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P00750

- TPA_HUMAN

UniProt

P00750 - TPA_HUMAN

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Protein

Tissue-type plasminogen activator

Gene

PLAT

Organism
Homo sapiens (Human)
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. Plays a direct role in facilitating neuronal migration.

Catalytic activityi

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

Enzyme regulationi

Inhibited by SERPINA5.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei102 – 1021Important for binding to LRP1
Sitei253 – 2531Not glycosylated
Active sitei357 – 3571Charge relay system
Active sitei406 – 4061Charge relay system
Sitei464 – 4641Important for single-chain activity
Sitei512 – 5121Important for single-chain activity
Active sitei513 – 5131Charge relay system

GO - Molecular functioni

  1. serine-type endopeptidase activity Source: BHF-UCL

GO - Biological processi

  1. blood coagulation Source: Reactome
  2. cellular protein modification process Source: ProtInc
  3. fibrinolysis Source: Reactome
  4. negative regulation of proteolysis Source: BHF-UCL
  5. plasminogen activation Source: UniProtKB
  6. platelet-derived growth factor receptor signaling pathway Source: Ensembl
  7. positive regulation of ovulation Source: Ensembl
  8. proteolysis Source: ProtInc
  9. regulation of synaptic plasticity Source: Ensembl
  10. response to cAMP Source: Ensembl
  11. response to glucocorticoid Source: Ensembl
  12. response to hypoxia Source: Ensembl
  13. response to peptide hormone Source: Ensembl
  14. smooth muscle cell migration Source: Ensembl
  15. synaptic transmission, glutamatergic 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. 2681.
ReactomeiREACT_16888. Signaling by PDGF.
REACT_267716. Orphan transporters.
REACT_641. Dissolution of Fibrin Clot.

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
Alternative name(s):
INN: Alteplase
INN: Reteplase
Cleaved into the following 2 chains:
Gene namesi
Name:PLAT
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 8

Organism-specific databases

HGNCiHGNC:9051. PLAT.

Subcellular locationi

GO - Cellular componenti

  1. apical part of cell Source: Ensembl
  2. cell surface Source: BHF-UCL
  3. cytoplasm Source: BHF-UCL
  4. extracellular region Source: Reactome
  5. extracellular space Source: Ensembl
  6. extracellular vesicular exosome Source: UniProt
  7. secretory granule Source: Ensembl
  8. synapse Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

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 usei

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.

Organism-specific databases

PharmGKBiPA33381.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 22221 PublicationAdd
BLAST
Propeptidei23 – 32101 PublicationPRO_0000028348
Propeptidei33 – 353Removed by plasmin1 PublicationPRO_0000028349
Chaini36 – 562527Tissue-type plasminogen activatorPRO_0000028350Add
BLAST
Chaini36 – 310275Tissue-type plasminogen activator chain APRO_0000028351Add
BLAST
Chaini311 – 562252Tissue-type plasminogen activator chain BPRO_0000028352Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi41 ↔ 711 Publication
Disulfide bondi69 ↔ 781 Publication
Disulfide bondi86 ↔ 971 Publication
Disulfide bondi91 ↔ 1081 Publication
Glycosylationi96 – 961O-linked (Fuc)1 PublicationCAR_000029
Disulfide bondi110 ↔ 1191 Publication
Disulfide bondi127 ↔ 208By similarity
Disulfide bondi148 ↔ 190By similarity
Glycosylationi152 – 1521N-linked (GlcNAc...)
Disulfide bondi179 ↔ 203By similarity
Disulfide bondi215 ↔ 2961 Publication
Glycosylationi219 – 2191N-linked (GlcNAc...); partialCAR_000030
Disulfide bondi236 ↔ 2781 Publication
Disulfide bondi267 ↔ 2911 Publication
Disulfide bondi299 ↔ 430Interchain (between A and B chains)1 PublicationPROSITE-ProRule annotation
Disulfide bondi342 ↔ 358By similarity
Disulfide bondi350 ↔ 419By similarity
Disulfide bondi444 ↔ 519By similarity
Disulfide bondi476 ↔ 492By similarity
Glycosylationi483 – 4831N-linked (GlcNAc...)CAR_000031
Disulfide bondi509 ↔ 537By 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-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.1 Publication
N-glycosylation of Asn-152; the bound oligomannosidic glycan is involved in the interaction with the mannose receptor.1 Publication
Characterization of O-linked glycan was studied in Bowes melanoma cell line.1 Publication

Keywords - PTMi

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

Proteomic databases

MaxQBiP00750.
PaxDbiP00750.
PRIDEiP00750.

PTM databases

PhosphoSiteiP00750.
UniCarbKBiP00750.

Miscellaneous databases

PMAP-CutDBB2R8E8.

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiP00750.
ExpressionAtlasiP00750. baseline and differential.
GenevestigatoriP00750.

Organism-specific databases

HPAiCAB009335.
HPA003412.

Interactioni

Subunit structurei

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.

Protein-protein interaction databases

BioGridi111343. 24 interactions.
IntActiP00750. 2 interactions.
MINTiMINT-8309345.

Structurei

Secondary structure

1
562
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi41 – 433Combined sources
Beta strandi44 – 463Combined sources
Beta strandi48 – 503Combined sources
Beta strandi55 – 595Combined sources
Beta strandi61 – 644Combined sources
Beta strandi66 – 705Combined sources
Beta strandi72 – 743Combined sources
Beta strandi77 – 815Combined sources
Beta strandi83 – 853Combined sources
Beta strandi96 – 1049Combined sources
Beta strandi106 – 1094Combined sources
Beta strandi115 – 1184Combined sources
Beta strandi221 – 2233Combined sources
Beta strandi229 – 2335Combined sources
Helixi242 – 2443Combined sources
Beta strandi248 – 2503Combined sources
Beta strandi251 – 2533Combined sources
Helixi256 – 2594Combined sources
Beta strandi262 – 2643Combined sources
Beta strandi277 – 2826Combined sources
Beta strandi285 – 2917Combined sources
Beta strandi309 – 3113Combined sources
Beta strandi312 – 3165Combined sources
Helixi319 – 3213Combined sources
Beta strandi325 – 3317Combined sources
Beta strandi338 – 3469Combined sources
Beta strandi348 – 3547Combined sources
Helixi356 – 3594Combined sources
Helixi365 – 3673Combined sources
Beta strandi368 – 3736Combined sources
Beta strandi375 – 3795Combined sources
Beta strandi385 – 39410Combined sources
Turni400 – 4023Combined sources
Beta strandi408 – 4125Combined sources
Beta strandi415 – 4173Combined sources
Beta strandi424 – 4263Combined sources
Beta strandi443 – 4497Combined sources
Beta strandi451 – 4533Combined sources
Beta strandi464 – 4707Combined sources
Helixi473 – 4753Combined sources
Turni478 – 4836Combined sources
Beta strandi490 – 4945Combined sources
Beta strandi499 – 5013Combined sources
Beta strandi516 – 5216Combined sources
Beta strandi524 – 53310Combined sources
Beta strandi535 – 5384Combined sources
Beta strandi544 – 5485Combined sources
Helixi549 – 5524Combined sources
Helixi553 – 5597Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliP00750.
SMRiP00750. Positions 36-562.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP00750.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini39 – 8143Fibronectin type-IPROSITE-ProRule annotationAdd
BLAST
Domaini82 – 12039EGF-likePROSITE-ProRule annotationAdd
BLAST
Domaini127 – 20882Kringle 1PROSITE-ProRule annotationAdd
BLAST
Domaini215 – 29682Kringle 2PROSITE-ProRule annotationAdd
BLAST
Domaini311 – 561251Peptidase S1PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni42 – 5211Important for binding to annexin A2Add
BLAST

Domaini

Both FN1 and one of the kringle domains are required for binding to fibrin.
Both FN1 and EGF-like domains are important for binding to LRP1.
The FN1 domain mediates binding to annexin A2.
The second kringle domain is implicated in binding to cytokeratin-8 and to the endothelial cell surface binding site.

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.
HOVERGENiHBG008633.
InParanoidiP00750.
KOiK01343.
OMAiAHVRLYP.
OrthoDBiEOG75B84T.
PhylomeDBiP00750.
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]

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P00750-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MDAMKRGLCC VLLLCGAVFV SPSQEIHARF RRGARSYQVI CRDEKTQMIY
60 70 80 90 100
QQHQSWLRPV LRSNRVEYCW CNSGRAQCHS VPVKSCSEPR CFNGGTCQQA
110 120 130 140 150
LYFSDFVCQC PEGFAGKCCE IDTRATCYED QGISYRGTWS TAESGAECTN
160 170 180 190 200
WNSSALAQKP YSGRRPDAIR LGLGNHNYCR NPDRDSKPWC YVFKAGKYSS
210 220 230 240 250
EFCSTPACSE GNSDCYFGNG SAYRGTHSLT ESGASCLPWN SMILIGKVYT
260 270 280 290 300
AQNPSAQALG LGKHNYCRNP DGDAKPWCHV LKNRRLTWEY CDVPSCSTCG
310 320 330 340 350
LRQYSQPQFR IKGGLFADIA SHPWQAAIFA KHRRSPGERF LCGGILISSC
360 370 380 390 400
WILSAAHCFQ ERFPPHHLTV ILGRTYRVVP GEEEQKFEVE KYIVHKEFDD
410 420 430 440 450
DTYDNDIALL QLKSDSSRCA QESSVVRTVC LPPADLQLPD WTECELSGYG
460 470 480 490 500
KHEALSPFYS ERLKEAHVRL YPSSRCTSQH LLNRTVTDNM LCAGDTRSGG
510 520 530 540 550
PQANLHDACQ GDSGGPLVCL NDGRMTLVGI ISWGLGCGQK DVPGVYTKVT
560
NYLDWIRDNM RP
Length:562
Mass (Da):62,917
Last modified:July 21, 1986 - v1
Checksum:iB7EC9B1A5E3FDC4D
GO
Isoform 2 (identifier: P00750-2) [UniParc]FASTAAdd to Basket

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.

Show »
Length:291
Mass (Da):32,175
Checksum:i874E38C52F50FF5D
GO
Isoform 3 (identifier: P00750-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     39-85: VICRDEKTQMIYQQHQSWLRPVLRSNRVEYCWCNSGRAQCHSVPVKS → G

Note: No experimental confirmation available.

Show »
Length:516
Mass (Da):57,371
Checksum:iBAB31901FDC96800
GO
Isoform 4 (identifier: P00750-4) [UniParc]FASTAAdd to Basket

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.

Show »
Length:395
Mass (Da):44,373
Checksum:i55BB9FB94F65DF4F
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti93 – 931N → T in AAB59510. (PubMed:6089198)Curated
Sequence conflicti159 – 1602KP → NA in CAA31489. (PubMed:2107528)Curated
Sequence conflicti247 – 2471K → N in AAO34406. 1 PublicationCurated
Sequence conflicti283 – 2831N → S in AAH95403. (PubMed:15489334)Curated
Sequence conflicti333 – 3342RR → EE in AAK11956. 1 PublicationCurated
Sequence conflicti389 – 3891V → C in AAK11956. 1 PublicationCurated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti34 – 341A → D.1 Publication
Corresponds to variant rs8178733 [ dbSNP | Ensembl ].
VAR_020181
Natural varianti136 – 1361R → S.1 Publication
Corresponds to variant rs8178747 [ dbSNP | Ensembl ].
VAR_038732
Natural varianti146 – 1461A → T.1 Publication
Corresponds to variant rs8178748 [ dbSNP | Ensembl ].
VAR_038733
Natural varianti164 – 1641R → W.1 Publication
Corresponds to variant rs2020921 [ dbSNP | Ensembl ].
VAR_011783

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 4040MDAMK…SYQVI → MAS in isoform 4. 1 PublicationVSP_028029Add
BLAST
Alternative sequencei39 – 8547VICRD…VPVKS → G in isoform 3. 2 PublicationsVSP_015957Add
BLAST
Alternative sequencei79 – 208130Missing in isoform 4. 1 PublicationVSP_028030Add
BLAST
Alternative sequencei269 – 29123NPDGD…TWEYC → TGRSVSSPATASMRPCPLSI RSG in isoform 2. 1 PublicationVSP_005411Add
BLAST
Alternative sequencei292 – 562271Missing in isoform 2. 1 PublicationVSP_005412Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L00153
, 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.
CCDSiCCDS6126.1. [P00750-1]
CCDS6127.1. [P00750-3]
PIRiA94004. UKHUT.
I38098.
RefSeqiNP_000921.1. NM_000930.3. [P00750-1]
NP_127509.1. NM_033011.2. [P00750-3]
UniGeneiHs.491582.

Genome annotation databases

EnsembliENST00000220809; ENSP00000220809; ENSG00000104368. [P00750-1]
ENST00000352041; ENSP00000270188; ENSG00000104368. [P00750-3]
ENST00000429089; ENSP00000392045; ENSG00000104368. [P00750-1]
GeneIDi5327.
KEGGihsa:5327.
UCSCiuc003xos.2. human. [P00750-1]
uc003xot.2. human. [P00750-3]

Polymorphism databases

DMDMi137119.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Tissue plasminogen activator entry

SeattleSNPs
SHMPD

The Singapore human mutation and polymorphism database

Activase

Clinical information on Activase

Retavase

Clinical information on Retavase

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L00153
, 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 .
CCDSi CCDS6126.1. [P00750-1 ]
CCDS6127.1. [P00750-3 ]
PIRi A94004. UKHUT.
I38098.
RefSeqi NP_000921.1. NM_000930.3. [P00750-1 ]
NP_127509.1. NM_033011.2. [P00750-3 ]
UniGenei Hs.491582.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1A5H X-ray 2.90 A/B 311-562 [» ]
C/D 298-304 [» ]
1BDA X-ray 3.35 A/B 298-562 [» ]
1PK2 NMR - A 209-298 [» ]
1PML X-ray 2.38 A/B/C 213-298 [» ]
1RTF X-ray 2.30 B 311-562 [» ]
1TPG NMR - A 36-126 [» ]
1TPK X-ray 2.40 A/B/C 211-298 [» ]
1TPM NMR - A 36-85 [» ]
1TPN NMR - A 36-85 [» ]
ProteinModelPortali P00750.
SMRi P00750. Positions 36-562.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 111343. 24 interactions.
IntActi P00750. 2 interactions.
MINTi MINT-8309345.

Chemistry

BindingDBi P00750.
ChEMBLi CHEMBL1873.
DrugBanki DB00513. Aminocaproic Acid.
DB01050. Ibuprofen.
DB01088. Iloprost.
DB00013. Urokinase.
GuidetoPHARMACOLOGYi 2392.

Protein family/group databases

MEROPSi S01.232.

PTM databases

PhosphoSitei P00750.
UniCarbKBi P00750.

Polymorphism databases

DMDMi 137119.

Proteomic databases

MaxQBi P00750.
PaxDbi P00750.
PRIDEi P00750.

Protocols and materials databases

DNASUi 5327.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000220809 ; ENSP00000220809 ; ENSG00000104368 . [P00750-1 ]
ENST00000352041 ; ENSP00000270188 ; ENSG00000104368 . [P00750-3 ]
ENST00000429089 ; ENSP00000392045 ; ENSG00000104368 . [P00750-1 ]
GeneIDi 5327.
KEGGi hsa:5327.
UCSCi uc003xos.2. human. [P00750-1 ]
uc003xot.2. human. [P00750-3 ]

Organism-specific databases

CTDi 5327.
GeneCardsi GC08M042032.
HGNCi HGNC:9051. PLAT.
HPAi CAB009335.
HPA003412.
MIMi 173370. gene.
neXtProti NX_P00750.
PharmGKBi PA33381.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG5640.
GeneTreei ENSGT00760000119133.
HOVERGENi HBG008633.
InParanoidi P00750.
KOi K01343.
OMAi AHVRLYP.
OrthoDBi EOG75B84T.
PhylomeDBi P00750.
TreeFami TF329901.

Enzyme and pathway databases

BRENDAi 3.4.21.68. 2681.
Reactomei REACT_16888. Signaling by PDGF.
REACT_267716. Orphan transporters.
REACT_641. Dissolution of Fibrin Clot.

Miscellaneous databases

ChiTaRSi PLAT. human.
EvolutionaryTracei P00750.
GeneWikii Tissue_plasminogen_activator.
GenomeRNAii 5327.
NextBioi 20622.
PMAP-CutDB B2R8E8.
PROi P00750.
SOURCEi Search...

Gene expression databases

Bgeei P00750.
ExpressionAtlasi P00750. baseline and differential.
Genevestigatori P00750.

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. 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.
    , 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. 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. 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.

Entry informationi

Entry nameiTPA_HUMAN
AccessioniPrimary (citable) accession number: P00750
Secondary accession number(s): A8K022
, B2R8E8, Q15103, Q503B0, Q6PJA5, Q7Z7N2, Q86YK8, Q9BU99, Q9BZW1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: November 26, 2014
This is version 204 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Pharmaceutical, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3