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Reviewed, UniProtKB/Swiss-Prot P11214 (TPA_MOUSE)

Last modified June 16, 2009. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Tissue-type plasminogen activator
      Short name=t-plasminogen activator
      Short name=t-PA
      Short name=tPA
    EC=3.4.21.68
Cleaved into the following 2 chains:
    1- Recommended name:
            Tissue-type plasminogen activator chain A
    2- Recommended name:
            Tissue-type plasminogen activator chain B
Gene names
Name: Plat
OrganismMus musculus (Mouse)
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

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Protein attributes

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

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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.

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 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.

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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 Ref.4
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

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Sequences

Sequence LengthMass (Da)Tools
P11214-1 [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

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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: 2826484] [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: 16141072] [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: 15489334] [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: 7523120] [Abstract]
Cited for: PROTEIN SEQUENCE OF 33-40 AND 309-316.
+Additional computationally mapped references.

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Cross-references

Sequence databases

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.
IPIIPI00319513.
PIRA29941.
RefSeqNP_032898.2.
UniGeneMm.154660

3D structure databases

HSSPHSSP built from PDB template 1RTF based on UniProtKB P00750.
SMRP11214. Positions 33-123, 210-296, 296-558.
ModBaseSearch...

Protein family/group databases

MEROPSS01.232.

Genome annotation databases

EnsemblENSMUSG00000031538. Mus musculus. [Contig view]
GeneID18791.
KEGGmmu:18791.

Organism-specific databases

MGIMGI:97610. Plat.

Phylogenomic databases

HOGENOMP11214.
HOVERGENP11214.
OMAP11214. TCGLRQY.

Enzyme and pathway databases

BRENDA3.4.21.68. 244.

Gene expression databases

ArrayExpressP11214.
BgeeP11214.
CleanExMM_PLAT.
GermOnlineENSMUSG00000031538. Mus musculus.

Family and domain databases

InterProIPR016060. Complement_control_module.
IPR006209. EGF.
IPR006210. EGF-like.
IPR013032. EGF-like_reg_CS.
IPR000742. EGF_3.
IPR000083. Fibrnctn1.
IPR000001. Kringle.
IPR018056. Kringle_CS.
IPR018059. Kringle_sub.
IPR018114. Peptidase_S1/S6_AS.
IPR001254. Peptidase_S1_S6.
IPR001314. Peptidase_S1A.
[Graphical view]
Gene3DG3DSA:2.10.70.10. Complement_control_module. 1 hit.
G3DSA:2.40.20.10. Kringle. 2 hits.
PfamPF00008. EGF. 1 hit.
PF00039. fn1. 1 hit.
PF00051. Kringle. 2 hits.
PF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSPR00722. CHYMOTRYPSIN.
PR00018. KRINGLE.
ProDomPD000395. Kringle. 2 hits.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00181. EGF. 1 hit.
SM00058. FN1. 1 hit.
SM00130. KR. 2 hits.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
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 Resources

NextBio295068.
SOURCESearch...

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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: June 16, 2009
This is version 102 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

MGD cross-references

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

Peptidase families

Classification of peptidase families and list of entries

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents