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  Tissue-type plasminogen activator

SourceBos taurus (cattle)
Taxonomy Bos taurus Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Laurasiatheria; Cetartiodactyla; Ruminantia; Pecora; Bovidae; Bovinae; Bos.
KeywordsCleavage on pair of basic residues; Disulfide bond; EGF-like domain; Glycoprotein; Hydrolase; Kringle; Plasminogen activation; Protease; Repeat; Secreted; Serine protease; Signal; Zymogen.
Details
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.

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.

Similarity: 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.

Subcellular location: Secreted, extracellular space.

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 (By similarity).

Sequence length: 566 AA.

Sequence
MMSAMKTEFLCVLLLCGAVFTSPSQETYRRLRRGARSYKVTCRDGKTQMTYRQHDSWLRP
LLRGNQVEHCWCDGGRAQCHSVPVRSCSEPWCFNGGTCRQALYSSDFVCQCPEGFMGKLC
EIDATATCYKDQGVAYRGTWSTAESGAECANWNSSGLAMKPYSGRRPNAIRLGLGNHNYC
RNPDQDSKPWCYVFKAGKYISEFCSTPACAKVAEEDGDCYTGNGLAYRGTRSHTKSGASC
LPWNSVFLTSKIYTAWKSNAPALGLGKHNHCRNPDGDAQPWCHVWKDRQLTWEYCDVPQC
VTCGLRQYKRPQFRIKGGLFADITSHPWQAAIFVKNRRSPGERFLCGGILISSCWVLSAA
HCFQERYPPHHLKVFLGRTYRLVPGEEEQTFEVEKYIIHKEFDDDTYDNDIALLHLKSDS
LTCARESASVRTICLPDASLQLPDWTECELSGYGKHESSSPFFSERLKEAHVRLYPSSRC
TSQHLFNRTVTNNMLCAGDTRSGGDHTNLHDACQGDSGGPLVCMKDNHMTLVGIISWGLG
CGRKDVPGVYTKVTNYLDWIRDNTRP
Accession NumberQ28198 
CTD DB281407
eggNOG DBmaNOG04276
Ensembl DBENSBTAT00000001642
CATHG3DSA:2.10.70.10, G3DSA:2.40.20.10
GeneID DB281407
GO DB0005615, 0004252
InterPro DBIPR016060, IPR006209, IPR006210, IPR013032, IPR000742, IPR000083, IPR000001, IPR013806, IPR018056, IPR018059, IPR018114, IPR001254, IPR001314, IPR009003
IPI DBIPI00694104
KEGGbta:281407
NCBIX85800, CAA59795, BC105348, AAI05349, NP_776571.2
OMATCGLRQY
OMIM105200, 134820, 202400, 134830, 202400, 134850, 202400, 176930, 601367, 134390, 188055, 227400, 600880, 601367, 612309, 227500, 134500, 306700, 300746, 306900, 227600, 176860, 188050, 612283, 612304, 176880, 612336, 264900, 612416, 234000, 610618, 610619, 229000, 612423, 107300, 188050, 134570, 134580, 193400, 277480
OrthoDBEOG9TQPVK
PfamPF00008, PF00039, PF00051, PF00089
PROSITE DBPS00022, PS01186, PS50026, PS01253, PS51091, PS00021, PS50070, PS50240, PS00134, PS00135
SMART DBSM00181, SM00058, SM00130, SM00020
UniGeneBt.12302



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