TPA_BOVIN
ID TPA_BOVIN Reviewed; 566 AA.
AC Q28198; Q2KJG9;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 167.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RX AGRICOLA=IND20546782; DOI=10.1016/0958-6946(94)00034-M;
RA Ravn P., Berglund L., Petersen T.E.;
RT "Cloning and characterization of the bovine plasminogen activators uPA and
RT tPA.";
RL Int. Dairy J. 5:605-617(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (SEP-2005) 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.
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 314 catalyzed by plasmin, tissue kallikrein or factor Xa.
CC -!- MISCELLANEOUS: Binds to the kringle structure of the fibrin A chain.
CC Binding to fibrin enhances its catalytic activity.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
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DR EMBL; X85800; CAA59795.1; -; mRNA.
DR EMBL; BC105348; AAI05349.1; -; mRNA.
DR RefSeq; NP_776571.2; NM_174146.3.
DR AlphaFoldDB; Q28198; -.
DR SMR; Q28198; -.
DR STRING; 9913.ENSBTAP00000001642; -.
DR MEROPS; S01.232; -.
DR PaxDb; Q28198; -.
DR PRIDE; Q28198; -.
DR GeneID; 281407; -.
DR KEGG; bta:281407; -.
DR CTD; 5327; -.
DR eggNOG; KOG3627; Eukaryota.
DR HOGENOM; CLU_006842_18_4_1; -.
DR InParanoid; Q28198; -.
DR OrthoDB; 1314811at2759; -.
DR TreeFam; TF329901; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005615; C:extracellular space; IDA:AgBase.
DR GO; GO:0051219; F:phosphoprotein binding; IPI:AgBase.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:AgBase.
DR GO; GO:0097655; F:serpin family protein binding; IPI:AgBase.
DR GO; GO:0031639; P:plasminogen activation; IDA:AgBase.
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; IDA:AgBase.
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; 1.
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..21
FT /evidence="ECO:0000250"
FT PROPEP 22..33
FT /evidence="ECO:0000250"
FT /id="PRO_0000028344"
FT PROPEP 34..36
FT /note="Removed by plasmin"
FT /evidence="ECO:0000250"
FT /id="PRO_0000285905"
FT CHAIN 37..566
FT /note="Tissue-type plasminogen activator"
FT /id="PRO_0000028345"
FT CHAIN 37..314
FT /note="Tissue-type plasminogen activator chain A"
FT /id="PRO_0000028346"
FT CHAIN 315..566
FT /note="Tissue-type plasminogen activator chain B"
FT /id="PRO_0000028347"
FT DOMAIN 40..82
FT /note="Fibronectin type-I"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00478"
FT DOMAIN 83..121
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 128..209
FT /note="Kringle 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 219..300
FT /note="Kringle 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 315..565
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT REGION 43..53
FT /note="Important for binding to annexin A2"
FT /evidence="ECO:0000250"
FT ACT_SITE 361
FT /note="Charge relay system"
FT ACT_SITE 410
FT /note="Charge relay system"
FT ACT_SITE 517
FT /note="Charge relay system"
FT SITE 103
FT /note="Important for binding to LRP1"
FT /evidence="ECO:0000250"
FT SITE 468
FT /note="Important for single-chain activity"
FT /evidence="ECO:0000250"
FT SITE 516
FT /note="Important for single-chain activity"
FT /evidence="ECO:0000250"
FT CARBOHYD 153
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 487
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 42..72
FT /evidence="ECO:0000250"
FT DISULFID 70..79
FT /evidence="ECO:0000250"
FT DISULFID 87..98
FT /evidence="ECO:0000250"
FT DISULFID 92..109
FT /evidence="ECO:0000250"
FT DISULFID 111..120
FT /evidence="ECO:0000250"
FT DISULFID 128..209
FT /evidence="ECO:0000250"
FT DISULFID 149..191
FT /evidence="ECO:0000250"
FT DISULFID 180..204
FT /evidence="ECO:0000250"
FT DISULFID 219..300
FT /evidence="ECO:0000250"
FT DISULFID 240..282
FT /evidence="ECO:0000250"
FT DISULFID 271..295
FT /evidence="ECO:0000250"
FT DISULFID 303..434
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 346..362
FT /evidence="ECO:0000250"
FT DISULFID 354..423
FT /evidence="ECO:0000250"
FT DISULFID 448..523
FT /evidence="ECO:0000250"
FT DISULFID 480..496
FT /evidence="ECO:0000250"
FT DISULFID 513..541
FT /evidence="ECO:0000250"
FT CONFLICT 370
FT /note="H -> L (in Ref. 2; AAI05349)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 566 AA; 63701 MW; 2EB6BEB4E32276C3 CRC64;
MMSAMKTEFL CVLLLCGAVF TSPSQETYRR LRRGARSYKV TCRDGKTQMT YRQHDSWLRP
LLRGNQVEHC WCDGGRAQCH SVPVRSCSEP WCFNGGTCRQ ALYSSDFVCQ CPEGFMGKLC
EIDATATCYK DQGVAYRGTW STAESGAECA NWNSSGLAMK PYSGRRPNAI RLGLGNHNYC
RNPDQDSKPW CYVFKAGKYI SEFCSTPACA KVAEEDGDCY TGNGLAYRGT RSHTKSGASC
LPWNSVFLTS KIYTAWKSNA PALGLGKHNH CRNPDGDAQP WCHVWKDRQL TWEYCDVPQC
VTCGLRQYKR PQFRIKGGLF ADITSHPWQA AIFVKNRRSP GERFLCGGIL ISSCWVLSAA
HCFQERYPPH HLKVFLGRTY RLVPGEEEQT FEVEKYIIHK EFDDDTYDND IALLHLKSDS
LTCARESASV RTICLPDASL QLPDWTECEL SGYGKHESSS PFFSERLKEA HVRLYPSSRC
TSQHLFNRTV TNNMLCAGDT RSGGDHTNLH DACQGDSGGP LVCMKDNHMT LVGIISWGLG
CGRKDVPGVY TKVTNYLDWI RDNTRP
