TPA_PIG
ID TPA_PIG Reviewed; 562 AA.
AC Q8SQ23;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 25-MAY-2022, entry version 114.
DE RecName: Full=Tissue-type plasminogen activator;
DE Short=t-PA;
DE Short=t-plasminogen activator;
DE Short=tPA;
DE EC=3.4.21.68;
DE Contains:
DE RecName: Full=Tissue-type plasminogen activator chain A;
DE Contains:
DE RecName: Full=Tissue-type plasminogen activator chain B;
DE Flags: Precursor;
GN Name=PLAT;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Enamel organ;
RA Ding Y., Xue J., Bartlett J.D.;
RT "T-plasminogen activator in tooth tissues.";
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Converts the abundant, but inactive, zymogen plasminogen to
CC plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By
CC controlling plasmin-mediated proteolysis, it plays an important role in
CC tissue remodeling and degradation, in cell migration and many other
CC physiopathological events. During oocyte activation, plays a role in
CC cortical granule reaction in the zona reaction, which contributes to
CC the block to polyspermy. {ECO:0000250|UniProtKB:P19637}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Specific cleavage of Arg-|-Val bond in plasminogen to form
CC plasmin.; EC=3.4.21.68;
CC -!- ACTIVITY REGULATION: Inhibited by SERPINA5. {ECO:0000250}.
CC -!- SUBUNIT: Heterodimer of chain A and chain B held by a disulfide bond.
CC Binds to fibrin with high affinity. This interaction leads to an
CC increase in the catalytic efficiency of the enzyme due to an increase
CC in affinity for plasminogen. Similarly, binding to heparin increases
CC the activation of plasminogen. Binds to annexin A2, cytokeratin-8,
CC fibronectin and laminin. Binds to mannose receptor and the low-density
CC lipoprotein receptor-related protein (LRP1); these proteins are
CC involved in TPA clearance. Binds LRP1B; binding is followed by
CC internalization and degradation. Forms heterodimer with SERPINA5 (By
CC similarity). In complex with SERPINE1, interacts with SORL1 (By
CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:P00750}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space {ECO:0000250}.
CC -!- DOMAIN: Both FN1 and one of the kringle domains are required for
CC binding to fibrin. {ECO:0000250}.
CC -!- DOMAIN: Both FN1 and EGF-like domains are important for binding to
CC LRP1. {ECO:0000250}.
CC -!- DOMAIN: The FN1 domain mediates binding to annexin A2. {ECO:0000250}.
CC -!- DOMAIN: The second kringle domain is implicated in binding to
CC cytokeratin-8 and to the endothelial cell surface binding site.
CC {ECO:0000250}.
CC -!- PTM: The single chain, almost fully active enzyme, can be further
CC processed into a two-chain fully active form by a cleavage after Arg-
CC 310 catalyzed by plasmin, tissue kallikrein or factor Xa.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
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DR EMBL; AF364605; AAM00297.1; -; mRNA.
DR RefSeq; NP_999219.1; NM_214054.1.
DR AlphaFoldDB; Q8SQ23; -.
DR SMR; Q8SQ23; -.
DR STRING; 9823.ENSSSCP00000007494; -.
DR MEROPS; S01.232; -.
DR PaxDb; Q8SQ23; -.
DR PRIDE; Q8SQ23; -.
DR Ensembl; ENSSSCT00025069714; ENSSSCP00025030040; ENSSSCG00025050832.
DR Ensembl; ENSSSCT00035092228; ENSSSCP00035038686; ENSSSCG00035068081.
DR Ensembl; ENSSSCT00045046551; ENSSSCP00045032313; ENSSSCG00045027101.
DR Ensembl; ENSSSCT00070029904; ENSSSCP00070024940; ENSSSCG00070015209.
DR GeneID; 397121; -.
DR KEGG; ssc:397121; -.
DR CTD; 5327; -.
DR eggNOG; KOG3627; Eukaryota.
DR InParanoid; Q8SQ23; -.
DR OrthoDB; 1314811at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Chromosome 17.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0031639; P:plasminogen activation; IBA:GO_Central.
DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0060468; P:prevention of polyspermy; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR GO; GO:0014909; P:smooth muscle cell migration; IBA:GO_Central.
DR CDD; cd00061; FN1; 1.
DR CDD; cd00108; KR; 2.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR Gene3D; 2.40.20.10; -; 2.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000083; Fibronectin_type1.
DR InterPro; IPR000001; Kringle.
DR InterPro; IPR013806; Kringle-like.
DR InterPro; IPR018056; Kringle_CS.
DR InterPro; IPR038178; Kringle_sf.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR026280; Tissue_plasm_act.
DR InterPro; IPR034811; tPA.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR PANTHER; PTHR24264:SF42; PTHR24264:SF42; 3.
DR Pfam; PF00008; EGF; 1.
DR Pfam; PF00039; fn1; 1.
DR Pfam; PF00051; Kringle; 2.
DR Pfam; PF00089; Trypsin; 1.
DR PIRSF; PIRSF001145; Tissue_plasm_act; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00181; EGF; 1.
DR SMART; SM00058; FN1; 1.
DR SMART; SM00130; KR; 2.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF57440; SSF57440; 2.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS50026; EGF_3; 1.
DR PROSITE; PS01253; FN1_1; 1.
DR PROSITE; PS51091; FN1_2; 1.
DR PROSITE; PS00021; KRINGLE_1; 2.
DR PROSITE; PS50070; KRINGLE_2; 2.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 2: Evidence at transcript level;
KW Cleavage on pair of basic residues; Disulfide bond; EGF-like domain;
KW Glycoprotein; Hydrolase; Kringle; Plasminogen activation; Protease;
KW Reference proteome; Repeat; Secreted; Serine protease; Signal; Zymogen.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT PROPEP 20..32
FT /evidence="ECO:0000250"
FT /id="PRO_0000285907"
FT PROPEP 33..35
FT /note="Removed by plasmin"
FT /evidence="ECO:0000250"
FT /id="PRO_0000285908"
FT CHAIN 36..562
FT /note="Tissue-type plasminogen activator"
FT /id="PRO_0000285909"
FT CHAIN 36..310
FT /note="Tissue-type plasminogen activator chain A"
FT /evidence="ECO:0000250"
FT /id="PRO_0000285910"
FT CHAIN 311..562
FT /note="Tissue-type plasminogen activator chain B"
FT /evidence="ECO:0000250"
FT /id="PRO_0000285911"
FT DOMAIN 39..81
FT /note="Fibronectin type-I"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00478"
FT DOMAIN 82..120
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 126..208
FT /note="Kringle 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 214..296
FT /note="Kringle 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 311..561
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT REGION 42..52
FT /note="Important for binding to annexin A2"
FT /evidence="ECO:0000250"
FT ACT_SITE 357
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 406
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 513
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT SITE 102
FT /note="Important for binding to LRP1"
FT /evidence="ECO:0000250"
FT SITE 464
FT /note="Important for single-chain activity"
FT /evidence="ECO:0000250"
FT SITE 512
FT /note="Important for single-chain activity"
FT /evidence="ECO:0000250"
FT CARBOHYD 96
FT /note="O-linked (Fuc) threonine"
FT /evidence="ECO:0000250"
FT CARBOHYD 152
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 483
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 41..71
FT /evidence="ECO:0000250"
FT DISULFID 69..78
FT /evidence="ECO:0000250"
FT DISULFID 86..97
FT /evidence="ECO:0000250"
FT DISULFID 91..108
FT /evidence="ECO:0000250"
FT DISULFID 110..119
FT /evidence="ECO:0000250"
FT DISULFID 127..208
FT /evidence="ECO:0000250"
FT DISULFID 148..190
FT /evidence="ECO:0000250"
FT DISULFID 179..203
FT /evidence="ECO:0000250"
FT DISULFID 215..296
FT /evidence="ECO:0000250"
FT DISULFID 236..278
FT /evidence="ECO:0000250"
FT DISULFID 267..291
FT /evidence="ECO:0000250"
FT DISULFID 299..430
FT /note="Interchain (between A and B chains)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000255|PROSITE-ProRule:PRU00121, ECO:0000255|PROSITE-
FT ProRule:PRU00274, ECO:0000255|PROSITE-ProRule:PRU00478"
FT DISULFID 342..358
FT /evidence="ECO:0000250"
FT DISULFID 350..419
FT /evidence="ECO:0000250"
FT DISULFID 444..519
FT /evidence="ECO:0000250"
FT DISULFID 476..492
FT /evidence="ECO:0000250"
FT DISULFID 509..537
FT /evidence="ECO:0000250"
SQ SEQUENCE 562 AA; 63668 MW; F9E6B4C77CB101E8 CRC64;
MYALKRELWC VLLLCGAICT SPSQETHRRL RRGVRSYRVT CRDEKTQMIY QQHQSWLRPL
LRGNRVEHCW CNDGQTQCHS VPVKSCSEPR CFNGGTCLQA IYFSDFVCQC PVGFIGRQCE
IDARATCYED QGITYRGTWS TTESGAECVN WNTSGLASMP YNGRRPDAVK LGLGNHNYCR
NPDKDSKPWC YIFKAEKYSP DFCSTPACTK EKEECYTGKG LDYRGTRSLT MSGAFCLPWN
SLVLMGKIYT AWNSNAQTLG LGKHNYCRNP DGDTQPWCHV LKDHKLTWEY CDLPQCVTCG
LRQYKEPQFR IKGGLYADIT SHPWQAAIFV KNRRSPGERF LCGGILISSC WVLSAAHCFQ
ERFPPHHVRV VLGRTYRLVP GEEEQAFEVE KYIVHKEFDD DTYDNDIALL QLKSDSLTCA
QESDAVRTVC LPEANLQLPD WTECELSGYG KHEASSPFYS ERLKEAHVRL YPSSRCTSKH
LFNKTITNNM LCAGDTRSGG DNANLHDACQ GDSGGPLVCM KGNHMTLVGV ISWGLGCGQK
DVPGVYTKVT NYLNWIRDNT RP
