PLG (plasminogen)

Gene

• Entrez ID: 5340
• Gene name: Plasminogen
• Gene symbol: PLG
• Synonyms: HAE4
• Chromosome: 6
• Chromosome location: 6q26
• Summary: The plasminogen protein encoded by this gene is a serine protease that circulates in blood plasma as an inactive zymogen and is converted to the active protease, plasmin, by several plasminogen activators such as tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), kallikrein, and factor XII (Hageman factor). The conversion of plasminogen to plasmin involves the cleavage of the peptide bond between Arg-561 and Val-562. Plasmin cleavage also releases the angiostatin protein which inhibits angiogenesis. Plasmin degrades many blood plasma proteins, including fibrin-containing blood clots. As a serine protease, plasmin cleaves many products in addition to fibrin such as fibronectin, thrombospondin, laminin, and von Willebrand factor. Plasmin is inactivated by proteins such as alpha-2-macroglobulin and alpha-2-antiplasmin in addition to inhibitors of the various plasminogen activators. Plasminogen also interacts with plasminogen receptors which results in the retention of plasmin on cell surfaces and in plasmin-induced cell signaling. The localization of plasminogen on cell surfaces plays a role in the degradation of extracellular matrices, cell migration, inflamation, wound healing, oncogenesis, metastasis, myogenesis, muscle regeneration, neurite outgrowth, and fibrinolysis. This protein may also play a role in acute respiratory distress syndrome (ARDS) which, in part, is caused by enhanced clot formation and the suppression of fibrinolysis. Compared to other mammals, the cluster of plasminogen-like genes to which this gene belongs has been rearranged in catarrhine primates. [provided by RefSeq, May 2020]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs73015965	A>G	Benign, pathogenic, pathogenic-likely-pathogenic	Coding sequence variant, missense variant
rs121918027	G>A	Conflicting-interpretations-of-pathogenicity, pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant
rs121918028	G>T	Pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant
rs121918029	T>C	Pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant
rs121918030	G>A	Pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant
rs121918031	G>A,C	Pathogenic	Genic downstream transcript variant, missense variant, stop gained, coding sequence variant
rs121918032	G>A,T	Pathogenic	Genic downstream transcript variant, missense variant, stop gained, coding sequence variant
rs121918033	G>A	Pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant
rs121918034	GAA>-	Pathogenic	Genic downstream transcript variant, inframe deletion, coding sequence variant
rs606231210	G>-	Pathogenic	Genic downstream transcript variant, splice donor variant, coding sequence variant
rs756287836	G>A	Risk-factor	Missense variant, coding sequence variant, genic downstream transcript variant
rs886042477	G>T	Pathogenic	Splice donor variant
rs889957249	A>G	Pathogenic	Genic downstream transcript variant, coding sequence variant, missense variant

Transcription factors

Transcription factor	Regulation	Reference
SRF	Activation	15514113

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002576	Process	Platelet degranulation	TAS
GO:0004175	Function	Endopeptidase activity	IDA	9603964
GO:0004252	Function	Serine-type endopeptidase activity	IBA	21873635
GO:0004252	Function	Serine-type endopeptidase activity	IDA	14688145, 14699093, 17307854
GO:0004252	Function	Serine-type endopeptidase activity	IMP	18070902, 19270100, 20727989
GO:0005102	Function	Signaling receptor binding	IPI	20028034
GO:0005515	Function	Protein binding	IPI	134998, 6438154, 9092705, 9102401, 9603964, 10077593, 11257124, 12456874, 12622818, 16319056, 16480936, 17557824, 17653767, 17849409, 19712047, 21949403, 22087329, 22321644, 23197176, 25978044, 26627825, 26667841, 26822058, 30082873, 32814053
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	HDA	16502470
GO:0005615	Component	Extracellular space	IDA	6216475, 6980881, 14688145, 17307854
GO:0005886	Component	Plasma membrane	TAS
GO:0006508	Process	Proteolysis	IDA	9603964
GO:0006508	Process	Proteolysis	IMP	18070902, 19270100
GO:0007596	Process	Blood coagulation	IMP	1986355
GO:0008236	Function	Serine-type peptidase activity	TAS	24263861
GO:0008285	Process	Negative regulation of cell population proliferation	TAS	8910613
GO:0009986	Component	Cell surface	IDA	14699093
GO:0010812	Process	Negative regulation of cell-substrate adhesion	IDA	14699093
GO:0019899	Function	Enzyme binding	IPI	12666133, 12818429, 12867553, 14688145, 17307854, 17849409, 17892475, 17964283, 18070902, 19270100, 19433310, 19574304, 20727989, 22025510, 22087329
GO:0019900	Function	Kinase binding	IPI	24196407
GO:0019904	Function	Protein domain specific binding	IPI	9786936, 20028034
GO:0022617	Process	Extracellular matrix disassembly	IDA	14699093
GO:0022617	Process	Extracellular matrix disassembly	TAS
GO:0031093	Component	Platelet alpha granule lumen	TAS
GO:0031232	Component	Extrinsic component of external side of plasma membrane	IDA	14699093
GO:0034185	Function	Apolipoprotein binding	IPI	16480936
GO:0042730	Process	Fibrinolysis	IDA	14688145, 17307854, 22025510
GO:0042730	Process	Fibrinolysis	TAS
GO:0044267	Process	Cellular protein metabolic process	TAS
GO:0048771	Process	Tissue remodeling	IEA
GO:0051087	Function	Chaperone binding	IPI	17307854, 17849409, 19574304
GO:0051702	Process	Biological process involved in interaction with symbiont	IDA	12818429
GO:0051918	Process	Negative regulation of fibrinolysis	IDA	14726399
GO:0051919	Process	Positive regulation of fibrinolysis	IDA	6438154, 26667841
GO:0062023	Component	Collagen-containing extracellular matrix	HDA	25037231, 28675934
GO:0070062	Component	Extracellular exosome	HDA	19199708, 23533145
GO:0072562	Component	Blood microparticle	HDA	22516433
GO:1990405	Function	Protein antigen binding	IPI	17849409
GO:2000048	Process	Negative regulation of cell-cell adhesion mediated by cadherin	TAS	17203182

Other IDs

• MIM: 173350
• HGNC: 9071
• e!Ensembl: ENSG00000122194

Protein

• UniProt ID: P00747
• Protein name: Plasminogen (EC 3.4.21.7) [Cleaved into: Plasmin heavy chain A; Activation peptide; Angiostatin; Plasmin heavy chain A, short form; Plasmin light chain B]
• Protein 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, weakens the walls of the Graafian follicle. It activates the urokinase-type plasminogen activator, collagenases and several complement zymogens, such as C1 and C5. Cleavage of fibronectin and laminin leads to cell detachment and apoptosis. Also cleaves fibrin, thrombospondin and von Willebrand factor. Its role in tissue remodeling and tumor invasion may be modulated by CSPG4. Binds to cells. ; Angiostatin is an angiogenesis inhibitor that blocks neovascularization and growth of experimental primary and metastatic tumors in vivo.
• PDB: 1B2I, 1BML, 1BUI, 1CEA, 1CEB, 1DDJ, 1HPJ, 1HPK, 1I5K, 1KI0, 1KRN, 1L4D, 1L4Z, 1PK4, 1PKR, 1PMK, 1QRZ, 1RJX, 2DOH, 2DOI, 2KNF, 2L0S, 2PK4, 3UIR, 4A5T, 4CIK, 4DCB, 4DUR, 4DUU, 5HPG, 5UGD, 5UGG, 6D3X, 6D3Y, 6D3Z, 6D40, 6OG4, 6OQJ, 6OQK, 6Q1U, 6UZ4, 6UZ5
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00024	PAN_1	23 → 99	PAN domain	Domain
  PF00051	Kringle	103 → 181	Kringle domain	Domain
  PF00051	Kringle	185 → 262	Kringle domain	Domain
  PF00051	Kringle	275 → 352	Kringle domain	Domain
  PF00051	Kringle	377 → 454	Kringle domain	Domain
  PF00051	Kringle	481 → 560	Kringle domain	Domain
  PF00089	Trypsin	581 → 803	Trypsin	Domain

• Sequence:

  MEHKEVVLLLLLFLKSGQGEPLDDYVNTQGASLFSVTKKQLGAGSIEECAAKCEEDEEFT
  CRAFQYHSKEQQCVIMAENRKSSIIIRMRDVVLFEKKVYLSECKTGNGKNYRGTMSKTKN
  GITCQKWSSTSPHRPRFSPATHPSEGLEENYCRNPDNDPQGPWCYTTDPEKRYDYCDILE
  CEEECMHCSGENYDGKISKTMSGLECQAWDSQSPHAHGYIPSKFPNKNLKKNYCRNPDRE
  LRPWCFTTDPNKRWELCDIPRCTTPPPSSGPTYQCLKGTGENYRGNVAVTVSGHTCQHWS
  AQTPHTHNRTPENFPCKNLDENYCRNPDGKRAPWCHTTNSQVRWEYCKIPSCDSSPVSTE
  QLAPTAPPELTPVVQDCYHGDGQSYRGTSSTTTTGKKCQSWSSMTPHRHQKTPENYPNAG
  LTMNYCRNPDADKGPWCFTTDPSVRWEYCNLKKCSGTEASVVAPPPVVLLPDVETPSEED
  CMFGNGKGYRGKRATTVTGTPCQDWAAQEPHRHSIFTPETNPRAGLEKNYCRNPDGDVGG
  PWCYTTNPRKLYDYCDVPQCAAPSFDCGKPQVEPKKCPGRVVGGCVAHPHSWPWQVSLRT
  RFGMHFCGGTLISPEWVLTAAHCLEKSPRPSSYKVILGAHQEVNLEPHVQEIEVSRLFLE
  PTRKDIALLKLSSPAVITDKVIPACLPSPNYVVADRTECFITGWGETQGTFGAGLLKEAQ
  LPVIENKVCNRYEFLNGRVQSTELCAGHLAGGTDSCQGDSGGPLVCFEKDKYILQGVTSW
  GLGCARPNKPGVYVRVSRFVTWIEGVMRNN

• Sequence length: 810

Pathways

KEGG:

Neuroactive ligand-receptor interaction
Complement and coagulation cascades
Staphylococcus aureus infection
Influenza A

Reactome:

Platelet degranulation
Degradation of the extracellular matrix
Activation of Matrix Metalloproteinases
Signaling by PDGF
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
Dissolution of Fibrin Clot

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Schizophrenia	Schizophrenia	rs74315508, rs74315509, rs13447324, rs1558507406, rs387906932, rs387906933, rs-1, rs863223354, rs863223355, rs776061422, rs863223349, rs748809996, rs759748655, rs863223353, rs863223350, rs863223356, rs781821239, rs863223348, rs863223346, rs863223347, rs863223351, rs863223352, rs61734270, rs797045205, rs869312829, rs869312830, rs770913157, rs869312832, rs869312831, rs781720548, rs1262969313	25205258
Developmental delay	Global developmental delay	rs28941770, rs199469464, rs281865469, rs143747297, rs398123009, rs587777428, rs786205133, rs606231459, rs-1, rs797044854, rs797045027, rs864309504, rs878853160, rs886039902, rs886042046, rs886041291, rs886041382, rs1057518991, rs1057518699, rs753254213, rs748294403, rs762552974, rs1135401795, rs1553121073, rs1553122926, rs1364690005, rs1554086554, rs1554210415, rs1554168326, rs1554776342, rs1553873247, rs1567860112, rs779009256, rs1557447255, rs1564568350, rs780011005, rs1597464953, rs1200336864, rs1569513017, rs1587459606, rs1570332505, rs748888652, rs1575155995, rs2087029320, rs1589669105, rs1601769604, rs1184981709, rs749201074
Angioedema	Angioedemas, Hereditary, PLG-related hereditary angioedema with normal C1Inh	rs-1, rs28940870, rs1554996819, rs1554996817, rs112565881, rs2135304804, rs121907951, rs281875174, rs281875178, rs281875168, rs281875170, rs281875171, rs1554995255, rs1554995860, rs886041353, rs978962357, rs1554995774, rs763451792, rs1554995271, rs1554996833, rs1554995260, rs1565169419, rs1565173405, rs1565168898, rs1590822296, rs1565169621, rs1565170287, rs1565170364, rs1565171906, rs1565173309, rs1565174105, rs922149386, rs1590822719, rs1590821401, rs1590822588, rs1590822739, rs1590823884, rs1590826571, rs1590829609, rs1590829616, rs1590829763, rs1590831385, rs1590831432, rs956390201, rs1590831545, rs1590829685, rs778625408, rs1582955358, rs1599142041, rs1945310324, rs1945307391, rs1945416520
Coronary artery disease	Coronary Artery Disease	rs137852988, rs121918313, rs-1, rs121918529, rs121918531, rs137852340, rs405509, rs1555800701, rs1215189537	23202125, 26343387
Periodontitis	Periodontitis	rs28937571, rs104894211, rs587777534
Hypertension	Hypertensive disease	rs13306026	6383834
Plasminogen deficiency	Plasminogen Deficiency, Type I	rs121918030, rs121918031, rs121918032, rs606231210, rs73015965, rs1777777927	10233898, 16849641, 6238949, 9834305, 29321155, 9858247, 1986355, 31064749, 1427790, 9473227, 9242524, 10215610, 8392398, 6216475, 9501859, 9375744, 11477736
Hydrocephalus	Hydrocephalus	rs387907320, rs369384363, rs387907321, rs372127610, rs770273135, rs797045095, rs797045707, rs769795916, rs781251438, rs922703465, rs376078512, rs1567043467, rs1587149916, rs1586841546
Macrocephaly	Macrocephaly	rs786204854, rs764333096, rs1557739557

Unknown
Disease name	Disease term	dbSNP ID	References
Otitis media	Recurrent otitis media	rs601338, rs1047781, rs1800028
Mental depression	Unipolar Depression, Major Depressive Disorder	rs587778876, rs587778877	18794724
Bronchitis	Recurrent bronchitis
Cerebellar hypoplasia	Cerebellar Hypoplasia
Conjunctivitis	Conjunctivitis, Chronic irritative conjunctivitis
Dandy-walker syndrome	Dandy-Walker Syndrome
Duodenal ulcer	Duodenal Ulcer
Excessive tearing	Excessive tearing
Congenital gallbladder anomaly	Gallbladder anomaly congenital
Gastrointestinal inflammation	Gastrointestinal inflammation
Gingivitis	Gingivitis
Hypoplasminogenemia	Hypoplasminogenemia		16849641, 10233898, 10215610, 29321155, 9473227, 9375744, 9834305, 9242524, 11477736, 9501859
Keratoconjunctivitis	Keratoconjunctivitis
Kidney failure	Kidney Failure, Acute		28885000
Leukocyte disorders	Leukocyte Disorders		30213540
Ligneous conjunctivitis	Ligneous conjunctivitis		17701212
Nephritis	Nephritis
Nephrolithiasis	Nephrolithiasis
Acute kidney insufficiency	Acute Kidney Insufficiency		28885000
Stomatitis	Stomatitis
Temporal arteritis	Temporal Arteritis		28041642
Thrombosis	Deep Vein Thrombosis		7215189
Uterine cervicitis	Uterine Cervicitis
Vaginitis	Vaginitis