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Protein

Plasminogen activator inhibitor 1

Gene

SERPINE1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Serine protease inhibitor. This inhibitor acts as 'bait' for tissue plasminogen activator, urokinase, protein C and matriptase-3/TMPRSS7. Its rapid interaction with PLAT may function as a major control point in the regulation of fibrinolysis.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei369 – 370Reactive bond2

GO - Molecular functioni

  • protease binding Source: UniProtKB
  • receptor binding Source: BHF-UCL
  • serine-type endopeptidase inhibitor activity Source: BHF-UCL

GO - Biological processi

  • angiogenesis Source: UniProtKB
  • cellular response to lipopolysaccharide Source: BHF-UCL
  • chronological cell aging Source: BHF-UCL
  • circadian rhythm Source: Reactome
  • defense response to Gram-negative bacterium Source: BHF-UCL
  • extracellular matrix organization Source: Reactome
  • fibrinolysis Source: Reactome
  • negative regulation of blood coagulation Source: BHF-UCL
  • negative regulation of cell adhesion mediated by integrin Source: BHF-UCL
  • negative regulation of cell migration Source: BHF-UCL
  • negative regulation of endopeptidase activity Source: BHF-UCL
  • negative regulation of endothelial cell apoptotic process Source: BHF-UCL
  • negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: BHF-UCL
  • negative regulation of fibrinolysis Source: BHF-UCL
  • negative regulation of plasminogen activation Source: BHF-UCL
  • negative regulation of smooth muscle cell-matrix adhesion Source: BHF-UCL
  • negative regulation of smooth muscle cell migration Source: BHF-UCL
  • negative regulation of vascular wound healing Source: BHF-UCL
  • negative regulation of wound healing Source: BHF-UCL
  • platelet degranulation Source: Reactome
  • positive regulation of angiogenesis Source: BHF-UCL
  • positive regulation of blood coagulation Source: BHF-UCL
  • positive regulation of inflammatory response Source: BHF-UCL
  • positive regulation of interleukin-8 production Source: BHF-UCL
  • positive regulation of leukotriene production involved in inflammatory response Source: BHF-UCL
  • positive regulation of monocyte chemotaxis Source: BHF-UCL
  • positive regulation of receptor-mediated endocytosis Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: Reactome
  • regulation of receptor activity Source: BHF-UCL

Keywordsi

Molecular functionProtease inhibitor, Serine protease inhibitor

Enzyme and pathway databases

ReactomeiR-HSA-114608. Platelet degranulation.
R-HSA-1368108. BMAL1:CLOCK,NPAS2 activates circadian gene expression.
R-HSA-2173796. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
R-HSA-3000178. ECM proteoglycans.
R-HSA-75205. Dissolution of Fibrin Clot.
SIGNORiP05121.

Protein family/group databases

MEROPSiI04.020.

Names & Taxonomyi

Protein namesi
Recommended name:
Plasminogen activator inhibitor 1
Short name:
PAI
Short name:
PAI-1
Alternative name(s):
Endothelial plasminogen activator inhibitor
Serpin E1
Gene namesi
Name:SERPINE1
Synonyms:PAI1, PLANH1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000106366.8.
HGNCiHGNC:8583. SERPINE1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Plasminogen activator inhibitor-1 deficiency (PAI-1D)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA hematologic disorder characterized by increased bleeding after trauma, injury, or surgery. Affected females have menorrhagia. The bleeding defect is due to increased fibrinolysis of fibrin blood clots due to deficiency of plasminogen activator inhibitor-1, which inhibits tissue and urinary activators of plasminogen.
See also OMIM:613329
High concentrations of SERPINE1 seem to contribute to the development of venous but not arterial occlusions.

Organism-specific databases

DisGeNETi5054.
MalaCardsiSERPINE1.
MIMi613329. phenotype.
OpenTargetsiENSG00000106366.
Orphaneti465. Congenital plasminogen activator inhibitor type 1 deficiency.
PharmGKBiPA261.

Chemistry databases

ChEMBLiCHEMBL3475.
DrugBankiDB00009. Alteplase.
DB00029. Anistreplase.
DB00055. Drotrecogin alfa.
DB05254. Plasmin.
DB00015. Reteplase.
DB00031. Tenecteplase.
DB00197. Troglitazone.
DB00013. Urokinase.

Polymorphism and mutation databases

BioMutaiSERPINE1.
DMDMi129576.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Add BLAST23
ChainiPRO_000003249924 – 402Plasminogen activator inhibitor 1Add BLAST379

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi232N-linked (GlcNAc...) asparagine1
Glycosylationi288N-linked (GlcNAc...) asparagine1
Glycosylationi352N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Inactivated by proteolytic attack of the urokinase-type (u-PA) and the tissue-type (TPA), cleaving the 369-Arg-|-Met-370 bond.

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiP05121.
MaxQBiP05121.
PaxDbiP05121.
PeptideAtlasiP05121.
PRIDEiP05121.

2D gel databases

OGPiP05121.
SWISS-2DPAGEiP05121.

PTM databases

iPTMnetiP05121.
PhosphoSitePlusiP05121.
UniCarbKBiP05121.

Miscellaneous databases

PMAP-CutDBiP05121.

Expressioni

Tissue specificityi

Found in plasma and platelets and in endothelial, hepatoma and fibrosarcoma cells.

Gene expression databases

BgeeiENSG00000106366.
CleanExiHS_SERPINE1.
ExpressionAtlasiP05121. baseline and differential.
GenevisibleiP05121. HS.

Organism-specific databases

HPAiHPA050039.

Interactioni

Subunit structurei

Forms protease inhibiting heterodimer with TMPRSS7. Interacts with VTN. Binds LRP1B; binding is followed by internalization and degradation.2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • protease binding Source: UniProtKB
  • receptor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi111091. 16 interactors.
IntActiP05121. 13 interactors.
MINTiMINT-202409.
STRINGi9606.ENSP00000223095.

Chemistry databases

BindingDBiP05121.

Structurei

Secondary structure

1402
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi27 – 49Combined sources23
Beta strandi51 – 53Combined sources3
Beta strandi55 – 57Combined sources3
Helixi59 – 72Combined sources14
Helixi75 – 85Combined sources11
Helixi94 – 106Combined sources13
Helixi108 – 110Combined sources3
Beta strandi111 – 123Combined sources13
Helixi132 – 140Combined sources9
Beta strandi145 – 147Combined sources3
Helixi149 – 151Combined sources3
Helixi152 – 165Combined sources14
Turni166 – 169Combined sources4
Beta strandi170 – 172Combined sources3
Helixi176 – 179Combined sources4
Beta strandi186 – 200Combined sources15
Helixi204 – 206Combined sources3
Beta strandi209 – 213Combined sources5
Beta strandi216 – 218Combined sources3
Beta strandi219 – 237Combined sources19
Turni239 – 241Combined sources3
Beta strandi243 – 251Combined sources9
Beta strandi254 – 265Combined sources12
Helixi271 – 274Combined sources4
Helixi279 – 288Combined sources10
Beta strandi290 – 299Combined sources10
Beta strandi301 – 308Combined sources8
Helixi310 – 315Combined sources6
Helixi320 – 322Combined sources3
Turni324 – 326Combined sources3
Turni330 – 332Combined sources3
Beta strandi334 – 336Combined sources3
Beta strandi340 – 351Combined sources12
Beta strandi353 – 368Combined sources16
Beta strandi374 – 376Combined sources3
Beta strandi380 – 387Combined sources8
Turni388 – 391Combined sources4
Beta strandi392 – 400Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A7CX-ray1.95A24-402[»]
1B3KX-ray2.99A/B/C/D24-402[»]
1C5GX-ray2.60A1-402[»]
1DB2X-ray2.70A/B26-402[»]
1DVMX-ray2.40A/B/C/D24-402[»]
1DVNX-ray2.10A24-402[»]
1LJ5X-ray1.80A24-402[»]
1OC0X-ray2.28A24-402[»]
3CVMX-ray2.02A/B21-402[»]
3EOXX-ray2.61A24-402[»]
3PB1X-ray2.30I24-402[»]
3Q02X-ray2.30A/B24-402[»]
3Q03X-ray2.64A/B24-402[»]
3R4LX-ray2.70A24-402[»]
3UT3X-ray2.42A/B/C/D28-402[»]
4AQHX-ray2.40A/B/C24-402[»]
4G8OX-ray2.71A/B/C/D28-402[»]
4G8RX-ray2.19A/B28-402[»]
4IC0X-ray2.32A/B/C/D24-402[»]
5BRRX-ray3.16I24-402[»]
9PAIX-ray2.70A24-369[»]
B370-402[»]
DisProtiDP00320.
ProteinModelPortaliP05121.
SMRiP05121.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP05121.

Family & Domainsi

Sequence similaritiesi

Belongs to the serpin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG2392. Eukaryota.
COG4826. LUCA.
GeneTreeiENSGT00900000140788.
HOGENOMiHOG000238519.
HOVERGENiHBG106493.
InParanoidiP05121.
KOiK03982.
OMAiPYEKEVP.
OrthoDBiEOG091G0ION.
PhylomeDBiP05121.
TreeFamiTF352620.

Family and domain databases

InterProiView protein in InterPro
IPR023795. Serpin_CS.
IPR023796. Serpin_dom.
IPR000215. Serpin_fam.
IPR036186. Serpin_sf.
PANTHERiPTHR11461. PTHR11461. 1 hit.
PfamiView protein in Pfam
PF00079. Serpin. 1 hit.
SMARTiView protein in SMART
SM00093. SERPIN. 1 hit.
SUPFAMiSSF56574. SSF56574. 1 hit.
PROSITEiView protein in PROSITE
PS00284. SERPIN. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P05121-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MQMSPALTCL VLGLALVFGE GSAVHHPPSY VAHLASDFGV RVFQQVAQAS
60 70 80 90 100
KDRNVVFSPY GVASVLAMLQ LTTGGETQQQ IQAAMGFKID DKGMAPALRH
110 120 130 140 150
LYKELMGPWN KDEISTTDAI FVQRDLKLVQ GFMPHFFRLF RSTVKQVDFS
160 170 180 190 200
EVERARFIIN DWVKTHTKGM ISNLLGKGAV DQLTRLVLVN ALYFNGQWKT
210 220 230 240 250
PFPDSSTHRR LFHKSDGSTV SVPMMAQTNK FNYTEFTTPD GHYYDILELP
260 270 280 290 300
YHGDTLSMFI AAPYEKEVPL SALTNILSAQ LISHWKGNMT RLPRLLVLPK
310 320 330 340 350
FSLETEVDLR KPLENLGMTD MFRQFQADFT SLSDQEPLHV AQALQKVKIE
360 370 380 390 400
VNESGTVASS STAVIVSARM APEEIIMDRP FLFVVRHNPT GTVLFMGQVM

EP
Length:402
Mass (Da):45,060
Last modified:August 13, 1987 - v1
Checksum:iA2E181ED28DD6082
GO
Isoform 2 (identifier: P05121-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     31-45: Missing.

Note: No experimental confirmation available.
Show »
Length:387
Mass (Da):43,404
Checksum:i9BFE4D37D0F81361
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti53R → A in CAA31208 (Ref. 7) Curated1
Sequence conflicti55V → L in AAA60009 (PubMed:2820474).Curated1
Sequence conflicti75G → V in CAA31208 (Ref. 7) Curated1
Sequence conflicti138R → K in CAA31208 (Ref. 7) Curated1
Sequence conflicti226A → V in BAH12656 (PubMed:14702039).Curated1
Sequence conflicti280 – 282QLI → HVM in CAA31208 (Ref. 7) Curated3

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00709915A → T3 PublicationsCorresponds to variant dbSNP:rs6092Ensembl.1
Natural variantiVAR_01175017V → I2 PublicationsCorresponds to variant dbSNP:rs6090Ensembl.1
Natural variantiVAR_01308625H → P1 PublicationCorresponds to variant dbSNP:rs2227647Ensembl.1
Natural variantiVAR_013087209R → H1 PublicationCorresponds to variant dbSNP:rs2227669Ensembl.1
Natural variantiVAR_013088255T → N1 PublicationCorresponds to variant dbSNP:rs2227685Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04549331 – 45Missing in isoform 2. 1 PublicationAdd BLAST15

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X04429 mRNA. Translation: CAA28025.1.
M14083 mRNA. Translation: AAA60008.1.
X04729 mRNA. Translation: CAA28438.1.
X04731 mRNA. Translation: CAA28442.1.
M16006 mRNA. Translation: AAA60003.1.
M22321
, M22314, M22315, M22316, M22317, M22318, M22319, M22320 Genomic DNA. Translation: AAA60009.1.
X13323 Genomic DNA. No translation available.
X13338 Genomic DNA. Translation: CAA31722.1.
X13339 Genomic DNA. Translation: CAB51639.1.
X13340 Genomic DNA. Translation: CAB51737.1.
X13341 Genomic DNA. Translation: CAB51606.1.
X13342 Genomic DNA. Translation: CAB51607.1.
X13343 Genomic DNA. Translation: CAB51738.1.
X13344 Genomic DNA. Translation: CAB51739.1.
X13345 Genomic DNA. Translation: CAA31729.1.
J03764 Genomic DNA. Translation: AAA60007.1.
X12701 mRNA. Translation: CAA31208.1.
AF386492 Genomic DNA. Translation: AAK60338.1.
AK297728 mRNA. Translation: BAH12656.1.
AC004876 Genomic DNA. Translation: AAD45828.1.
BC010860 mRNA. Translation: AAH10860.1.
X04744 mRNA. Translation: CAA28444.1.
CCDSiCCDS5711.1. [P05121-1]
PIRiA28107. ITHUP1.
RefSeqiNP_000593.1. NM_000602.4. [P05121-1]
UniGeneiHs.414795.
Hs.713079.
Hs.741440.

Genome annotation databases

EnsembliENST00000223095; ENSP00000223095; ENSG00000106366. [P05121-1]
GeneIDi5054.
KEGGihsa:5054.
UCSCiuc003uxt.4. human. [P05121-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPAI1_HUMAN
AccessioniPrimary (citable) accession number: P05121
Secondary accession number(s): B7Z4S0, F8WD53
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: August 13, 1987
Last modified: October 25, 2017
This is version 211 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families