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Protein

Tissue-type plasminogen activator

Gene

PLAT

Organism
Sus scrofa (Pig)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript leveli

Functioni

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).By similarity

Catalytic activityi

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

Enzyme regulationi

Inhibited by SERPINA5.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei102 – 1021Important for binding to LRP1By similarity
Active sitei357 – 3571Charge relay systemBy similarity
Active sitei406 – 4061Charge relay systemBy similarity
Sitei464 – 4641Important for single-chain activityBy similarity
Sitei512 – 5121Important for single-chain activityBy similarity
Active sitei513 – 5131Charge relay systemBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Plasminogen activation

Protein family/group databases

MEROPSiS01.232.

Names & Taxonomyi

Protein namesi
Recommended name:
Tissue-type plasminogen activator (EC:3.4.21.68)
Short name:
t-PA
Short name:
t-plasminogen activator
Short name:
tPA
Cleaved into the following 2 chains:
Gene namesi
Name:PLAT
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
Proteomesi
  • UP000008227 Componenti: Unplaced

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1919Sequence analysisAdd
BLAST
Propeptidei20 – 3213By similarityPRO_0000285907Add
BLAST
Propeptidei33 – 353Removed by plasminBy similarityPRO_0000285908
Chaini36 – 562527Tissue-type plasminogen activatorPRO_0000285909Add
BLAST
Chaini36 – 310275Tissue-type plasminogen activator chain ABy similarityPRO_0000285910Add
BLAST
Chaini311 – 562252Tissue-type plasminogen activator chain BBy similarityPRO_0000285911Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi41 ↔ 71By similarity
Disulfide bondi69 ↔ 78By similarity
Disulfide bondi86 ↔ 97By similarity
Disulfide bondi91 ↔ 108By similarity
Glycosylationi96 – 961O-linked (Fuc)By similarity
Disulfide bondi110 ↔ 119By similarity
Disulfide bondi127 ↔ 208By similarity
Disulfide bondi148 ↔ 190By similarity
Glycosylationi152 – 1521N-linked (GlcNAc...)Sequence analysis
Disulfide bondi179 ↔ 203By similarity
Disulfide bondi215 ↔ 296By similarity
Disulfide bondi236 ↔ 278By similarity
Disulfide bondi267 ↔ 291By similarity
Disulfide bondi299 ↔ 430Interchain (between A and B chains)PROSITE-ProRule annotation
Disulfide bondi342 ↔ 358By similarity
Disulfide bondi350 ↔ 419By similarity
Disulfide bondi444 ↔ 519By similarity
Disulfide bondi476 ↔ 492By similarity
Glycosylationi483 – 4831N-linked (GlcNAc...)Sequence analysis
Disulfide bondi509 ↔ 537By similarity

Post-translational modificationi

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

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiQ8SQ23.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000007494.

Structurei

3D structure databases

ProteinModelPortaliQ8SQ23.
SMRiQ8SQ23. Positions 36-126, 214-562.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini39 – 8143Fibronectin type-IPROSITE-ProRule annotationAdd
BLAST
Domaini82 – 12039EGF-likePROSITE-ProRule annotationAdd
BLAST
Domaini126 – 20883Kringle 1PROSITE-ProRule annotationAdd
BLAST
Domaini214 – 29683Kringle 2PROSITE-ProRule annotationAdd
BLAST
Domaini311 – 561251Peptidase S1PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni42 – 5211Important for binding to annexin A2By similarityAdd
BLAST

Domaini

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

Sequence similaritiesi

Belongs to the peptidase S1 family.PROSITE-ProRule annotation
Contains 1 EGF-like domain.PROSITE-ProRule annotation
Contains 1 fibronectin type-I domain.PROSITE-ProRule annotation
Contains 2 kringle domains.PROSITE-ProRule annotation
Contains 1 peptidase S1 domain.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Kringle, Repeat, Signal

Phylogenomic databases

eggNOGiKOG3627. Eukaryota.
COG5640. LUCA.
HOGENOMiHOG000237314.
HOVERGENiHBG008633.
InParanoidiQ8SQ23.
KOiK01343.

Family and domain databases

InterProiIPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR000083. Fibronectin_type1.
IPR000001. Kringle.
IPR013806. Kringle-like.
IPR018056. Kringle_CS.
IPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR026280. Tissue_plasm_act.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[Graphical view]
PfamiPF00008. EGF. 1 hit.
PF00039. fn1. 1 hit.
PF00051. Kringle. 2 hits.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFiPIRSF001145. Tissue_plasm_act. 1 hit.
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00181. EGF. 1 hit.
SM00058. FN1. 1 hit.
SM00130. KR. 2 hits.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF57440. SSF57440. 2 hits.
PROSITEiPS00022. 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]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q8SQ23-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MYALKRELWC VLLLCGAICT SPSQETHRRL RRGVRSYRVT CRDEKTQMIY
60 70 80 90 100
QQHQSWLRPL LRGNRVEHCW CNDGQTQCHS VPVKSCSEPR CFNGGTCLQA
110 120 130 140 150
IYFSDFVCQC PVGFIGRQCE IDARATCYED QGITYRGTWS TTESGAECVN
160 170 180 190 200
WNTSGLASMP YNGRRPDAVK LGLGNHNYCR NPDKDSKPWC YIFKAEKYSP
210 220 230 240 250
DFCSTPACTK EKEECYTGKG LDYRGTRSLT MSGAFCLPWN SLVLMGKIYT
260 270 280 290 300
AWNSNAQTLG LGKHNYCRNP DGDTQPWCHV LKDHKLTWEY CDLPQCVTCG
310 320 330 340 350
LRQYKEPQFR IKGGLYADIT SHPWQAAIFV KNRRSPGERF LCGGILISSC
360 370 380 390 400
WVLSAAHCFQ ERFPPHHVRV VLGRTYRLVP GEEEQAFEVE KYIVHKEFDD
410 420 430 440 450
DTYDNDIALL QLKSDSLTCA QESDAVRTVC LPEANLQLPD WTECELSGYG
460 470 480 490 500
KHEASSPFYS ERLKEAHVRL YPSSRCTSKH LFNKTITNNM LCAGDTRSGG
510 520 530 540 550
DNANLHDACQ GDSGGPLVCM KGNHMTLVGV ISWGLGCGQK DVPGVYTKVT
560
NYLNWIRDNT RP
Length:562
Mass (Da):63,668
Last modified:June 1, 2002 - v1
Checksum:iF9E6B4C77CB101E8
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF364605 mRNA. Translation: AAM00297.1.
RefSeqiNP_999219.1. NM_214054.1.
UniGeneiSsc.196.

Genome annotation databases

GeneIDi397121.
KEGGissc:397121.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF364605 mRNA. Translation: AAM00297.1.
RefSeqiNP_999219.1. NM_214054.1.
UniGeneiSsc.196.

3D structure databases

ProteinModelPortaliQ8SQ23.
SMRiQ8SQ23. Positions 36-126, 214-562.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000007494.

Protein family/group databases

MEROPSiS01.232.

Proteomic databases

PaxDbiQ8SQ23.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi397121.
KEGGissc:397121.

Organism-specific databases

CTDi5327.

Phylogenomic databases

eggNOGiKOG3627. Eukaryota.
COG5640. LUCA.
HOGENOMiHOG000237314.
HOVERGENiHBG008633.
InParanoidiQ8SQ23.
KOiK01343.

Family and domain databases

InterProiIPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR000083. Fibronectin_type1.
IPR000001. Kringle.
IPR013806. Kringle-like.
IPR018056. Kringle_CS.
IPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR026280. Tissue_plasm_act.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[Graphical view]
PfamiPF00008. EGF. 1 hit.
PF00039. fn1. 1 hit.
PF00051. Kringle. 2 hits.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFiPIRSF001145. Tissue_plasm_act. 1 hit.
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00181. EGF. 1 hit.
SM00058. FN1. 1 hit.
SM00130. KR. 2 hits.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF57440. SSF57440. 2 hits.
PROSITEiPS00022. 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]
ProtoNetiSearch...

Publicationsi

  1. "T-plasminogen activator in tooth tissues."
    Ding Y., Xue J., Bartlett J.D.
    Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Enamel organ.

Entry informationi

Entry nameiTPA_PIG
AccessioniPrimary (citable) accession number: Q8SQ23
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: June 1, 2002
Last modified: March 16, 2016
This is version 90 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.