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Q5R8J0 (TPA_PONAB) Reviewed, UniProtKB/Swiss-Prot

Last modified December 14, 2011. Version 50. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
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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

Cleaved into the following 2 chains:

  1. Tissue-type plasminogen activator chain A
  2. Tissue-type plasminogen activator chain B
Gene names
Name:PLAT
OrganismPongo abelii (Sumatran orangutan)
Taxonomic identifier9601 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Pongo

Protein attributes

Sequence length562 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript 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 By similarity.

Catalytic activity

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

Enzyme regulation

Inhibited by SERPINA5 By similarity.

Subunit structure

Heterodimer of chain A and chain B held by a disulfide bond. Binds to fibrin with high affinity. This interaction leads to an increase in the catalytic efficiency of the enzyme due to an increase in affinity for plasminogen. Similarly, binding to heparin increases the activation of plasminogen. Binds to annexin A2, cytokeratin-8, fibronectin and laminin. Binds to mannose receptor and the low-density lipoprotein receptor-related protein (LRP1); these proteins are involved in TPA clearance. Binds LRP1B; binding is followed by internalization and degradation. Forms heterodimer with SERPINA5 By similarity.

Subcellular location

Secreted › extracellular space By similarity.

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

Sequence similarities

Belongs to the peptidase S1 family.

Contains 1 EGF-like domain.

Contains 1 fibronectin type-I domain.

Contains 2 kringle domains.

Contains 1 peptidase S1 domain.

Ontologies

Keywords
   Biological processPlasminogen activation
   Cellular componentSecreted
   DomainEGF-like domain
Kringle
Repeat
Signal
   Molecular functionHydrolase
Protease
Serine protease
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
Zymogen
Gene Ontology (GO)
   Biological processproteolysis

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular componentextracellular space

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular functionserine-type endopeptidase activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 Potential
Propeptide21 – 3212 By similarity
PRO_0000285912
Propeptide33 – 353Removed by plasmin By similarity
PRO_0000285913
Chain36 – 562527Tissue-type plasminogen activator
PRO_0000285914
Chain36 – 310275Tissue-type plasminogen activator chain A By similarity
PRO_0000285915
Chain311 – 562252Tissue-type plasminogen activator chain B By similarity
PRO_0000285916

Regions

Domain39 – 8143Fibronectin type-I
Domain82 – 12039EGF-like
Domain126 – 20883Kringle 1
Domain214 – 29683Kringle 2
Domain311 – 561251Peptidase S1
Region42 – 5211Important for binding to annexin A2 By similarity

Sites

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

Amino acid modifications

Glycosylation961O-linked (Fuc) By similarity
Glycosylation1521N-linked (GlcNAc...) Potential
Glycosylation4831N-linked (GlcNAc...) Potential
Disulfide bond41 ↔ 71 By similarity
Disulfide bond69 ↔ 78 By similarity
Disulfide bond86 ↔ 97 By similarity
Disulfide bond91 ↔ 108 By similarity
Disulfide bond110 ↔ 119 By similarity
Disulfide bond127 ↔ 208 By similarity
Disulfide bond148 ↔ 190 By similarity
Disulfide bond179 ↔ 203 By similarity
Disulfide bond215 ↔ 296 By similarity
Disulfide bond236 ↔ 278 By similarity
Disulfide bond267 ↔ 291 By similarity
Disulfide bond299 ↔ 430Interchain (between A and B chains) By similarity
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

Sequences

Sequence LengthMass (Da)Tools
Q5R8J0 [UniParc].

Last modified December 21, 2004. Version 1.
Checksum: 3FBD145D4DE117EE

FASTA56262,943
        10         20         30         40         50         60 
MNAMKRGLCC VLLLCGAVFA LPSQEIHARV RRGARSYQVI CRDEKTQMIY QQHQSWLRPV 

        70         80         90        100        110        120 
LRSNRVEYCW CNSGRAQCHS VPVRSCSEPR 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 LAYRGTHSLT ESGASCLLWN 

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

       310        320        330        340        350        360 
LRQYSQPQFR IKGGLFADIA SHPWQAAIFA RHRRSPGERF 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 
LLNRTVADNM LCAGDTRSGG PQANLHDACQ GDSGGPLVCL NDGRMTLVGI ISWGLGCGEK 

       550        560 
DVPGVYTKVT NYLDWIHDNM RP

« Hide

References

[1]The German cDNA consortium
Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Kidney.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		CR859762 mRNA. Translation: CAH91920.1.
RefSeqNP_001126112.1. NM_001132640.1.
UniGenePab.12714.

3D structure databases

HSSPHSSP built from PDB template 1RTF based on UniProtKB P00750.
ProteinModelPortalQ5R8J0.
SMRQ5R8J0. Positions 36-126, 209-562.
ModBaseSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID100173068.
KEGGpon:100173068.

Organism-specific databases

CTD5327.

Phylogenomic databases

HOVERGENHBG008633.
InParanoidQ5R8J0.

Family and domain databases

InterProIPR016060. Complement_control_module.
IPR006209. EGF.
IPR006210. EGF-like.
IPR013032. EGF-like_reg_CS.
IPR000742. EGF_3.
IPR000083. Fibronectin_type1.
IPR000001. Kringle.
IPR013806. Kringle-like.
IPR018056. Kringle_CS.
IPR009003. Pept_cys/ser_Trypsin-like.
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.
KOK01343.
PfamPF00008. EGF. 1 hit.
PF00039. fn1. 1 hit.
PF00051. Kringle. 2 hits.
PF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSPR00722. CHYMOTRYPSIN.
PR00018. KRINGLE.
SMARTSM00181. EGF. 1 hit.
SM00058. FN1. 1 hit.
SM00130. KR. 2 hits.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMSSF57440. Kringle-like. 2 hits.
SSF50494. Pept_Ser_Cys. 1 hit.
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...

Entry information

Entry nameTPA_PONAB
AccessionPrimary (citable) accession number: Q5R8J0
Entry history
Integrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: December 21, 2004
Last modified: December 14, 2011
This is version 50 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

Peptidase families

Classification of peptidase families and list of entries

SIMILARITY comments

Index of protein domains and families

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