PAI1_MOUSE
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 03-AUG-2022, entry version 154.
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 GlyGen; P22777; 3 sites.
DR PhosphoSitePlus; P22777; -.
DR CPTAC; non-CPTAC-4049; -.
DR MaxQB; P22777; -.
DR PaxDb; P22777; -.
DR PeptideAtlas; P22777; -.
DR PRIDE; P22777; -.
DR ProteomicsDB; 287939; -.
DR ABCD; P22777; 1 sequenced antibody.
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:0005737; C:cytoplasm; 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:0010951; P:negative regulation of endopeptidase activity; 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:0010469; P:regulation of signaling receptor activity; ISO:MGI.
DR GO; GO:0090399; P:replicative senescence; ISO:MGI.
DR Gene3D; 2.30.39.10; -; 1.
DR Gene3D; 3.30.497.10; -; 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; PTHR11461; 1.
DR Pfam; PF00079; Serpin; 1.
DR SMART; SM00093; SERPIN; 1.
DR SUPFAM; SSF56574; SSF56574; 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
