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  Tissue-type plasminogen activator

SourcePongo abelii (Sumatran orangutan)
Taxonomy Pongo abelii Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Pongo.
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 (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).

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 (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 (By similarity).

Sequence length: 562 AA.

Sequence
MNAMKRGLCCVLLLCGAVFALPSQEIHARVRRGARSYQVICRDEKTQMIYQQHQSWLRPV
LRSNRVEYCWCNSGRAQCHSVPVRSCSEPRCFNGGTCQQALYFSDFVCQCPEGFAGKCCE
IDTRATCYEDQGISYRGTWSTAESGAECTNWNSSALAQKPYSGRRPDAIRLGLGNHNYCR
NPDRDSKPWCYVFKAGKYSSEFCSTPACSEGNSDCYFGNGLAYRGTHSLTESGASCLLWN
SMILIGKVYTAQNPNAQALGLGKHNYCRNPDGDAKPWCHVLKNRRLTWEYCDVPSCSTCG
LRQYSQPQFRIKGGLFADIASHPWQAAIFARHRRSPGERFLCGGILISSCWILSAAHCFQ
ERFPPHHLTVILGRTYRVVPGEEEQKFEVEKYIVHKEFDDDTYDNDIALLQLKSDSSRCA
QESSVVRTVCLPPADLQLPDWTECELSGYGKHEALSPFYSERLKEAHVRLYPSSRCTSQH
LLNRTVADNMLCAGDTRSGGPQANLHDACQGDSGGPLVCLNDGRMTLVGIISWGLGCGEK
DVPGVYTKVTNYLDWIHDNMRP
Accession NumberQ5R8J0 
CTD DB100173068
CATHG3DSA:2.10.70.10, G3DSA:2.40.20.10
GeneID DB100173068
GO DB0005615, 0004252
InterPro DBIPR016060, IPR006209, IPR006210, IPR013032, IPR000742, IPR000083, IPR000001, IPR013806, IPR018056, IPR018059, IPR018114, IPR001254, IPR001314, IPR009003
NCBICR859762, CAH91920
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, 228960, 612358, 176895, 173350, 188050, 217090, 173370, 142360, 188050, 612356
PfamPF00008, PF00039, PF00051, PF00089
PROSITE DBPS00022, PS01186, PS50026, PS01253, PS51091, PS00021, PS50070, PS50240, PS00134, PS00135
SMART DBSM00181, SM00058, SM00130, SM00020
UniGenePab.12714



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