ID   PAI1_MOUSE              Reviewed;         402 AA.
AC   P22777;
DT   01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1991, sequence version 1.
DT   08-NOV-2023, entry version 159.
DE   RecName: Full=Plasminogen activator inhibitor 1;
DE            Short=PAI;
DE            Short=PAI-1;
DE   AltName: Full=Endothelial plasminogen activator inhibitor;
DE   AltName: Full=Serpin E1;
DE   Flags: Precursor;
GN   Name=Serpine1; Synonyms=Mr1, Pai1, Planh1;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2406566; DOI=10.1128/mcb.10.3.1265-1269.1990;
RA   Prendergast G.C., Diamond L.E., Dahl D., Cole M.D.;
RT   "The c-myc-regulated gene mr1 encodes plasminogen activator inhibitor 1.";
RL   Mol. Cell. Biol. 10:1265-1269(1990).
RN   [2]
RP   PROTEIN SEQUENCE OF 23-29.
RX   PubMed=7523120; DOI=10.1111/j.1432-1033.1994.00863.x;
RA   Lijnen H.R., van Hoef B., Beelen V., Collen D.;
RT   "Characterization of the murine plasma fibrinolytic system.";
RL   Eur. J. Biochem. 224:863-871(1994).
RN   [3]
RP   FUNCTION.
RX   PubMed=16862142; DOI=10.1038/ncb1448;
RA   Kortlever R.M., Higgins P.J., Bernards R.;
RT   "Plasminogen activator inhibitor-1 is a critical downstream target of p53
RT   in the induction of replicative senescence.";
RL   Nat. Cell Biol. 8:877-884(2006).
RN   [4]
RP   INDUCTION.
RX   PubMed=23291174; DOI=10.1016/j.bbrc.2012.12.098;
RA   Oishi K., Koyanagi S., Ohkura N.;
RT   "The molecular clock regulates circadian transcription of tissue factor
RT   gene.";
RL   Biochem. Biophys. Res. Commun. 431:332-335(2013).
RN   [5]
RP   FUNCTION.
RX   PubMed=28722352; DOI=10.1111/acel.12643;
RA   Jiang C., Liu G., Luckhardt T., Antony V., Zhou Y., Carter A.B.,
RA   Thannickal V.J., Liu R.M.;
RT   "Serpine 1 induces alveolar type II cell senescence through activating p53-
RT   p21-Rb pathway in fibrotic lung disease.";
RL   Aging Cell 16:1114-1124(2017).
CC   -!- FUNCTION: Serine protease inhibitor. Inhibits TMPRSS7. Is a primary
CC       inhibitor of tissue-type plasminogen activator (PLAT) and urokinase-
CC       type plasminogen activator (PLAU). As PLAT inhibitor, it is required
CC       for fibrinolysis down-regulation and is responsible for the controlled
CC       degradation of blood clots. As PLAU inhibitor, it is involved in the
CC       regulation of cell adhesion and spreading. Acts as a regulator of cell
CC       migration, independently of its role as protease inhibitor. It is
CC       required for stimulation of keratinocyte migration during cutaneous
CC       injury repair (By similarity). Involved in cellular and replicative
CC       senescence (PubMed:16862142). Plays a role in alveolar type 2 cells
CC       senescence in the lung (PubMed:28722352). Is involved in the regulation
CC       of cementogenic differentiation of periodontal ligament stem cells, and
CC       regulates odontoblast differentiation and dentin formation during
CC       odontogenesis (By similarity). {ECO:0000250|UniProtKB:P05121,
CC       ECO:0000269|PubMed:16862142, ECO:0000269|PubMed:28722352}.
CC   -!- SUBUNIT: Forms a heterodimer with TMPRSS7. Interacts with VTN. Binds
CC       LRP1B; binding is followed by internalization and degradation.
CC       Interacts with PPP1CB. In complex with PLAU/uPA, interacts with
CC       PLAUR/uPAR (By similarity). Interacts with SORL1 and LRP1, either alone
CC       or in complex with PLAU; these interactions are abolished in the
CC       presence of LRPAP1/RAP (By similarity). The ternary complex composed of
CC       PLAUR-PLAU-PAI1 also interacts with SORL1 (By similarity). Also
CC       interacts with SORL1, when complexed to PLAT/tPA (By similarity).
CC       {ECO:0000250|UniProtKB:P05121}.
CC   -!- INTERACTION:
CC       P22777; Q5S248: Tmprss11e; NbExp=2; IntAct=EBI-490898, EBI-490889;
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P05121}.
CC   -!- INDUCTION: Expression in the liver oscillates in a circadian manner.
CC       {ECO:0000269|PubMed:23291174}.
CC   -!- SIMILARITY: Belongs to the serpin family. {ECO:0000305}.
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DR   EMBL; M33960; AAA39887.1; -; mRNA.
DR   CCDS; CCDS19761.1; -.
DR   PIR; A34761; A34761.
DR   PDB; 3LW2; X-ray; 1.93 A; A=24-402.
DR   PDBsum; 3LW2; -.
DR   AlphaFoldDB; P22777; -.
DR   SMR; P22777; -.
DR   ComplexPortal; CPX-492; Vitronectin-PAI-1 complex.
DR   ComplexPortal; CPX-495; uPA-PAI-1 complex.
DR   ComplexPortal; CPX-518; tPA-PAI-1 complex.
DR   CORUM; P22777; -.
DR   IntAct; P22777; 1.
DR   STRING; 10090.ENSMUSP00000039586; -.
DR   MEROPS; I04.020; -.
DR   GlyCosmos; P22777; 3 sites, No reported glycans.
DR   GlyGen; P22777; 5 sites, 1 O-linked glycan (2 sites).
DR   PhosphoSitePlus; P22777; -.
DR   CPTAC; non-CPTAC-4049; -.
DR   MaxQB; P22777; -.
DR   PaxDb; 10090-ENSMUSP00000039586; -.
DR   PeptideAtlas; P22777; -.
DR   ProteomicsDB; 287939; -.
DR   Pumba; P22777; -.
DR   ABCD; P22777; 1 sequenced antibody.
DR   AGR; MGI:97608; -.
DR   MGI; MGI:97608; Serpine1.
DR   eggNOG; KOG2392; Eukaryota.
DR   InParanoid; P22777; -.
DR   PhylomeDB; P22777; -.
DR   Reactome; R-MMU-114608; Platelet degranulation.
DR   Reactome; R-MMU-3000178; ECM proteoglycans.
DR   Reactome; R-MMU-75205; Dissolution of Fibrin Clot.
DR   ChiTaRS; Serpine1; mouse.
DR   EvolutionaryTrace; P22777; -.
DR   PRO; PR:P22777; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; P22777; Protein.
DR   GO; GO:0042583; C:chromaffin granule; ISO:MGI.
DR   GO; GO:0062023; C:collagen-containing extracellular matrix; ISO:MGI.
DR   GO; GO:0070062; C:extracellular exosome; ISO:MGI.
DR   GO; GO:0005576; C:extracellular region; ISO:MGI.
DR   GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR   GO; GO:1904090; C:peptidase inhibitor complex; ISO:MGI.
DR   GO; GO:0097180; C:serine protease inhibitor complex; ISO:MGI.
DR   GO; GO:0002020; F:protease binding; ISO:MGI.
DR   GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IDA:MGI.
DR   GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR   GO; GO:0001525; P:angiogenesis; IMP:MGI.
DR   GO; GO:0071347; P:cellular response to interleukin-1; ISO:MGI.
DR   GO; GO:0071222; P:cellular response to lipopolysaccharide; ISO:MGI.
DR   GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IDA:MGI.
DR   GO; GO:0071466; P:cellular response to xenobiotic stimulus; ISO:MGI.
DR   GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:BHF-UCL.
DR   GO; GO:0097187; P:dentinogenesis; ISO:MGI.
DR   GO; GO:0008585; P:female gonad development; ISO:MGI.
DR   GO; GO:0033629; P:negative regulation of cell adhesion mediated by integrin; ISO:MGI.
DR   GO; GO:0030336; P:negative regulation of cell migration; ISO:MGI.
DR   GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; ISO:MGI.
DR   GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; ISO:MGI.
DR   GO; GO:0051918; P:negative regulation of fibrinolysis; ISO:MGI.
DR   GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR   GO; GO:0010757; P:negative regulation of plasminogen activation; IMP:BHF-UCL.
DR   GO; GO:0014912; P:negative regulation of smooth muscle cell migration; ISO:MGI.
DR   GO; GO:2000098; P:negative regulation of smooth muscle cell-matrix adhesion; ISO:MGI.
DR   GO; GO:0061044; P:negative regulation of vascular wound healing; IMP:BHF-UCL.
DR   GO; GO:0001890; P:placenta development; IMP:MGI.
DR   GO; GO:0045766; P:positive regulation of angiogenesis; IMP:BHF-UCL.
DR   GO; GO:0030194; P:positive regulation of blood coagulation; ISO:MGI.
DR   GO; GO:0090280; P:positive regulation of calcium ion import; ISO:MGI.
DR   GO; GO:0050820; P:positive regulation of coagulation; ISO:MGI.
DR   GO; GO:0032967; P:positive regulation of collagen biosynthetic process; ISO:MGI.
DR   GO; GO:1905043; P:positive regulation of epithelium regeneration; ISO:MGI.
DR   GO; GO:0048146; P:positive regulation of fibroblast proliferation; ISO:MGI.
DR   GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR   GO; GO:0050729; P:positive regulation of inflammatory response; ISO:MGI.
DR   GO; GO:0032757; P:positive regulation of interleukin-8 production; ISO:MGI.
DR   GO; GO:0051549; P:positive regulation of keratinocyte migration; ISO:MGI.
DR   GO; GO:0035491; P:positive regulation of leukotriene production involved in inflammatory response; ISO:MGI.
DR   GO; GO:0090026; P:positive regulation of monocyte chemotaxis; ISO:MGI.
DR   GO; GO:1901331; P:positive regulation of odontoblast differentiation; ISO:MGI.
DR   GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; ISO:MGI.
DR   GO; GO:0045765; P:regulation of angiogenesis; IDA:MGI.
DR   GO; GO:0042127; P:regulation of cell population proliferation; IGI:MGI.
DR   GO; GO:0090399; P:replicative senescence; ISO:MGI.
DR   Gene3D; 2.30.39.10; Alpha-1-antitrypsin, domain 1; 1.
DR   Gene3D; 3.30.497.10; Antithrombin, subunit I, domain 2; 1.
DR   InterPro; IPR023795; Serpin_CS.
DR   InterPro; IPR023796; Serpin_dom.
DR   InterPro; IPR000215; Serpin_fam.
DR   InterPro; IPR036186; Serpin_sf.
DR   InterPro; IPR042178; Serpin_sf_1.
DR   InterPro; IPR042185; Serpin_sf_2.
DR   PANTHER; PTHR11461:SF49; PLASMINOGEN ACTIVATOR INHIBITOR 1; 1.
DR   PANTHER; PTHR11461; SERINE PROTEASE INHIBITOR, SERPIN; 1.
DR   Pfam; PF00079; Serpin; 1.
DR   SMART; SM00093; SERPIN; 1.
DR   SUPFAM; SSF56574; Serpins; 1.
DR   PROSITE; PS00284; SERPIN; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; Glycoprotein; Protease inhibitor;
KW   Reference proteome; Secreted; Serine protease inhibitor; Signal.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000305|PubMed:7523120"
FT   CHAIN           23..402
FT                   /note="Plasminogen activator inhibitor 1"
FT                   /id="PRO_0000032500"
FT   SITE            369..370
FT                   /note="Reactive bond"
FT   CARBOHYD        232
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        288
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        352
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CONFLICT        23
FT                   /note="T -> M (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   HELIX           31..50
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   STRAND          55..57
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   HELIX           59..72
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   HELIX           75..85
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   HELIX           94..106
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   HELIX           108..110
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   STRAND          111..123
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   HELIX           132..140
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   STRAND          145..147
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   HELIX           152..166
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   TURN            167..169
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   STRAND          186..200
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   HELIX           204..206
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   STRAND          208..210
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   STRAND          222..237
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   STRAND          243..265
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   HELIX           271..274
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   HELIX           279..288
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   STRAND          290..299
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   STRAND          301..308
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   HELIX           310..315
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   HELIX           320..322
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   TURN            324..326
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   TURN            330..332
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   STRAND          334..336
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   STRAND          344..351
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   STRAND          353..365
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   STRAND          381..387
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   TURN            388..391
FT                   /evidence="ECO:0007829|PDB:3LW2"
FT   STRAND          392..399
FT                   /evidence="ECO:0007829|PDB:3LW2"
SQ   SEQUENCE   402 AA;  45170 MW;  765FF1659C70F68C CRC64;
     MQMSSALACL ILGLVLVSGK GFTLPLRESH TAHQATDFGV KVFQQVVQAS KDRNVVFSPY
     GVSSVLAMLQ MTTAGKTRRQ IQDAMGFKVN EKGTAHALRQ LSKELMGPWN KNEISTADAI
     FVQRDLELVQ GFMPHFFKLF QTMVKQVDFS EVERARFIIN DWVERHTKGM INDLLAKGAV
     DELTRLVLVN ALYFSGQWKT PFLEASTHQR LFHKSDGSTV SVPMMAQSNK FNYTEFTTPD
     GLEYDVVELP YQRDTLSMFI AAPFEKDVHL SALTNILDAE LIRQWKGNMT RLPRLLILPK
     FSLETEVDLR GPLEKLGMPD MFSATLADFT SLSDQEQLSV AQALQKVRIE VNESGTVASS
     STAFVISARM APTEMVIDRS FLFVVRHNPT ETILFMGQVM EP
//