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; AllianceGenome:HGNC:9071
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
Also known as: HAE4
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]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is relevant for disease process.
Expression: Restricted expression toward liver (RPKM 588.1) See more
Orthologs: mouse all
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Genomic context

Location:: 6q26

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (160702193..160754097)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (162049910..162101977)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (161123225..161175129)

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?

Identification and characterization of calreticulin as a novel plasminogen receptor.
Title: Identification and characterization of calreticulin as a novel plasminogen receptor.
Proteoform-Resolved Profiling of Plasminogen Activation Reveals Novel Abundant Phosphorylation Site and Primary N-Terminal Cleavage Site.
Title: Proteoform-Resolved Profiling of Plasminogen Activation Reveals Novel Abundant Phosphorylation Site and Primary N-Terminal Cleavage Site.
Plasminogen deficiency suppresses pancreatic ductal adenocarcinoma disease progression.
Title: Plasminogen deficiency suppresses pancreatic ductal adenocarcinoma disease progression.
A dual role for ERK-1/2 in the regulation of plasmin activity and cell migration in metastatic NSCLC-H1299 cells.
Title: A dual role for ERK-1/2 in the regulation of plasmin activity and cell migration in metastatic NSCLC-H1299 cells.
Crosstalk between the plasminogen/plasmin system and inflammation resolution.
Title: Crosstalk between the plasminogen/plasmin system and inflammation resolution.
Increased glutamate in type 2 diabetes in the Korean population is associated with increased plasminogen levels.
Title: Increased glutamate in type 2 diabetes in the Korean population is associated with increased plasminogen levels.
A Missense Mutation of the Plasminogen Gene in a Japanese Family with Hereditary Angioedema with Normal C1 Inhibitor: Third Family Survey in Asia.
Title: A Missense Mutation of the Plasminogen Gene in a Japanese Family with Hereditary Angioedema with Normal C1 Inhibitor: Third Family Survey in Asia.
Angiopoietin-like protein 4/8 complex-mediated plasmin generation leads to cleavage of the complex and restoration of LPL activity.
Title: Angiopoietin-like protein 4/8 complex-mediated plasmin generation leads to cleavage of the complex and restoration of LPL activity.
The Role of the Plasminogen/Plasmin System in Inflammation of the Oral Cavity.
Title: The Role of the Plasminogen/Plasmin System in Inflammation of the Oral Cavity.
Distinguishing Plasmin-Generating Microvesicles: Tiny Messengers Involved in Fibrinolysis and Proteolysis.
Title: Distinguishing Plasmin-Generating Microvesicles: Tiny Messengers Involved in Fibrinolysis and Proteolysis.

Submit: New GeneRIF Correction See all GeneRIFs (245)

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
Angioedema, hereditary, 4 MedGen: C5543503 OMIM: 619360 GeneReviews: Not available	Compare labs
Plasminogen deficiency, type I MedGen: C1968804 OMIM: 217090 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

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

Gene Ontology Provided by GOA

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

Process	Evidence Code	Pubs
involved_in biological process involved in interaction with symbiont	IDA Inferred from Direct Assay more info	PubMed
involved_in blood coagulation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in extracellular matrix disassembly	IDA Inferred from Direct Assay more info	PubMed
involved_in fibrinolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in labyrinthine layer blood vessel development	IEA Inferred from Electronic Annotation more info
involved_in mononuclear cell migration	IEA Inferred from Electronic Annotation more info
involved_in muscle cell cellular homeostasis	IEA Inferred from Electronic Annotation more info
involved_in myoblast differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cell population proliferation	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of cell-cell adhesion mediated by cadherin	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of cell-substrate adhesion	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of fibrinolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of blood vessel endothelial cell migration	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of fibrinolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in proteolysis	IBA Inferred from Biological aspect of Ancestor more info
involved_in proteolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in proteolysis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in tissue regeneration	IEA Inferred from Electronic Annotation more info
involved_in tissue remodeling	IEA Inferred from Electronic Annotation more info
involved_in trans-synaptic signaling by BDNF, modulating synaptic transmission	IEA Inferred from Electronic Annotation more info
involved_in trophoblast giant cell differentiation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in Schaffer collateral - CA1 synapse	IEA Inferred from Electronic Annotation more info
located_in blood microparticle	HDA more info	PubMed
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in collagen-containing extracellular matrix	HDA more info	PubMed
located_in external side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular space	HDA more info	PubMed
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in 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, Q15146, Q5TEH4, Q6PA00

UniProtKB/TrEMBL

B2R7F8

Related

ENSP00000308938.9, ENST00000308192.14

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 ...