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Protein

Plasminogen activator inhibitor 1

Gene

SERPINE1

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

Functioni

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).By similarity11 Publications

Sites

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

GO - Molecular functioni

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

GO - Biological processi

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
MIMi173360 gene
neXtProtiNX_P05121

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)2 Publications
The disease is caused by mutations affecting the gene represented in this entry. A rare PAI-1D mutation resulting in a frameshift and protein truncation has been found in an Old Order Amish community. Homozygous mutation carriers suffer from episodes of major hemorrhage, while heterozygous carriers do not manifest abnormal bleeding (PubMed:9207454). Heterozygosity for the mutation is associated with longer leukocyte telomere length, lower fasting insulin levels, lower prevalence of diabetes mellitus, and a longer life span (PubMed:29152572).2 Publications
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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi197Q → C: Increased half-life of the active form when associated with C-355. 1 Publication1
Mutagenesisi355G → C: Increased half-life of the active form when associated with C-197. 1 Publication1

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
ProteomicsDBi51802

2D gel databases

OGPiP05121
SWISS-2DPAGEiP05121

PTM databases

GlyConnecti639
iPTMnetiP05121
PhosphoSitePlusiP05121
UniCarbKBiP05121

Miscellaneous databases

PMAP-CutDBiP05121

Expressioni

Tissue specificityi

Expressed in endothelial cells (PubMed:2430793, PubMed:3097076). Found in plasma, platelets, and hepatoma and fibrosarcoma cells.2 Publications

Gene expression databases

BgeeiENSG00000106366 Expressed in 173 organ(s), highest expression level in left coronary artery
CleanExiHS_SERPINE1
ExpressionAtlasiP05121 baseline and differential
GenevisibleiP05121 HS

Organism-specific databases

HPAiCAB068501
HPA050039

Interactioni

Subunit structurei

Forms a heterodimer with TMPRSS7 (PubMed:15853774). Interacts with VTN (PubMed:7522053). Binds LRP1B; binding is followed by internalization and degradation (PubMed:11384978). Interacts with PPP1CB (PubMed:28296156).4 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111091, 17 interactors
ComplexPortaliCPX-475 Vitronectin-PAI-1 complex
CPX-483 uPA-PAI-1 complex
CPX-494 tPA-PAI-1 complex
IntActiP05121, 14 interactors
MINTiP05121
STRINGi9606.ENSP00000223095

Chemistry databases

BindingDBiP05121

Structurei

Secondary structure

1402
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
GeneTreeiENSGT00930000150820
HOGENOMiHOG000238519
HOVERGENiHBG106493
InParanoidiP05121
KOiK03982
OMAiYFNGQWK
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:rs6092EnsemblClinVar.1
Natural variantiVAR_01175017V → I2 PublicationsCorresponds to variant dbSNP:rs6090EnsemblClinVar.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

Cross-referencesi

Web resourcesi

Wikipedia

Plasminogen activator inhibitor-1 entry

SeattleSNPs
Protein Spotlight

Giving in to time - Issue 203 of May 2018

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

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...

Protein-protein interaction databases

BioGridi111091, 17 interactors
ComplexPortaliCPX-475 Vitronectin-PAI-1 complex
CPX-483 uPA-PAI-1 complex
CPX-494 tPA-PAI-1 complex
IntActiP05121, 14 interactors
MINTiP05121
STRINGi9606.ENSP00000223095

Chemistry databases

BindingDBiP05121
ChEMBLiCHEMBL3475
DrugBankiDB00009 Alteplase
DB00029 Anistreplase
DB00055 Drotrecogin alfa
DB05254 Plasmin
DB00015 Reteplase
DB00031 Tenecteplase
DB00197 Troglitazone
DB00013 Urokinase

Protein family/group databases

MEROPSiI04.020

PTM databases

GlyConnecti639
iPTMnetiP05121
PhosphoSitePlusiP05121
UniCarbKBiP05121

Polymorphism and mutation databases

BioMutaiSERPINE1
DMDMi129576

2D gel databases

OGPiP05121
SWISS-2DPAGEiP05121

Proteomic databases

EPDiP05121
MaxQBiP05121
PaxDbiP05121
PeptideAtlasiP05121
PRIDEiP05121
ProteomicsDBi51802

Protocols and materials databases

DNASUi5054
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi5054
DisGeNETi5054
EuPathDBiHostDB:ENSG00000106366.8
GeneCardsiSERPINE1
HGNCiHGNC:8583 SERPINE1
HPAiCAB068501
HPA050039
MalaCardsiSERPINE1
MIMi173360 gene
613329 phenotype
neXtProtiNX_P05121
OpenTargetsiENSG00000106366
Orphaneti465 Congenital plasminogen activator inhibitor type 1 deficiency
PharmGKBiPA261
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2392 Eukaryota
COG4826 LUCA
GeneTreeiENSGT00930000150820
HOGENOMiHOG000238519
HOVERGENiHBG106493
InParanoidiP05121
KOiK03982
OMAiYFNGQWK
OrthoDBiEOG091G0ION
PhylomeDBiP05121
TreeFamiTF352620

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

Miscellaneous databases

ChiTaRSiSERPINE1 human
EvolutionaryTraceiP05121
GeneWikiiPlasminogen_activator_inhibitor-1
GenomeRNAii5054
PMAP-CutDBiP05121
PROiPR:P05121
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000106366 Expressed in 173 organ(s), highest expression level in left coronary artery
CleanExiHS_SERPINE1
ExpressionAtlasiP05121 baseline and differential
GenevisibleiP05121 HS

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
ProtoNetiSearch...

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: November 7, 2018
This is version 220 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  7. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
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Main funding by: National Institutes of Health

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