PLG

Protein identityUniProt · HPA

UniProt accession

P00747

Gene

PLG

Ensembl

ENSG00000122194

Chromosome

6

Canonical length

810 aa

Protein class

Cancer-related genes, Candidate cardiovascular disease genes, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins

Subcellular location

Vesicles

Secretome location

Secreted to blood

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

810 residues, UniProt reviewed canonical sequence.

>P00747|PLG
     1  MEHKEVVLLL LLFLKSGQGE PLDDYVNTQG ASLFSVTKKQ LGAGSIEECA AKCEEDEEFT
    61  CRAFQYHSKE QQCVIMAENR KSSIIIRMRD VVLFEKKVYL SECKTGNGKN YRGTMSKTKN
   121  GITCQKWSST SPHRPRFSPA THPSEGLEEN YCRNPDNDPQ GPWCYTTDPE KRYDYCDILE
   181  CEEECMHCSG ENYDGKISKT MSGLECQAWD SQSPHAHGYI PSKFPNKNLK KNYCRNPDRE
   241  LRPWCFTTDP NKRWELCDIP RCTTPPPSSG PTYQCLKGTG ENYRGNVAVT VSGHTCQHWS
   301  AQTPHTHNRT PENFPCKNLD ENYCRNPDGK RAPWCHTTNS QVRWEYCKIP SCDSSPVSTE
   361  QLAPTAPPEL TPVVQDCYHG DGQSYRGTSS TTTTGKKCQS WSSMTPHRHQ KTPENYPNAG
   421  LTMNYCRNPD ADKGPWCFTT DPSVRWEYCN LKKCSGTEAS VVAPPPVVLL PDVETPSEED
   481  CMFGNGKGYR GKRATTVTGT PCQDWAAQEP HRHSIFTPET NPRAGLEKNY CRNPDGDVGG
   541  PWCYTTNPRK LYDYCDVPQC AAPSFDCGKP QVEPKKCPGR VVGGCVAHPH SWPWQVSLRT
   601  RFGMHFCGGT LISPEWVLTA AHCLEKSPRP SSYKVILGAH QEVNLEPHVQ EIEVSRLFLE
   661  PTRKDIALLK LSSPAVITDK VIPACLPSPN YVVADRTECF ITGWGETQGT FGAGLLKEAQ
   721  LPVIENKVCN RYEFLNGRVQ STELCAGHLA GGTDSCQGDS GGPLVCFEKD KYILQGVTSW
   781  GLGCARPNKP GVYVRVSRFV TWIEGVMRNN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PLG can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.29

Highest tissue expression

2,480 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PLG.

Disease | AllUniProt

Conditions PLG is implicated in, by any mechanism.

• Plasminogen deficiency (PLGD) MIM:217090
• Angioedema, hereditary, 4 (HAE4) MIM:619360

Disease | GeneticClinVar

29 pathogenic / likely-pathogenic of 634 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Plasminogen deficiency, type I
• Angioedema, hereditary, 4
• PLG-related disorder
• Dysplasminogenemia
• Deep venous thrombosis

Disease | ImmuneIEDB

Conditions an epitope on PLG was assayed in.

• rheumatoid arthritis B cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against PLG are reported. Each links to that disease's full target list.

• Lupus Erythematosus, Systemic 4
• Thrombosis 3

ReferencesPubMed · IEDB

Publications for PLG from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.44

gnomAD pLI

0.01

gnomAD missense Z

0.21

DepMap mean gene effect

-0.18

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• biological process involved in interaction with symbiont
• blood coagulation
• extracellular matrix disassembly
• fibrinolysis
• labyrinthine layer blood vessel development
• mononuclear cell migration
• muscle cell cellular homeostasis
• myoblast differentiation
• negative regulation of cell population proliferation
• negative regulation of cell-cell adhesion mediated by cadherin
• negative regulation of cell-substrate adhesion
• negative regulation of fibrinolysis
• positive regulation of blood vessel endothelial cell migration
• positive regulation of fibrinolysis
• protein processing
• proteolysis
• tissue regeneration
• tissue remodeling
• trans-synaptic signaling by BDNF, modulating synaptic transmission
• trophoblast giant cell differentiation

Molecular functions

• apolipoprotein binding
• endopeptidase activity
• enzyme binding
• kinase binding
• protease binding
• protein antigen binding
• protein domain specific binding
• protein-folding chaperone binding
• serine-type endopeptidase activity
• serine-type peptidase activity
• signaling receptor binding

Cellular components

• blood microparticle
• cell surface
• external side of plasma membrane
• extracellular exosome
• extracellular matrix
• extracellular region
• extracellular space
• glutamatergic synapse
• plasma membrane
• platelet alpha granule lumen
• Schaffer collateral - CA1 synapse

Protein domainsUniProt · Pfam · InterPro

• Kringle
• Serine proteases, trypsin domain
• Peptidase S1A, chymotrypsin family
• PAN/Apple domain
• Peptidase S1, PA clan
• Kringle-like fold
• Kringle, conserved site
• Serine proteases, trypsin family, histidine active site
• Serine proteases, trypsin family, serine active site
• Kringle superfamily
• Serine proteases and regulators with kringle domains
• PAN domain
• Kringle domain
• Trypsin
• Peptidase S1A, plasmin

KeywordsUniProt

• Blood coagulation
• Cleavage on pair of basic residues
• Disulfide bond
• Fibrinolysis
• Glycoprotein
• Hemostasis
• Hydrolase
• Kringle
• Phosphoprotein
• Protease
• Repeat
• Secreted
• Serine protease
• Signal
• Thrombophilia
• Tissue remodeling
• Zymogen

InteractionsUniProt · HPA

Protein binding partners of PLG in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ATP5F1A
• ENO1
• ADA
• HRG
• CSPG4