Gene Report

Basic Information

Approved Symbol	SERPINE1
Approved Name	serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1
Previous Symbol	PLANH1, PAI1
Previous Name	"serine (or cysteine) proteinase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1"
Symbol Alias	PAI
Name Alias	"plasminogen activator inhibitor, type I"
Location	7q22.1
Position	chr7:100780724-100782531 (+)
External Links	Entrez Gene: 5054 Ensembl: ENSG00000106366 UCSC: uc003uxt.4 HGNC ID: 8583
No. of Studies (Positive/Negative)	1(1/0)
Type	Literature-origin

Positive relationships between SERPINE1 and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
SERPINE1	Tsai, 2008	patients and normal controls	P-value=0.010	In single-marker-based analysis, the rs2227684-G and rs7242-...... In single-marker-based analysis, the rs2227684-G and rs7242-T alleles were more frequent in MDD patients than in controls (P=0.010 and 0.010, respectively) More...

Positive relationships between SERPINE1 and other components at different levels (count: 0)

Positive relationship network of SERPINE1 in MK4MDD

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Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between SERPINE1 and MDD (count: 0)

Negative relationships between SERPINE1 and other components at different levels (count: 0)

SERPINE1 related SNPs in MK4MDD (count: 0)

SERPINE1 related proteins in MK4MDD (count: 0)

SERPINE1 related GO terms (count: 47)

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0030195	negative regulation of blood coagulation	biological process	IC[1695900]
GO:0031012	extracellular matrix	cellular component	IDA[1632457]
GO:0007623	circadian rhythm	biological process	TAS
GO:0005886	plasma membrane	cellular component	TAS
GO:0002576	platelet degranulation	biological process	TAS
GO:0006367	transcription initiation from RNA polymerase II promoter	biological process	TAS
GO:0030198	extracellular matrix organization	biological process	TAS
GO:1902042	negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	biological process	IMP[18835034]
GO:0005615	extracellular space	cellular component	IDA[1695900\|18835034]
GO:0061044	negative regulation of vascular wound healing	biological process	IGI[9386191]
GO:0004867	serine-type endopeptidase inhibitor activity	molecular function	IDA[1695900\|8508955]
GO:0042127	regulation of cell proliferation	biological process	IEA
GO:2000352	negative regulation of endothelial cell apoptotic process	biological process	IMP[18835034]
GO:0005515	protein binding	molecular function	IPI[16272158\|25416956]
GO:0033629	negative regulation of cell adhesion mediated by integrin	biological process	IDA[8837777]
GO:0048260	positive regulation of receptor-mediated endocytosis	biological process	IDA[8626514]
GO:0014912	negative regulation of smooth muscle cell migration	biological process	IDA[8837777]
GO:0030336	negative regulation of cell migration	biological process	IDA[10902815]
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	biological process	TAS
GO:0007179	transforming growth factor beta receptor signaling pathway	biological process	TAS
GO:0001890	placenta development	biological process	IEA
GO:0031093	platelet alpha granule lumen	cellular component	TAS
GO:0061045	negative regulation of wound healing	biological process	IC[8837777]
GO:0010469	regulation of receptor activity	biological process	IDA[8837777]
GO:0001300	chronological cell aging	biological process	IEP[18974388]
GO:0007596	blood coagulation	biological process	TAS
GO:2000098	negative regulation of smooth muscle cell-matrix adhesion	biological process	IDA[8837777]
GO:0010951	negative regulation of endopeptidase activity	biological process	IDA[1695900]
GO:0071222	cellular response to lipopolysaccharide	biological process	IMP[19916862]
GO:0032757	positive regulation of interleukin-8 production	biological process	IMP[19916862]
GO:0005102	receptor binding	molecular function	IPI[8626514]
GO:0001525	angiogenesis	biological process	IEP[11866539]
GO:0002020	protease binding	molecular function	IPI[2503541\|8508955\|8626514\|12114510\|15853774]
GO:0030168	platelet activation	biological process	TAS
GO:0090026	positive regulation of monocyte chemotaxis	biological process	IMP[19916862]
GO:0042730	fibrinolysis	biological process	TAS
GO:0010757	negative regulation of plasminogen activation	biological process	IDA[8508955]; IMP[18835034\|19855083]
GO:0010467	gene expression	biological process	TAS
GO:0070062	extracellular exosome	cellular component	IDA[21276792]
GO:0045766	positive regulation of angiogenesis	biological process	IMP[18835034]
GO:0030194	positive regulation of blood coagulation	biological process	IMP[9207454]
GO:0051918	negative regulation of fibrinolysis	biological process	IDA[2503541]
GO:0050729	positive regulation of inflammatory response	biological process	IGI[17032919]
GO:0035491	positive regulation of leukotriene production involved in inflammatory response	biological process	IMP[19916862]
GO:0005576	extracellular region	cellular component	IDA[9386191]; TAS
GO:0006351	transcription, DNA-templated	biological process	TAS
GO:0050829	defense response to Gram-negative bacterium	biological process	IGI[17032919]

SERPINE1 related KEGG pathways (count: 2)

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa04610	complement and_coagulation_cascades	Complement and coagulation cascades	Blood coagulation is a series of coordinated and calcium-dep...... Blood coagulation is a series of coordinated and calcium-dependent proenzyme-to-serine protease conversions likely to be localized on the surfaces of activated cells in vivo. It culminates in the formation of thrombin, the enzyme responsible for the conversion of soluble fibrinogen to the insoluble fibrin clot. The kallikrein-kinin system is an endogenous metabolic cascade, triggering of which results in the release of vasoactive kinins (bradykinin-related peptides). Kinin peptides are implicated in many physiological and pathological processes including the regulation of blood pressure and sodium homeostasis, inflammatory processes, and the cardioprotective effects of preconditioning. Complement is a system of plasma proteins that is activated by the presence of pathogens. There are three pathways of complement activation: the classical pathway, the lectin pathway, and the alternative pathway. All of these pathways generate a crucial enzymatic activity that, intern, generates the effector molecules of complement. The three main consequences of complement activation are the opsonization of pathogens, the recruitment of inflammatory and immunocompetent cells, and the direct killing of pathogens. More...
hsa04115	p53 signaling_pathway	p53 signaling pathway	p53 activation is induced by a number of stress signals, inc...... p53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated genes. This results in three major outputs; cell cycle arrest, cellular senescence or apoptosis. Other p53-regulated gene functions communicate with adjacent cells, repair the damaged DNA or set up positive and negative feedback loops that enhance or attenuate the functions of the p53 protein and integrate these stress responses with other signal transduction pathways. More...

SERPINE1 related BioCarta pathways (count: 2)

ID	Name	Brief Description	Full Description
Gene mapped BioCarta pathways
PLATELETAPP_PATHWAY	plateletapp pathway	Platelet Amyloid Precursor Protein Pathway	The amyloid -beta peptide (Ab), a proteolytic fragment of am...... The amyloid -beta peptide (Ab), a proteolytic fragment of amyloid precursor protein (APP), is the major componenet of senile plaques, the hallmark of alzhemiers disease. Platelets contain both APP and Ab and probably contribute greater than 90% of circulating APP. The soluble APP is the major inhibitor of coagulation factors IXa and XIa, and platelet aggregation. Agonists such as ADP, thrombin, epinephrine and collagen activate the release of APP and plasminogen activator inhibitor I (an important regulator of coagulation) from platelet storage granules. These important molecules released from platelets are key regulators of hemostasis, the physiologic arrest of hemorrhage at site of vascular leakage. More...
FIBRINOLYSIS_PATHWAY	fibrinolysis pathway	Fibrinolysis Pathway	Clot formation and fibrinolysis is a balance of plasmin acti...... Clot formation and fibrinolysis is a balance of plasmin activation/inhibition and thrombin-thrombomodulin activity that regulates fibrin polymer formation and degradation. Active thrombin is produced by the cleavage of prothrombin in the intrinsic thrombin activation pathway or the extrinsic thrombin activation pathway. Cleavage of fibrinogen by thrombin releases the fibrin monomers that auto-polymerize within seconds into fibrin threads or fibers. The coagulation cascade has many feedback loops. One example is the binding of thrombin to the fibrin polymers resulting in a reduction in soluble thrombin. The fibers form a more stable clot as a result of the covalent bonds formed by activated factor XIII enzyme (also known as Fibrin stabilizing factor). These fibers form a mesh the traps platelets, blood cells and plasma to form a clot. The removal of the clot is caused by plasmin cleavage of the fibrin monomers into soluble fibrin degradation products. Plasmin is formed by the cleavage of plasminogen between Arg561 and Val562. Plasmin is a two-chain trypsin-like serine protease. Plasminogen activator inhibitor 1 (PAI1) and plasminogen activator inhibitor 2 (PAI2) inhibit cleavage of plasminogen by tissue-type plasminogen activator (tPA) or urokinase plasminogen activator (uPA). The presence of fibrin fibers and fibrin degradation products exert a two-fold stimulation of tPA and uPA. Plasmin activity is also inhibited by alpha2-antiplasmin. Thrombin activatable fibrinolysis inhibitor (TAFI) is a carboxy-peptidase B-like proenzyme activated by the thrombin-thrombomodulin dimer. TAFI cleaves (DD)E2 to separate DD and E fragments which do not enhance the activation of tPA or uPA and results in a reduced feedback signal. Disease Significance: Overabundance or increased activity of the plamsminogen activator inhibitors or reduced presence or function of tPA or uPA can result in atherosclerotic disease and venous thrombosis due to an increase in fibrin deposition or formation of a thrombus. Thrombosis can also result from plasminogen deficiency caused by a lack of protein or lack of functional protein. Reduced or depleted levels of alpha2-antiplamin can result in severe bleeding disorders. More...

SERPINE1 related Reactome pathways (count: 4)

ID	Name	Description
Gene mapped Reactome pathways
REACT_604	hemostasis	Two principal mechanisms limit blood loss after vascular inj...... Two principal mechanisms limit blood loss after vascular injury. Initially, platelets are activated, adhere to the site of the injury, and aggregate into a plug that limits blood loss. Proteins and small molecules released from activated platelets stimulate the plug formation process, and fibrinogen from the plasma forms bridges between activated platelets. These events allow the initiation of the clotting cascade, the second mechanism to limit blood loss. Negatively charged phospholipids exposed on cell surfaces at the site of injury and on activated platelets interact with tissue factor, setting off a cascade of reactions leading to generation of fibrin and the formation of an insoluble fibrin clot that strengthens the platelet plug. More...
REACT_20	formation of_platelet_plug	Hemostasis is a physiological response that culminates in th...... Hemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Acute vessel injury results in its constriction to reduce the loss of blood. Under normal conditions vascular endothelium supports vasodilation, inhibits platelet adhesion and activation, suppresses coagulation, enhances fibrin cleavage and is anti-inflammatory in character. Under acute vascular trauma vasoconstrictor mechanisms predominate and the endothelium becomes prothrombotic, procoagulatory and proinflammatory in nature. This is achieved by a reduction of endothelial dilating agents: adenosine, NO and prostacyclin; and the direct action of ADP, serotonin and thromboxane on vascular smooth muscle cells to elicit their contraction. The chief trigger for the change in endothelial function that leads to the formation of haemostatic thrombus is the loss of the endothelial cell barrier between blood and ECM components. Circulating platelets identify and discriminate areas of endothelial lesions; here, they adhere to the exposed sub endothelium. Their interaction with the various thrombogenic substrates and locally generated or released agonists results in platelet activation. This process is described as possessing two stages, firstly, adhesion - the initial tethering to a surface, and secondly aggregation - the platelet-platelet cohesion. More...
REACT_798	platelet activation	Platelet activation begins with the initial binding of adhes...... Platelet activation begins with the initial binding of adhesive ligands and of the excitatory platelet agonists. Intracellular signaling reactions will then enhance the adhesive and procoagulant properties of tethered platelets or of platelets circulating in the proximity. From the subendothelial adhesive substrates, collagen and possibly vWF are the main inducers of platelet activation. GP VI is the most potent collagen receptor initiating signal generation, an ability derived from its interaction with the FcRI gamma chain. This results in the phosphorylation of the gamma-chain by the non-receptor tyrosine kinases of the Src family. The phosphotyrosine motif is recognized by the SH2 domains of Syk, a tyrosine kinase. This association activates the Syk enzyme, leading to activation. Four PARs are identified, of which PARs 1 ,3 and 4 are substrates for thrombin. PAR 1 is the predominant thrombin receptor, PAR 3 is minimally expressed and PAR 4 is less responsive to thrombin. Platelets do not store PAR1, due to limited protein synthesis, they are capable of responding to thrombin only once. Platelet activation further results in the scramblase-mediated transport of negatively-charged phospholipids to the platelet surface. These phospholipids provide a catalytic surface (with the charge provided by phosphatidylserine and phosphatidylethanolamine) for the tenase complex (formed by the activated forms of the blood coagulation factors factor VIII and factor I). More...
REACT_318	platelet degranulation	Platelets function as exocytotic cells, secreting a plethora...... Platelets function as exocytotic cells, secreting a plethora of effector molecules at sites of vascular injury. Platelets contain a number of distinguishable storage granules including alpha granules, dense granules and lysosomes. On activation platelets release a variety of proteins, largely from storage granules but also as the result of apparent cell lysis. These act in an autocrine or paracrine fashion to modulate cell signaling. Alpha granules contain mainly polypeptides such as fibrinogen, von Willebrand factor, growth factors and protease inhibitors that that supplement thrombin generation at the site of injury. Dense granules contain small molecules, particularly adenosine diphosphate (ADP), adenosine triphosphate (ATP), serotonin and calcium, all recruit platelets to the site of injury. More...

SERPINE1 related interactors from protein-protein interaction data in HPRD (count: 17)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
SERPINE1	LRP2	No	in vitro	8344937
SERPINE1	ACTN4	No	in vitro;in vivo;yeast 2-hybrid	15493875
SERPINE1	SERPINE1	Yes	in vitro	10731421
SERPINE1	VTN	No	in vitro;in vivo	8830783 , 11796824 , 9065424 , 12808446
SERPINE1	IGFBP5	No	in vitro;in vivo	9202242
SERPINE1	ORM1	No	in vitro;yeast 2-hybrid	11418606
SERPINE1	LRP1B	No	in vivo	11384978
SERPINE1	PLAU	No	in vitro;in vivo	2161846 , 2544876 , 3090045
SERPINE1	MMP3	No	in vitro	10967118
SERPINE1	KRT18	No	in vitro;yeast 2-hybrid	15493875
SERPINE1	LRP1	No	in vitro;in vivo	15001579
SERPINE1	KLK2	No	in vivo	10209959
SERPINE1	ELANE	No	in vitro	7521069
SERPINE1	PLAT	No	in vitro;in vivo	2110366 , 8607113 , 3090045
SERPINE1	F2	No	in vitro	10543954
SERPINE1	UBQLN4	No	yeast 2-hybrid	16713569
SERPINE1	PLG	No	in vitro	11113116

Gene Report

Gene mapped GO terms

Gene mapped KEGG pathways

Gene mapped BioCarta pathways

Gene mapped Reactome pathways