Human Gene PLG (uc003qtm.4)
  Description: Homo sapiens plasminogen (PLG), transcript variant 1, mRNA.
RefSeq Summary (NM_000301): 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].
Transcript (Including UTRs)
   Position: hg19 chr6:161,123,225-161,175,085 Size: 51,861 Total Exon Count: 19 Strand: +
Coding Region
   Position: hg19 chr6:161,123,337-161,174,093 Size: 50,757 Coding Exon Count: 19 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr6:161,123,225-161,175,085)mRNA (may differ from genome)Protein (810 aa)
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neXtProtOMIMPubMedReactomeTreefamUniProtKB
WikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: PLMN_HUMAN
DESCRIPTION: RecName: Full=Plasminogen; EC=3.4.21.7; Contains: RecName: Full=Plasmin heavy chain A; Contains: RecName: Full=Activation peptide; Contains: RecName: Full=Angiostatin; Contains: RecName: Full=Plasmin heavy chain A, short form; Contains: RecName: Full=Plasmin light chain B; Flags: Precursor;
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.
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. Plasmin activity inhibited by SERPINE2.
SUBUNIT: Interacts (both mature PLG and the angiostatin peptide) with CSPG4 and AMOT. Interacts (via the Kringle domains) with HRG; the interaction tethers PLG to the cell surface and enhances its activation (By similarity).
INTERACTION: 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=2; IntAct=EBI-999394, EBI-1035089;
SUBCELLULAR LOCATION: Secreted. Note=Locates to the cell surface where it is proteolytically cleaved to produce the active plasmin. Interaction with HRG tethers it to the cell surface.
TISSUE SPECIFICITY: Present in plasma and many other extracellular fluids. It is synthesized in the liver.
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 the cause of plasminogen deficiency (PLGD) [MIM:217090]. PLGD is characterized by decreased serum plasminogen activity. Two forms of the disorder are distinguished: type 1 deficiency is additionally characterized by decreased plasminogen antigen levels and clinical symptoms, whereas type 2 deficiency, also known as dysplasminogenemia, is characterized by normal, or slightly reduced antigen levels, and absence of clinical manifestations. Plasminogen deficiency type 1 results in markedly impaired extracellular fibrinolysis and chronic mucosal pseudomembranous lesions due to subepithelial fibrin deposition and inflammation. The most common clinical manifestation of type 1 deficiency is ligneous conjunctivitis in which pseudomembranes formation on the palpebral surfaces of the eye progresses to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa.
MISCELLANEOUS: Plasmin is inactivated by alpha-2-antiplasmin immediately after dissociation from the clot.
SIMILARITY: Belongs to the peptidase S1 family. Plasminogen subfamily.
SIMILARITY: Contains 5 kringle domains.
SIMILARITY: Contains 1 PAN domain.
SIMILARITY: Contains 1 peptidase S1 domain.
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/";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): PLG
CDC HuGE Published Literature: PLG
Positive Disease Associations: Body Height , lipoprotein A-I , Lipoprotein(a) , Lipoproteins , Parkinson Disease , vascular disease
Related Studies:
  1. Body Height
    , , . [PubMed 0]
  2. Body Height
    , , . [PubMed 0]
  3. Body Height
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           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: PLG
Diseases sorted by gene-association score: plasminogen deficiency, type i* (1669), congenital plasminogen deficiency* (418), conjunctivitis (43), ligneous conjunctivitis (40), pseudomembranous conjunctivitis (16), intracranial embolism (16), acute poststreptococcal glomerulonephritis (13), basilar artery occlusion (12), corneal neovascularization (12), occlusion precerebral artery (12), carotid artery disease (12), pneumonic plague (11), hemangioendothelioma (11), hepatic veno-occlusive disease (10), acute anterolateral myocardial infarction (10), posterolateral myocardial infarction (10), central retinal artery occlusion (9), vitreous detachment (9), globe disease (9), locked-in syndrome (9), hemopericardium (8), conjugate gaze palsy (8), amusia (8), perforated corneal ulcer (8), cerebral falx meningioma (8), ascaridiasis (8), alpha-2-plasmin inhibitor deficiency (8), thrombosis (8), retinal vascular occlusion (8), acute pulmonary heart disease (7), anteroseptal myocardial infarction (7), chronic myocardial ischemia (7), anterior spinal artery syndrome (7), basilar artery insufficiency (7), facial neuralgia (7), intestinal impaction (7), pulmonary artery leiomyosarcoma (7), apical myocardial infarction (7), bubonic plague (7), acute cor pulmonale (7), brain stem infarction (7), vertebral artery occlusion (7), disseminated intravascular coagulation (7), retinal vascular disease (6), inferior myocardial infarction (6), vitreous disease (6), lateral myocardial infarction (6), tuberculous empyema (6), leech infestation (6), erysipeloid (6), methylmalonic aciduria and homocystinuria, cblc type (6), endophthalmitis (6), corneal abscess (5), alveolar periostitis (5), femoral neuropathy (5), septicemic plague (5), osteonecrosis (5), speech and communication disorders (5), lemierre's syndrome (5), hepatic vascular disease (5), kuhnt-junius degeneration (5), vein disease (5), newborn respiratory distress syndrome (5), anterior cranial fossa meningioma (5), giant hemangioma (5), blue toe syndrome (5), brown-sequard syndrome (5), plague (4), korean hemorrhagic fever (4), carotid artery dissection (4), conjunctival disease (4), dysbaric osteonecrosis (4), intermediate coronary syndrome (4), retinitis pigmentosa 42 (4), osteosclerotic myeloma (4), dirofilariasis (4), lateral medullary syndrome (4), thrombophilia due to activated protein c resistance (4), acute myocardial infarction (4), histidinemia (4), histidine metabolism disease (4), artery disease (3), pulmonary hypertension (2), macular degeneration, age-related, 1 (2), pancreatic cancer (2), uveal melanoma (2), stroke, ischemic (2), myocardial infarction (2), blood coagulation disease (2), prostate cancer (1), ocular cancer (1), degeneration of macula and posterior pole (1), ovarian cancer, somatic (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 201.76 RPKM in Liver
Total median expression: 208.90 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -26.40112-0.236 Picture PostScript Text
3' UTR -287.32992-0.290 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000001 - Kringle
IPR013806 - Kringle-like
IPR018056 - Kringle_CS
IPR003014 - PAN-1_domain
IPR003609 - Pan_app
IPR009003 - Pept_cys/ser_Trypsin-like
IPR023317 - Pept_S1A_plasmin
IPR018114 - Peptidase_S1/S6_AS
IPR001254 - Peptidase_S1_S6
IPR001314 - Peptidase_S1A

Pfam Domains:
PF00024 - PAN domain
PF00051 - Kringle domain
PF00089 - Trypsin
PF09342 - Domain of unknown function (DUF1986)
PF13365 - Trypsin-like peptidase domain

SCOP Domains:
50494 - Trypsin-like serine proteases
57414 - Hairpin loop containing domain-like
57440 - Kringle-like

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1B2I - NMR MuPIT 1BML - X-ray MuPIT 1BUI - X-ray MuPIT 1CEA - X-ray MuPIT 1CEB - X-ray MuPIT 1DDJ - X-ray MuPIT 1HPJ - NMR 1HPK - NMR 1I5K - X-ray MuPIT 1KI0 - X-ray MuPIT 1KRN - X-ray 1L4D - X-ray MuPIT 1L4Z - X-ray MuPIT 1PK4 - X-ray MuPIT 1PKR - X-ray MuPIT 1PMK - X-ray MuPIT 1QRZ - X-ray MuPIT 1RJX - X-ray MuPIT 2DOH - X-ray MuPIT 2DOI - X-ray MuPIT 2KNF - NMR MuPIT 2L0S - NMR MuPIT 2PK4 - X-ray MuPIT 4A5T - X-ray 4DCB - X-ray 4DUR - X-ray 4DUU - X-ray 5HPG - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P00747
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserGenome BrowserGenome BrowserNo ortholog
Gene Details  Gene DetailsGene Details 
Gene Sorter  Gene SorterGene Sorter 
  EnsemblFlyBaseWormBase 
  Protein SequenceProtein SequenceProtein Sequence 
  AlignmentAlignmentAlignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004175 endopeptidase activity
GO:0004252 serine-type endopeptidase activity
GO:0005102 receptor binding
GO:0005515 protein binding
GO:0008233 peptidase activity
GO:0008236 serine-type peptidase activity
GO:0016787 hydrolase activity
GO:0019899 enzyme binding
GO:0019900 kinase binding
GO:0019904 protein domain specific binding
GO:0034185 apolipoprotein binding
GO:0051087 chaperone binding
GO:1904854 proteasome core complex binding
GO:1990405 protein antigen binding

Biological Process:
GO:0002576 platelet degranulation
GO:0006508 proteolysis
GO:0007596 blood coagulation
GO:0007599 hemostasis
GO:0008285 negative regulation of cell proliferation
GO:0010812 negative regulation of cell-substrate adhesion
GO:0022617 extracellular matrix disassembly
GO:0042730 fibrinolysis
GO:0043536 positive regulation of blood vessel endothelial cell migration
GO:0044267 cellular protein metabolic process
GO:0048771 tissue remodeling
GO:0051702 interaction with symbiont
GO:0051918 negative regulation of fibrinolysis
GO:0051919 positive regulation of fibrinolysis
GO:0052182 modification by host of symbiont morphology or physiology via secreted substance
GO:0052213 interaction with symbiont via secreted substance involved in symbiotic interaction
GO:2000048 negative regulation of cell-cell adhesion mediated by cadherin

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005886 plasma membrane
GO:0009986 cell surface
GO:0031093 platelet alpha granule lumen
GO:0031232 extrinsic component of external side of plasma membrane
GO:0044218 other organism cell membrane
GO:0070062 extracellular exosome
GO:0072562 blood microparticle


-  Descriptions from all associated GenBank mRNAs
  AK308036 - Homo sapiens cDNA, FLJ97984.
AK312966 - Homo sapiens cDNA, FLJ93426, highly similar to Homo sapiens plasminogen (PLG), mRNA.
A22096 - plasminogen cDNA.
AK298338 - Homo sapiens cDNA FLJ58778 complete cds, highly similar to Plasminogen precursor (EC 3.4.21.7).
X05199 - Human mRNA for plasminogen.
JD049318 - Sequence 30342 from Patent EP1572962.
M74220 - Human plasminogen mRNA, complete cds.
JD184075 - Sequence 165099 from Patent EP1572962.
BC060513 - Homo sapiens plasminogen, mRNA (cDNA clone MGC:61954 IMAGE:4609795), complete cds.
JD167131 - Sequence 148155 from Patent EP1572962.
JD167140 - Sequence 148164 from Patent EP1572962.
KJ897343 - Synthetic construct Homo sapiens clone ccsbBroadEn_06737 PLG gene, encodes complete protein.
KR712023 - Synthetic construct Homo sapiens clone CCSBHm_00034755 PLG (PLG) mRNA, encodes complete protein.
KR712024 - Synthetic construct Homo sapiens clone CCSBHm_00034771 PLG (PLG) mRNA, encodes complete protein.
KR712025 - Synthetic construct Homo sapiens clone CCSBHm_00034789 PLG (PLG) mRNA, encodes complete protein.
JD469575 - Sequence 450599 from Patent EP1572962.
K02922 - Human plasminogen mRNA, 3' end.
CR749293 - Homo sapiens mRNA; cDNA DKFZp779M0222 (from clone DKFZp779M0222).
JD092613 - Sequence 73637 from Patent EP1572962.
JD301185 - Sequence 282209 from Patent EP1572962.
JD207876 - Sequence 188900 from Patent EP1572962.
MP559974 - Sequence 3 from Patent WO2020053808.
MP559976 - Sequence 5 from Patent WO2020053808.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04080 - Neuroactive ligand-receptor interaction
hsa04610 - Complement and coagulation cascades

BioCarta from NCI Cancer Genome Anatomy Project
h_fibrinolysisPathway - Fibrinolysis Pathway
h_plateletAppPathway - Platelet Amyloid Precursor Protein Pathway
h_amiPathway - Acute Myocardial Infarction

Reactome (by CSHL, EBI, and GO)

Protein P00747 (Reactome details) participates in the following event(s):

R-HSA-158722 histidine-rich glycoprotein + plasminogen <-> histidine-rich glycoprotein:plasminogen
R-HSA-158756 crosslinked fibrin multimer:tissue plasminogen activator (two-chain) + plasminogen -> crosslinked fibrin multimer:tissue plasminogen activator (two-chain):plasminogen
R-HSA-158784 crosslinked fibrin multimer:tissue plasminogen activator (one-chain) + plasminogen -> crosslinked fibrin multimer:tissue plasminogen activator (one-chain):plasminogen
R-HSA-158941 plasminogen + histidine-rich glycoprotein -> plasminogen:histidine-rich glycoprotein
R-HSA-158721 histidine-rich glycoprotein:plasminogen <-> histidine-rich glycoprotein + plasminogen
R-HSA-481007 Exocytosis of platelet alpha granule contents
R-HSA-158750 crosslinked fibrin multimer:tissue plasminogen activator (one-chain):plasminogen -> crosslinked fibrin multimer:tissue plasminogen activator (one-chain) + plasmin
R-HSA-158744 crosslinked fibrin multimer:tissue plasminogen activator (two-chain):plasminogen -> crosslinked fibrin multimer:tissue plasminogen activator (two-chain) + plasmin
R-HSA-158893 alpha-2-antiplasmin + plasmin -> alpha-2-antiplasmin:plasmin
R-HSA-158925 plasminogen:histidine-rich glycoprotein -> plasmin + histidine-rich glycoprotein (uPA [two-chain] catalyst)
R-HSA-158982 plasminogen:histidine-rich glycoprotein -> plasmin + histidine-rich glycoprotein (uPA [one-chain] catalyst)
R-HSA-158747 crosslinked fibrin multimer:tissue plasminogen activator (one-chain) -> crosslinked fibrin multimer:tissue plasminogen activator (two-chain)
R-HSA-158766 fibrin multimer, crosslinked -> fibrin digestion products (plasmin)
R-HSA-158942 urokinase plasminogen activator (one-chain):uPAR -> urokinase plasminogen activator (two-chain):uPAR
R-HSA-381461 Plasmin proteolyzes IGF:IGFBP-3:ALS
R-HSA-382061 Extracellular processing of novel PDGFs
R-HSA-1592316 Initial activation of proMMP1
R-HSA-1602488 Initial activation of proMMP13 by plasmin and trypsin
R-HSA-1592371 Initial activation of proMMP3
R-HSA-1592314 HSPG2 (perlecan) degradation by MMP3, plasmin, (MMP12)
R-HSA-1454843 E-cadherin degradation by MMP3, MMP7 and plasmin.
R-NUL-2534162 E-cadherin strand dimer degradation by MMP3, MMP7 and Plasmin
R-HSA-1604712 Initial activation of proMMP7 by trypsin
R-HSA-1566979 Laminin-332 degradation by laminin-322 degrading extracellular proteinases
R-HSA-75205 Dissolution of Fibrin Clot
R-HSA-114608 Platelet degranulation
R-HSA-109582 Hemostasis
R-HSA-76005 Response to elevated platelet cytosolic Ca2+
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-76002 Platelet activation, signaling and aggregation
R-HSA-186797 Signaling by PDGF
R-HSA-1592389 Activation of Matrix Metalloproteinases
R-HSA-1474228 Degradation of the extracellular matrix
R-HSA-392499 Metabolism of proteins
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-1474244 Extracellular matrix organization
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: NM_000301, NP_000292, P00747, PLMN_HUMAN, Q15146, Q5TEH4, Q6PA00
UCSC ID: uc003qtm.4
RefSeq Accession: NM_000301
Protein: P00747 (aka PLMN_HUMAN)
CCDS: CCDS5279.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_000301.3
exon count: 19CDS single in 3' UTR: no RNA size: 3538
ORF size: 2433CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 5027.50frame shift in genome: no % Coverage: 99.97
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.