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P00750 (TPA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 200. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·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
Alternative name(s):
INN=Alteplase
INN=Reteplase
Gene names
Name:PLAT
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length562 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. Plays a direct role in facilitating neuronal migration.

Catalytic activity

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

Enzyme regulation

Inhibited by SERPINA5. Ref.24

Subunit structure

Heterodimer of chain A and chain B held by a disulfide bond. Forms a heterodimer with SERPINA5. Binds to fibrin with high affinity. This interaction leads to an increase in the catalytic efficiency of the enzyme between 100-fold and 1000-fold, 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. Yet unidentified interactions on endothelial cells and vascular smooth muscle cells (VSMC) lead to a 100-fold stimulation of plasminogen activation. In addition, binding to VSMC reduces TPA inhibition by PAI-1 by 30-fold. Binds LRP1B; binding is followed by internalization and degradation. Ref.25

Subcellular location

Secretedextracellular space.

Tissue specificity

Synthesized in numerous tissues (including tumors) and secreted into most extracellular body fluids, such as plasma, uterine fluid, saliva, gingival crevicular fluid, tears, seminal fluid, and milk.

Domain

Both FN1 and one of the kringle domains are required for binding to fibrin. Ref.23 Ref.33 Ref.34

Both FN1 and EGF-like domains are important for binding to LRP1. Ref.23 Ref.33 Ref.34

The FN1 domain mediates binding to annexin A2. Ref.23 Ref.33 Ref.34

The second kringle domain is implicated in binding to cytokeratin-8 and to the endothelial cell surface binding site. Ref.23 Ref.33 Ref.34

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-310 catalyzed by plasmin, tissue kallikrein or factor Xa.

Differential cell-specific N-linked glycosylation gives rise to two glycoforms, type I (glycosylated at Asn-219) and type II (not glycosylated at Asn-219). The single chain type I glycoform is less readily converted into the two-chain form by plasmin, and the two-chain type I glycoform has a lower activity than the two-chain type II glycoform in the presence of fibrin. Ref.21 Ref.22

N-glycosylation of Asn-152; the bound oligomannosidic glycan is involved in the interaction with the mannose receptor.

Characterization of O-linked glycan was studied in Bowes melanoma cell line.

Involvement in disease

Increased activity of TPA results in increased fibrinolysis of fibrin blood clots that is associated with excessive bleeding. Defective release of TPA results in hypofibrinolysis that can lead to thrombosis or embolism.

Pharmaceutical use

Available under the names Activase (Genentech) and Retavase (Centocor and Roche) [Retavase is a fragment of TPA that contains kringle 2 and the protease domain; it was also known as BM 06.022]. Used in Acute Myocardial Infarction (AMI), in Acute Ischemic Stroke (AIS) and Pulmonary Embolism (PE) to initiate fibrinolysis.

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
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainEGF-like domain
Kringle
Repeat
Signal
   Molecular functionHydrolase
Protease
Serine protease
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
Zymogen
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Pharmaceutical
Reference proteome
Gene Ontology (GO)
   Biological_processblood coagulation

Traceable author statement. Source: Reactome

cellular protein modification process

Traceable author statement PubMed 3087818. Source: ProtInc

fibrinolysis

Traceable author statement. Source: Reactome

negative regulation of proteolysis

Inferred from direct assay PubMed 1695900. Source: BHF-UCL

plasminogen activation

Inferred from direct assay PubMed 12694198. Source: UniProtKB

platelet-derived growth factor receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of ovulation

Inferred from electronic annotation. Source: Ensembl

proteolysis

Traceable author statement PubMed 3087818. Source: ProtInc

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 electronic annotation. Source: Ensembl

response to peptide hormone

Inferred from electronic annotation. Source: Ensembl

smooth muscle cell migration

Inferred from electronic annotation. Source: Ensembl

synaptic transmission, glutamatergic

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentapical part of cell

Inferred from electronic annotation. Source: Ensembl

cell surface

Inferred from direct assay PubMed 1632457. Source: BHF-UCL

cytoplasm

Inferred from direct assay PubMed 1632457. Source: BHF-UCL

extracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular vesicular exosome

Inferred from direct assay PubMed 20458337PubMed 23376485. Source: UniProt

secretory granule

Inferred from electronic annotation. Source: Ensembl

synapse

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionprotein binding

Inferred from physical interaction Ref.24PubMed 12694198. Source: UniProtKB

serine-type endopeptidase activity

Inferred from direct assay PubMed 1695900PubMed 8508955. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P00750-1)

Also known as: Long;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P00750-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     269-291: NPDGDAKPWCHVLKNRRLTWEYC → TGRSVSSPATASMRPCPLSIRSG
     292-562: Missing.
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Isoform 3 (identifier: P00750-3)

The sequence of this isoform differs from the canonical sequence as follows:
     39-85: VICRDEKTQMIYQQHQSWLRPVLRSNRVEYCWCNSGRAQCHSVPVKS → G
Note: No experimental confirmation available.
Isoform 4 (identifier: P00750-4)

Also known as: Neonatal;

The sequence of this isoform differs from the canonical sequence as follows:
     1-40: MDAMKRGLCCVLLLCGAVFVSPSQEIHARFRRGARSYQVI → MAS
     79-208: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222
Propeptide23 – 3210
PRO_0000028348
Propeptide33 – 353Removed by plasmin
PRO_0000028349
Chain36 – 562527Tissue-type plasminogen activator
PRO_0000028350
Chain36 – 310275Tissue-type plasminogen activator chain A
PRO_0000028351
Chain311 – 562252Tissue-type plasminogen activator chain B
PRO_0000028352

Regions

Domain39 – 8143Fibronectin type-I
Domain82 – 12039EGF-like
Domain127 – 20882Kringle 1
Domain215 – 29682Kringle 2
Domain311 – 561251Peptidase S1
Region42 – 5211Important for binding to annexin A2

Sites

Active site3571Charge relay system
Active site4061Charge relay system
Active site5131Charge relay system
Site1021Important for binding to LRP1
Site2531Not glycosylated
Site4641Important for single-chain activity
Site5121Important for single-chain activity

Amino acid modifications

Glycosylation961O-linked (Fuc) Ref.22
CAR_000029
Glycosylation1521N-linked (GlcNAc...)
Glycosylation2191N-linked (GlcNAc...); partial
CAR_000030
Glycosylation4831N-linked (GlcNAc...)
CAR_000031
Disulfide bond41 ↔ 71 Ref.23
Disulfide bond69 ↔ 78 Ref.23
Disulfide bond86 ↔ 97 Ref.23
Disulfide bond91 ↔ 108 Ref.23
Disulfide bond110 ↔ 119 Ref.23
Disulfide bond127 ↔ 208 By similarity
Disulfide bond148 ↔ 190 By similarity
Disulfide bond179 ↔ 203 By similarity
Disulfide bond215 ↔ 296 Ref.23
Disulfide bond236 ↔ 278 Ref.23
Disulfide bond267 ↔ 291 Ref.23
Disulfide bond299 ↔ 430Interchain (between A and B chains) Ref.23
Disulfide bond342 ↔ 358 By similarity
Disulfide bond350 ↔ 419 By similarity
Disulfide bond444 ↔ 519 By similarity
Disulfide bond476 ↔ 492 By similarity
Disulfide bond509 ↔ 537 By similarity

Natural variations

Alternative sequence1 – 4040MDAMK…SYQVI → MAS in isoform 4.
VSP_028029
Alternative sequence39 – 8547VICRD…VPVKS → G in isoform 3.
VSP_015957
Alternative sequence79 – 208130Missing in isoform 4.
VSP_028030
Alternative sequence269 – 29123NPDGD…TWEYC → TGRSVSSPATASMRPCPLSI RSG in isoform 2.
VSP_005411
Alternative sequence292 – 562271Missing in isoform 2.
VSP_005412
Natural variant341A → D. Ref.12
Corresponds to variant rs8178733 [ dbSNP | Ensembl ].
VAR_020181
Natural variant1361R → S. Ref.12
Corresponds to variant rs8178747 [ dbSNP | Ensembl ].
VAR_038732
Natural variant1461A → T. Ref.12
Corresponds to variant rs8178748 [ dbSNP | Ensembl ].
VAR_038733
Natural variant1641R → W. Ref.12
Corresponds to variant rs2020921 [ dbSNP | Ensembl ].
VAR_011783

Experimental info

Sequence conflict931N → T in AAB59510. Ref.2
Sequence conflict159 – 1602KP → NA in CAA31489. Ref.7
Sequence conflict2471K → N in AAO34406. Ref.9
Sequence conflict2831N → S in AAH95403. Ref.14
Sequence conflict333 – 3342RR → EE in AAK11956. Ref.8
Sequence conflict3891V → C in AAK11956. Ref.8

Secondary structure

............................................................................................. 562
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Long) [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: B7EC9B1A5E3FDC4D

FASTA56262,917
        10         20         30         40         50         60 
MDAMKRGLCC VLLLCGAVFV SPSQEIHARF RRGARSYQVI CRDEKTQMIY QQHQSWLRPV 

        70         80         90        100        110        120 
LRSNRVEYCW CNSGRAQCHS VPVKSCSEPR CFNGGTCQQA LYFSDFVCQC PEGFAGKCCE 

       130        140        150        160        170        180 
IDTRATCYED QGISYRGTWS TAESGAECTN WNSSALAQKP YSGRRPDAIR LGLGNHNYCR 

       190        200        210        220        230        240 
NPDRDSKPWC YVFKAGKYSS EFCSTPACSE GNSDCYFGNG SAYRGTHSLT ESGASCLPWN 

       250        260        270        280        290        300 
SMILIGKVYT AQNPSAQALG LGKHNYCRNP DGDAKPWCHV LKNRRLTWEY CDVPSCSTCG 

       310        320        330        340        350        360 
LRQYSQPQFR IKGGLFADIA SHPWQAAIFA KHRRSPGERF LCGGILISSC WILSAAHCFQ 

       370        380        390        400        410        420 
ERFPPHHLTV ILGRTYRVVP GEEEQKFEVE KYIVHKEFDD DTYDNDIALL QLKSDSSRCA 

       430        440        450        460        470        480 
QESSVVRTVC LPPADLQLPD WTECELSGYG KHEALSPFYS ERLKEAHVRL YPSSRCTSQH 

       490        500        510        520        530        540 
LLNRTVTDNM LCAGDTRSGG PQANLHDACQ GDSGGPLVCL NDGRMTLVGI ISWGLGCGQK 

       550        560 
DVPGVYTKVT NYLDWIRDNM RP 

« Hide

Isoform 2 (Short) [UniParc].

Checksum: 874E38C52F50FF5D
Show »

FASTA29132,175
Isoform 3 [UniParc].

Checksum: BAB31901FDC96800
Show »

FASTA51657,371
Isoform 4 (Neonatal) [UniParc].

Checksum: 55BB9FB94F65DF4F
Show »

FASTA39544,373

References

« Hide 'large scale' references
[1]"Cloning and expression of human tissue-type plasminogen activator cDNA in E. coli."
Pennica D., Holmes W.E., Kohr W.J., Harkins R.N., Vehar G.A., Ward C.A., Bennett W.F., Yelverton E., Seeburg P.H., Heyneker H.L., Goeddel D.V., Collen D.
Nature 301:214-221(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Melanoma.
[2]"The structure of the human tissue-type plasminogen activator gene: correlation of intron and exon structures to functional and structural domains."
Ny T., Elgh F., Lund B.
Proc. Natl. Acad. Sci. U.S.A. 81:5355-5359(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"The human tissue plasminogen activator gene."
Friezner Degen S.J., Rajput B., Reich E.
J. Biol. Chem. 261:6972-6985(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Cloning of cDNA coding for human tissue-type plasminogen activator and its expression in Escherichia coli."
Harris T.J., Patel T., Marston F.A., Little S., Emtage J.S., Opdenakker G., Volckaert G., Rombauts W., Billiau A., Somer P.
Mol. Biol. Med. 3:279-292(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[5]"Expression of human uterine tissue-type plasminogen activator in mouse cells using BPV vectors."
Reddy V.B., Garramone A.J., Sasak H., Wei C.-M., Watkins P., Galli J., Hsiung N.
DNA 6:461-472(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[6]"Nucleotide sequence of the tissue-type plasminogen activator cDNA from human fetal lung cells."
Sasaki H., Saito Y., Hayashi M., Otsuka K., Niwa M.
Nucleic Acids Res. 16:5695-5695(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Fetal lung.
[7]"Variant tissue-type plasminogen activator (PLAT) cDNA obtained from human endothelial cells."
Siebert P.D., Fong K.
Nucleic Acids Res. 18:1086-1086(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Umbilical vein.
[8]"A brain-type plasminogen activator."
Dou D.
Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
[9]"cDNA of tissue plasminogen activator."
Liu Y., Xu L., Zeng Y., He X.
Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[10]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
Tissue: Testis.
[11]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[12]SeattleSNPs variation discovery resource
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ASP-34; SER-136; THR-146 AND TRP-164.
[13]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[14]"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] (ISOFORMS 1 AND 3).
Tissue: Brain, Placenta and Skin.
[15]"Isolation and characterization of the human tissue-type plasminogen activator structural gene including its 5' flanking region."
Fisher R., Waller E.K., Grossi G., Thompson D., Tizard R., Schleuning W.-D.
J. Biol. Chem. 260:11223-11230(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-36.
[16]"Purification and characterization of tissue plasminogen activator secreted by human embryonic lung diploid fibroblasts, IMR-90 cells."
Itagaki Y., Yasuda H., Morinaga T., Mitsuda S., Higashio K.
Agric. Biol. Chem. 55:1225-1232(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 31-562.
[17]"Purification and characterization of a melanoma cell plasminogen activator."
Wallen P., Pohl G., Bergsdorf N., Raanby M., Ny T., Joernvall H.
Eur. J. Biochem. 132:681-686(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 33-52 AND 311-330.
Tissue: Melanoma.
[18]"Tissue plasminogen activator: peptide analyses confirm an indirectly derived amino acid sequence, identify the active site serine residue, establish glycosylation sites, and localize variant differences."
Pohl G., Kaellstroem M., Bergsdorf N., Wallen P., Joernvall H.
Biochemistry 23:3701-3707(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 36-562.
Tissue: Melanoma.
[19]"Isolation of cDNA sequences coding for a part of human tissue plasminogen activator."
Edlund T., Ny T., Raanby M., Heden L.-O., Palm G., Holmgren E., Josephson S.
Proc. Natl. Acad. Sci. U.S.A. 80:349-352(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 251-358.
[20]Jalah R., Pavlakis G.N., Felber B.J.
Submitted (JUL-2007) to UniProtKB
Cited for: PARTIAL PROTEIN SEQUENCE, SIGNAL SEQUENCE CLEAVAGE SITE.
[21]"Carbohydrate structure of recombinant human uterine tissue plasminogen activator expressed in mouse epithelial cells."
Pfeiffer G., Schmidt M., Strube K.-H., Geyer R.
Eur. J. Biochem. 186:273-286(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE OF CARBOHYDRATES.
[22]"Tissue plasminogen activator has an O-linked fucose attached to threonine-61 in the epidermal growth factor domain."
Harris R.J., Leonard C.K., Guzzetta A.W., Spellman M.W.
Biochemistry 30:2311-2314(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT THR-96.
[23]"Disulfide pairing of the recombinant kringle-2 domain of tissue plasminogen activator produced in Escherichia coli."
Vlahos C.J., Wilhelm O.G., Hassell T., Jaskunas S.R., Bang N.U.
J. Biol. Chem. 266:10070-10072(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: DISULFIDE BONDS IN KRINGLE 2 DOMAIN.
[24]"Functionally inactive protein C inhibitor in seminal plasma may be associated with infertility."
He S., Lin Y.L., Liu Y.X.
Mol. Hum. Reprod. 5:513-519(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, HETERODIMER WITH SERPINA5.
[25]"The putative tumor suppressor LRP1B, a novel member of the low density lipoprotein (LDL) receptor family, exhibits both overlapping and distinct properties with the LDL receptor-related protein."
Liu C.-X., Li Y., Obermoeller-McCormick L.M., Schwartz A.L., Bu G.
J. Biol. Chem. 276:28889-28896(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LRP1B.
[26]"An unappreciated role for RNA surveillance."
Hillman R.T., Green R.E., Brenner S.E.
Genome Biol. 5:R8.1-R8.16(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[27]"1H NMR structural characterization of a recombinant kringle 2 domain from human tissue-type plasminogen activator."
Byeon I.-J.L., Kelley R.F., Llinas M.
Biochemistry 28:9350-9360(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF KRINGLE 2.
[28]"Kringle-2 domain of the tissue-type plasminogen activator. 1H-NMR assignments and secondary structure."
Byeon I.-J.L., Kelley R.F., Llinas M.
Eur. J. Biochem. 197:155-165(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF KRINGLE 2.
[29]"Solution structure of the tissue-type plasminogen activator kringle 2 domain complexed to 6-aminohexanoic acid an antifibrinolytic drug."
Byeon I.-J.L., Llinas M.
J. Mol. Biol. 222:1035-1051(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF KRINGLE 2.
[30]"Crystal structure of the kringle 2 domain of tissue plasminogen activator at 2.4-A resolution."
de Vos A., Ultsch M.H., Kelley R.F., Padmanabhan K., Tulinskly A., Westbrook M.L., Kossiakof A.A.
Biochemistry 31:270-279(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF KRINGLE 2.
[31]"Solution structure of the fibrin binding finger domain of tissue-type plasminogen activator determined by 1H nuclear magnetic resonance."
Downing A.K., Driscoll P.C., Harvey T.S., Dudgeon T.J., Smith B.O., Baron M., Campbell I.D.
J. Mol. Biol. 225:821-833(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 38-85.
[32]"The solution structure and backbone dynamics of the fibronectin type I and epidermal growth factor-like pair of modules of tissue-type plasminogen activator."
Smith B.O., Downing A.K., Driscoll P.C., Dudgeon T.J., Campbell I.D.
Structure 3:823-833(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 36-126.
[33]"The 2.3 A crystal structure of the catalytic domain of recombinant two-chain human tissue-type plasminogen activator."
Lamba D., Bauer M., Huber R., Fischer S., Rudolph R., Kohnert U., Bode W.
J. Mol. Biol. 258:117-135(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF CATALYTIC DOMAIN.
[34]"Lysine 156 promotes the anomalous proenzyme activity of tPA: X-ray crystal structure of single-chain human tPA."
Renatus M., Engh R.A., Stubbs M.T., Huber R., Fischer S., Kohnert U., Bode W.
EMBO J. 16:4797-4805(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF CATALYTIC DOMAIN.
+Additional computationally mapped references.

Web resources

Wikipedia

Tissue plasminogen activator entry

SeattleSNPs
SHMPD

The Singapore human mutation and polymorphism database

Activase

Clinical information on Activase

Retavase

Clinical information on Retavase

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L00153 expand/collapse EMBL AC list , L00141, L00142, L00143, L00144, L00145, L00146, L00147, L00148, L00149, L00150, L00151 Genomic DNA. Translation: AAB59510.1.
K03021 Genomic DNA. Translation: AAA98809.1.
M15518 mRNA. Translation: AAA60111.1.
M18182 mRNA. Translation: AAA36800.1.
X07393 mRNA. Translation: CAA30302.1.
X13097 mRNA. Translation: CAA31489.1.
AF260825 mRNA. Translation: AAK11956.1.
AY221101 mRNA. Translation: AAO34406.1.
AK289387 mRNA. Translation: BAF82076.1.
AK290575 mRNA. Translation: BAF83264.1.
AK313342 mRNA. Translation: BAG36145.1.
BT007060 mRNA. Translation: AAP35709.1.
AY291060 Genomic DNA. Translation: AAP34246.1.
CH471080 Genomic DNA. Translation: EAW63235.1.
CH471080 Genomic DNA. Translation: EAW63233.1.
BC002795 mRNA. Translation: AAH02795.3.
BC007231 mRNA. Translation: AAH07231.1.
BC013968 mRNA. Translation: AAH13968.3.
BC018636 mRNA. Translation: AAH18636.3.
BC095403 mRNA. Translation: AAH95403.1.
M11890, M11889 Genomic DNA. Translation: AAA61213.1.
D01096 mRNA. Translation: BAA00881.1.
V00570 mRNA. Translation: CAA23833.1.
CCDSCCDS6126.1. [P00750-1]
CCDS6127.1. [P00750-3]
PIRUKHUT. A94004.
I38098.
RefSeqNP_000921.1. NM_000930.3. [P00750-1]
NP_127509.1. NM_033011.2. [P00750-3]
UniGeneHs.491582.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1A5HX-ray2.90A/B311-562[»]
C/D298-304[»]
1BDAX-ray3.35A/B298-562[»]
1PK2NMR-A209-298[»]
1PMLX-ray2.38A/B/C213-298[»]
1RTFX-ray2.30B311-562[»]
1TPGNMR-A36-126[»]
1TPKX-ray2.40A/B/C211-298[»]
1TPMNMR-A36-85[»]
1TPNNMR-A36-85[»]
ProteinModelPortalP00750.
SMRP00750. Positions 36-562.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111343. 19 interactions.
IntActP00750. 2 interactions.
MINTMINT-8309345.

Chemistry

BindingDBP00750.
ChEMBLCHEMBL1873.
DrugBankDB00009. Alteplase.
DB00513. Aminocaproic Acid.
DB00029. Anistreplase.
DB01088. Iloprost.
DB00015. Reteplase.
DB00031. Tenecteplase.
DB00302. Tranexamic Acid.
DB00013. Urokinase.
GuidetoPHARMACOLOGY2392.

Protein family/group databases

MEROPSS01.232.

PTM databases

PhosphoSiteP00750.
UniCarbKBP00750.

Polymorphism databases

DMDM137119.

Proteomic databases

MaxQBP00750.
PaxDbP00750.
PRIDEP00750.

Protocols and materials databases

DNASU5327.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000220809; ENSP00000220809; ENSG00000104368. [P00750-1]
ENST00000352041; ENSP00000270188; ENSG00000104368. [P00750-3]
ENST00000429089; ENSP00000392045; ENSG00000104368. [P00750-1]
GeneID5327.
KEGGhsa:5327.
UCSCuc003xos.2. human. [P00750-1]
uc003xot.2. human. [P00750-3]

Organism-specific databases

CTD5327.
GeneCardsGC08M042032.
HGNCHGNC:9051. PLAT.
HPACAB009335.
HPA003412.
MIM173370. gene.
neXtProtNX_P00750.
PharmGKBPA33381.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5640.
HOVERGENHBG008633.
InParanoidP00750.
KOK01343.
OMAAHVRLYP.
OrthoDBEOG75B84T.
PhylomeDBP00750.
TreeFamTF329901.

Enzyme and pathway databases

BRENDA3.4.21.68. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpressP00750.
BgeeP00750.
GenevestigatorP00750.

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

ChiTaRSPLAT. human.
EvolutionaryTraceP00750.
GeneWikiTissue_plasminogen_activator.
GenomeRNAi5327.
NextBio20622.
PMAP-CutDBB2R8E8.
PROP00750.
SOURCESearch...

Entry information

Entry nameTPA_HUMAN
AccessionPrimary (citable) accession number: P00750
Secondary accession number(s): A8K022 expand/collapse secondary AC list , B2R8E8, Q15103, Q503B0, Q6PJA5, Q7Z7N2, Q86YK8, Q9BU99, Q9BZW1
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: July 9, 2014
This is version 200 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM