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P11214 (TPA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 148. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tissue-type plasminogen activator

Short name=t-PA
Short name=t-plasminogen activator
Short name=tPA
EC=3.4.21.68
Gene names
Name:Plat
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length559 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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

Secretedextracellular 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 processPlasminogen activation
   Cellular componentSecreted
   DomainEGF-like domain
Kringle
Repeat
Signal
   Molecular functionHydrolase
Protease
Serine protease
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
Zymogen
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processnegative regulation of proteolysis

Inferred from electronic annotation. Source: Ensembl

plasminogen activation

Inferred from electronic annotation. Source: Ensembl

platelet-derived growth factor receptor signaling pathway

Inferred from direct assay PubMed 15372073. Source: MGI

positive regulation of ovulation

Inferred from electronic annotation. Source: Ensembl

proteolysis

Inferred from direct assay PubMed 15372073. Source: MGI

regulation of synaptic plasticity

Inferred from electronic annotation. Source: Ensembl

response to cAMP

Inferred from electronic annotation. Source: Ensembl

response to glucocorticoid

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from mutant phenotype PubMed 17382917. Source: MGI

response to peptide hormone

Inferred from electronic annotation. Source: Ensembl

smooth muscle cell migration

Inferred from mutant phenotype PubMed 17382917. Source: MGI

synaptic transmission, glutamatergic

Inferred from electronic annotation. Source: Ensembl

wound healing

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentapical part of cell

Inferred from direct assay PubMed 15978259. Source: MGI

cell surface

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay PubMed 15978259. Source: MGI

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: Ensembl

   Molecular_functionserine-type endopeptidase activity

Inferred from direct assay PubMed 15372073. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717 Potential
Propeptide18 – 2912 By similarity
PRO_0000028353
Propeptide30 – 323Removed by plasmin
PRO_0000285906
Chain33 – 559527Tissue-type plasminogen activator
PRO_0000028354
Chain33 – 308276Tissue-type plasminogen activator chain A
PRO_0000028355
Chain309 – 559251Tissue-type plasminogen activator chain B
PRO_0000028356

Regions

Domain36 – 7843Fibronectin type-I
Domain79 – 11739EGF-like
Domain124 – 20582Kringle 1
Domain213 – 29482Kringle 2
Domain309 – 558250Peptidase S1
Region39 – 4911Important for binding to annexin A2 By similarity

Sites

Active site3551Charge relay system
Active site4041Charge relay system
Active site5101Charge relay system
Site991Important for binding to LRP1 By similarity
Site4621Important for single-chain activity By similarity
Site5091Important for single-chain activity By similarity

Amino acid modifications

Glycosylation1491N-linked (GlcNAc...) Potential
Glycosylation4811N-linked (GlcNAc...) Potential
Disulfide bond38 ↔ 68 By similarity
Disulfide bond66 ↔ 75 By similarity
Disulfide bond83 ↔ 94 By similarity
Disulfide bond88 ↔ 105 By similarity
Disulfide bond107 ↔ 116 By similarity
Disulfide bond124 ↔ 205 By similarity
Disulfide bond145 ↔ 187 By similarity
Disulfide bond176 ↔ 200 By similarity
Disulfide bond213 ↔ 294 By similarity
Disulfide bond234 ↔ 276 By similarity
Disulfide bond265 ↔ 289 By similarity
Disulfide bond297 ↔ 428Interchain (between A and B chains) By similarity
Disulfide bond340 ↔ 356 By similarity
Disulfide bond348 ↔ 417 By similarity
Disulfide bond442 ↔ 516 By similarity
Disulfide bond474 ↔ 490 By similarity
Disulfide bond506 ↔ 534 By similarity

Experimental info

Sequence conflict2601G → A in AAA40470. Ref.1
Sequence conflict3251A → P in AAH11256. Ref.3

Sequences

Sequence LengthMass (Da)Tools
P11214 [UniParc].

Last modified October 2, 2007. Version 3.
Checksum: 0A158A5A273CFAA0

FASTA55963,097
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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.
PIRA29941.
RefSeqNP_032898.2. NM_008872.2.
UniGeneMm.154660.

3D structure databases

ProteinModelPortalP11214.
SMRP11214. Positions 33-558.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP11214. 2 interactions.
MINTMINT-8178492.

Protein family/group databases

MEROPSS01.232.

PTM databases

PhosphoSiteP11214.

Proteomic databases

PaxDbP11214.
PRIDEP11214.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000033941; ENSMUSP00000033941; ENSMUSG00000031538.
GeneID18791.
KEGGmmu:18791.
UCSCuc009ldx.2. mouse.

Organism-specific databases

CTD5327.
MGIMGI:97610. Plat.

Phylogenomic databases

eggNOGCOG5640.
GeneTreeENSGT00740000115235.
HOGENOMHOG000237314.
HOVERGENHBG008633.
InParanoidP11214.
KOK01343.
OMAAHVRLYP.
OrthoDBEOG75B84T.
PhylomeDBP11214.
TreeFamTF329901.

Enzyme and pathway databases

BRENDA3.4.21.68. 3474.

Gene expression databases

BgeeP11214.
CleanExMM_PLAT.
GenevestigatorP11214.

Family and domain databases

Gene3D2.40.20.10. 2 hits.
InterProIPR000742. 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]
PfamPF00008. EGF. 1 hit.
PF00039. fn1. 1 hit.
PF00051. Kringle. 2 hits.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFPIRSF001145. Tissue_plasm_act. 1 hit.
PRINTSPR00722. CHYMOTRYPSIN.
SMARTSM00181. EGF. 1 hit.
SM00058. FN1. 1 hit.
SM00130. KR. 2 hits.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMSSF50494. SSF50494. 1 hit.
SSF57440. SSF57440. 2 hits.
PROSITEPS00022. 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]
ProtoNetSearch...

Other

NextBio295068.
PROP11214.
SOURCESearch...

Entry information

Entry nameTPA_MOUSE
AccessionPrimary (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: April 16, 2014
This is version 148 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot