SERPINE1: Polycystic Ovarian Syndrome Database

Home

Search
- Quick Search
- Advanced Search

Browse
- Genes
- miRNAs
- SNPs
- Diseases
  - Genes
  - miRNAs
- Pathways
- Ontologies

Tools

Help

SERPINE1

Gene Information

Gene Ontology (GO)

Protein Information

Associated Diseases

Pathways

References

Gene Information

Gene Symbol

SERPINE1

Aliases

PAI, PAI-1, PAI1, PLANH1

Entrez Gene ID

5054

Gene Name

Serpin family E member 1

Chromosomal Location

7q22.1

HGNC ID

HGNC:8583

Summary

This gene encodes a member of the serine proteinase inhibitor (serpin) superfamily. This member is the principal inhibitor of tissue plasminogen activator (tPA) and urokinase (uPA), and hence is an inhibitor of fibrinolysis. Defects in this gene are the cause of plasminogen activator inhibitor-1 deficiency (PAI-1 deficiency), and high concentrations of the gene product are associated with thrombophilia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

RefSeq DNA

NG_013213.1

RefSeq mRNA

NM_000602.5, NM_000602.4

e!Ensembl

Gene	ENSG00000106366
Transcript	ENST00000223095
Protein	ENSP00000223095

Gene Ontology (GO)

Show/Hide all(41 )

GO ID	Ontology	Function	Evidence	Reference
GO:0001300	Biological process	Chronological cell aging	IEP	18974388
GO:0001525	Biological process	Angiogenesis	IEP	11866539
GO:0010469	Biological process	Regulation of signaling receptor activity	IDA	8837777
GO:0010757	Biological process	Negative regulation of plasminogen activation	IDA	8508955
GO:0010757	Biological process	Negative regulation of plasminogen activation	IMP	18835034, 19855083
GO:0010951	Biological process	Negative regulation of endopeptidase activity	IBA	21873635
GO:0010951	Biological process	Negative regulation of endopeptidase activity	IDA	1695900
GO:0014912	Biological process	Negative regulation of smooth muscle cell migration	IDA	8837777
GO:0030194	Biological process	Positive regulation of blood coagulation	IMP	9207454
GO:0030195	Biological process	Negative regulation of blood coagulation	IC	1695900
GO:0030336	Biological process	Negative regulation of cell migration	IDA	10902815
GO:0032757	Biological process	Positive regulation of interleukin-8 production	IMP	19916862
GO:0033629	Biological process	Negative regulation of cell adhesion mediated by integrin	IDA	8837777
GO:0035491	Biological process	Positive regulation of leukotriene production involved in inflammatory response	IMP	19916862
GO:0045766	Biological process	Positive regulation of angiogenesis	IMP	18835034
GO:0048260	Biological process	Positive regulation of receptor-mediated endocytosis	IDA	8626514
GO:0050729	Biological process	Positive regulation of inflammatory response	IGI	17032919
GO:0050829	Biological process	Defense response to Gram-negative bacterium	IGI	17032919
GO:0051918	Biological process	Negative regulation of fibrinolysis	IDA	2503541
GO:0061044	Biological process	Negative regulation of vascular wound healing	IGI	9386191
GO:0061045	Biological process	Negative regulation of wound healing	IC	8837777
GO:0071222	Biological process	Cellular response to lipopolysaccharide	IMP	19916862
GO:0090026	Biological process	Positive regulation of monocyte chemotaxis	IMP	19916862
GO:0090399	Biological process	Replicative senescence	IMP	16862142
GO:0097187	Biological process	Dentinogenesis	IDA	27046084
GO:1901331	Biological process	Positive regulation of odontoblast differentiation	IDA	27046084
GO:1902042	Biological process	Negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	IMP	18835034
GO:2000098	Biological process	Negative regulation of smooth muscle cell-matrix adhesion	IDA	8837777
GO:2000352	Biological process	Negative regulation of endothelial cell apoptotic process	IMP	18835034
GO:0005576	Cellular component	Extracellular region	IDA	9386191
GO:0005615	Cellular component	Extracellular space	IBA	21873635
GO:0005615	Cellular component	Extracellular space	IDA	1695900, 18835034
GO:0062023	Cellular component	Collagen-containing extracellular matrix	HDA	23979707
GO:0062023	Cellular component	Collagen-containing extracellular matrix	HDA	28327460
GO:0062023	Cellular component	Collagen-containing extracellular matrix	IDA	1632457
GO:0070062	Cellular component	Extracellular exosome	IDA	21276792
GO:0002020	Molecular function	Protease binding	IPI	2503541, 8508955, 8626514, 12114510, 15853774
GO:0004867	Molecular function	Serine-type endopeptidase inhibitor activity	IBA	21873635
GO:0004867	Molecular function	Serine-type endopeptidase inhibitor activity	IDA	1695900, 8508955
GO:0005102	Molecular function	Signaling receptor binding	IPI	8626514
GO:0005515	Molecular function	Protein binding	IPI	16272158, 25416956, 28296156

Protein Information

Protein Name

Plasminogen activator inhibitor 1, endothelial plasminogen activator inhibitor, serine (or cysteine) proteinase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1, serpin E1, serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1

Function

Serine protease inhibitor. Inhibits TMPRSS7. Is a primary inhibitor of tissue-type plasminogen activator (PLAT) and urokinase-type plasminogen activator (PLAU). As PLAT inhibitor, it is required for fibrinolysis down-regulation and is responsible for the controlled degradation of blood clots. As PLAU inhibitor, it is involved in the regulation of cell adhesion and spreading (PubMed:9175705). Acts as a regulator of cell migration, independently of its role as protease inhibitor. It is required for stimulation of keratinocyte migration during cutaneous injury repair (PubMed:18386027). It is involved in cellular and replicative senescence. Plays a role in alveolar type 2 cells senescence in the lung (By similarity). Is involved in the regulation of cementogenic differentiation of periodontal ligament stem cells, and regulates odontoblast differentiation and dentin formation during odontogenesis

Refseq Proteins

NP_000593.1

UniProt

P05121

PDB

1A7C, 1B3K, 1C5G, 1DB2, 1DVM, 1DVN, 1LJ5, 1OC0, 3CVM, 3EOX, 3PB1, 3Q02, 3Q03, 3R4L, 3UT3, 4AQH, 4G8O, 4G8R, 4IC0, 5BRR, 5ZLZ, 6I8S, 9PAI

Pfam

Pfam Accession	Pfam ID
PF00079	Serpin

Pathways
	KEGG	Reactome
	HIF-1 signaling pathway p53 signaling pathway Cellular senescence Apelin signaling pathway Hippo signaling pathway Complement and coagulation cascades AGE-RAGE signaling pathway in diabetic complications Chagas disease (American trypanosomiasis)	Platelet degranulation BMAL1:CLOCK,NPAS2 activates circadian gene expression SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription ECM proteoglycans Dissolution of Fibrin Clot

Interactions

STRING	MINT	IntAct
ENSP00000358903	P05093	P05093

View interactions

Associated Diseases

Show/Hide all(8 )

Disease group	Disease Name	References
Cardiovascular Diseases
	Heart Failure	22352330
	Hypertensive disease	22352330, 21051829
	Atherosclerosis	12677255
	Myocardial Failure	22352330
Digestive System Diseases
	Fatty Liver	18641190
	Cholestasis	21224055
Endocrine System Diseases
	Glomerulosclerosis	18682491
	PCOS	15935829
Immune System Diseases
Immune System Diseases	Behcet Syndrome	12074830
Neoplasms
	Prostate cancer	16172807
	Stomach Cancer	16367923
	Liver Cancer	21159647
	Gastric Cancer	16367923
Nutritional and Metabolic Diseases
Nutritional and Metabolic Diseases	Obesity	23819014
Psychiatric/Brain disorders
	Autistic Disorder	19360663
	Mental Depression	18794724
	Obstructive Sleep Apnea	29968150, 24497664
Renal Disorder
	Glomerular Hyalinosis	18682491
	Glomerulosclerosis	18682491
	Nephrotic Syndrome	17513194
	Diabetic Nephropathy	18682491
	Kidney Failure	19420110

References

Show/Hide all(33)

PubMed ID	Associated gene/s	Associated condition	Genetic Mutation	Diagnostic Criteria	Association with PCOS	Ethnicity	Conclusion
16483878		Obesity, hyperinsulinemia, PCOS and hypertriglyceridemia	PAI-1 4G/5G gene polymorphisms		Related	101 Chinese�PCOS�patients and 42 controls	The PAI-1 gene 4G polymorphism is more common in women withPCOSthan in normal women and, in concert with obesity, hyperinsulinemia, and hypertriglyceridemia, contributes to treatable, hypofibrinolytic, miscarriage-promoting, high PAI-1 activity.
25558663		Pregnanacy loss	675 4G/5G		Direct	67 women with PCOS, 70 healthy controls	The carriers of polymorphism 4G are at greater risk for early pregnancy loss than those with 5G (61.45% as compared to 36.8%), which confirms that carriage of the polymorphism 4G/5G 675 gene PAI-1 has a specific in multifactorial pathogenesis and expression ofPCOS.
24435452			-675 4G/5G	NIH-NIHCD criteria, Rotterdam criteria	Direct	2,079 cases, 1,556 controls	The meta-analysis study suggests that PAI-1 -675 4G/5G polymorphism may contribute to increasing susceptibility to PCOS in Asians and might be a promising marker for the susceptibility of PCOS
23898913			-675 4G/5G		Related	79 PCOS, 79 healthy women	PAI-1 levels are positively correlated with proinflammatory factors in PCOS group
22995747	sVCAM-1, sICAM-1				Related	14 overweight women with and 13 overweight women without PCOS	Women with PCOS have elevated inflammatory markers, which are partially reduced by weight loss
19856137		Hypofibrinolysis	Promoter polymorphism (-844 A/G and -675 4G/5G) in the PAI-1 gene		Related		A trend to a positive interaction between PAI-1 -675 4G/5G and -844 A/G gene polymorphism may elevate plasma PAI-1 levels and hypofibrinolysis, which is probably an important hereditary risk factor inPCOS
19636212	ACE	Hypofibrinolysis,spontaneous abortions	PAI-1 4G/5G gene polymorphisms		Related	142 PCOS and 107 controls	PAI-1 4G/5G gene polymorphisms might represent risk factor inPCOS
19066200	MTHFR	PCOS	MTHFR C677T polymorphism		Related	7 concerning PAI-1 (1538 cases, 710 controls) and 6 concerning MTHFR C677T (223 cases, 392 controls)	PAI-1 4G/5G polymorphism seems to be associated with the risk of developing PCOS
19253106	TAFI, D-dimer, AT III, thrombomodulin				Direct	48 PCOS women, 43 BMI matched controls	This study showed that plasma levels of TAFI, PAI-1, D-dimer, AT III and thrombomodulin were significantly increased in women withPCOScompared with age- and BMI-matched controls.
22882325	MTHFR	Recurrent pregnancy loss	PAI-1 4G/5G mutations		Related	Iranian women-38 PCOS & 106 without PCOS(RPL-recurrent pregnancy loss)	Significance of MTHFR A1298C and PAI-1 4G/5G mutations in Iranian women suffering from RPL with and without PCOS.
21996594				Rotterdam criteria	Related	199 PCOS and 50 Control	Plasma PAI-1 levels are elevated in overweight/obese women with PCOS but not in normal weight women
21824047	INSR and IGF2				Related	117 PCOS and 105 control	PAI1 polymorphism seems to be associated with the risk of PCOS development
21468253	tPA				Related	101 PCOS	tPA and PAI-1 levels were higher, while D-dimer levels were lower in the PQ group than in the controls, implying that ROS stimulate tPA and PAI-1, but PAI-1 activity overrides tPA activity
20500107	tPA				Related	135 PCOSand 81controls	obese patients with PCOS displayed increased PAI-1 activity
17661167	TPAI			Rotterdam criteria	Related	86 young women with PCOS and 70 healthy control women	In this study it is shown by the analysis of TPA gene's Alu-repeat insertion/deletion (I/D) polymorphism the PCOS patients with genotype II had lowers total cholesterol and LDL-cholesterol levels.
16202290			4G/5G polymorphisms of PAI-1		Related	Chinese population (101 PCOS and 42 control)	PAI-1 gene polymorphism 4G genetype may be correlated with PCOS in Chinese women, especially in PCOS patients with non-obese PCOS and spontaneous miscarriage
16102886					Direct	Caucasian population (106 PCOS and 102 controls)	The 5G/4G polymorphism of the PAI1 promoter is not associated with occurrence and phenotype of the PCOS
15588467					Related	30 PCOS and 30women	PCOS have significantly elevated PAI-1 activity independent of obesity, and it is speculated that elevated PAI-1 activity may be a factor in the increased cardiovascular morbidity seen in PCOS
15516780				The diagnosis of PCOS was based on the clinical, menustral, laboratory and/or ultrasound criteria	Related	32 PCOS and 25 controls	PAI-1 Ag levels and activity were increased in lean PCOS women and these were directly correlated with insulin resistance
15191349			4G/5G polymorphism of PAI1		Related	98 patients and 64 controls	The genotypic subtypes 4G/4G and 4G/5G, in PCOS, were present with a statistically higher frequency compared with controls. PCOS women have higher levels of PAI-1 compared with the control group. The presence of the 4G allele in PAI-1 promoter region of the gene further increases the PAI-1 levels
12857431		Hyperinsulinism			Related	39 PCOS and 20 Control	associations between insulin and PAI-1 derangements, this is the first study to quantify discrete PAI-1 elevations that persist in the setting of PCOS even with normal or low ambient insulin levels
11809921					Related	33 PCOS and 13 controls	increased plasma PAI-1-act levels in early pubertal PP girls may indicate those girls with greater risk of developing hyperinsulinemic-hyperandrogenism features of PCOS
10923276					Related	5 PCOS	PAI-1 plays a role in human ovulation, but its role in PCOS requires further research
10762292					Direct	41 PCOS and 25 controls	PAI1 activity is not raised in women with PCOS independent of obesity and these results do not support the hypothesis that it may contribute to their anovulatory infertility, or increase their risk of thrombosis
10599993					Related	149 PCOS	PAI-Fx is a predominant independent significant positive reversible risk factor for miscarriage in women with PCOS.
23769971		PCOS	4G/5G polymorphism		Related	79�PCOS�and 79 healthy women	PAI-1 levels are positively correlated with proinflammatory factors inPCOSgroup
25731152		PCOS	4G/5G polymorphism		Direct	Chinese (Meta analysis)	The meta-analysis study suggest evidence for a major role of PAI-1 gene 4G/5G polymorphism in the pathogenesis of PCOS among Chinese patients.
25262763		PCOS, insulin resistance			Related	84 ( 22 overweight and 22 lean women with�PCOS, 18 overweight and 22 lean women without�PCOS)	PAI-1 may also be a novel independent biomarker and predictor of insulin resistance in women with and withoutPCOS
24439532		PCOS	4G/5G		Direct	2384 subjects (1615 with PCOS, 769 controls)	Meta-analysis suggests the PAI-1 4G/5G polymorphism is associated with susceptibility toPCOSin European, Turkish, and Asian populations
18812482		PCOS, metabolicsyndrome		NIH criteria	Related	43 with�PCOS, 31 controls	PCOSis associated with increased incidence of glucose intolerance and increasedplasminogen activatorinhibitor-1.
15935829		PCOS, insulin resistance			Related	64 patients with�polycystic ovary syndrome�(19 insulin-resistant and 45 insulin-sensitive) and 25 controls	Elevated basalplasminogen activatorinhibitor-1 levels were found in women withpolycystic ovary syndrome, correlating directly with insulin levels.
8977761					Related	24 PCO, 26 matched controls with a normal menstrual cycle and an ultrasound appearance of PCO, 10 matched controls with a normal menstrual cycle and normal ovarian ultrasound	The study finds that the only measurable vascular risk factor associated with hyperinsulinaemia and menstrual disturbance in non-obese women with PCOS is an elevated plasma PAI-1 activity
9496335					Related	11 PCOS and 12 controls	Women with the PCOS may have an imbalance in the PAI system that is tilted toward a reduced production of the proteolytic enzyme plasmin

Statistics

About BIC

Feedback

Links

Contact Us