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FLASH GENE
Symbol SERPINE1 contributors: mct/npt - updated : 28-08-2016
HGNC name serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1
HGNC id 8583
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
  • HMGA1 has a direct role in regulating the transcription of PLAU and SERPINE1 which may constitute an important mechanism by which HMGA1 promotes cancer progression
  • 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