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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001165413 - - 3153 NP_001158885 - 387 - Cajot (1990) NM_000602 9 - 3198 NP_000593 - 402 - Cajot (1990)

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular vessel       highly Lymphoid/Immune spleen       lowly   thymus       lowly Nervous brain       lowly   nerve       moderately Reproductive female system placenta     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     highly Connective       moderately

cells

System Cell Pubmed Species Stage Rna 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
	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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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