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 04-NOV-2026, entry version 222. 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 (By similarity). Inhibited CC by SERPINE1 (By similarity). {ECO:0000250|UniProtKB:P00750}. 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). Interacts with SERPINE1 (By similarity). In complex with CC SERPINE1, interacts with SORL1 (By similarity). {ECO:0000250, CC 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 RefSeq; XP_036009719.1; XM_036153826.1. DR AlphaFoldDB; P11214; -. DR SMR; P11214; -. DR BioGRID; 202229; 5. DR ComplexPortal; CPX-518; tPA-PAI-1 complex. DR FunCoup; P11214; 301. DR IntAct; P11214; 2. DR STRING; 10090.ENSMUSP00000033941; -. DR BindingDB; P11214; -. DR ChEMBL; CHEMBL3259492; -. DR MEROPS; S01.232; -. DR GlyCosmos; P11214; 2 sites, No reported glycans. DR GlyGen; P11214; 2 sites, 1 N-linked glycan (1 site). DR iPTMnet; P11214; -. DR PhosphoSitePlus; P11214; -. DR PaxDb; 10090-ENSMUSP00000033941; -. DR PeptideAtlas; P11214; -. DR ProteomicsDB; 258819; -. DR Pumba; P11214; -. DR ABCD; P11214; 5 sequenced antibodies. DR Antibodypedia; 998; 872 antibodies from 43 providers. DR DNASU; 18791; -. DR Ensembl; ENSMUST00000033941.7; ENSMUSP00000033941.6; ENSMUSG00000031538.7. DR GeneID; 18791; -. DR KEGG; mmu:18791; -. DR UCSC; uc009ldx.2; mouse. DR AGR; MGI:97610; -. 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; AACLRWD; -. DR OrthoDB; 6219at9989; -. DR PhylomeDB; P11214; -. 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 77 CRISPR screens. DR PRO; PR:P11214; -. DR Proteomes; UP000000589; Chromosome 8. DR RNAct; P11214; protein. DR Bgee; ENSMUSG00000031538; Expressed in primary oocyte and 277 other cell types or tissues. DR GO; GO:0045177; C:apical part of cell; IDA:MGI. DR GO; GO:0009986; C:cell surface; ISO:GO_Central. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0005576; C:extracellular region; IDA:MGI. DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO. DR GO; GO:0098992; C:neuronal dense core vesicle; ISO:GO_Central. DR GO; GO:0099544; C:perisynaptic space; ISO:GO_Central. DR GO; GO:0098794; C:postsynapse; ISO:GO_Central. DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IDA:SynGO. DR GO; GO:0030141; C:secretory granule; IDA:MGI. DR GO; GO:0097180; C:serine protease inhibitor complex; ISO:GO_Central. DR GO; GO:0051219; F:phosphoprotein binding; ISO:GO_Central. DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:MGI. DR GO; GO:0005102; F:signaling receptor binding; ISO:GO_Central. DR GO; GO:0051918; P:negative regulation of fibrinolysis; NAS:ComplexPortal. DR GO; GO:0010757; P:negative regulation of plasminogen activation; NAS:ComplexPortal. DR GO; GO:0045861; P:negative regulation of proteolysis; ISO:GO_Central. DR GO; GO:0031639; P:plasminogen activation; ISO:GO_Central. DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IDA:MGI. DR GO; GO:0060468; P:prevention of polyspermy; ISS:UniProtKB. DR GO; GO:0006508; P:proteolysis; IDA:MGI. 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:GO_Central. DR GO; GO:0099183; P:trans-synaptic signaling by BDNF, modulating synaptic transmission; IDA:SynGO. DR CDD; cd00054; EGF_CA; 1. DR CDD; cd00061; FN1; 1. DR CDD; cd00108; KR; 2. DR CDD; cd00190; Tryp_SPc; 1. DR FunFam; 2.40.10.10:FF:000054; Complement C1r subcomponent; 1. DR FunFam; 2.10.70.10:FF:000043; Plasminogen activator; 1. DR FunFam; 2.10.25.10:FF:000483; Tissue-type plasminogen activator; 1. DR FunFam; 2.40.10.10:FF:000058; Tissue-type plasminogen activator; 1. DR FunFam; 2.40.20.10:FF:000001; Urokinase-type plasminogen activator; 2. DR Gene3D; 2.10.70.10; Complement Module, domain 1; 1. DR Gene3D; 2.10.25.10; Laminin; 1. DR Gene3D; 2.40.20.10; Plasminogen Kringle 4; 2. DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2. DR InterPro; IPR000742; EGF. 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; IPR001314; Peptidase_S1A. DR InterPro; IPR050127; Serine_Proteases_S1. DR InterPro; IPR026280; Tissue_plasm_act. DR InterPro; IPR001254; Trypsin_dom. DR InterPro; IPR018114; TRYPSIN_HIS. DR InterPro; IPR033116; TRYPSIN_SER. DR PANTHER; PTHR24264:SF42; TISSUE-TYPE PLASMINOGEN ACTIVATOR; 1. DR PANTHER; PTHR24264; TRYPSIN-RELATED; 1. 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 PRINTS; PR00018; KRINGLE. DR SMART; SM00181; EGF; 1. DR SMART; SM00058; FN1; 1. DR SMART; SM00130; KR; 2. DR SMART; SM00020; Tryp_SPc; 1. DR SUPFAM; SSF57603; FnI-like domain; 1. DR SUPFAM; SSF57440; Kringle-like; 2. DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1. 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 //