PLG plasminogen [Homo sapiens (human)] - Gene

Summary

Official Symbol: PLGprovided by HGNC
Official Full Name: plasminogenprovided by HGNC
Primary source: HGNC:HGNC:9071
See related: Ensembl:ENSG00000122194 MIM:173350; Vega:OTTHUMG00000015957
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary: The protein encoded by this gene is a secreted blood zymogen that is activated by proteolysis and converted to plasmin and angiostatin. Plasmin dissolves fibrin in blood clots and is an important protease in many other cellular processes while angiostatin inhibits angiogenesis. Defects in this gene are likely a cause of thrombophilia and ligneous conjunctivitis. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Dec 2009]
Expression: Restricted expression toward liver (RPKM 588.1) See more
Orthologs: mouse all

Genomic context

Location:: 6q26

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	6	NC_000006.12 (160702193..160754054)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (161123225..161175086)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Urinary angiostatin and VCAM-1 are predictive of specific histological changes in concurrent lupus nephritis renal biopsies.
Title: Urine angiostatin and VCAM-1 surpass conventional metrics in predicting elevated renal pathology activity indices in lupus nephritis.
We did not find an association of the AgP risk variant rs4252120 with CP. However, we identified a haplotype block downstream of PLG, which showed shared association with CP and AgP.
Title: A haplotype block downstream of plasminogen is associated with chronic and aggressive periodontitis.
The homozygous alleles in F12 (rs1801020) and F13 (rs5985) was identified a genetic risk profile of thromboembolism in a Family.
Title: The Unravelling of the Genetic Architecture of Plasminogen Deficiency and its Relation to Thrombotic Disease.
Our findings that plasminogen and pSTAT3 are significantly associated with LI suggest that they may represent signaling nodes or biomarkers of pathways common to the processes of postlactational involution and LI.
Title: Postlactational involution biomarkers plasminogen and phospho-STAT3 are linked with active age-related lobular involution.
A rare non-conservative missense mutation was newly identified in exon 9 of the PLG gene.
Title: A missense mutation in the plasminogen gene, within the plasminogen kringle 3 domain, in hereditary angioedema with normal C1 inhibitor.
Plasminogen binds to the cell surface-exposed proteins of Candida parapsilosis.
Title: Binding of human plasminogen and high-molecular-mass kininogen by cell surface-exposed proteins of Candida parapsilosis.
plasmin cleaves surface-bound CCL21 to release the C-terminal peptide responsible for CCL21 binding to glycosaminoglycans on the extracellular matrix and cell surfaces, thereby generating the soluble form.
Title: Plasmin and regulators of plasmin activity control the migratory capacity and adhesion of human T cells and dendritic cells by regulating cleavage of the chemokine CCL21.
Analysis of plasminogen genetic variants in multiple sclerosis patients has been reported.
Title: Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients.
Enolase of Mtb is present on its surface and binds human plasminogen with high affinity.
Title: Enolase of Mycobacterium tuberculosis is a surface exposed plasminogen binding protein.
Data suggest that protein aggregates interact with tissue-type plasminogen activator and plasminogen to efficiently generate plasmin; this aggregate-bound plasmin is shielded from inhibition by alpha-2-antiplasmin and degrades protein aggregates to release smaller, soluble but relatively hydrophobic peptide fragments; these fragments bind to and are cytotoxic to microglia (by not vascular endothelial cells).
Title: Amorphous protein aggregates stimulate plasminogen activation, leading to release of cytotoxic fragments that are clients for extracellular chaperones.

Submit: New GeneRIF Correction See all GeneRIFs (202)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Plasminogen deficiency, type I MedGen: C1968804 OMIM: 217090 GeneReviews: Not available	Compare labs

NHGRI GWAS Catalog

Description
Genetic variants in PLG, LPA and SIGLEC 14 as well as smoking contribute to plasma plasminogen levels. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genetic variants, plasma lipoprotein(a) levels, and risk of cardiovascular morbidity and mortality among two prospective cohorts of type 2 diabetes. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Linkage and association of successful aging to the 6q25 region in large Amish kindreds. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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Activation of Matrix Metalloproteinases, organism-specific biosystem (from REACTOME)
Activation of Matrix Metalloproteinases, organism-specific biosystemThe matrix metalloproteinases (MMPs), previously known as matrixins, are classically known to be involved in the turnover of extracellular matrix (ECM) components. However, recent high throughput pro...
Angiopoietin receptor Tie2-mediated signaling, organism-specific biosystem (from Pathway Interaction Database)
Angiopoietin receptor Tie2-mediated signaling, organism-specific biosystem
Angiopoietin receptor Tie2-mediated signaling
Blood Clotting Cascade, organism-specific biosystem (from WikiPathways)
Blood Clotting Cascade, organism-specific biosystemCoagulation is a complex process by which blood forms clots. It is an important part of hemostasis (the cessation of blood loss from a damaged vessel), wherein a damaged blood vessel wall is covered ...
Complement and Coagulation Cascades, organism-specific biosystem (from WikiPathways)
Complement and Coagulation Cascades, organism-specific biosystemBlood coagulation is a series of coordinated and calcium-dependent proenzyme-to-serine protease conversions likely to be localized on the surfaces of activated cells in vivo. It culminates in the for...
Complement and coagulation cascades, organism-specific biosystem (from KEGG)
Complement and coagulation cascades, organism-specific biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
Complement and coagulation cascades, conserved biosystem (from KEGG)
Complement and coagulation cascades, conserved biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
Degradation of the extracellular matrix, organism-specific biosystem (from REACTOME)
Degradation of the extracellular matrix, organism-specific biosystemMatrix metalloproteinases (MMPs), previously referred to as matrixins because of their role in degradation of the extracellular matrix (ECM), are zinc and calcium dependent proteases belonging to the...
Dissolution of Fibrin Clot, organism-specific biosystem (from REACTOME)
Dissolution of Fibrin Clot, organism-specific biosystemThe crosslinked fibrin multimers in a clot are broken down to soluble polypeptides by plasmin, a serine protease. Plasmin can be generated from its inactive precursor plasminogen and recruited to the...
Extracellular matrix organization, organism-specific biosystem (from REACTOME)
Extracellular matrix organization, organism-specific biosystemThe extracellular matrix is a component of all mammalian tissues, a network consisting largely of the fibrous proteins collagen, elastin and associated-microfibrils, fibronectin and laminins embedded...
Folate Metabolism, organism-specific biosystem (from WikiPathways)
Folate Metabolism, organism-specific biosystem
Folate Metabolism
Hemostasis, organism-specific biosystem (from REACTOME)
Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
Influenza A, organism-specific biosystem (from KEGG)
Influenza A, organism-specific biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
Influenza A, conserved biosystem (from KEGG)
Influenza A, conserved biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
Metabolism of proteins, organism-specific biosystem (from REACTOME)
Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
Neuroactive ligand-receptor interaction, organism-specific biosystem (from KEGG)
Neuroactive ligand-receptor interaction, organism-specific biosystem
Neuroactive ligand-receptor interaction
Neuroactive ligand-receptor interaction, conserved biosystem (from KEGG)
Neuroactive ligand-receptor interaction, conserved biosystem
Neuroactive ligand-receptor interaction
Platelet activation, signaling and aggregation, organism-specific biosystem (from REACTOME)
Platelet activation, signaling and aggregation, organism-specific biosystemPlatelet activation begins with the initial binding of adhesive ligands and of the excitatory platelet agonists (released or generated at the sites of vascular trauma) to cognate receptors on the pla...
Platelet degranulation, organism-specific biosystem (from REACTOME)
Platelet degranulation, organism-specific biosystemPlatelets function as exocytotic cells, secreting a plethora of effector molecules at sites of vascular injury. Platelets contain a number of distinguishable storage granules including alpha granules...
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs), organism-specific biosystem (from REACTOME)
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs), organism-specific biosystemThe family of Insulin like Growth Factor Binding Proteins (IGFBPs) share 50% amino acid identity with conserved N terminal and C terminal regions responsible for binding Insulin like Growth Factors I...
Response to elevated platelet cytosolic Ca2+, organism-specific biosystem (from REACTOME)
Response to elevated platelet cytosolic Ca2+, organism-specific biosystemActivation of phospholipase C enzymes results in the generation of second messengers of the phosphatidylinositol pathway. The events resulting from this pathway are a rise in intracellular calcium an...
Selenium Micronutrient Network, organism-specific biosystem (from WikiPathways)
Selenium Micronutrient Network, organism-specific biosystem
Selenium Micronutrient Network
Signal Transduction, organism-specific biosystem (from REACTOME)
Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
Signaling by PDGF, organism-specific biosystem (from REACTOME)
Signaling by PDGF, organism-specific biosystemPlatelet-derived Growth Factor (PDGF) is a potent stimulator of growth and motility of connective tissue cells such as fibroblasts and smooth muscle cells as well as other cells such as capillary end...
Staphylococcus aureus infection, organism-specific biosystem (from KEGG)
Staphylococcus aureus infection, organism-specific biosystemStaphylococcus aureus can cause multiple forms of infections ranging from superficial skin infections to food poisoning and life-threatening infections. The organism has several ways to divert the ef...
Staphylococcus aureus infection, conserved biosystem (from KEGG)
Staphylococcus aureus infection, conserved biosystemStaphylococcus aureus can cause multiple forms of infections ranging from superficial skin infections to food poisoning and life-threatening infections. The organism has several ways to divert the ef...
Syndecan-4-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
Syndecan-4-mediated signaling events, organism-specific biosystem
Syndecan-4-mediated signaling events
Vitamin B12 Metabolism, organism-specific biosystem (from WikiPathways)
Vitamin B12 Metabolism, organism-specific biosystem
Vitamin B12 Metabolism
amb2 Integrin signaling, organism-specific biosystem (from Pathway Interaction Database)
amb2 Integrin signaling, organism-specific biosystem
amb2 Integrin signaling
p75(NTR)-mediated signaling, organism-specific biosystem (from Pathway Interaction Database)
p75(NTR)-mediated signaling, organism-specific biosystem
p75(NTR)-mediated signaling

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

A009P38 (e-PCR)
- UniSTS:1839

RH69724 (e-PCR)
- UniSTS:42565

RH70350 (e-PCR)
- UniSTS:48720

G32750 (e-PCR)
- UniSTS:117331

PLG_3841 (e-PCR)
- UniSTS:462421

G17083 (e-PCR)
- UniSTS:25453

D6S2067 (e-PCR)
- UniSTS:19074

D6S2151 (e-PCR)
- UniSTS:15753

EMT_F1R1 (e-PCR)
- UniSTS:241039

SHGC-33362 (e-PCR)
- UniSTS:59028

SHGC-33485 (e-PCR)
- UniSTS:82589

RH1524 (e-PCR)
- UniSTS:24737

RH79781 (e-PCR)
- UniSTS:89765

RH65147 (e-PCR)
- UniSTS:91607

D6S2067 (e-PCR)
- UniSTS:9197

Homology

Homologs of the PLG gene: The PLG gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, C.elegans, and frog.
Orthologs from Annotation Pipeline: 189 organisms have orthologs with human gene PLG
The Hierarchical Catalog of Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
apolipoprotein binding	IPI Inferred from Physical Interaction more info	PubMed
chaperone binding	IPI Inferred from Physical Interaction more info	PubMed
endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
kinase binding	IPI Inferred from Physical Interaction more info	PubMed
proteasome core complex binding	IPI Inferred from Physical Interaction more info	PubMed
protein antigen binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein domain specific binding	IPI Inferred from Physical Interaction more info	PubMed
serine-type endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
serine-type endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
serine-type endopeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
serine-type endopeptidase activity	TAS Traceable Author Statement more info
serine-type peptidase activity	TAS Traceable Author Statement more info	PubMed
signaling receptor binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
blood coagulation	IMP Inferred from Mutant Phenotype more info	PubMed
cellular protein metabolic process	TAS Traceable Author Statement more info
extracellular matrix disassembly	IDA Inferred from Direct Assay more info	PubMed
extracellular matrix disassembly	TAS Traceable Author Statement more info
fibrinolysis	IDA Inferred from Direct Assay more info	PubMed
fibrinolysis	TAS Traceable Author Statement more info
interaction with symbiont	IDA Inferred from Direct Assay more info	PubMed
interaction with symbiont via secreted substance involved in symbiotic interaction	IDA Inferred from Direct Assay more info	PubMed
modification by host of symbiont morphology or physiology via secreted substance	IDA Inferred from Direct Assay more info	PubMed
modification by host of symbiont morphology or physiology via secreted substance	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of cell proliferation	TAS Traceable Author Statement more info	PubMed
negative regulation of cell-cell adhesion mediated by cadherin	TAS Traceable Author Statement more info	PubMed
negative regulation of cell-substrate adhesion	IDA Inferred from Direct Assay more info	PubMed
negative regulation of fibrinolysis	IDA Inferred from Direct Assay more info	PubMed
platelet degranulation	TAS Traceable Author Statement more info
positive regulation of fibrinolysis	IDA Inferred from Direct Assay more info	PubMed
proteolysis	IDA Inferred from Direct Assay more info	PubMed
proteolysis	IMP Inferred from Mutant Phenotype more info	PubMed
tissue remodeling	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
blood microparticle	HDA more info	PubMed
cell surface	IDA Inferred from Direct Assay more info	PubMed
collagen-containing extracellular matrix	HDA more info	PubMed
extracellular exosome	HDA more info	PubMed
extracellular region	TAS Traceable Author Statement more info
extracellular space	HDA more info	PubMed
extracellular space	IDA Inferred from Direct Assay more info	PubMed
extrinsic component of external side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
other organism cell membrane	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	TAS Traceable Author Statement more info
platelet alpha granule lumen	TAS Traceable Author Statement more info

General protein information

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Preferred Names: plasminogen

Names: plasmin

NP_000292.1

EC 3.4.21.7

NP_001161810.1

EC 3.4.21.7

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_016200.1 RefSeqGene

Range

5001..56862

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_571

mRNA and Protein(s)

NM_000301.3 → NP_000292.1 plasminogen isoform 1 precursor

See identical proteins and their annotated locations for NP_000292.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AL109933, DR004070, M74220, X05199

Consensus CDS

CCDS5279.1

UniProtKB/Swiss-Prot

P00747

Related

ENSP00000308938.9, OTTHUMP00000017544, ENST00000308192.13, OTTHUMT00000042959

Conserved Domains (4) summary

smart00020
Location:580 → 803

Tryp_SPc; Trypsin-like serine protease

smart00130
Location:101 → 183

KR; Kringle domain

cd00190
Location:581 → 804

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

cd01099
Location:38 → 97

PAN_AP_HGF; Subfamily of PAN/APPLE-like domains; present in N-terminal (N) domains of plasminogen/hepatocyte growth factor proteins, and various proteins found in Bilateria, such as leech anti-platelet proteins. PAN/APPLE domains fulfill diverse biological functions ...
NM_001168338.1 → NP_001161810.1 plasminogen isoform 2 precursor

See identical proteins and their annotated locations for NP_001161810.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 3' UTR and coding sequence compared to variant 1. The resulting isoform (2) is shorter at the C-terminus compared to isoform 1.

Source sequence(s)

AL109933, DR004070

Consensus CDS

CCDS55074.1

UniProtKB/TrEMBL

Q5TEH5

Related

ENSP00000355891.2, OTTHUMP00000017545, ENST00000366924.6, OTTHUMT00000042960

Conserved Domains (2) summary

cd01099
Location:38 → 97

PAN_AP_HGF; Subfamily of PAN/APPLE-like domains; present in N-terminal (N) domains of plasminogen/hepatocyte growth factor proteins, and various proteins found in Bilateria, such as leech anti-platelet proteins. PAN/APPLE domains fulfill diverse biological functions ...

cl00100
Location:102 → 136

KR; Kringle domain; Kringle domains are believed to play a role in binding mediators, such as peptides, other proteins, membranes, or phospholipids. They are autonomous structural domains, found in a varying number of copies, in blood clotting and ...