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P11214

- TPA_MOUSE

UniProt

P11214 - TPA_MOUSE

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Protein

Tissue-type plasminogen activator

Gene

Plat

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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 activityi

Specific cleavage of Arg-|-Val bond in plasminogen to form plasmin.

Enzyme regulationi

Inhibited by SERPINA5.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei99 – 991Important for binding to LRP1By similarity
Active sitei355 – 3551Charge relay system
Active sitei404 – 4041Charge relay system
Sitei462 – 4621Important for single-chain activityBy similarity
Sitei509 – 5091Important for single-chain activityBy similarity
Active sitei510 – 5101Charge relay system

GO - Molecular functioni

  1. serine-type endopeptidase activity Source: MGI

GO - Biological processi

  1. negative regulation of proteolysis Source: Ensembl
  2. plasminogen activation Source: Ensembl
  3. platelet-derived growth factor receptor signaling pathway Source: MGI
  4. positive regulation of ovulation Source: Ensembl
  5. proteolysis Source: MGI
  6. regulation of synaptic plasticity Source: Ensembl
  7. response to cAMP Source: Ensembl
  8. response to glucocorticoid Source: Ensembl
  9. response to hypoxia Source: MGI
  10. response to peptide hormone Source: Ensembl
  11. smooth muscle cell migration Source: MGI
  12. synaptic transmission, glutamatergic Source: Ensembl
  13. wound healing Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Plasminogen activation

Enzyme and pathway databases

BRENDAi3.4.21.68. 3474.

Protein family/group databases

MEROPSiS01.232.

Names & Taxonomyi

Protein namesi
Recommended name:
Tissue-type plasminogen activator (EC:3.4.21.68)
Short name:
t-PA
Short name:
t-plasminogen activator
Short name:
tPA
Cleaved into the following 2 chains:
Gene namesi
Name:Plat
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 8

Organism-specific databases

MGIiMGI:97610. Plat.

Subcellular locationi

GO - Cellular componenti

  1. apical part of cell Source: MGI
  2. cell surface Source: Ensembl
  3. cytoplasm Source: MGI
  4. extracellular space Source: MGI
  5. extracellular vesicular exosome Source: Ensembl
  6. secretory granule Source: MGI
  7. synapse Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1717Sequence AnalysisAdd
BLAST
Propeptidei18 – 2912By similarityPRO_0000028353Add
BLAST
Propeptidei30 – 323Removed by plasmin1 PublicationPRO_0000285906
Chaini33 – 559527Tissue-type plasminogen activatorPRO_0000028354Add
BLAST
Chaini33 – 308276Tissue-type plasminogen activator chain APRO_0000028355Add
BLAST
Chaini309 – 559251Tissue-type plasminogen activator chain BPRO_0000028356Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi38 ↔ 68By similarity
Disulfide bondi66 ↔ 75By similarity
Disulfide bondi83 ↔ 94By similarity
Disulfide bondi88 ↔ 105By similarity
Disulfide bondi107 ↔ 116By similarity
Disulfide bondi124 ↔ 205By similarity
Disulfide bondi145 ↔ 187By similarity
Glycosylationi149 – 1491N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi176 ↔ 200By similarity
Disulfide bondi213 ↔ 294By similarity
Disulfide bondi234 ↔ 276By similarity
Disulfide bondi265 ↔ 289By similarity
Disulfide bondi297 ↔ 428Interchain (between A and B chains)PROSITE-ProRule annotation
Disulfide bondi340 ↔ 356By similarity
Disulfide bondi348 ↔ 417By similarity
Disulfide bondi442 ↔ 516By similarity
Disulfide bondi474 ↔ 490By similarity
Glycosylationi481 – 4811N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi506 ↔ 534By similarity

Post-translational modificationi

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.

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

MaxQBiP11214.
PaxDbiP11214.
PRIDEiP11214.

PTM databases

PhosphoSiteiP11214.

Expressioni

Gene expression databases

BgeeiP11214.
CleanExiMM_PLAT.
GenevestigatoriP11214.

Interactioni

Subunit structurei

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.By similarity

Protein-protein interaction databases

IntActiP11214. 2 interactions.
MINTiMINT-8178492.

Structurei

3D structure databases

ProteinModelPortaliP11214.
SMRiP11214. Positions 33-558.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini36 – 7843Fibronectin type-IPROSITE-ProRule annotationAdd
BLAST
Domaini79 – 11739EGF-likePROSITE-ProRule annotationAdd
BLAST
Domaini124 – 20582Kringle 1PROSITE-ProRule annotationAdd
BLAST
Domaini213 – 29482Kringle 2PROSITE-ProRule annotationAdd
BLAST
Domaini309 – 558250Peptidase S1PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni39 – 4911Important for binding to annexin A2By similarityAdd
BLAST

Domaini

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

Sequence similaritiesi

Belongs to the peptidase S1 family.PROSITE-ProRule annotation
Contains 1 EGF-like domain.PROSITE-ProRule annotation
Contains 1 fibronectin type-I domain.PROSITE-ProRule annotation
Contains 2 kringle domains.PROSITE-ProRule annotation
Contains 1 peptidase S1 domain.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Kringle, Repeat, Signal

Phylogenomic databases

eggNOGiCOG5640.
GeneTreeiENSGT00760000119133.
HOGENOMiHOG000237314.
HOVERGENiHBG008633.
InParanoidiP11214.
KOiK01343.
OMAiAHVRLYP.
OrthoDBiEOG75B84T.
PhylomeDBiP11214.
TreeFamiTF329901.

Family and domain databases

Gene3Di2.40.20.10. 2 hits.
InterProiIPR000742. 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]
PfamiPF00008. EGF. 1 hit.
PF00039. fn1. 1 hit.
PF00051. Kringle. 2 hits.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFiPIRSF001145. Tissue_plasm_act. 1 hit.
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00181. EGF. 1 hit.
SM00058. FN1. 1 hit.
SM00130. KR. 2 hits.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF57440. SSF57440. 2 hits.
PROSITEiPS00022. 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]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P11214-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MKRELLCVLL LCGLAFPLPD QGIHGRFRRG ARSYRATCRD EPTQTTYQQH
60 70 80 90 100
QSWLRPMLRS SRVEYCRCNS GLVQCHSVPV RSCSEPRCFN GGTCQQALYF
110 120 130 140 150
SDFVCQCPDG FVGKRCDIDT RATCFEEQGI TYRGTWSTAE SGAECINWNS
160 170 180 190 200
SVLSLKPYNA RRPNAIKLGL GNHNYCRNPD RDLKPWCYVF KAGKYTTEFC
210 220 230 240 250
STPACPKGKS EDCYVGKGVT YRGTHSLTTS QASCLPWNSI VLMGKSYTAW
260 270 280 290 300
RTNSQALGLG RHNYCRNPDG DARPWCHVMK DRKLTWEYCD MSPCSTCGLR
310 320 330 340 350
QYKRPQFRIK GGLYTDITSH PWQAAIFVKN KRSPGERFLC GGVLISSCWV
360 370 380 390 400
LSAAHCFLER FPPNHLKVVL GRTYRVVPGE EEQTFEIEKY IVHEEFDDDT
410 420 430 440 450
YDNDIALLQL RSQSKQCAQE SSSVGTACLP DPNLQLPDWT ECELSGYGKH
460 470 480 490 500
EASSPFFSDR LKEAHVRLYP SSRCTSQHLF NKTVTNNMLC AGDTRSGGNQ
510 520 530 540 550
DLHDACQGDS GGPLVCMINK QMTLTGIISW GLGCGQKDVP GVYTKVTNYL

DWIHDNMKQ
Length:559
Mass (Da):63,097
Last modified:October 2, 2007 - v3
Checksum:i0A158A5A273CFAA0
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti260 – 2601G → A in AAA40470. (PubMed:2826484)Curated
Sequence conflicti325 – 3251A → P in AAH11256. (PubMed:15489334)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS22183.1.
PIRiA29941.
RefSeqiNP_032898.2. NM_008872.2.
UniGeneiMm.154660.

Genome annotation databases

EnsembliENSMUST00000033941; ENSMUSP00000033941; ENSMUSG00000031538.
GeneIDi18791.
KEGGimmu:18791.
UCSCiuc009ldx.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS22183.1.
PIRi A29941.
RefSeqi NP_032898.2. NM_008872.2.
UniGenei Mm.154660.

3D structure databases

ProteinModelPortali P11214.
SMRi P11214. Positions 33-558.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi P11214. 2 interactions.
MINTi MINT-8178492.

Protein family/group databases

MEROPSi S01.232.

PTM databases

PhosphoSitei P11214.

Proteomic databases

MaxQBi P11214.
PaxDbi P11214.
PRIDEi P11214.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000033941 ; ENSMUSP00000033941 ; ENSMUSG00000031538 .
GeneIDi 18791.
KEGGi mmu:18791.
UCSCi uc009ldx.2. mouse.

Organism-specific databases

CTDi 5327.
MGIi MGI:97610. Plat.

Phylogenomic databases

eggNOGi COG5640.
GeneTreei ENSGT00760000119133.
HOGENOMi HOG000237314.
HOVERGENi HBG008633.
InParanoidi P11214.
KOi K01343.
OMAi AHVRLYP.
OrthoDBi EOG75B84T.
PhylomeDBi P11214.
TreeFami TF329901.

Enzyme and pathway databases

BRENDAi 3.4.21.68. 3474.

Miscellaneous databases

NextBioi 295068.
PROi P11214.
SOURCEi Search...

Gene expression databases

Bgeei P11214.
CleanExi MM_PLAT.
Genevestigatori P11214.

Family and domain databases

Gene3Di 2.40.20.10. 2 hits.
InterProi 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 ]
Pfami PF00008. EGF. 1 hit.
PF00039. fn1. 1 hit.
PF00051. Kringle. 2 hits.
PF00089. Trypsin. 1 hit.
[Graphical view ]
PIRSFi PIRSF001145. Tissue_plasm_act. 1 hit.
PRINTSi PR00722. CHYMOTRYPSIN.
SMARTi SM00181. EGF. 1 hit.
SM00058. FN1. 1 hit.
SM00130. KR. 2 hits.
SM00020. Tryp_SPc. 1 hit.
[Graphical view ]
SUPFAMi SSF50494. SSF50494. 1 hit.
SSF57440. SSF57440. 2 hits.
PROSITEi 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 ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiTPA_MOUSE
AccessioniPrimary (citable) accession number: P11214
Secondary accession number(s): Q6P7U0, Q91VP2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: October 2, 2007
Last modified: October 29, 2014
This is version 152 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3