PAI1_RAT
ID PAI1_RAT Reviewed; 402 AA.
AC P20961;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 25-MAY-2022, entry version 144.
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=Pai1, Planh1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2298740; DOI=10.1016/s0021-9258(19)39942-9;
RA Bruzdzinski C.J., Riordan-Johnson M., Nordby E.C., Suter S.M.,
RA Gelehrter T.D.;
RT "Isolation and characterization of the rat plasminogen activator inhibitor-
RT 1 gene.";
RL J. Biol. Chem. 265:2078-2085(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3149611; DOI=10.1016/0378-1119(88)90510-0;
RA Zeheb R., Gelehrter T.D.;
RT "Cloning and sequencing of cDNA for the rat plasminogen activator
RT inhibitor-1.";
RL Gene 73:459-468(1988).
RN [3]
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. It is involved in cellular and replicative senescence
CC (By similarity). Plays a role in alveolar type 2 cells senescence in
CC the lung (By similarity). Is involved in the regulation of cementogenic
CC differentiation of periodontal ligament stem cells, and regulates
CC odontoblast differentiation and dentin formation during odontogenesis
CC (By similarity). {ECO:0000250|UniProtKB:P05121,
CC ECO:0000250|UniProtKB:P22777}.
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 -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P05121}.
CC -!- SIMILARITY: Belongs to the serpin family. {ECO:0000305}.
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DR EMBL; J05206; AAA41796.1; -; Genomic_DNA.
DR EMBL; M24067; AAA56856.1; -; mRNA.
DR PIR; A35032; A35032.
DR RefSeq; NP_036752.1; NM_012620.1.
DR AlphaFoldDB; P20961; -.
DR SMR; P20961; -.
DR BioGRID; 246756; 3.
DR STRING; 10116.ENSRNOP00000001916; -.
DR BindingDB; P20961; -.
DR ChEMBL; CHEMBL2155; -.
DR MEROPS; I04.020; -.
DR GlyGen; P20961; 4 sites.
DR PhosphoSitePlus; P20961; -.
DR jPOST; P20961; -.
DR PaxDb; P20961; -.
DR PRIDE; P20961; -.
DR ABCD; P20961; 1 sequenced antibody.
DR GeneID; 24617; -.
DR KEGG; rno:24617; -.
DR UCSC; RGD:3249; rat.
DR CTD; 5054; -.
DR RGD; 3249; Serpine1.
DR eggNOG; KOG2392; Eukaryota.
DR InParanoid; P20961; -.
DR OrthoDB; 1024816at2759; -.
DR PhylomeDB; P20961; -.
DR Reactome; R-RNO-114608; Platelet degranulation.
DR Reactome; R-RNO-3000178; ECM proteoglycans.
DR Reactome; R-RNO-75205; Dissolution of Fibrin Clot.
DR PRO; PR:P20961; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0042583; C:chromaffin granule; IDA:RGD.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0070062; C:extracellular exosome; ISO:RGD.
DR GO; GO:0005576; C:extracellular region; IDA:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:1904090; C:peptidase inhibitor complex; ISO:RGD.
DR GO; GO:0097180; C:serine protease inhibitor complex; ISO:RGD.
DR GO; GO:0002020; F:protease binding; IDA:RGD.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IDA:RGD.
DR GO; GO:0005102; F:signaling receptor binding; ISO:RGD.
DR GO; GO:0001525; P:angiogenesis; ISO:RGD.
DR GO; GO:1904045; P:cellular response to aldosterone; IEP:RGD.
DR GO; GO:1904385; P:cellular response to angiotensin; IEP:RGD.
DR GO; GO:0071318; P:cellular response to ATP; IEP:RGD.
DR GO; GO:0071320; P:cellular response to cAMP; IEP:RGD.
DR GO; GO:0071321; P:cellular response to cGMP; IEP:RGD.
DR GO; GO:0071409; P:cellular response to cycloheximide; IEP:RGD.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEP:RGD.
DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; IEP:RGD.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IEP:RGD.
DR GO; GO:0071377; P:cellular response to glucagon stimulus; IEP:RGD.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEP:RGD.
DR GO; GO:0071258; P:cellular response to gravity; IEP:RGD.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IEP:RGD.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEP:RGD.
DR GO; GO:0071456; P:cellular response to hypoxia; IEP:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD.
DR GO; GO:0071347; P:cellular response to interleukin-1; IDA:RGD.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEP:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; IEP:RGD.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:RGD.
DR GO; GO:0071248; P:cellular response to metal ion; IEP:RGD.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IEP:RGD.
DR GO; GO:0071316; P:cellular response to nicotine; IEP:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEP:RGD.
DR GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; IEP:RGD.
DR GO; GO:0035865; P:cellular response to potassium ion; IEP:RGD.
DR GO; GO:1904639; P:cellular response to resveratrol; IEP:RGD.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEP:RGD.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IDA:RGD.
DR GO; GO:0046697; P:decidualization; IEP:RGD.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; ISO:RGD.
DR GO; GO:0097187; P:dentinogenesis; ISO:RGD.
DR GO; GO:0008585; P:female gonad development; IDA:RGD.
DR GO; GO:0042593; P:glucose homeostasis; IEP:RGD.
DR GO; GO:0045576; P:mast cell activation; IEP:RGD.
DR GO; GO:0033629; P:negative regulation of cell adhesion mediated by integrin; ISO:RGD.
DR GO; GO:0030336; P:negative regulation of cell migration; IDA:RGD.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IDA:RGD.
DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; ISO:RGD.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; ISO:RGD.
DR GO; GO:0051918; P:negative regulation of fibrinolysis; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:RGD.
DR GO; GO:0010757; P:negative regulation of plasminogen activation; ISO:RGD.
DR GO; GO:0014912; P:negative regulation of smooth muscle cell migration; ISO:RGD.
DR GO; GO:2000098; P:negative regulation of smooth muscle cell-matrix adhesion; ISO:RGD.
DR GO; GO:0061044; P:negative regulation of vascular wound healing; ISO:RGD.
DR GO; GO:0001890; P:placenta development; ISO:RGD.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:RGD.
DR GO; GO:0030194; P:positive regulation of blood coagulation; ISO:RGD.
DR GO; GO:0090280; P:positive regulation of calcium ion import; IMP:RGD.
DR GO; GO:0050820; P:positive regulation of coagulation; IMP:RGD.
DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; IMP:RGD.
DR GO; GO:1905043; P:positive regulation of epithelium regeneration; IMP:RGD.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IMP:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:RGD.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISO:RGD.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISO:RGD.
DR GO; GO:0051549; P:positive regulation of keratinocyte migration; IMP:RGD.
DR GO; GO:0035491; P:positive regulation of leukotriene production involved in inflammatory response; ISO:RGD.
DR GO; GO:0090026; P:positive regulation of monocyte chemotaxis; ISO:RGD.
DR GO; GO:1901331; P:positive regulation of odontoblast differentiation; ISO:RGD.
DR GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; IMP:BHF-UCL.
DR GO; GO:0045765; P:regulation of angiogenesis; ISO:RGD.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0010469; P:regulation of signaling receptor activity; ISO:RGD.
DR GO; GO:0090399; P:replicative senescence; ISS:UniProtKB.
DR GO; GO:0034097; P:response to cytokine; IEP:RGD.
DR GO; GO:0070849; P:response to epidermal growth factor; IEP:RGD.
DR GO; GO:0043627; P:response to estrogen; IEP:RGD.
DR GO; GO:0055093; P:response to hyperoxia; IEP:RGD.
DR GO; GO:0034616; P:response to laminar fluid shear stress; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0000302; P:response to reactive oxygen species; IEP:RGD.
DR GO; GO:0042594; P:response to starvation; IEP:RGD.
DR GO; GO:0071559; P:response to transforming growth factor beta; IEP:RGD.
DR GO; GO:0042246; P:tissue regeneration; IEP:RGD.
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 2: Evidence at transcript level;
KW Glycoprotein; Protease inhibitor; Reference proteome; Secreted;
KW Serine protease inhibitor; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000250"
FT CHAIN 24..402
FT /note="Plasminogen activator inhibitor 1"
FT /id="PRO_0000032503"
FT SITE 369..370
FT /note="Reactive bond"
FT CARBOHYD 88
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
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"
SQ SEQUENCE 402 AA; 45010 MW; 2B639140F475EB53 CRC64;
MQMSSALTCL TLGLVLVFGK GFASPLPESH TAQQATNFGV KVFQHVVQAS KDRNVVFSPY
GVSSVLAMLQ LTTAGKTRQQ IQDAMGFNIS ERGTAPALRK LSKELMGSWN KNEISTADAI
FVQRDLELVQ GFMPHFFKLF RTTVKQVDFS EVERARFIIN DWVERHTKGM ISDLLAKGAV
NELTRLVLVN ALYFNGQWKT PFLEASTHQR LFHKSDGSTI SVPMMAQNNK FNYTEFTTPD
GHEYDILELP YHGETLSMFI AAPFEKDVPL SAITNILDAE LIRQWKSNMT RLPRLLILPK
FSLETEVDLR GPLEKLGMTD IFSSTQADFT SLSDQEQLSV AQALQKVKIE VNESGTVASS
STAILVSARM APTEMVLDRS FLFVVRHNPT ETILFMGQLM EP
