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FLASH GENE
Symbol SERPINE1 contributors: mct/npt - updated : 28-08-2013
HGNC name serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1
HGNC id 8583
Corresponding disease
PAI1 plasminogen activator inhibitor 1 deficiency
TRBR thrombosis, recurrent (PAI1 overexpression)
Location 7q22.1      Physical location : 100.770.378 - 100.782.546
Synonym name
  • serine (or cysteine) proteinase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1
  • plasminogen activator inhibitor, type I
  • endothelial plasminogen activator inhibitor
    • Synonym symbol(s) PLANH1, PAI, PAI-1
    DNA
    TYPE functioning gene
    STRUCTURE 12.16 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure
  • several putative hypoxia - response element
  • positive regulation of the promoter by circadian clock components (CLOCK, BMAL1 and BMAL2)
  • Greater promoter activation (2-fold) by BMAL/CLOCK heterodimers, acting on two E-boxes
    • MAPPING cloned Y linked Y status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    - - 3153 - 387 - Cajot (1990)
    9 - 3198 - 402 - Cajot (1990)
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessel   highly
    Lymphoid/Immunespleen   lowly
     thymus   lowly
    Nervousbrain   lowly
     nerve   moderately
    Reproductivefemale systemplacenta  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    Connective   moderately
    cells
    SystemCellPubmedSpeciesStageRna symbol
     fibroblast
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, pregnancy
    Text placenta, umbilical cord, embryonic tissue
    IMPRINTING maternally
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    conjugated GlycoP
    HOMOLOGY
    interspecies homolog to rattus Serpine1 (80.85 pc)
    homolog to murine Serpine1 (78.61 pc)
    Homologene
    FAMILY
  • serpin family
    • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    text
  • expressed in chromaffin cells, sorted into the regulated pathway of secretion (into catecholamine storage vesicles)
    • basic FUNCTION
  • inhibiting extracellular matrix degradation by PLAU
  • putative upregulated c-Myc target gene
  • playing a key role in control of coagulation and tissue remodeling
  • is an intracellular inhibitor of furin, having an active role in the development of metabolic disorders
  • antiapoptotic role for SERPINE1 that may contribute to its participation in neutrophil-associated inflammatory responses (
  • endothelial plasminogen activator inhibitor SERPINE1, controls vascular remodeling, angiogenesis and fibrinolysis
  • playing a role in regulation of angiogenesis
  • involved in the innate immunity by regulating cell migration and phagocytosis
  • glia-derived SERPINE1 may regulate microglial migration and phagocytosis in an autocrine or paracrine manner
  • promotes the proliferation, transforming into myofibroblasts, collagen synthesis, and inhibits apoptosis of pulmonary fibroblasts by activating Ca(2+), ERK and AKT signaling pathway
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS coagulation/hemostasis
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding of ELK1 to the SERPINE1 promoter and ELK1 phosphorylation on the Ets binding site is EGF-dependent
  • while SERPINE1 and SERPINB2 function similarly in the control of cellular plasmin generation by PLAT, they may have disparate effects on the alternative functions of PLAT via modulation of its engagement with endocytosis receptors
  • plays a critical role in mediating fibrosis caused by AGT and lends weight-of-evidence to a pro-fibrotic role of this protein in liver
  • DLC1 modulates the expression of SERPINE1, which is a negative regulator for cell migration, in a GAP domain and EGFR-MEK-dependent manner
  • the contribution of EGF to the regulation of SERPINE1 involves the MAPK pathway, and the synergistic interface with the TGFB pathway is downstream of MEK1/2 and involves phosphorylation of neither ERK1/2 nor SMAD2/3
  • estrogen regulates endothelial migration via SERPINE1
  • critical downstream target of SERPINE1-induced senescence
  • PLAT-SERPINE1 system regulates the senescence-inducing activity of IGFBP3
  • proapoptotic function of SERPINE1 is mediated through vitronectin (VTN) inhibition
    • cell & other
    REGULATION
    activated by oxygen
    Other regulated diferentially by CLOCK, BMAL1 and BMAL2
    ASSOCIATED DISORDERS
    corresponding disease(s) PAI1 , TRBR
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    by demethylation in oral squamous cell carcinomas but also normal oral mucosa (Gao 2010)
    Susceptibility
  • contributor in association with ITGB3 in susceptibility to myocardial infarction in Finnish population (see ITGB3)
  • to meningococcal sepsis and to bleeding diathesis
  • to thrombosis in vessels of internal organs
  • to preterm delivery
    • Variant & Polymorphism SNP , other
  • 4G/4G homozygosity, risk factor for severe preeclampsia and thrombosis in vessels of internal organs
  • 4G/5G risk factor for deep venous thrombosis (in subjects with other thrombophilic defects)
  • polymorphisms protecting against preterm delivery
    • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • transient impaired placental morphology in Pai1-deficient mice that is then normalized, leading to normal embryonic development