P11214 (TPA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tissue-type plasminogen activator
Short name=t-PA
Short name=t-plasminogen activator
Short name=tPA
EC=3.4.21.68

Cleaved into the following 2 chains:

1. Tissue-type plasminogen activator chain A
2. Tissue-type plasminogen activator chain B

Gene names

Name:

Plat

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	559 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By controlling plasmin-mediated proteolysis, it plays an important role in tissue remodeling and degradation, in cell migration and many other physiopathological events.
Catalytic activity	Specific cleavage of Arg-|-Val bond in plasminogen to form plasmin.
Enzyme regulation	Inhibited by SERPINA5 By similarity.
Subunit structure	Heterodimer of chain A and chain B held by a disulfide bond. Binds to fibrin with high affinity. This interaction leads to an increase in the catalytic efficiency of the enzyme due to an increase in affinity for plasminogen. Similarly, binding to heparin increases the activation of plasminogen. Binds to annexin A2, cytokeratin-8, fibronectin and laminin. Binds to mannose receptor and the low-density lipoprotein receptor-related protein (LRP1); these proteins are involved in TPA clearance. Binds LRP1B; binding is followed by internalization and degradation. Forms heterodimer with SERPINA5 By similarity.
Subcellular location	Secreted › extracellular space.
Domain	Both FN1 and one of the kringle domains are required for binding to fibrin By similarity. Both FN1 and EGF-like domains are important for binding to LRP1 By similarity. The FN1 domain mediates binding to annexin A2 By similarity. The second kringle domain is implicated in binding to cytokeratin-8 and to the endothelial cell surface binding site By similarity.
Post-translational modification	The single chain, almost fully active enzyme, can be further processed into a two-chain fully active form by a cleavage after Arg-308 catalyzed by plasmin, tissue kallikrein or factor Xa.
Sequence similarities	Belongs to the peptidase S1 family. Contains 1 EGF-like domain. Contains 1 fibronectin type-I domain. Contains 2 kringle domains. Contains 1 peptidase S1 domain.

Ontologies

Keywords
Biological process	Plasminogen activation
Cellular component	Secreted
Domain	EGF-like domain Kringle Repeat Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Zymogen
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of proteolysis Inferred from electronic annotation. Source: Compara plasminogen activation Inferred from electronic annotation. Source: Compara platelet-derived growth factor receptor signaling pathway Inferred from direct assay PubMed 15372073. Source: MGI positive regulation of ovulation Inferred from electronic annotation. Source: Compara proteolysis Inferred from direct assay PubMed 15372073. Source: MGI regulation of synaptic plasticity Inferred from electronic annotation. Source: Compara response to cAMP Inferred from electronic annotation. Source: Compara response to glucocorticoid stimulus Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from mutant phenotype PubMed 17382917. Source: MGI response to peptide hormone stimulus Inferred from electronic annotation. Source: Compara smooth muscle cell migration Inferred from mutant phenotype PubMed 17382917. Source: MGI synaptic transmission, glutamatergic Inferred from electronic annotation. Source: Compara wound healing Inferred from electronic annotation. Source: Compara
Cellular_component	apical part of cell Inferred from direct assay PubMed 15978259. Source: MGI cell surface Inferred from electronic annotation. Source: Compara extracellular space Inferred from direct assay PubMed 15372073. Source: MGI secretory granule Inferred from direct assay PubMed 15978259. Source: MGI synapse Inferred from electronic annotation. Source: Compara
Molecular_function	serine-type endopeptidase activity Inferred from direct assay PubMed 15372073. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 17	17	Potential
	Propeptide	18 – 29	12	By similarity		PRO_0000028353
	Propeptide	30 – 32	3	Removed by plasmin		PRO_0000285906
	Chain	33 – 559	527	Tissue-type plasminogen activator		PRO_0000028354
	Chain	33 – 308	276	Tissue-type plasminogen activator chain A		PRO_0000028355
	Chain	309 – 559	251	Tissue-type plasminogen activator chain B		PRO_0000028356
Regions
	Domain	36 – 78	43	Fibronectin type-I
	Domain	79 – 117	39	EGF-like
	Domain	124 – 205	82	Kringle 1
	Domain	213 – 294	82	Kringle 2
	Domain	309 – 558	250	Peptidase S1
	Region	39 – 49	11	Important for binding to annexin A2 By similarity
Sites
	Active site	355	1	Charge relay system
	Active site	404	1	Charge relay system
	Active site	510	1	Charge relay system
	Site	99	1	Important for binding to LRP1 By similarity
	Site	462	1	Important for single-chain activity By similarity
	Site	509	1	Important for single-chain activity By similarity
Amino acid modifications
	Glycosylation	149	1	N-linked (GlcNAc...) Potential
	Glycosylation	481	1	N-linked (GlcNAc...) Potential
	Disulfide bond	38 ↔ 68		By similarity
	Disulfide bond	66 ↔ 75		By similarity
	Disulfide bond	83 ↔ 94		By similarity
	Disulfide bond	88 ↔ 105		By similarity
	Disulfide bond	107 ↔ 116		By similarity
	Disulfide bond	124 ↔ 205		By similarity
	Disulfide bond	145 ↔ 187		By similarity
	Disulfide bond	176 ↔ 200		By similarity
	Disulfide bond	213 ↔ 294		By similarity
	Disulfide bond	234 ↔ 276		By similarity
	Disulfide bond	265 ↔ 289		By similarity
	Disulfide bond	297 ↔ 428		Interchain (between A and B chains) By similarity
	Disulfide bond	340 ↔ 356		By similarity
	Disulfide bond	348 ↔ 417		By similarity
	Disulfide bond	442 ↔ 516		By similarity
	Disulfide bond	474 ↔ 490		By similarity
	Disulfide bond	506 ↔ 534		By similarity
Experimental info
	Sequence conflict	260	1	G → A in AAA40470. Ref.1
	Sequence conflict	325	1	A → P in AAH11256. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P11214 [UniParc]. Last modified October 2, 2007. Version 3. Checksum: 0A158A5A273CFAA0	FASTA	559	63,097
	10 20 30 40 50 60 MKRELLCVLL LCGLAFPLPD QGIHGRFRRG ARSYRATCRD EPTQTTYQQH QSWLRPMLRS 70 80 90 100 110 120 SRVEYCRCNS GLVQCHSVPV RSCSEPRCFN GGTCQQALYF SDFVCQCPDG FVGKRCDIDT 130 140 150 160 170 180 RATCFEEQGI TYRGTWSTAE SGAECINWNS SVLSLKPYNA RRPNAIKLGL GNHNYCRNPD 190 200 210 220 230 240 RDLKPWCYVF KAGKYTTEFC STPACPKGKS EDCYVGKGVT YRGTHSLTTS QASCLPWNSI 250 260 270 280 290 300 VLMGKSYTAW RTNSQALGLG RHNYCRNPDG DARPWCHVMK DRKLTWEYCD MSPCSTCGLR 310 320 330 340 350 360 QYKRPQFRIK GGLYTDITSH PWQAAIFVKN KRSPGERFLC GGVLISSCWV LSAAHCFLER 370 380 390 400 410 420 FPPNHLKVVL GRTYRVVPGE EEQTFEIEKY IVHEEFDDDT YDNDIALLQL RSQSKQCAQE 430 440 450 460 470 480 SSSVGTACLP DPNLQLPDWT ECELSGYGKH EASSPFFSDR LKEAHVRLYP SSRCTSQHLF 490 500 510 520 530 540 NKTVTNNMLC AGDTRSGGNQ DLHDACQGDS GGPLVCMINK QMTLTGIISW GLGCGQKDVP 550 GVYTKVTNYL DWIHDNMKQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of complementary DNA to mouse tissue plasminogen activator mRNA and its expression during F9 teratocarcinoma cell differentiation." Rickles R.J., Darrow A.L., Strickland S. J. Biol. Chem. 263:1563-1569(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N and NMRI. Tissue: Mammary gland and Mammary tumor.
[4]	"Characterization of the murine plasma fibrinolytic system." Lijnen H.R., van Hoef B., Beelen V., Collen D. Eur. J. Biochem. 224:863-871(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 33-40 AND 309-316.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	J03520 mRNA. Translation: AAA40470.1. AK135857 mRNA. Translation: BAE22698.1. AK135965 mRNA. Translation: BAE22749.1. BC011256 mRNA. Translation: AAH11256.1. BC057967 mRNA. Translation: AAH57967.1. BC061508 mRNA. Translation: AAH61508.1.
IPI	IPI00319513.
PIR	A29941.
RefSeq	NP_032898.2. NM_008872.2.
UniGene	Mm.154660.
3D structure databases
ProteinModelPortal	P11214.
SMR	P11214. Positions 33-558.
ModBase	Search...
Protein-protein interaction databases
IntAct	P11214. 1 interaction.
Protein family/group databases
MEROPS	S01.232.
PTM databases
PhosphoSite	P11214.
Proteomic databases
PaxDb	P11214.
PRIDE	P11214.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000033941; ENSMUSP00000033941; ENSMUSG00000031538.
GeneID	18791.
KEGG	mmu:18791.
UCSC	uc009ldx.2. mouse.
Organism-specific databases
CTD	5327.
MGI	MGI:97610. Plat.
Phylogenomic databases
eggNOG	COG5640.
GeneTree	ENSGT00570000078945.
HOGENOM	HOG000237314.
HOVERGEN	HBG008633.
InParanoid	P11214.
KO	K01343.
OMA	AHVRLYP.
OrthoDB	EOG4BVRTC.
Enzyme and pathway databases
BRENDA	3.4.21.68. 3474.
Gene expression databases
Bgee	P11214.
CleanEx	MM_PLAT.
Genevestigator	P11214.
GermOnline	ENSMUSG00000031538. Mus musculus.
Family and domain databases
Gene3D	2.40.20.10. 2 hits.
InterPro	IPR000742. EG-like_dom. IPR013032. EGF-like_CS. IPR000083. Fibronectin_type1. IPR000001. Kringle. IPR013806. Kringle-like. IPR018056. Kringle_CS. IPR001254. Peptidase_S1. IPR018114. Peptidase_S1_AS. IPR001314. Peptidase_S1A. IPR026280. Tissue_plasm_act. IPR009003. Trypsin-like_Pept_dom. [Graphical view]
Pfam	PF00008. EGF. 1 hit. PF00039. fn1. 1 hit. PF00051. Kringle. 2 hits. PF00089. Trypsin. 1 hit. [Graphical view]
PIRSF	PIRSF001145. Tissue_plasm_act. 1 hit.
PRINTS	PR00722. CHYMOTRYPSIN.
SMART	SM00181. EGF. 1 hit. SM00058. FN1. 1 hit. SM00130. KR. 2 hits. SM00020. Tryp_SPc. 1 hit. [Graphical view]
SUPFAM	SSF57440. Kringle-like. 2 hits. SSF50494. Pept_Ser_Cys. 1 hit.
PROSITE	PS00022. EGF_1. 1 hit. PS01186. EGF_2. 1 hit. PS50026. EGF_3. 1 hit. PS01253. FN1_1. 1 hit. PS51091. FN1_2. 1 hit. PS00021. KRINGLE_1. 2 hits. PS50070. KRINGLE_2. 2 hits. PS50240. TRYPSIN_DOM. 1 hit. PS00134. TRYPSIN_HIS. 1 hit. PS00135. TRYPSIN_SER. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	295068.
SOURCE	Search...

Entry information

Entry name

TPA_MOUSE

Accession

Primary (citable) accession number: P11214
Secondary accession number(s): Q6P7U0, Q91VP2

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	October 2, 2007
Last modified:	May 1, 2013
This is version 141 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program