct 15;58(2):539-47. Pubmed
  6. Wiman B: Primary structure of the B-chain of human plasmin. Eur J Biochem. 1977 Jun 1;76(1):129-37. Pubmed
  7. Robbins KC, 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. 1973 Mar 10;248(5):1631-3. Pubmed
  8. Groskopf WR, Summaria L, Robbins KC: Studies on the active center of human plasmin. Partial amino acid sequence of a peptide containing the active center serine residue. J Biol Chem. 1969 Jul 10;244(13):3590-7. Pubmed
  9. 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. 1982 Jul 10;257(13):7401-6. Pubmed
  10. 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. 1984 Nov 25;259(22):13690-4. Pubmed
  11. Wang H, Prorok M, Bretthauer RK, Castellino FJ: Serine-578 is a major phosphorylation locus in human plasma plasminogen. Biochemistry. 1997 Jul 1;36(26):8100-6. Pubmed
  12. Marti T, Schaller J, Rickli EE, Schmid K, Kamerling JP, Gerwig GJ, van Halbeek H, Vliegenthart JF: 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. 1988 Apr 5;173(1):57-63. Pubmed
  13. Pirie-Shepherd SR, Stevens RD, Andon NL, Enghild JJ, Pizzo SV: Evidence for a novel O-linked sialylated trisaccharide on Ser-248 of human plasminogen 2. J Biol Chem. 1997 Mar 14;272(11):7408-11. Pubmed
  14. O’Reilly MS, Holmgren L, Shing Y, Chen C, Rosenthal RA, Moses M, Lane WS, Cao Y, Sage EH, Folkman J: Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell. 1994 Oct 21;79(2):315-28. Pubmed
  15. Sim BK, O’Reilly MS, Liang H, Fortier AH, He W, Madsen JW, Lapcevich R, Nacy CA: A recombinant human angiostatin protein inhibits experimental primary and metastatic cancer. Cancer Res. 1997 Apr 1;57(7):1329-34. Pubmed
  16. Mulichak AM, Tulinsky A, Ravichandran KG: Crystal and molecular structure of human plasminogen kringle 4 refined at 1.9-A resolution. Biochemistry. 1991 Oct 29;30(43):10576-88. Pubmed
  17. Wu TP, Padmanabhan K, Tulinsky A, Mulichak AM: The refined structure of the epsilon-aminocaproic acid complex of human plasminogen kringle 4. Biochemistry. 1991 Oct 29;30(43):10589-94. Pubmed
  18. Mathews II, Vanderhoff-Hanaver P, Castellino FJ, 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. 1996 Feb 27;35(8):2567-76. Pubmed
  19. Chang Y, Mochalkin I, McCance SG, Cheng B, Tulinsky A, Castellino FJ: Structure and ligand binding determinants of the recombinant kringle 5 domain of human plasminogen. Biochemistry. 1998 Mar 10;37(10):3258-71. Pubmed
  20. Rejante MR, Llinas M: 1H-NMR assignments and secondary structure of human plasminogen kringle 1. Eur J Biochem. 1994 May 1;221(3):927-37. Pubmed
  21. Rejante MR, Llinas M: Solution structure of the epsilon-aminohexanoic acid complex of human plasminogen kringle 1. Eur J Biochem. 1994 May 1;221(3):939-49. Pubmed
  22. Sohndel S, Hu CK, Marti D, Affolter M, Schaller J, Llinas M, Rickli EE: Recombinant gene expression and 1H NMR characteristics of the kringle (2 + 3) supermodule: spectroscopic/functional individuality of plasminogen kringle domains. Biochemistry. 1996 Feb 20;35(7):2357-64. Pubmed
  23. Atkinson RA, Williams RJ: Solution structure of the kringle 4 domain from human plasminogen by 1H nuclear magnetic resonance spectroscopy and distance geometry. J Mol Biol. 1990 Apr 5;212(3):541-52. Pubmed
  24. Ichinose A, Espling ES, Takamatsu J, Saito H, Shinmyozu K, Maruyama I, Petersen TE, Davie EW: Two types of abnormal genes for plasminogen in families with a predisposition for thrombosis. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):115-9. Pubmed
  25. Azuma H, Uno Y, Shigekiyo T, Saito S: Congenital plasminogen deficiency caused by a Ser572 to Pro mutation. Blood. 1993 Jul 15;82(2):475-80. Pubmed
  26. 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. 1982 Oct;79(20):6132-6. Pubmed
  27. 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 (Tokyo). 1984 Aug;96(2):277-87. Pubmed
  28. 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. 1992 Sep-Oct;90(1-2):7-11. Pubmed
  29. Schuster V, Mingers AM, Seidenspinner S, Nussgens Z, Pukrop T, Kreth HW: Homozygous mutations in the plasminogen gene of two unrelated girls with ligneous conjunctivitis. Blood. 1997 Aug 1;90(3):958-66. Pubmed
  30. 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. 1998 Dec;103(3):867-70. Pubmed
  31. Schuster V, Seidenspinner S, Zeitler P, Escher C, Pleyer U, Bernauer W, Stiehm ER, Isenberg S, Seregard S, Olsson T, Mingers AM, Schambeck C, Kreth HW: Compound-heterozygous mutations in the plasminogen gene predispose to the development of ligneous conjunctivitis. Blood. 1999 May 15;93(10):3457-66. Pubmed
Drugs
# DrugBank ID Drug Name Drug Type Drug Groups
1 DB00009 Alteplase biotech approved
2 DB00513 Aminocaproic Acid small molecule approved, investigational
3 DB00029 Anistreplase biotech approved
4 DB06692 Aprotinin biotech approved, withdrawn
5 DB03709 Bicine small molecule experimental
6 DB00015 Reteplase biotech approved
7 DB00086 Streptokinase biotech approved
8 DB00031 Tenecteplase biotech approved
9 DB00302 Tranexamic Acid small molecule approved
10 DB00013 Urokinase biotech approved, investigational