SERPINE1 (serpin family E member 1)

Gene

• Entrez ID: 5054
• Gene name: Serpin family E member 1
• Gene symbol: SERPINE1
• Synonyms: PAI, PAI-1, PAI1, PLANH1
• Chromosome: 7
• Chromosome location: 7q22.1
• 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. The protein also functions as a component of innate antiviral immunity. 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. [provided by RefSeq, Aug 2020]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1799762	->G	Pathogenic, other	Upstream transcript variant
rs1194865614	->TA	Pathogenic	Coding sequence variant, frameshift variant
rs1554362148	->C	Pathogenic	Coding sequence variant, frameshift variant
rs1584902091	ACATGAGTTCATCTATTTCCTGCCCACATCTGGTATAAAAGGAGGCAGTGGCCCACAGAGGAGCACAGCTGTGTTTGGCTGCAGGGCCAAGAGCGCTGTCAAGAAGACCCACACGCCCCCCTCCAGCAGCTGAATTCCTGCAGCTCAGCAGCCGCCGCCAGAGCAGGACGAACCGCCAATCGCAAGGCACCTCTGAGAACTTCAGGTAGGAGAAAAGCAAACTCCCTCCAACCTCTTACTTCGGGCTTAAGGCAG	Likely-pathogenic	5 prime UTR variant, upstream transcript variant, intron variant, splice donor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT005844	hsa-miR-204-5p	Microarray	21282569
MIRT005971	hsa-miR-30c-5p	Luciferase reporter assay	21175428
MIRT005971	hsa-miR-30c-5p	PAR-CLIP	22012620
MIRT005971	hsa-miR-30c-5p	Luciferase reporter assay, qRT-PCR, Western blot	27819307
MIRT005972	hsa-miR-301a-3p	Luciferase reporter assay	21175428
MIRT005973	hsa-miR-99a-5p	Luciferase reporter assay	21175428
MIRT006316	hsa-miR-143-3p	Immunoblot, Luciferase reporter assay, qRT-PCR, Western blot	22108519
MIRT006316	hsa-miR-143-3p	Luciferase reporter assay, Western blot	26817521
MIRT006317	hsa-miR-145-5p	Immunoblot, Luciferase reporter assay, qRT-PCR, Western blot	22108519
MIRT006317	hsa-miR-145-5p	qRT-PCR	23312222
MIRT021688	hsa-miR-138-5p	qRT-PCR	21770894
MIRT022189	hsa-miR-124-3p	Microarray	18668037
MIRT053477	hsa-miR-148a-3p	Luciferase reporter assay, Microarray, qRT-PCR	21703006
MIRT054106	hsa-miR-486-5p	qRT-PCR	22995304
MIRT054139	hsa-miR-30b-5p	GFP reporter assay, Luciferase reporter assay, Northern blot, qRT-PCR, Western blot	25170877
MIRT054139	hsa-miR-30b-5p	PAR-CLIP	22012620
MIRT244292	hsa-miR-30a-5p	PAR-CLIP	22012620
MIRT244293	hsa-miR-30d-5p	PAR-CLIP	22012620
MIRT244294	hsa-miR-224-5p	PAR-CLIP	22012620
MIRT244295	hsa-miR-30e-5p	PAR-CLIP	22012620
MIRT244297	hsa-miR-6882-5p	PAR-CLIP	22012620
MIRT534384	hsa-miR-3977	PAR-CLIP	22012620
MIRT534385	hsa-miR-519d-5p	PAR-CLIP	22012620
MIRT534386	hsa-miR-3145-5p	PAR-CLIP	22012620
MIRT534387	hsa-miR-1273d	PAR-CLIP	22012620
MIRT731180	hsa-miR-10a-5p	qRT-PCR, ELISA, Luciferase reporter assay, Western blot	25554417
MIRT735499	hsa-miR-192-5p	Luciferase reporter assay, qRT-PCR, Western blot	27216198

Transcription factors

Transcription factor	Regulation	Reference
ARNTL2	Activation	22198637
E2F1	Repression	11402043;11559366
EPAS1	Activation	15039136
ESR1	Activation	15217907
ESR2	Repression	15217907
HIF1A	Unknown	11877282;14567996;17570486
HSF1	Activation	17259369;19401454
KLF10	Activation	12173049
NFKB1	Activation	11757833;12675842
NFKB1	Repression	15631825
NR4A1	Unknown	12506026
PARP1	Activation	22159350
PPARA	Activation	15631825
PPARA	Unknown	12667383
PPARG	Unknown	10073956
RELA	Activation	11757833;12675842
RELA	Repression	15631825
SMAD3	Activation	17761371;24330518;9765209
SMAD3	Unknown	10557285
SMAD4	Activation	9765209
SP1	Activation	15039136
SP1	Unknown	10880342;11251188
SRF	Repression	15514113
TGIF1	Repression	19524896
USF1	Activation	16902162
USF1	Unknown	12235287

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001525	Process	Angiogenesis	IEP	11866539
GO:0002020	Function	Protease binding	IPI	2503541, 8508955, 8626514, 12114510, 15853774
GO:0002576	Process	Platelet degranulation	TAS
GO:0004867	Function	Serine-type endopeptidase inhibitor activity	IBA	21873635
GO:0004867	Function	Serine-type endopeptidase inhibitor activity	IDA	1695900, 8508955
GO:0005102	Function	Signaling receptor binding	IPI	8626514
GO:0005515	Function	Protein binding	IPI	16272158, 25416956, 28296156, 32296183
GO:0005576	Component	Extracellular region	IDA	9386191
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA	21873635
GO:0005615	Component	Extracellular space	IDA	1695900, 18835034
GO:0005886	Component	Plasma membrane	TAS
GO:0007623	Process	Circadian rhythm	TAS
GO:0010469	Process	Regulation of signaling receptor activity	IDA	8837777
GO:0010757	Process	Negative regulation of plasminogen activation	IDA	8508955
GO:0010757	Process	Negative regulation of plasminogen activation	IMP	18835034, 19855083
GO:0010951	Process	Negative regulation of endopeptidase activity	IBA	21873635
GO:0010951	Process	Negative regulation of endopeptidase activity	IDA	1695900
GO:0014912	Process	Negative regulation of smooth muscle cell migration	IDA	8837777
GO:0030194	Process	Positive regulation of blood coagulation	IMP	9207454
GO:0030195	Process	Negative regulation of blood coagulation	IC	1695900
GO:0030198	Process	Extracellular matrix organization	TAS
GO:0030336	Process	Negative regulation of cell migration	IDA	10902815
GO:0031093	Component	Platelet alpha granule lumen	TAS
GO:0032757	Process	Positive regulation of interleukin-8 production	IMP	19916862
GO:0033629	Process	Negative regulation of cell adhesion mediated by integrin	IDA	8837777
GO:0035491	Process	Positive regulation of leukotriene production involved in inflammatory response	IMP	19916862
GO:0042730	Process	Fibrinolysis	TAS
GO:0045766	Process	Positive regulation of angiogenesis	IMP	18835034
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	TAS
GO:0048260	Process	Positive regulation of receptor-mediated endocytosis	IDA	8626514
GO:0050729	Process	Positive regulation of inflammatory response	IGI	17032919
GO:0050829	Process	Defense response to Gram-negative bacterium	IGI	17032919
GO:0051918	Process	Negative regulation of fibrinolysis	IDA	2503541
GO:0061044	Process	Negative regulation of vascular wound healing	IGI	9386191
GO:0061045	Process	Negative regulation of wound healing	IC	8837777
GO:0062023	Component	Collagen-containing extracellular matrix	HDA	23979707
GO:0062023	Component	Collagen-containing extracellular matrix	HDA	28327460
GO:0062023	Component	Collagen-containing extracellular matrix	IDA	1632457
GO:0070062	Component	Extracellular exosome	IDA	21276792
GO:0071222	Process	Cellular response to lipopolysaccharide	IMP	19916862
GO:0090026	Process	Positive regulation of monocyte chemotaxis	IMP	19916862
GO:0090399	Process	Replicative senescence	IMP	16862142
GO:0097187	Process	Dentinogenesis	IDA	27046084
GO:1901331	Process	Positive regulation of odontoblast differentiation	IDA	27046084
GO:1902042	Process	Negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	IMP	18835034
GO:2000098	Process	Negative regulation of smooth muscle cell-matrix adhesion	IDA	8837777
GO:2000352	Process	Negative regulation of endothelial cell apoptotic process	IMP	18835034

Other IDs

• MIM: 173360
• HGNC: 8583
• e!Ensembl: ENSG00000106366

Protein

• UniProt ID: P05121
• Protein name: Plasminogen activator inhibitor 1 (PAI) (PAI-1) (Endothelial plasminogen activator inhibitor) (Serpin E1)
• Protein function: Serine protease inhibitor. Inhibits TMPRSS7 (PubMed:15853774). 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 (PubMed:8481516, PubMed:9207454, PubMed:17912461). 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 (PubMed:15001579, PubMed:9168821). It is required for stimulation of keratinocyte migration during cutaneous injury repair (PubMed:18386027). It is involved in cellular and replicative senescence (PubMed:16862142). 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 (PubMed:25808697, PubMed:27046084).
• PDB: 1A7C, 1B3K, 1C5G, 1DB2, 1DVM, 1DVN, 1LJ5, 1OC0, 3CVM, 3EOX, 3PB1, 3Q02, 3Q03, 3R4L, 3UT3, 4AQH, 4G8O, 4G8R, 4IC0, 5BRR, 5ZLZ, 6GWN, 6GWP, 6GWQ, 6I8S, 6ZRV, 7AQF, 7AQG, 9PAI
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00079	Serpin	33 → 402	Serpin (serine protease inhibitor)	Domain

• Sequence:

  MQMSPALTCLVLGLALVFGEGSAVHHPPSYVAHLASDFGVRVFQQVAQASKDRNVVFSPY
  GVASVLAMLQLTTGGETQQQIQAAMGFKIDDKGMAPALRHLYKELMGPWNKDEISTTDAI
  FVQRDLKLVQGFMPHFFRLFRSTVKQVDFSEVERARFIINDWVKTHTKGMISNLLGKGAV
  DQLTRLVLVNALYFNGQWKTPFPDSSTHRRLFHKSDGSTVSVPMMAQTNKFNYTEFTTPD
  GHYYDILELPYHGDTLSMFIAAPYEKEVPLSALTNILSAQLISHWKGNMTRLPRLLVLPK
  FSLETEVDLRKPLENLGMTDMFRQFQADFTSLSDQEPLHVAQALQKVKIEVNESGTVASS
  STAVIVSARMAPEEIIMDRPFLFVVRHNPTGTVLFMGQVMEP

• Sequence length: 402