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Database: UniProt
Entry: P19637
LinkDB: P19637
Original site: P19637 
ID   TPA_RAT                 Reviewed;         559 AA.
AC   P19637;
DT   01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1991, sequence version 2.
DT   03-SEP-2014, entry version 133.
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   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC   Muroidea; Muridae; Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=3148445; DOI=10.1089/dna.1988.7.671;
RA   Ny T., Leonardsson G., Hsueh A.J.W.;
RT   "Cloning and characterization of a cDNA for rat tissue-type
RT   plasminogen activator.";
RL   DNA 7:671-677(1988).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2105315;
RA   Feng P., Ohlsson M., Ny T.;
RT   "The structure of the TATA-less rat tissue-type plasminogen activator
RT   gene. Species-specific sequence divergences in the promoter predict
RT   differences in regulation of gene expression.";
RL   J. Biol. Chem. 265:2022-2027(1990).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Pituitary;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
CC   -!- FUNCTION: Converts the abundant, but inactive, zymogen plasminogen
CC       to plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By
CC       controlling plasmin-mediated proteolysis, it plays an important
CC       role in tissue remodeling and degradation, in cell migration and
CC       many other physiopathological events.
CC   -!- CATALYTIC ACTIVITY: Specific cleavage of Arg-|-Val bond in
CC       plasminogen to form plasmin.
CC   -!- ENZYME REGULATION: Inhibited by SERPINA5 (By similarity).
CC   -!- SUBUNIT: Heterodimer of chain A and chain B held by a disulfide
CC       bond. Binds to fibrin with high affinity. This interaction leads
CC       to an increase in the catalytic efficiency of the enzyme due to an
CC       increase in affinity for plasminogen. Similarly, binding to
CC       heparin increases the activation of plasminogen. Binds to annexin
CC       A2, cytokeratin-8, fibronectin and laminin. Binds to mannose
CC       receptor and the low-density lipoprotein receptor-related protein
CC       (LRP1); these proteins are involved in TPA clearance. Binds LRP1B;
CC       binding is followed by internalization and degradation. Forms
CC       heterodimer with SERPINA5 (By similarity).
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space.
CC   -!- DOMAIN: Both FN1 and one of the kringle domains are required for
CC       binding to fibrin (By similarity).
CC   -!- DOMAIN: Both FN1 and EGF-like domains are important for binding to
CC       LRP1 (By similarity).
CC   -!- DOMAIN: The FN1 domain mediates binding to annexin A2 (By
CC       similarity).
CC   -!- DOMAIN: The second kringle domain is implicated in binding to
CC       cytokeratin-8 and to the endothelial cell surface binding site (By
CC       similarity).
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
CC       Arg-308 catalyzed by plasmin, tissue kallikrein or factor Xa.
CC   -!- SIMILARITY: Belongs to the peptidase S1 family.
CC   -!- SIMILARITY: Contains 1 EGF-like domain.
CC   -!- SIMILARITY: Contains 1 fibronectin type-I domain.
CC   -!- SIMILARITY: Contains 2 kringle domains.
CC   -!- SIMILARITY: Contains 1 peptidase S1 domain.
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DR   EMBL; M23697; AAA41812.1; -; mRNA.
DR   EMBL; M31197; AAA42261.1; -; Genomic_DNA.
DR   EMBL; M31185; AAA42261.1; JOINED; Genomic_DNA.
DR   EMBL; M31186; AAA42261.1; JOINED; Genomic_DNA.
DR   EMBL; M31187; AAA42261.1; JOINED; Genomic_DNA.
DR   EMBL; M31188; AAA42261.1; JOINED; Genomic_DNA.
DR   EMBL; M31189; AAA42261.1; JOINED; Genomic_DNA.
DR   EMBL; M31190; AAA42261.1; JOINED; Genomic_DNA.
DR   EMBL; M31191; AAA42261.1; JOINED; Genomic_DNA.
DR   EMBL; M31192; AAA42261.1; JOINED; Genomic_DNA.
DR   EMBL; M31193; AAA42261.1; JOINED; Genomic_DNA.
DR   EMBL; M31194; AAA42261.1; JOINED; Genomic_DNA.
DR   EMBL; M31195; AAA42261.1; JOINED; Genomic_DNA.
DR   EMBL; M31196; AAA42261.1; JOINED; Genomic_DNA.
DR   EMBL; BC061565; AAH61565.1; -; mRNA.
DR   PIR; A35029; A35029.
DR   RefSeq; NP_037283.2; NM_013151.2.
DR   RefSeq; XP_006253410.1; XM_006253348.1.
DR   UniGene; Rn.107102; -.
DR   ProteinModelPortal; P19637; -.
DR   SMR; P19637; 33-123, 212-558.
DR   IntAct; P19637; 1.
DR   MINT; MINT-7138910; -.
DR   STRING; 10116.ENSRNOP00000025764; -.
DR   MEROPS; S01.232; -.
DR   PRIDE; P19637; -.
DR   Ensembl; ENSRNOT00000025763; ENSRNOP00000025764; ENSRNOG00000019018.
DR   GeneID; 25692; -.
DR   KEGG; rno:25692; -.
DR   UCSC; RGD:3342; rat.
DR   CTD; 5327; -.
DR   RGD; 3342; Plat.
DR   eggNOG; COG5640; -.
DR   GeneTree; ENSGT00740000115235; -.
DR   HOGENOM; HOG000237314; -.
DR   HOVERGEN; HBG008633; -.
DR   InParanoid; P19637; -.
DR   KO; K01343; -.
DR   OMA; AHVRLYP; -.
DR   OrthoDB; EOG75B84T; -.
DR   PhylomeDB; P19637; -.
DR   TreeFam; TF329901; -.
DR   BRENDA; 3.4.21.68; 5301.
DR   Reactome; REACT_212371; Signaling by PDGF.
DR   NextBio; 607693; -.
DR   PRO; PR:P19637; -.
DR   Genevestigator; P19637; -.
DR   GO; GO:0045177; C:apical part of cell; IEA:Ensembl.
DR   GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR   GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR   GO; GO:0005615; C:extracellular space; IDA:RGD.
DR   GO; GO:0030141; C:secretory granule; IEA:Ensembl.
DR   GO; GO:0045202; C:synapse; IDA:RGD.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; IEA:Ensembl.
DR   GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEP:RGD.
DR   GO; GO:0045861; P:negative regulation of proteolysis; IEA:Ensembl.
DR   GO; GO:0031639; P:plasminogen activation; IEA:Ensembl.
DR   GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IEA:Ensembl.
DR   GO; GO:0060279; P:positive regulation of ovulation; IMP:RGD.
DR   GO; GO:0048167; P:regulation of synaptic plasticity; IEP:RGD.
DR   GO; GO:0051591; P:response to cAMP; IEP:RGD.
DR   GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR   GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR   GO; GO:0014909; P:smooth muscle cell migration; IEA:Ensembl.
DR   GO; GO:0035249; P:synaptic transmission, glutamatergic; IMP:RGD.
DR   GO; GO:0042060; P:wound healing; IEP:RGD.
DR   Gene3D; 2.40.20.10; -; 2.
DR   InterPro; IPR000742; EG-like_dom.
DR   InterPro; IPR013032; EGF-like_CS.
DR   InterPro; IPR000083; Fibronectin_type1.
DR   InterPro; IPR000001; Kringle.
DR   InterPro; IPR013806; Kringle-like.
DR   InterPro; IPR018056; Kringle_CS.
DR   InterPro; IPR001254; Peptidase_S1.
DR   InterPro; IPR018114; Peptidase_S1_AS.
DR   InterPro; IPR001314; Peptidase_S1A.
DR   InterPro; IPR026280; Tissue_plasm_act.
DR   InterPro; IPR009003; Trypsin-like_Pept_dom.
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; Complete proteome; Disulfide bond;
KW   EGF-like domain; Glycoprotein; Hydrolase; Kringle;
KW   Plasminogen activation; Protease; Reference proteome; Repeat;
KW   Secreted; Serine protease; Signal; Zymogen.
FT   SIGNAL        1     17       Potential.
FT   PROPEP       18     29       By similarity.
FT                                /FTId=PRO_0000028357.
FT   PROPEP       30     32       Removed by plasmin.
FT                                /FTId=PRO_0000285917.
FT   CHAIN        33    559       Tissue-type plasminogen activator (By
FT                                similarity).
FT                                /FTId=PRO_0000028358.
FT   CHAIN        33    308       Tissue-type plasminogen activator chain
FT                                A.
FT                                /FTId=PRO_0000028359.
FT   CHAIN       309    559       Tissue-type plasminogen activator chain
FT                                B.
FT                                /FTId=PRO_0000028360.
FT   DOMAIN       36     78       Fibronectin type-I.
FT   DOMAIN       79    117       EGF-like.
FT   DOMAIN      124    205       Kringle 1.
FT   DOMAIN      213    294       Kringle 2.
FT   DOMAIN      309    558       Peptidase S1.
FT   REGION       39     49       Important for binding to annexin A2 (By
FT                                similarity).
FT   ACT_SITE    355    355       Charge relay system.
FT   ACT_SITE    404    404       Charge relay system.
FT   ACT_SITE    510    510       Charge relay system.
FT   SITE         99     99       Important for binding to LRP1 (By
FT                                similarity).
FT   SITE        462    462       Important for single-chain activity (By
FT                                similarity).
FT   SITE        509    509       Important for single-chain activity (By
FT                                similarity).
FT   CARBOHYD    149    149       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    481    481       N-linked (GlcNAc...) (Potential).
FT   DISULFID     38     68       By similarity.
FT   DISULFID     66     75       By similarity.
FT   DISULFID     83     94       By similarity.
FT   DISULFID     88    105       By similarity.
FT   DISULFID    107    116       By similarity.
FT   DISULFID    124    205       By similarity.
FT   DISULFID    145    187       By similarity.
FT   DISULFID    176    200       By similarity.
FT   DISULFID    213    294       By similarity.
FT   DISULFID    234    276       By similarity.
FT   DISULFID    265    289       By similarity.
FT   DISULFID    297    428       Interchain (between A and B chains) (By
FT                                similarity).
FT   DISULFID    340    356       By similarity.
FT   DISULFID    348    417       By similarity.
FT   DISULFID    442    516       By similarity.
FT   DISULFID    474    490       By similarity.
FT   DISULFID    506    534       By similarity.
FT   CONFLICT    380    380       E -> K (in Ref. 1; AAA41812).
SQ   SEQUENCE   559 AA;  62903 MW;  7DBD3809C1D1C921 CRC64;
     MKGELLCVLL LCGVAFTLPD QGIHRRFRRG ARSYRATCRD EQTQTTYQQH QSWLRPMLRG
     NRVEYCRCNS GLAQCHSVPV RSCSEPRCFN GGTCQQALYF SDFVCQCPDG FVGKRCDIDT
     RATCFEGQGI TYRGTWSTAE NGAECINWNS SALSQKPYSA RRPNAIKLGL GNHNYCRNPD
     RDVKPWCYVF KAGKYTTEFC STPACPKGPT EDCYVGKGVT YRGTHSFTTS KASCLPWNSM
     ILIGKTYTAW RANSQALGLG RHNYCRNPDG DAKPWCHVMK DRKLTWEYCD MSPCSTCGLR
     QYKQPQFRIK GGLFTDITSH PWQAAIFVKN KRSPGERFLC GGVLISSCWV LSAAHCFVER
     FPPHHLKVVL GRTYRVVPGE EEQTFEIEKY IVHKEFDDDT YDNDIALLQL RSDSSQCAQE
     SSSVGTACLP DPDVQLPDWT ECELSGYGKH EASSPFFSDR LKEAHVRLYP SSRCTSQHLF
     NKTITSNMLC AGDTRTGGNQ DVHDACQGDS GGPLVCMIDK RMTLLGIISW GLGCGQKDVP
     GIYTKVTNYL NWIQDNMKQ
//
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