TPA_MOUSE
ID TPA_MOUSE Reviewed; 559 AA.
AC P11214; Q6P7U0; Q91VP2;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 02-OCT-2007, sequence version 3.
DT 03-AUG-2022, entry version 203.
DE RecName: Full=Tissue-type plasminogen activator;
DE Short=t-PA;
DE Short=t-plasminogen activator;
DE Short=tPA;
DE EC=3.4.21.68;
DE Contains:
DE RecName: Full=Tissue-type plasminogen activator chain A;
DE Contains:
DE RecName: Full=Tissue-type plasminogen activator chain B;
DE Flags: Precursor;
GN Name=Plat;
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=2826484; DOI=10.1016/s0021-9258(19)57341-0;
RA Rickles R.J., Darrow A.L., Strickland S.;
RT "Molecular cloning of complementary DNA to mouse tissue plasminogen
RT activator mRNA and its expression during F9 teratocarcinoma cell
RT differentiation.";
RL J. Biol. Chem. 263:1563-1569(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N, and NMRI; TISSUE=Mammary gland, and Mammary tumor;
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 [4]
RP PROTEIN SEQUENCE OF 33-40 AND 309-316.
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).
CC -!- FUNCTION: Converts the abundant, but inactive, zymogen plasminogen to
CC plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By
CC controlling plasmin-mediated proteolysis, it plays an important role in
CC tissue remodeling and degradation, in cell migration and many other
CC physiopathological events. During oocyte activation, plays a role in
CC cortical granule reaction in the zona reaction, which contributes to
CC the block to polyspermy (By similarity).
CC {ECO:0000250|UniProtKB:P19637}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Specific cleavage of Arg-|-Val bond in plasminogen to form
CC plasmin.; EC=3.4.21.68;
CC -!- ACTIVITY REGULATION: Inhibited by SERPINA5. {ECO:0000250}.
CC -!- SUBUNIT: Heterodimer of chain A and chain B held by a disulfide bond.
CC Binds to fibrin with high affinity. This interaction leads to an
CC increase in the catalytic efficiency of the enzyme due to an increase
CC in affinity for plasminogen. Similarly, binding to heparin increases
CC the activation of plasminogen. Binds to annexin A2, cytokeratin-8,
CC fibronectin and laminin. Binds to mannose receptor and the low-density
CC lipoprotein receptor-related protein (LRP1); these proteins are
CC involved in TPA clearance. Binds LRP1B; binding is followed by
CC internalization and degradation. Forms heterodimer with SERPINA5 (By
CC similarity). In complex with SERPINE1, interacts with SORL1 (By
CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:P00750}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space.
CC -!- DOMAIN: Both FN1 and one of the kringle domains are required for
CC binding to fibrin. {ECO:0000250}.
CC -!- DOMAIN: Both FN1 and EGF-like domains are important for binding to
CC LRP1. {ECO:0000250}.
CC -!- DOMAIN: The FN1 domain mediates binding to annexin A2. {ECO:0000250}.
CC -!- DOMAIN: The second kringle domain is implicated in binding to
CC cytokeratin-8 and to the endothelial cell surface binding site.
CC {ECO:0000250}.
CC -!- PTM: The single chain, almost fully active enzyme, can be further
CC processed into a two-chain fully active form by a cleavage after Arg-
CC 308 catalyzed by plasmin, tissue kallikrein or factor Xa.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
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DR EMBL; J03520; AAA40470.1; -; mRNA.
DR EMBL; AK135857; BAE22698.1; -; mRNA.
DR EMBL; AK135965; BAE22749.1; -; mRNA.
DR EMBL; BC011256; AAH11256.1; -; mRNA.
DR EMBL; BC057967; AAH57967.1; -; mRNA.
DR EMBL; BC061508; AAH61508.1; -; mRNA.
DR CCDS; CCDS22183.1; -.
DR PIR; A29941; A29941.
DR RefSeq; NP_032898.2; NM_008872.3.
DR AlphaFoldDB; P11214; -.
DR SMR; P11214; -.
DR BioGRID; 202229; 4.
DR ComplexPortal; CPX-518; tPA-PAI-1 complex.
DR IntAct; P11214; 2.
DR MINT; P11214; -.
DR STRING; 10090.ENSMUSP00000033941; -.
DR BindingDB; P11214; -.
DR ChEMBL; CHEMBL3259492; -.
DR MEROPS; S01.232; -.
DR GlyGen; P11214; 2 sites.
DR iPTMnet; P11214; -.
DR PhosphoSitePlus; P11214; -.
DR MaxQB; P11214; -.
DR PaxDb; P11214; -.
DR PeptideAtlas; P11214; -.
DR PRIDE; P11214; -.
DR ProteomicsDB; 258819; -.
DR ABCD; P11214; 5 sequenced antibodies.
DR Antibodypedia; 998; 804 antibodies from 39 providers.
DR DNASU; 18791; -.
DR Ensembl; ENSMUST00000033941; ENSMUSP00000033941; ENSMUSG00000031538.
DR GeneID; 18791; -.
DR KEGG; mmu:18791; -.
DR UCSC; uc009ldx.2; mouse.
DR CTD; 5327; -.
DR MGI; MGI:97610; Plat.
DR VEuPathDB; HostDB:ENSMUSG00000031538; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000158930; -.
DR HOGENOM; CLU_006842_18_4_1; -.
DR InParanoid; P11214; -.
DR OMA; EYCNVPT; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; P11214; -.
DR TreeFam; TF329901; -.
DR BRENDA; 3.4.21.68; 3474.
DR Reactome; R-MMU-186797; Signaling by PDGF.
DR Reactome; R-MMU-75205; Dissolution of Fibrin Clot.
DR BioGRID-ORCS; 18791; 3 hits in 72 CRISPR screens.
DR PRO; PR:P11214; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P11214; protein.
DR Bgee; ENSMUSG00000031538; Expressed in primary oocyte and 273 other tissues.
DR Genevisible; P11214; MM.
DR GO; GO:0045177; C:apical part of cell; IDA:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; IMP:SynGO.
DR GO; GO:0098992; C:neuronal dense core vesicle; ISO:MGI.
DR GO; GO:0099544; C:perisynaptic space; ISO:MGI.
DR GO; GO:0098794; C:postsynapse; ISO:MGI.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IMP:SynGO.
DR GO; GO:0030141; C:secretory granule; IDA:MGI.
DR GO; GO:0097180; C:serine protease inhibitor complex; ISO:MGI.
DR GO; GO:0045202; C:synapse; ISO:MGI.
DR GO; GO:0051219; F:phosphoprotein binding; ISO:MGI.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IEA:Ensembl.
DR GO; GO:0071373; P:cellular response to luteinizing hormone stimulus; IEA:Ensembl.
DR GO; GO:0051918; P:negative regulation of fibrinolysis; IC:ComplexPortal.
DR GO; GO:0010757; P:negative regulation of plasminogen activation; IC:ComplexPortal.
DR GO; GO:0045861; P:negative regulation of proteolysis; ISO:MGI.
DR GO; GO:0031639; P:plasminogen activation; ISO:MGI.
DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IDA:MGI.
DR GO; GO:0060279; P:positive regulation of ovulation; ISO:MGI.
DR GO; GO:0060468; P:prevention of polyspermy; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IDA:MGI.
DR GO; GO:0048167; P:regulation of synaptic plasticity; IEA:Ensembl.
DR GO; GO:0051591; P:response to cAMP; IEA:Ensembl.
DR GO; GO:0070542; P:response to fatty acid; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IMP:MGI.
DR GO; GO:0014909; P:smooth muscle cell migration; IMP:MGI.
DR GO; GO:0035249; P:synaptic transmission, glutamatergic; ISO:MGI.
DR GO; GO:0099183; P:trans-synaptic signaling by BDNF, modulating synaptic transmission; IMP:SynGO.
DR GO; GO:0042060; P:wound healing; IEA:Ensembl.
DR CDD; cd00061; FN1; 1.
DR CDD; cd00108; KR; 2.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR Gene3D; 2.40.20.10; -; 2.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000083; Fibronectin_type1.
DR InterPro; IPR000001; Kringle.
DR InterPro; IPR013806; Kringle-like.
DR InterPro; IPR018056; Kringle_CS.
DR InterPro; IPR038178; Kringle_sf.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR026280; Tissue_plasm_act.
DR InterPro; IPR034811; tPA.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR PANTHER; PTHR24264:SF42; PTHR24264:SF42; 3.
DR Pfam; PF00008; EGF; 1.
DR Pfam; PF00039; fn1; 1.
DR Pfam; PF00051; Kringle; 2.
DR Pfam; PF00089; Trypsin; 1.
DR PIRSF; PIRSF001145; Tissue_plasm_act; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00181; EGF; 1.
DR SMART; SM00058; FN1; 1.
DR SMART; SM00130; KR; 2.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF57440; SSF57440; 2.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS50026; EGF_3; 1.
DR PROSITE; PS01253; FN1_1; 1.
DR PROSITE; PS51091; FN1_2; 1.
DR PROSITE; PS00021; KRINGLE_1; 2.
DR PROSITE; PS50070; KRINGLE_2; 2.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW Cleavage on pair of basic residues; Direct protein sequencing;
KW Disulfide bond; EGF-like domain; Glycoprotein; Hydrolase; Kringle;
KW Plasminogen activation; Protease; Reference proteome; Repeat; Secreted;
KW Serine protease; Signal; Zymogen.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT PROPEP 18..29
FT /evidence="ECO:0000250"
FT /id="PRO_0000028353"
FT PROPEP 30..32
FT /note="Removed by plasmin"
FT /evidence="ECO:0000269|PubMed:7523120"
FT /id="PRO_0000285906"
FT CHAIN 33..559
FT /note="Tissue-type plasminogen activator"
FT /id="PRO_0000028354"
FT CHAIN 33..308
FT /note="Tissue-type plasminogen activator chain A"
FT /id="PRO_0000028355"
FT CHAIN 309..559
FT /note="Tissue-type plasminogen activator chain B"
FT /id="PRO_0000028356"
FT DOMAIN 36..78
FT /note="Fibronectin type-I"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00478"
FT DOMAIN 79..117
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 124..205
FT /note="Kringle 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 213..294
FT /note="Kringle 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 309..558
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT REGION 39..49
FT /note="Important for binding to annexin A2"
FT /evidence="ECO:0000250"
FT ACT_SITE 355
FT /note="Charge relay system"
FT ACT_SITE 404
FT /note="Charge relay system"
FT ACT_SITE 510
FT /note="Charge relay system"
FT SITE 99
FT /note="Important for binding to LRP1"
FT /evidence="ECO:0000250"
FT SITE 462
FT /note="Important for single-chain activity"
FT /evidence="ECO:0000250"
FT SITE 509
FT /note="Important for single-chain activity"
FT /evidence="ECO:0000250"
FT CARBOHYD 149
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 481
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 38..68
FT /evidence="ECO:0000250"
FT DISULFID 66..75
FT /evidence="ECO:0000250"
FT DISULFID 83..94
FT /evidence="ECO:0000250"
FT DISULFID 88..105
FT /evidence="ECO:0000250"
FT DISULFID 107..116
FT /evidence="ECO:0000250"
FT DISULFID 124..205
FT /evidence="ECO:0000250"
FT DISULFID 145..187
FT /evidence="ECO:0000250"
FT DISULFID 176..200
FT /evidence="ECO:0000250"
FT DISULFID 213..294
FT /evidence="ECO:0000250"
FT DISULFID 234..276
FT /evidence="ECO:0000250"
FT DISULFID 265..289
FT /evidence="ECO:0000250"
FT DISULFID 297..428
FT /note="Interchain (between A and B chains)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000255|PROSITE-ProRule:PRU00121, ECO:0000255|PROSITE-
FT ProRule:PRU00274, ECO:0000255|PROSITE-ProRule:PRU00478"
FT DISULFID 340..356
FT /evidence="ECO:0000250"
FT DISULFID 348..417
FT /evidence="ECO:0000250"
FT DISULFID 442..516
FT /evidence="ECO:0000250"
FT DISULFID 474..490
FT /evidence="ECO:0000250"
FT DISULFID 506..534
FT /evidence="ECO:0000250"
FT CONFLICT 260
FT /note="G -> A (in Ref. 1; AAA40470)"
FT /evidence="ECO:0000305"
FT CONFLICT 325
FT /note="A -> P (in Ref. 3; AAH11256)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 559 AA; 63097 MW; 0A158A5A273CFAA0 CRC64;
MKRELLCVLL LCGLAFPLPD QGIHGRFRRG ARSYRATCRD EPTQTTYQQH QSWLRPMLRS
SRVEYCRCNS GLVQCHSVPV RSCSEPRCFN GGTCQQALYF SDFVCQCPDG FVGKRCDIDT
RATCFEEQGI TYRGTWSTAE SGAECINWNS SVLSLKPYNA RRPNAIKLGL GNHNYCRNPD
RDLKPWCYVF KAGKYTTEFC STPACPKGKS EDCYVGKGVT YRGTHSLTTS QASCLPWNSI
VLMGKSYTAW RTNSQALGLG RHNYCRNPDG DARPWCHVMK DRKLTWEYCD MSPCSTCGLR
QYKRPQFRIK GGLYTDITSH PWQAAIFVKN KRSPGERFLC GGVLISSCWV LSAAHCFLER
FPPNHLKVVL GRTYRVVPGE EEQTFEIEKY IVHEEFDDDT YDNDIALLQL RSQSKQCAQE
SSSVGTACLP DPNLQLPDWT ECELSGYGKH EASSPFFSDR LKEAHVRLYP SSRCTSQHLF
NKTVTNNMLC AGDTRSGGNQ DLHDACQGDS GGPLVCMINK QMTLTGIISW GLGCGQKDVP
GVYTKVTNYL DWIHDNMKQ
