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Protein

Tissue-type plasminogen activator

Gene

PLAT

Organism
Sus scrofa (Pig)
Status
Reviewed-Annotation score: -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)DescriptionActionsGraphical viewLength
Sitei102Important for binding to LRP1By similarity1
Active sitei357Charge relay systemBy similarity1
Active sitei406Charge relay systemBy similarity1
Sitei464Important for single-chain activityBy similarity1
Sitei512Important for single-chain activityBy similarity1
Active sitei513Charge relay systemBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Serine protease
Biological processPlasminogen 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

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
PropeptideiPRO_000028590720 – 32By similarityAdd BLAST13
PropeptideiPRO_000028590833 – 35Removed by plasminBy similarity3
ChainiPRO_000028590936 – 562Tissue-type plasminogen activatorAdd BLAST527
ChainiPRO_000028591036 – 310Tissue-type plasminogen activator chain ABy similarityAdd BLAST275
ChainiPRO_0000285911311 – 562Tissue-type plasminogen activator chain BBy similarityAdd BLAST252

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi41 ↔ 71By similarity
Disulfide bondi69 ↔ 78By similarity
Disulfide bondi86 ↔ 97By similarity
Disulfide bondi91 ↔ 108By similarity
Glycosylationi96O-linked (Fuc) threonineBy similarity1
Disulfide bondi110 ↔ 119By similarity
Disulfide bondi127 ↔ 208By similarity
Disulfide bondi148 ↔ 190By similarity
Glycosylationi152N-linked (GlcNAc...) asparagineSequence analysis1
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
Glycosylationi483N-linked (GlcNAc...) asparagineSequence analysis1
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
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini39 – 81Fibronectin type-IPROSITE-ProRule annotationAdd BLAST43
Domaini82 – 120EGF-likePROSITE-ProRule annotationAdd BLAST39
Domaini126 – 208Kringle 1PROSITE-ProRule annotationAdd BLAST83
Domaini214 – 296Kringle 2PROSITE-ProRule annotationAdd BLAST83
Domaini311 – 561Peptidase S1PROSITE-ProRule annotationAdd BLAST251

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni42 – 52Important for binding to annexin A2By similarityAdd BLAST11

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

Keywords - Domaini

EGF-like domain, Kringle, Repeat, Signal

Phylogenomic databases

eggNOGiKOG3627 Eukaryota
COG5640 LUCA
HOGENOMiHOG000237314
HOVERGENiHBG008633
InParanoidiQ8SQ23
KOiK01343

Family and domain databases

CDDicd00190 Tryp_SPc, 1 hit
Gene3Di2.40.20.10, 2 hits
InterProiView protein in InterPro
IPR013032 EGF-like_CS
IPR000742 EGF-like_dom
IPR000083 Fibronectin_type1
IPR000001 Kringle
IPR013806 Kringle-like
IPR018056 Kringle_CS
IPR038178 Kringle_sf
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR026280 Tissue_plasm_act
IPR034811 tPA
IPR001254 Trypsin_dom
IPR018114 TRYPSIN_HIS
IPR033116 TRYPSIN_SER
PANTHERiPTHR44617 PTHR44617, 1 hit
PfamiView protein in Pfam
PF00008 EGF, 1 hit
PF00039 fn1, 1 hit
PF00051 Kringle, 2 hits
PF00089 Trypsin, 1 hit
PIRSFiPIRSF001145 Tissue_plasm_act, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
SMARTiView protein in SMART
SM00181 EGF, 1 hit
SM00058 FN1, 1 hit
SM00130 KR, 2 hits
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
SSF57440 SSF57440, 2 hits
PROSITEiView protein in 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, 2 hits
PS50070 KRINGLE_2, 2 hits
PS50240 TRYPSIN_DOM, 1 hit
PS00134 TRYPSIN_HIS, 1 hit
PS00135 TRYPSIN_SER, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiTPA_PIG
AccessioniPrimary (citable) accession number: Q8SQ23
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: June 1, 2002
Last modified: March 28, 2018
This is version 98 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health