Cloning and expression of human tissue-type plasminogen activator cDNA in E. coli.
The structure of the human tissue-type plasminogen activator gene: correlation of intron and exon structures to functional and structural domains.
The human tissue plasminogen activator gene.
Cloning of cDNA coding for human tissue-type plasminogen activator and its expression in Escherichia coli.
Expression of human uterine tissue-type plasminogen activator in mouse cells using BPV vectors.
Nucleotide sequence of the tissue-type plasminogen activator cDNA from human fetal lung cells.
Variant tissue-type plasminogen activator (PLAT) cDNA obtained from human endothelial cells.
Complete sequencing and characterization of 21,243 full-length human cDNAs.
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3)
Cloning of human full-length CDSs in BD Creator(TM) system donor vector.
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)
SeattleSNPs variation discovery resource
VARIANTS ASP-34; SER-136; THR-146 AND TRP-164
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
Isolation and characterization of the human tissue-type plasminogen activator structural gene including its 5' flanking region.
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-36
Purification and characterization of tissue plasminogen activator secreted by human embryonic lung diploid fibroblasts, IMR-90 cells.
Purification and characterization of a melanoma cell plasminogen activator.
Tissue plasminogen activator: peptide analyses confirm an indirectly derived amino acid sequence, identify the active site serine residue, establish glycosylation sites, and localize variant differences.
Isolation of cDNA sequences coding for a part of human tissue plasminogen activator.
Carbohydrate structure of recombinant human uterine tissue plasminogen activator expressed in mouse epithelial cells.
Tissue plasminogen activator has an O-linked fucose attached to threonine-61 in the epidermal growth factor domain.
Disulfide pairing of the recombinant kringle-2 domain of tissue plasminogen activator produced in Escherichia coli.
The putative tumor suppressor LRP1B, a novel member of the low density lipoprotein (LDL) receptor family, exhibits both overlapping and distinct properties with the LDL receptor-related protein.
An unappreciated role for RNA surveillance.
SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S)
1H NMR structural characterization of a recombinant kringle 2 domain from human tissue-type plasminogen activator.
Kringle-2 domain of the tissue-type plasminogen activator. 1H-NMR assignments and secondary structure.
Solution structure of the tissue-type plasminogen activator kringle 2 domain complexed to 6-aminohexanoic acid an antifibrinolytic drug.
Crystal structure of the kringle 2 domain of tissue plasminogen activator at 2.4-A resolution.
X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF KRINGLE 2
Solution structure of the fibrin binding finger domain of tissue-type plasminogen activator determined by 1H nuclear magnetic resonance.
The solution structure and backbone dynamics of the fibronectin type I and epidermal growth factor-like pair of modules of tissue-type plasminogen activator.
The 2.3 A crystal structure of the catalytic domain of recombinant two-chain human tissue-type plasminogen activator.
X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF CATALYTIC DOMAIN
Lysine 156 promotes the anomalous proenzyme activity of tPA: X-ray crystal structure of single-chain human tPA.
X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF CATALYTIC DOMAIN
Wikipedia; Tissue plasminogen activator entry
SHMPD; The Singapore human mutation and polymorphism database
Activase; Clinical information on Activase
Retavase; Clinical information on Retavase
Tissue-type plasminogen activator chain A
Tissue-type plasminogen activator chain B
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. Play a direct role in facilitating neuronal migration.
Specific cleavage of Arg-|-Val bond in plasminogen to form plasmin.
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 between 100-fold and 1000-fold, 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. Yet unidentified interactions on endothelial cells and vascular smooth muscle cells (VSMC) lead to a 100-fold stimulation of plasminogen activation. In addition, binding to VSMC reduces TPA inhibition by PAI-1 by 30-fold. Binds LRP1B; binding is followed by internalization and degradation.
Synthesized in numerous tissues (including tumors) and secreted into most extracellular body fluids, such as plasma, uterine fluid, saliva, gingival crevicular fluid, tears, seminal fluid, and milk.
Both FN1 and one of the kringle domains are required for binding to fibrin.
Both FN1 and EGF-like domains are important for binding to LRP1.
The FN1 domain mediates binding to annexin A2.
The second kringle domain is implicated in binding to cytokeratin-8 and to the endothelial cell surface binding site.
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.
Differential cell-specific N-linked glycosylation gives rise to two glycoforms, type I (glycosylated at Asn-219) and type II (not glycosylated at Asn-219). The single chain type I glycoform is less readily converted into the two-chain form by plasmin, and the two-chain type I glycoform has a lower activity than the two-chain type II glycoform in the presence of fibrin.
N-glycosylation of Asn-152; the bound oligomannosidic glycan is involved in the interaction with the mannose receptor.
Characterization of O-linked glycan was studied in Bowes melanoma cell line.
Note=Increased activity of TPA results in increased fibrinolysis of fibrin blood clots that is associated with excessive bleeding. Defective release of TPA results in hypofibrinolysis that can lead to thrombosis or embolism.
Available under the names Activase (Genentech) and Retavase (Centocor and Roche) [Retavase is a fragment of TPA that contains kringle 2 and the protease domain; it was also known as BM 06.022]. Used in Acute Myocardial Infarction (AMI), in Acute Ischemic Stroke (AIS) and Pulmonary Embolism (PE) to initiate fibrinolysis.
May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
MDAMKRGLCC VLLLCGAVFV SPSQEIHARF RRGARSYQVI CRDEKTQMIY QQHQSWLRPV LRSNRVEYCW CNSGRAQCHS VPVKSCSEPR CFNGGTCQQA LYFSDFVCQC PEGFAGKCCE IDTRATCYED QGISYRGTWS TAESGAECTN WNSSALAQKP YSGRRPDAIR LGLGNHNYCR NPDRDSKPWC YVFKAGKYSS EFCSTPACSE GNSDCYFGNG SAYRGTHSLT ESGASCLPWN SMILIGKVYT AQNPSAQALG LGKHNYCRNP DGDAKPWCHV LKNRRLTWEY CDVPSCSTCG LRQYSQPQFR IKGGLFADIA SHPWQAAIFA KHRRSPGERF LCGGILISSC WILSAAHCFQ ERFPPHHLTV ILGRTYRVVP GEEEQKFEVE KYIVHKEFDD DTYDNDIALL QLKSDSSRCA QESSVVRTVC LPPADLQLPD WTECELSGYG KHEALSPFYS ERLKEAHVRL YPSSRCTSQH LLNRTVTDNM LCAGDTRSGG PQANLHDACQ GDSGGPLVCL NDGRMTLVGI ISWGLGCGQK DVPGVYTKVT NYLDWIRDNM RP
Expressed genes for plant-type ribulose 1,5-bisphosphate carboxylase/oxygenase in the photosynthetic bacterium Chromatium vinosum, which possesses two complete sets of the genes.
Genes encoding RubisCO in Pseudomonas hydrogenothermophila are followed by a novel cbbQ gene similar to nirQ of the denitrification gene cluster from Pseudomonas species.
May affect the post-translational activation and/or assembly of the oligomeric structure of RuBisCO.
Belongs to the CbbQ/NirQ/NorQ/GpvN family.
MSDIDRNQFL IDHEPYYRPV SNEVALYEAA YAARMPVMLK GPTGCGKTRF VEYMAWKLGK PLITVACNED MTAS
MDLRNQYLVR SEPYYHAVGD EIERFEAAYA NRIPMMLKGP TGCGKSRFVE YMAWKLGKPL ITVACNEDMT AADLVGRFLL DKEGTRWQDG PLTTAARIGA ICYLDEVVEA RQDTTVVIHP LTDHRRILPL DKKGEVVEAH PDFQIVISYN PGYQSAMKDL KTSTKQRFAA MDFDYPAPEV ESEIVAHESG VDAATAKKLV EVAIRSRHLK GHGLDEGIST RLLVYAGSLI TKGIAPLIAC EMALICPITD DPDLRYALRA AAQTLFA
Structure and ANR-dependent transcription of the nir genes for denitrification from Pseudomonas aeruginosa.
Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen.
Activator of nitrite and nitric oxide reductases.
MRDATPFYEA TGHEIEVFER AWRHGLPVLL KGPTGCGKTR FVQYMARRLE LPLYSVACHD DLGAADLLGR HLIGADGTWW QDGPLTRAVR EGGICYLDEV VEARQDTTVA IHPLADDRRE LYLERTGETL QAPPSFMLVV SYNPGYQNLL KGLKPSTRQR FVALRFDYPA AQQEARILVG ESGCAETLAQ RLVQLGQALR RLEQHDLEEV ASTRLLIFAA RLIGDGMDPR EACRVALAEP LSDDPATVAA LMDIVDLHVA
The DNA sequence, annotation and analysis of human chromosome 3.
Analysis of a putative tumor suppressor gene region of 100 kb at chromosome 3p21.1 in conventional renal cell carcinoma.
Choline + acceptor = betaine aldehyde + reduced acceptor.
Amine and polyamine biosynthesis; betaine biosynthesis via choline pathway; betaine aldehyde from choline (cytochrome c reductase route): step 1/1.
Belongs to the GMC oxidoreductase family.
MWCLLRGLGR PGALARGALG QQQSLGARAL ASAGSESRDE YSYVVVGAGS AGCVLAGRLT EDPAERVLLL EAGPKDVLAG SKRLSWKIHM PAALVANLCD DRYNWCYHTE VQRGLDGRVL YWPRGRVWGG SSSLNAMVYV RGHAEDYERW QRQGARGWDY AHCLPYFRKA QGHELGASRY RGADGPLRVS RGKTNHPLHC AFLEATQQAG YPLTEDMNGF QQEGFGWMDM TIHEGKRWSA ACAYLHPALS RTNLKAEAET LVSRVLFEGT RAVGVEYVKN GQSHRAYASK EVILSGGAIN SPQLLMLSGI GNADDLKKLG IPVVCHLPGV GQNLQDHLEI YIQQACTRPI TLHSAQKPLR KVCIGLEWLW KFTGEGATAH LETGGFIRSQ PGVPHPDIQF HFLPSQVIDH GRVPTQQEAY QVHVGPMRGT SVGWLKLRSA NPQDHPVIQP NYLSTETDIE DFRLCVKLTR EIFAQEALAP FRGKELQPGS HIQSDKEIDA FVRAKADSAY HPSCTCKMGQ PSDPTAVVDP QTRVLGVENL RVVDASIMPS MVSGNLNAPT IMIAEKAADI IKGQPALWDK DVPVYKPRTL ATQR
Cloning and functional expression of dendrotoxin K from black mamba, a K+ channel blocker.
Snake venom toxins. The amino acid sequence of toxin Vi2, a homologue of pancreatic trypsin inhibitor, from Dendroaspis polylepis polylepis (black mamba) venom.
Nuclear magnetic resonance solution structure of dendrotoxin K from the venom of Dendroaspis polylepis polylepis.
This protein is much less toxic to mice than is whole venom. It inhibits trypsin slightly, but chymotrypsin not at all. It is a highly selective blocker of voltage-gated potassium channels.
LD(50) is 30 mg/kg by intravenous injection.
Contains 1 BPTI/Kunitz inhibitor domain.
SGHLLLLLGL LTLWAELTPV SGAAKYCKLP LRIGPCKRKI PSFYYKWKAK QCLPFDYSGC GGNANRFKTI EECRRTCVG
Structure and chromosomal location of the human granulin gene.
The epithelin precursor encodes two proteins with opposing activities on epithelial cell growth.
Isolation and sequence of the granulin precursor cDNA from human bone marrow reveals tandem cysteine-rich granulin domains.
PCDGF sequence from lambda phage human Jurkat T cell cDNA library (Clontech).
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)
Granulins, a novel class of peptide from leukocytes.
Characterisation of UGP and its relationship with beta-core fragment.
Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.
GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-265
Design and solution structure of a well-folded stack of two beta-hairpins based on the amino-terminal fragment of human granulin A.
Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17.
HDDD2 is a familial frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions caused by a missense mutation in the signal peptide of progranulin.
Molecular characterization of novel progranulin (GRN) mutations in frontotemporal dementia.
CHARACTERIZATION OF VARIANT UP-FTD ASP-9
Atlas of Genetics and Cytogenetics in Oncology and Haematology
Frontotemporal dementia with motor neuron-disease type inclusions
Granulins have possible cytokine-like activity. They may play a role in inflammation, wound repair, and tissue remodeling.
Granulin-4 promotes proliferation of the epithelial cell line A431 in culture while granulin-3 acts as an antagonist to granulin-4, inhibiting the growth.
In myelogenous leukemic cell lines of promonocytic, promyelocytic, and proerythroid lineage, in fibroblasts, and very strongly in epithelial cell lines. Present in inflammatory cells and bone marrow. Highest levels in kidney.
Defects in GRN are the cause of ubiquitin-positive frontotemporal dementia (UP-FTD) [MIM:607485]; also known as tau-negative frontotemporal dementia linked to chromosome 17. Frontotemporal dementia (FTD) is the second most common cause of dementia in people under the age of 65 years. It is an autosomal dominant neurodegenerative disease.
In UP-FTD; no significant difference in the total mRNA between cases and controls; although the mutant protein is expressed it is not secreted and appears to be trapped within an intracellular compartment.
MWTLVSWVAL TAGLVAGTRC PDGQFCPVAC CLDPGGASYS CCRPLLDKWP TTLSRHLGGP CQVDAHCSAG HSCIFTVSGT SSCCPFPEAV ACGDGHHCCP RGFHCSADGR SCFQRSGNNS VGAIQCPDSQ FECPDFSTCC VMVDGSWGCC PMPQASCCED RVHCCPHGAF CDLVHTRCIT PTGTHPLAKK LPAQRTNRAV ALSSSVMCPD ARSRCPDGST CCELPSGKYG CCPMPNATCC SDHLHCCPQD TVCDLIQSKC LSKENATTDL LTKLPAHTVG DVKCDMEVSC PDGYTCCRLQ SGAWGCCPFT QAVCCEDHIH CCPAGFTCDT QKGTCEQGPH QVPWMEKAPA HLSLPDPQAL KRDVPCDNVS SCPSSDTCCQ LTSGEWGCCP IPEAVCCSDH QHCCPQGYTC VAEGQCQRGS EIVAGLEKMP ARRASLSHPR DIGCDQHTSC PVGQTCCPSL GGSWACCQLP HAVCCEDRQH CCPAGYTCNV KARSCEKEVV SAQPATFLAR SPHVGVKDVE CGEGHFCHDN QTCCRDNRQG WACCPYRQGV CCADRRHCCP AGFRCAARGT KCLRREAPRW DAPLRDPALR QLL
Sequence and characterization of the bacteriophage T4 comC alpha gene product, a possible transcription antitermination factor.
MKRKIVQNCT NDEFEDVLFD PNLVVVQKEH TSKFTHLTSV YVYEKVGDKQ PIYGVFREIT EDGTTYWKEI Y