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Q28198 (TPA_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified December 14, 2011. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·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
Gene names
Name:PLAT
OrganismBos taurus (Bovine)
Taxonomic identifier9913 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos

Protein attributes

Sequence length566 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.

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

Secretedextracellular space.

Domain

Both FN1 and one of the kringle domains are required for binding to fibrin By similarity.

Both FN1 and EGF-like domains are important for binding to LRP1 By similarity.

The FN1 domain mediates binding to annexin A2 By similarity.

The second kringle domain is implicated in binding to cytokeratin-8 and to the endothelial cell surface binding site By similarity.

Post-translational modification

The single chain, almost fully active enzyme, can be further processed into a two-chain fully active form by a cleavage after Arg-314 catalyzed by plasmin, tissue kallikrein or factor Xa.

Miscellaneous

Binds to the kringle structure of the fibrin A chain. Binding to fibrin enhances its catalytic activity.

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
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological processproteolysis

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular componentextracellular space

Inferred from electronic annotation. Source: UniProtKB-SubCell

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 By similarity
Propeptide22 – 3312 By similarity
PRO_0000028344
Propeptide34 – 363Removed by plasmin By similarity
PRO_0000285905
Chain37 – 566530Tissue-type plasminogen activator
PRO_0000028345
Chain37 – 314278Tissue-type plasminogen activator chain A
PRO_0000028346
Chain315 – 566252Tissue-type plasminogen activator chain B
PRO_0000028347

Regions

Domain40 – 8243Fibronectin type-I
Domain83 – 12139EGF-like
Domain128 – 20982Kringle 1
Domain219 – 30082Kringle 2
Domain315 – 565251Peptidase S1
Region43 – 5311Important for binding to annexin A2 By similarity

Sites

Active site3611Charge relay system
Active site4101Charge relay system
Active site5171Charge relay system
Site1031Important for binding to LRP1 By similarity
Site4681Important for single-chain activity By similarity
Site5161Important for single-chain activity By similarity

Amino acid modifications

Glycosylation1531N-linked (GlcNAc...) Potential
Glycosylation4871N-linked (GlcNAc...) Potential
Disulfide bond42 ↔ 72 By similarity
Disulfide bond70 ↔ 79 By similarity
Disulfide bond87 ↔ 98 By similarity
Disulfide bond92 ↔ 109 By similarity
Disulfide bond111 ↔ 120 By similarity
Disulfide bond128 ↔ 209 By similarity
Disulfide bond149 ↔ 191 By similarity
Disulfide bond180 ↔ 204 By similarity
Disulfide bond219 ↔ 300 By similarity
Disulfide bond240 ↔ 282 By similarity
Disulfide bond271 ↔ 295 By similarity
Disulfide bond303 ↔ 434Interchain (between A and B chains) By similarity
Disulfide bond346 ↔ 362 By similarity
Disulfide bond354 ↔ 423 By similarity
Disulfide bond448 ↔ 523 By similarity
Disulfide bond480 ↔ 496 By similarity
Disulfide bond513 ↔ 541 By similarity

Experimental info

Sequence conflict3701H → L in AAI05349. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q28198 [UniParc].

Last modified November 1, 1997. Version 1.
Checksum: 2EB6BEB4E32276C3

FASTA56663,701
        10         20         30         40         50         60 
MMSAMKTEFL CVLLLCGAVF TSPSQETYRR LRRGARSYKV TCRDGKTQMT YRQHDSWLRP 

        70         80         90        100        110        120 
LLRGNQVEHC WCDGGRAQCH SVPVRSCSEP WCFNGGTCRQ ALYSSDFVCQ CPEGFMGKLC 

       130        140        150        160        170        180 
EIDATATCYK DQGVAYRGTW STAESGAECA NWNSSGLAMK PYSGRRPNAI RLGLGNHNYC 

       190        200        210        220        230        240 
RNPDQDSKPW CYVFKAGKYI SEFCSTPACA KVAEEDGDCY TGNGLAYRGT RSHTKSGASC 

       250        260        270        280        290        300 
LPWNSVFLTS KIYTAWKSNA PALGLGKHNH CRNPDGDAQP WCHVWKDRQL TWEYCDVPQC 

       310        320        330        340        350        360 
VTCGLRQYKR PQFRIKGGLF ADITSHPWQA AIFVKNRRSP GERFLCGGIL ISSCWVLSAA 

       370        380        390        400        410        420 
HCFQERYPPH HLKVFLGRTY RLVPGEEEQT FEVEKYIIHK EFDDDTYDND IALLHLKSDS 

       430        440        450        460        470        480 
LTCARESASV RTICLPDASL QLPDWTECEL SGYGKHESSS PFFSERLKEA HVRLYPSSRC 

       490        500        510        520        530        540 
TSQHLFNRTV TNNMLCAGDT RSGGDHTNLH DACQGDSGGP LVCMKDNHMT LVGIISWGLG 

       550        560 
CGRKDVPGVY TKVTNYLDWI RDNTRP 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and characterization of the bovine plasminogen activators uPA and tPA."
Ravn P., Berglund L., Petersen T.E.
Int. Dairy J. 5:605-617(1995) [Agricola: IND20546782]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Kidney.
[2]NIH - Mammalian Gene Collection (MGC) project
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: Crossbred X Angus.
Tissue: Ileum.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X85800 mRNA. Translation: CAA59795.1.
BC105348 mRNA. Translation: AAI05349.1.
IPIIPI00694104.
RefSeqNP_776571.2. NM_174146.3.
UniGeneBt.12302.

3D structure databases

ProteinModelPortalQ28198.
SMRQ28198. Positions 37-127, 213-566.
ModBaseSearch...

Protein-protein interaction databases

STRINGQ28198.

Protein family/group databases

MEROPSS01.232.

Proteomic databases

PRIDEQ28198.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSBTAT00000001642; ENSBTAP00000001642; ENSBTAG00000001244.
GeneID281407.
KEGGbta:281407.

Organism-specific databases

CTD5327.

Phylogenomic databases

eggNOGmaNOG04276.
HOVERGENHBG008633.
InParanoidQ28198.
OMATCGLRQY.
OrthoDBEOG4BVRTC.

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. 1 hit.
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_BOVIN
AccessionPrimary (citable) accession number: Q28198
Secondary accession number(s): Q2KJG9
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: December 14, 2011
This is version 99 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