ID   PLMN_MOUSE              Reviewed;         812 AA.
AC   P20918; Q8CIS2; Q91WJ5;
DT   01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT   28-JUN-2011, sequence version 3.
DT   24-JAN-2024, entry version 229.
DE   RecName: Full=Plasminogen;
DE            EC=3.4.21.7;
DE   Contains:
DE     RecName: Full=Plasmin heavy chain A;
DE   Contains:
DE     RecName: Full=Activation peptide;
DE   Contains:
DE     RecName: Full=Angiostatin;
DE   Contains:
DE     RecName: Full=Plasmin heavy chain A, short form;
DE   Contains:
DE     RecName: Full=Plasmin light chain B;
DE   Flags: Precursor;
GN   Name=Plg;
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=2081600; DOI=10.1016/0888-7543(90)90225-j;
RA   Degen S.J., Bell S.M., Schaefer L.A., Elliott R.W.;
RT   "Characterization of the cDNA coding for mouse plasminogen and localization
RT   of the gene to mouse chromosome 17.";
RL   Genomics 8:49-61(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=129/Sv;
RA   Brathwaite M.E., Waeltz P., Qian Y., Dudekula D., Schlessinger D.,
RA   Nagaraja R.;
RT   "Genomic sequence analysis in the mouse T-complex region.";
RL   Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Liver;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-16.
RC   STRAIN=129/SvJ; TISSUE=Liver;
RX   PubMed=12149246; DOI=10.1074/jbc.m202509200;
RA   Bannach F.G., Gutierrez A., Fowler B.J., Bugge T.H., Degen J.L.,
RA   Parmer R.J., Miles L.A.;
RT   "Localization of regulatory elements mediating constitutive and cytokine-
RT   stimulated plasminogen gene expression.";
RL   J. Biol. Chem. 277:38579-38588(2002).
RN   [6]
RP   CHARACTERIZATION OF ANGIOSTATIN, AND PARTIAL PROTEIN SEQUENCE.
RX   PubMed=7525077; DOI=10.1016/0092-8674(94)90200-3;
RA   O'Reilly M.S., Holmgren L., Shing Y., Chen C., Rosenthal R.A., Moses M.,
RA   Lane W.S., Cao Y., Sage E.H., Folkman J.;
RT   "Angiostatin: a novel angiogenesis inhibitor that mediates the suppression
RT   of metastases by a Lewis lung carcinoma.";
RL   Cell 79:315-328(1994).
RN   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC   Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Plasmin dissolves the fibrin of blood clots and acts as a
CC       proteolytic factor in a variety of other processes including embryonic
CC       development, tissue remodeling, tumor invasion, and inflammation. In
CC       ovulation, weakens the walls of the Graafian follicle. It activates the
CC       urokinase-type plasminogen activator, collagenases and several
CC       complement zymogens, such as C1 and C5. Cleavage of fibronectin and
CC       laminin leads to cell detachment and apoptosis. Also cleaves fibrin,
CC       thrombospondin and von Willebrand factor. Its role in tissue remodeling
CC       and tumor invasion may be modulated by CSPG4. Binds to cells (By
CC       similarity). {ECO:0000250}.
CC   -!- FUNCTION: Angiostatin is an angiogenesis inhibitor that blocks
CC       neovascularization and growth of experimental primary and metastatic
CC       tumors in vivo.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Preferential cleavage: Lys-|-Xaa > Arg-|-Xaa, higher
CC         selectivity than trypsin. Converts fibrin into soluble products.;
CC         EC=3.4.21.7;
CC   -!- ACTIVITY REGULATION: Converted into plasmin by plasminogen activators,
CC       both plasminogen and its activator being bound to fibrin. Cannot be
CC       activated with streptokinase.
CC   -!- SUBUNIT: Interacts (both mature PLG and the angiostatin peptide) with
CC       AMOT and CSPG4. Interacts (via the Kringle domains) with HRG; the
CC       interaction tethers PLG to the cell surface and enhances its
CC       activation. Interacts (via Kringle 4 domain) with ADA; the interaction
CC       stimulates PLG activation when in complex with DPP4. Angiostatin:
CC       Interacts with ATP5F1A; the interaction inhibits most of the angiogenic
CC       effects of angiostatin. {ECO:0000250|UniProtKB:P00747}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}. Note=Locates to the cell
CC       surface where it is proteolytically cleaved to produce the active
CC       plasmin. Interaction with HRG tethers it to the cell surface (By
CC       similarity). {ECO:0000250}.
CC   -!- DOMAIN: Kringle domains mediate interaction with CSPG4. {ECO:0000250}.
CC   -!- PTM: In the presence of the inhibitor, the activation involves only
CC       cleavage after Arg-581, yielding two chains held together by two
CC       disulfide bonds. In the absence of the inhibitor, the activation
CC       involves additionally the removal of the activation peptide (By
CC       similarity). {ECO:0000250}.
CC   -!- MISCELLANEOUS: Plasmin is inactivated by alpha-2-antiplasmin
CC       immediately after dissociation from the clot.
CC   -!- MISCELLANEOUS: In the presence of the inhibitor, the activation
CC       involves only cleavage after Arg-581, resulting in 2 chains held
CC       together by 2 disulfide bonds. Without the inhibitor, the activation
CC       involves also removal of the activation peptide.
CC   -!- SIMILARITY: Belongs to the peptidase S1 family. Plasminogen subfamily.
CC       {ECO:0000255|PROSITE-ProRule:PRU00274}.
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DR   EMBL; J04766; AAA50168.1; -; mRNA.
DR   EMBL; AF481053; AAM22156.1; -; Genomic_DNA.
DR   EMBL; AC087901; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC014773; AAH14773.1; -; mRNA.
DR   EMBL; BC057186; AAH57186.1; -; mRNA.
DR   EMBL; AY134430; AAN15805.1; -; Genomic_DNA.
DR   CCDS; CCDS28390.1; -.
DR   PIR; A38514; PLMS.
DR   RefSeq; NP_032903.3; NM_008877.3.
DR   AlphaFoldDB; P20918; -.
DR   SMR; P20918; -.
DR   BioGRID; 202248; 10.
DR   IntAct; P20918; 4.
DR   MINT; P20918; -.
DR   STRING; 10090.ENSMUSP00000014578; -.
DR   BindingDB; P20918; -.
DR   ChEMBL; CHEMBL1075299; -.
DR   MEROPS; S01.233; -.
DR   iPTMnet; P20918; -.
DR   PhosphoSitePlus; P20918; -.
DR   SwissPalm; P20918; -.
DR   REPRODUCTION-2DPAGE; P20918; -.
DR   CPTAC; non-CPTAC-3345; -.
DR   jPOST; P20918; -.
DR   MaxQB; P20918; -.
DR   PaxDb; 10090-ENSMUSP00000014578; -.
DR   PeptideAtlas; P20918; -.
DR   ProteomicsDB; 289622; -.
DR   DNASU; 18815; -.
DR   Ensembl; ENSMUST00000014578.7; ENSMUSP00000014578.6; ENSMUSG00000059481.6.
DR   GeneID; 18815; -.
DR   KEGG; mmu:18815; -.
DR   UCSC; uc008akt.2; mouse.
DR   AGR; MGI:97620; -.
DR   CTD; 5340; -.
DR   MGI; MGI:97620; Plg.
DR   VEuPathDB; HostDB:ENSMUSG00000059481; -.
DR   eggNOG; ENOG502QVNP; Eukaryota.
DR   GeneTree; ENSGT00940000155208; -.
DR   HOGENOM; CLU_017565_0_0_1; -.
DR   InParanoid; P20918; -.
DR   OMA; NSQTPHA; -.
DR   OrthoDB; 211181at2759; -.
DR   PhylomeDB; P20918; -.
DR   TreeFam; TF329901; -.
DR   Reactome; R-MMU-114608; Platelet degranulation.
DR   Reactome; R-MMU-1592389; Activation of Matrix Metalloproteinases.
DR   Reactome; R-MMU-186797; Signaling by PDGF.
DR   Reactome; R-MMU-75205; Dissolution of Fibrin Clot.
DR   Reactome; R-MMU-8964041; LDL remodeling.
DR   BioGRID-ORCS; 18815; 2 hits in 78 CRISPR screens.
DR   ChiTaRS; Plg; mouse.
DR   PRO; PR:P20918; -.
DR   Proteomes; UP000000589; Chromosome 17.
DR   RNAct; P20918; Protein.
DR   Bgee; ENSMUSG00000059481; Expressed in left lobe of liver and 52 other cell types or tissues.
DR   GO; GO:0009986; C:cell surface; IDA:MGI.
DR   GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR   GO; GO:0009897; C:external side of plasma membrane; ISO:MGI.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; ISS:HGNC-UCL.
DR   GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR   GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IDA:SynGO.
DR   GO; GO:0034185; F:apolipoprotein binding; ISO:MGI.
DR   GO; GO:0004175; F:endopeptidase activity; ISO:MGI.
DR   GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR   GO; GO:0019900; F:kinase binding; IPI:CAFA.
DR   GO; GO:0002020; F:protease binding; ISO:MGI.
DR   GO; GO:1990405; F:protein antigen binding; ISO:MGI.
DR   GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR   GO; GO:0051087; F:protein-folding chaperone binding; ISO:MGI.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; ISO:MGI.
DR   GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR   GO; GO:0051702; P:biological process involved in interaction with symbiont; ISO:MGI.
DR   GO; GO:0007596; P:blood coagulation; ISS:HGNC-UCL.
DR   GO; GO:0022617; P:extracellular matrix disassembly; ISO:MGI.
DR   GO; GO:0042730; P:fibrinolysis; ISO:MGI.
DR   GO; GO:0060716; P:labyrinthine layer blood vessel development; IMP:MGI.
DR   GO; GO:0071674; P:mononuclear cell migration; IMP:MGI.
DR   GO; GO:0046716; P:muscle cell cellular homeostasis; IMP:MGI.
DR   GO; GO:0045445; P:myoblast differentiation; IMP:MGI.
DR   GO; GO:0016525; P:negative regulation of angiogenesis; TAS:MGI.
DR   GO; GO:0010812; P:negative regulation of cell-substrate adhesion; ISO:MGI.
DR   GO; GO:0051918; P:negative regulation of fibrinolysis; ISO:MGI.
DR   GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:MGI.
DR   GO; GO:0051919; P:positive regulation of fibrinolysis; ISO:MGI.
DR   GO; GO:0006508; P:proteolysis; ISO:MGI.
DR   GO; GO:0051603; P:proteolysis involved in protein catabolic process; ISO:MGI.
DR   GO; GO:0042246; P:tissue regeneration; IMP:MGI.
DR   GO; GO:0048771; P:tissue remodeling; IEA:UniProtKB-KW.
DR   GO; GO:0099183; P:trans-synaptic signaling by BDNF, modulating synaptic transmission; IDA:SynGO.
DR   GO; GO:0060707; P:trophoblast giant cell differentiation; IMP:MGI.
DR   CDD; cd00108; KR; 5.
DR   CDD; cd01099; PAN_AP_HGF; 1.
DR   CDD; cd00190; Tryp_SPc; 1.
DR   Gene3D; 3.50.4.10; Hepatocyte Growth Factor; 1.
DR   Gene3D; 2.40.20.10; Plasminogen Kringle 4; 4.
DR   Gene3D; 2.40.10.10; Trypsin-like serine proteases; 1.
DR   InterPro; IPR000001; Kringle.
DR   InterPro; IPR013806; Kringle-like.
DR   InterPro; IPR018056; Kringle_CS.
DR   InterPro; IPR038178; Kringle_sf.
DR   InterPro; IPR003609; Pan_app.
DR   InterPro; IPR023317; Pept_S1A_plasmin.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR   InterPro; IPR001314; Peptidase_S1A.
DR   InterPro; IPR001254; Trypsin_dom.
DR   InterPro; IPR018114; TRYPSIN_HIS.
DR   InterPro; IPR033116; TRYPSIN_SER.
DR   PANTHER; PTHR24261:SF13; PLASMINOGEN; 1.
DR   PANTHER; PTHR24261; PLASMINOGEN-RELATED; 1.
DR   Pfam; PF00051; Kringle; 5.
DR   Pfam; PF00024; PAN_1; 1.
DR   Pfam; PF00089; Trypsin; 1.
DR   PIRSF; PIRSF001150; Plasmin; 1.
DR   PRINTS; PR00722; CHYMOTRYPSIN.
DR   PRINTS; PR00018; KRINGLE.
DR   SMART; SM00130; KR; 5.
DR   SMART; SM00473; PAN_AP; 1.
DR   SMART; SM00020; Tryp_SPc; 1.
DR   SUPFAM; SSF57414; Hairpin loop containing domain-like; 1.
DR   SUPFAM; SSF57440; Kringle-like; 5.
DR   SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR   PROSITE; PS00021; KRINGLE_1; 5.
DR   PROSITE; PS50070; KRINGLE_2; 5.
DR   PROSITE; PS50948; PAN; 1.
DR   PROSITE; PS50240; TRYPSIN_DOM; 1.
DR   PROSITE; PS00134; TRYPSIN_HIS; 1.
DR   PROSITE; PS00135; TRYPSIN_SER; 1.
DR   Genevisible; P20918; MM.
PE   1: Evidence at protein level;
KW   Blood coagulation; Cleavage on pair of basic residues;
KW   Direct protein sequencing; Disulfide bond; Fibrinolysis; Hemostasis;
KW   Hydrolase; Kringle; Phosphoprotein; Protease; Reference proteome; Repeat;
KW   Secreted; Serine protease; Signal; Tissue remodeling; Zymogen.
FT   SIGNAL          1..19
FT   CHAIN           20..812
FT                   /note="Plasminogen"
FT                   /id="PRO_0000028069"
FT   CHAIN           20..581
FT                   /note="Plasmin heavy chain A"
FT                   /id="PRO_0000028070"
FT   PEPTIDE         20..97
FT                   /note="Activation peptide"
FT                   /id="PRO_0000028071"
FT   CHAIN           98..581
FT                   /note="Plasmin heavy chain A, short form"
FT                   /id="PRO_0000028072"
FT   CHAIN           98..?436
FT                   /note="Angiostatin"
FT                   /id="PRO_0000028073"
FT   CHAIN           582..812
FT                   /note="Plasmin light chain B"
FT                   /id="PRO_0000028074"
FT   DOMAIN          20..98
FT                   /note="PAN"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00315"
FT   DOMAIN          103..181
FT                   /note="Kringle 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT   DOMAIN          184..262
FT                   /note="Kringle 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT   DOMAIN          275..352
FT                   /note="Kringle 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT   DOMAIN          377..454
FT                   /note="Kringle 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT   DOMAIN          481..560
FT                   /note="Kringle 5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT   DOMAIN          582..810
FT                   /note="Peptidase S1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   ACT_SITE        624
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        667
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        762
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         598
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P00747"
FT   MOD_RES         690
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P00747"
FT   DISULFID        49..73
FT                   /evidence="ECO:0000250"
FT   DISULFID        53..61
FT                   /evidence="ECO:0000250"
FT   DISULFID        103..181
FT                   /evidence="ECO:0000250"
FT   DISULFID        124..164
FT                   /evidence="ECO:0000250"
FT   DISULFID        152..176
FT                   /evidence="ECO:0000250"
FT   DISULFID        185..262
FT                   /evidence="ECO:0000250"
FT   DISULFID        188..316
FT                   /evidence="ECO:0000250"
FT   DISULFID        206..245
FT                   /evidence="ECO:0000250"
FT   DISULFID        234..257
FT                   /evidence="ECO:0000250"
FT   DISULFID        275..352
FT                   /evidence="ECO:0000250"
FT   DISULFID        296..335
FT                   /evidence="ECO:0000250"
FT   DISULFID        324..347
FT                   /evidence="ECO:0000250"
FT   DISULFID        377..454
FT                   /evidence="ECO:0000250"
FT   DISULFID        398..437
FT                   /evidence="ECO:0000250"
FT   DISULFID        426..449
FT                   /evidence="ECO:0000250"
FT   DISULFID        481..560
FT                   /evidence="ECO:0000250"
FT   DISULFID        502..543
FT                   /evidence="ECO:0000250"
FT   DISULFID        531..555
FT                   /evidence="ECO:0000250"
FT   DISULFID        568..687
FT                   /note="Interchain (between A and B chains)"
FT                   /evidence="ECO:0000250"
FT   DISULFID        578..586
FT                   /note="Interchain (between A and B chains)"
FT                   /evidence="ECO:0000250"
FT   DISULFID        609..625
FT                   /evidence="ECO:0000250"
FT   DISULFID        701..768
FT                   /evidence="ECO:0000250"
FT   DISULFID        731..747
FT                   /evidence="ECO:0000250"
FT   DISULFID        758..786
FT                   /evidence="ECO:0000250"
FT   CONFLICT        235
FT                   /note="R -> H (in Ref. 1; AAA50168)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        525
FT                   /note="G -> D (in Ref. 1; AAA50168)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        649
FT                   /note="L -> S (in Ref. 2; AAM22156 and 4;
FT                   AAH14773/AAH57186)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   812 AA;  90808 MW;  E70E1AC8E52844E9 CRC64;
     MDHKEVILLF LLLLKPGQGD SLDGYISTQG ASLFSLTKKQ LAAGGVSDCL AKCEGETDFV
     CRSFQYHSKE QQCVIMAENS KTSSIIRMRD VILFEKRVYL SECKTGIGNG YRGTMSRTKS
     GVACQKWGAT FPHVPNYSPS THPNEGLEEN YCRNPDNDEQ GPWCYTTDPD KRYDYCNIPE
     CEEECMYCSG EKYEGKISKT MSGLDCQAWD SQSPHAHGYI PAKFPSKNLK MNYCRNPDGE
     PRPWCFTTDP TKRWEYCDIP RCTTPPPPPS PTYQCLKGRG ENYRGTVSVT VSGKTCQRWS
     EQTPHRHNRT PENFPCKNLE ENYCRNPDGE TAPWCYTTDS QLRWEYCEIP SCESSASPDQ
     SDSSVPPEEQ TPVVQECYQS DGQSYRGTSS TTITGKKCQS WAAMFPHRHS KTPENFPDAG
     LEMNYCRNPD GDKGPWCYTT DPSVRWEYCN LKRCSETGGS VVELPTVSQE PSGPSDSETD
     CMYGNGKDYR GKTAVTAAGT PCQGWAAQEP HRHSIFTPQT NPRAGLEKNY CRNPDGDVNG
     PWCYTTNPRK LYDYCDIPLC ASASSFECGK PQVEPKKCPG RVVGGCVANP HSWPWQISLR
     TRFTGQHFCG GTLIAPEWVL TAAHCLEKSS RPEFYKVILG AHEEYIRGLD VQEISVAKLI
     LEPNNRDIAL LKLSRPATIT DKVIPACLPS PNYMVADRTI CYITGWGETQ GTFGAGRLKE
     AQLPVIENKV CNRVEYLNNR VKSTELCAGQ LAGGVDSCQG DSGGPLVCFE KDKYILQGVT
     SWGLGCARPN KPGVYVRVSR FVDWIEREMR NN
//