Reviewed, UniProtKB/Swiss-Prot Q28198 (TPA_BOVIN)

Names and origin

Protein names

Recommended name:
    Tissue-type plasminogen activator
      Short name=t-plasminogen activator
      Short name=t-PA
      Short name=tPA
    EC=3.4.21.68
Cleaved into the following 2 chains:
    1- Recommended name:
            Tissue-type plasminogen activator chain A
    2- Recommended name:
            Tissue-type plasminogen activator chain B

Gene names

Name:

PLAT

Organism

Bos taurus (Bovine)

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	566 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.
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.
Subcellular location	Secreted › extracellular 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 process	Plasminogen activation
Cellular component	Secreted
Domain	EGF-like domain Kringle Repeat Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Zymogen
Gene Ontology (GO)
Cellular component	extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	serine-type endopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	By similarity
	Propeptide	22 – 33	12	By similarity		PRO_0000028344
	Propeptide	34 – 36	3	Removed by plasmin By similarity		PRO_0000285905
	Chain	37 – 566	530	Tissue-type plasminogen activator		PRO_0000028345
	Chain	37 – 314	278	Tissue-type plasminogen activator chain A		PRO_0000028346
	Chain	315 – 566	252	Tissue-type plasminogen activator chain B		PRO_0000028347
Regions
	Domain	40 – 82	43	Fibronectin type-I
	Domain	83 – 121	39	EGF-like
	Domain	128 – 209	82	Kringle 1
	Domain	219 – 300	82	Kringle 2
	Domain	315 – 565	251	Peptidase S1
	Region	43 – 53	11	Important for binding to annexin A2 By similarity
Sites
	Active site	361	1	Charge relay system
	Active site	410	1	Charge relay system
	Active site	517	1	Charge relay system
	Site	103	1	Important for binding to LRP1 By similarity
	Site	468	1	Important for single-chain activity By similarity
	Site	516	1	Important for single-chain activity By similarity
Amino acid modifications
	Glycosylation	153	1	N-linked (GlcNAc...) Potential
	Glycosylation	487	1	N-linked (GlcNAc...) Potential
	Disulfide bond	42 ↔ 72		By similarity
	Disulfide bond	70 ↔ 79		By similarity
	Disulfide bond	87 ↔ 98		By similarity
	Disulfide bond	92 ↔ 109		By similarity
	Disulfide bond	111 ↔ 120		By similarity
	Disulfide bond	128 ↔ 209		By similarity
	Disulfide bond	149 ↔ 191		By similarity
	Disulfide bond	180 ↔ 204		By similarity
	Disulfide bond	219 ↔ 300		By similarity
	Disulfide bond	240 ↔ 282		By similarity
	Disulfide bond	271 ↔ 295		By similarity
	Disulfide bond	303 ↔ 434		Interchain (between A and B chains) By similarity
	Disulfide bond	346 ↔ 362		By similarity
	Disulfide bond	354 ↔ 423		By similarity
	Disulfide bond	448 ↔ 523		By similarity
	Disulfide bond	480 ↔ 496		By similarity
	Disulfide bond	513 ↔ 541		By similarity
Experimental info
	Sequence conflict	370	1	H → L in AAI05349. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q28198-1 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: 2EB6BEB4E32276C3	FASTA	566	63,701
	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

References

	« Hide 'large scale' referencesShow '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.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X85800 mRNA. Translation: CAA59795.1. BC105348 mRNA. Translation: AAI05349.1.
IPI	IPI00694104.
RefSeq	NP_776571.2.
UniGene	Bt.12302
3D structure databases
HSSP	HSSP built from PDB template 1RTF based on UniProtKB P00750.
SMR	Q28198. Positions 37-127, 216-302, 302-566.
ModBase	Search...
Protein family/group databases
MEROPS	S01.232.
Genome annotation databases
Ensembl	ENSBTAG00000001244. Bos taurus. [Contig view]
GeneID	281407.
KEGG	bta:281407.
Phylogenomic databases
HOVERGEN	Q28198.
OMA	Q28198. TCGLRQY.
Enzyme and pathway databases
BRENDA	3.4.21.68. 251.
Family and domain databases
InterPro	IPR016060. Complement_control_module. IPR006209. EGF. IPR006210. EGF-like. IPR013032. EGF-like_reg_CS. IPR000742. EGF_3. IPR000083. Fibrnctn1. IPR000001. Kringle. IPR018056. Kringle_CS. IPR018059. Kringle_sub. IPR018114. Peptidase_S1/S6_AS. IPR001254. Peptidase_S1_S6. IPR001314. Peptidase_S1A. [Graphical view]
Gene3D	G3DSA:2.10.70.10. Complement_control_module. 1 hit. G3DSA:2.40.20.10. Kringle. 2 hits.
Pfam	PF00008. EGF. 1 hit. PF00039. fn1. 1 hit. PF00051. Kringle. 2 hits. PF00089. Trypsin. 1 hit. [Graphical view]
PRINTS	PR00722. CHYMOTRYPSIN. PR00018. KRINGLE.
ProDom	PD000395. Kringle. 2 hits. [Graphical view] [Entries sharing at least one domain]
SMART	SM00181. EGF. 1 hit. SM00058. FN1. 1 hit. SM00130. KR. 2 hits. SM00020. Tryp_SPc. 1 hit. [Graphical view]
PROSITE	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. 1 hit. PS50070. KRINGLE_2. 2 hits. PS50240. TRYPSIN_DOM. 1 hit. PS00134. TRYPSIN_HIS. 1 hit. PS00135. TRYPSIN_SER. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

TPA_BOVIN

Accession

Primary (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:	June 16, 2009
This is version 78 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)