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
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 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]
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
109.20200522	current	GRCh38.p13 (GCF_000001405.39)	6	NC_000006.12 (160702193..160754097)
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 Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Regulation of innate immunity by the fibrinolysis system may reflect the nature of the stimulus and a balance between the potentially opposing activities of tPA and plasmin.
Title: Tissue-type plasminogen activator neutralizes LPS but not protease-activated receptor-mediated inflammatory responses to plasmin.
Cell type-specific roles for uPAR, alphaMbeta2, and alphaVbeta3 are involved in promoting plasminogen activation and mediating the inhibitory effects of apo(a) in this process.
Title: Inhibition of pericellular plasminogen activation by apolipoprotein(a): Roles of urokinase plasminogen activator receptor and integrins αMβ2 and αVβ3.
These results reveal an up-to-now undetermined function of M6P/IGF2R in clearance of apoptotic cells, which is crucial for tissue homeostasis.
Title: The mannose 6-phosphate/insulin-like growth factor 2 receptor mediates plasminogen-induced efferocytosis.
we identified a missense mutation, K330E, in the PLG gene in four patients from two unrelated families with HAEnCI in Japan. To our knowledge, the F12 mutations, as well as other genetic abnormalities, have not been reported in Asian patients.
Title: A missense mutation of the plasminogen gene in hereditary angioedema with normal C1 inhibitor in Japan.
The presence of active plasmin in urine in hydronephrosis could cause abnormal proteolytic activation of ENaC-gamma and impaired ability to excrete Na via NCC.
Title: Hydronephrosis is associated with elevated plasmin in urine in pediatric patients and rats and changes in NCC and γ-ENaC abundance in rat kidney.
The ability of HMGA1 to regulate the plasminogen activator system may constitute an important mechanism by which HMGA1 promotes cancer progression.
Title: HMGA1 regulates the Plasminogen activation system in the secretome of breast cancer cells.
Hereditary angioedema with a mutation in the PLG gene is a novel type of hereditary angioedema. It is associated with a high risk of tongue swellings.
Title: Hereditary angioedema with a mutation in the plasminogen gene.
Here, the authors show that PspC is a pneumococcal plasminogen receptor and that plasmin generated on the surface of hemolytic uremic syndrome pneumococci damages endothelial cells, causing endothelial retraction and exposure of the underlying matrix.
Title: Streptococcus pneumoniae From Patients With Hemolytic Uremic Syndrome Binds Human Plasminogen via the Surface Protein PspC and Uses Plasmin to Damage Human Endothelial Cells.
This study shows that suppression of PKC-alpha attenuates TNF-alpha-evoked cerebral barrier breakdown via regulations of MMP-2 and plasminogen-plasmin system.
Title: Suppression of PKC-α attenuates TNF-α-evoked cerebral barrier breakdown via regulations of MMP-2 and plasminogen-plasmin system.
This article gives an update of the current knowledge about the role of the plasminogen activation system on different aspects of neuroinflammation. [review]
Title: The plasminogen activation system in neuroinflammation.

Submit: New GeneRIF Correction See all GeneRIFs (213)

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)

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: 254 organisms have orthologs with human gene PLG
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
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 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
labyrinthine layer blood vessel development	IEA Inferred from Electronic Annotation more info
mononuclear cell migration	IEA Inferred from Electronic Annotation more info
muscle cell cellular homeostasis	IEA Inferred from Electronic Annotation more info
myoblast differentiation	IEA Inferred from Electronic Annotation more info
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
proteolysis involved in cellular protein catabolic process	IEA Inferred from Electronic Annotation more info
tissue regeneration	IEA Inferred from Electronic Annotation more info
tissue remodeling	IEA Inferred from Electronic Annotation more info
trans-synaptic signaling by BDNF, modulating synaptic transmission	IEA Inferred from Electronic Annotation more info
trophoblast giant cell differentiation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
Schaffer collateral - CA1 synapse	IEA Inferred from Electronic Annotation more info
blood microparticle	HDA more info	PubMed
cell	IEA Inferred from Electronic Annotation more info
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
glutamatergic synapse	IEA Inferred from Electronic Annotation more info
intracellular membrane-bounded organelle	IEA Inferred from Electronic Annotation more info
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_000301.5 → 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

Consensus CDS

CCDS5279.1

UniProtKB/Swiss-Prot

P00747

Related

ENSP00000308938.9, ENST00000308192.13

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, ENST00000366924.6

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 ...