P00750 A8K022 B2R8E8 Q15103 Q503B0 Q6PJA5 Q7Z7N2 Q86YK8 Q9BU99 Q9BZW1 TPA_HUMAN Tissue-type plasminogen activator t-PA t-plasminogen activator tPA Alteplase Reteplase Tissue-type plasminogen activator chain A Tissue-type plasminogen activator chain B PLAT Homo sapiens Human Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Primates Haplorrhini Catarrhini Hominidae Homo NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1) Melanoma NUCLEOTIDE SEQUENCE [GENOMIC DNA] NUCLEOTIDE SEQUENCE [GENOMIC DNA] NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1) NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1) NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1) Fetal lung NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2) Umbilical vein NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4) NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1) NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3) Testis NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1) NUCLEOTIDE SEQUENCE [GENOMIC DNA] VARIANTS ASP-34; SER-136; THR-146 AND TRP-164 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3) Brain Placenta Skin NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-36 NUCLEOTIDE SEQUENCE [MRNA] OF 31-562 PROTEIN SEQUENCE OF 33-52 AND 311-330 Melanoma PROTEIN SEQUENCE OF 36-562 Melanoma NUCLEOTIDE SEQUENCE [MRNA] OF 251-358 PARTIAL PROTEIN SEQUENCE SIGNAL SEQUENCE CLEAVAGE SITE STRUCTURE OF CARBOHYDRATES GLYCOSYLATION AT THR-96 DISULFIDE BONDS IN KRINGLE 2 INTERACTION WITH LRP1B SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S) STRUCTURE BY NMR OF KRINGLE 2 STRUCTURE BY NMR OF KRINGLE 2 STRUCTURE BY NMR OF KRINGLE 2 X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF KRINGLE 2 STRUCTURE BY NMR OF 38-85 STRUCTURE BY NMR OF 36-126 X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF CATALYTIC DOMAIN X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF CATALYTIC DOMAIN 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. Secreted Extracellular space P00750-1 1 Long P00750-2 2 Short May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. P00750-3 3 No experimental confirmation available. P00750-4 4 Neonatal No experimental confirmation available. 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. Belongs to the peptidase S1 family. Contains 1 EGF-like domain. Contains 1 fibronectin type-I domain. Contains 2 kringle domains. Contains 1 peptidase S1 domain. Tissue plasminogen activator entry The Singapore human mutation and polymorphism database Clinical information on Activase Clinical information on Retavase 3D-structure Alternative splicing Cleavage on pair of basic residues Complete proteome Direct protein sequencing Disulfide bond EGF-like domain Glycoprotein Hydrolase Kringle Pharmaceutical Plasminogen activation Polymorphism Protease Repeat Secreted Serine protease Signal Zymogen MDAMKRGLCCVLLLCGAVFVSPSQEIHARFRRGARSYQVI MAS VICRDEKTQMIYQQHQSWLRPVLRSNRVEYCWCNSGRAQCHSVPVKS G NPDGDAKPWCHVLKNRRLTWEYC TGRSVSSPATASMRPCPLSIRSG A D R S A T R W N T KP NA K N N S RR EE V C MDAMKRGLCCVLLLCGAVFVSPSQEIHARFRRGARSYQVICRDEKTQMIYQQHQSWLRPV LRSNRVEYCWCNSGRAQCHSVPVKSCSEPRCFNGGTCQQALYFSDFVCQCPEGFAGKCCE IDTRATCYEDQGISYRGTWSTAESGAECTNWNSSALAQKPYSGRRPDAIRLGLGNHNYCR NPDRDSKPWCYVFKAGKYSSEFCSTPACSEGNSDCYFGNGSAYRGTHSLTESGASCLPWN SMILIGKVYTAQNPSAQALGLGKHNYCRNPDGDAKPWCHVLKNRRLTWEYCDVPSCSTCG LRQYSQPQFRIKGGLFADIASHPWQAAIFAKHRRSPGERFLCGGILISSCWILSAAHCFQ ERFPPHHLTVILGRTYRVVPGEEEQKFEVEKYIVHKEFDDDTYDNDIALLQLKSDSSRCA QESSVVRTVCLPPADLQLPDWTECELSGYGKHEALSPFYSERLKEAHVRLYPSSRCTSQH LLNRTVTDNMLCAGDTRSGGPQANLHDACQGDSGGPLVCLNDGRMTLVGIISWGLGCGQK DVPGVYTKVTNYLDWIRDNMRP P56540 CBBQ_CHRVI Protein CbbQ cbbQ Chromatium vinosum Allochromatium vinosum Bacteria Proteobacteria Gammaproteobacteria Chromatiales Chromatiaceae Allochromatium NUCLEOTIDE SEQUENCE [GENOMIC DNA] IDENTIFICATION May affect the post-translational activation and/or assembly of the oligomeric structure of RuBisCO. Belongs to the CbbQ/NirQ/NorQ/GpvN family. ATP-binding Nucleotide-binding MSDIDRNQFLIDHEPYYRPVSNEVALYEAAYAARMPVMLKGPTGCGKTRFVEYMAWKLGK PLITVACNEDMTAS Q51858 CBBQ_PSEHY Protein CbbQ cbbQ Pseudomonas hydrogenothermophila Bacteria Proteobacteria Betaproteobacteria Hydrogenophilales Hydrogenophilaceae Hydrogenophilus NUCLEOTIDE SEQUENCE [GENOMIC DNA] TH-1 May affect the post-translational activation and/or assembly of the oligomeric structure of RuBisCO. Belongs to the CbbQ/NirQ/NorQ/GpvN family. ATP-binding Nucleotide-binding MDLRNQYLVRSEPYYHAVGDEIERFEAAYANRIPMMLKGPTGCGKSRFVEYMAWKLGKPL ITVACNEDMTAADLVGRFLLDKEGTRWQDGPLTTAARIGAICYLDEVVEARQDTTVVIHP LTDHRRILPLDKKGEVVEAHPDFQIVISYNPGYQSAMKDLKTSTKQRFAAMDFDYPAPEV ESEIVAHESGVDAATAKKLVEVAIRSRHLKGHGLDEGISTRLLVYAGSLITKGIAPLIAC EMALICPITDDPDLRYALRAAAQTLFA Q51481 NIRQ_PSEAE Denitrification regulatory protein nirQ nirQ PA0520 Pseudomonas aeruginosa Bacteria Proteobacteria Gammaproteobacteria Pseudomonadales Pseudomonadaceae Pseudomonas NUCLEOTIDE SEQUENCE [GENOMIC DNA] PAO1161 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228 Activator of nitrite and nitric oxide reductases. Cytoplasm Under denitrifying conditions. Belongs to the CbbQ/NirQ/NorQ/GpvN family. ATP-binding Activator Complete proteome Cytoplasm DNA-binding Nucleotide-binding Transcription Transcription regulation MRDATPFYEATGHEIEVFERAWRHGLPVLLKGPTGCGKTRFVQYMARRLELPLYSVACHD DLGAADLLGRHLIGADGTWWQDGPLTRAVREGGICYLDEVVEARQDTTVAIHPLADDRRE LYLERTGETLQAPPSFMLVVSYNPGYQNLLKGLKPSTRQRFVALRFDYPAAQQEARILVG ESGCAETLAQRLVQLGQALRRLEQHDLEEVASTRLLIFAARLIGDGMDPREACRVALAEP LSDDPATVAALMDIVDLHVA Q8NE62 Q9NY17 CHDH_HUMAN Choline dehydrogenase, mitochondrial CDH CHD CHDH Homo sapiens Human Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Primates Haplorrhini Catarrhini Hominidae Homo NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] VARIANT ARG-78 Testis NUCLEOTIDE SEQUENCE [MRNA] OF 113-594 Kidney Choline + acceptor = betaine aldehyde + reduced acceptor. FAD (By similarity). Amine and polyamine biosynthesis; betaine biosynthesis via choline pathway; betaine aldehyde from choline (cytochrome c reductase route): step 1/1. Mitochondrion Belongs to the GMC oxidoreductase family. Acetylation Complete proteome FAD Flavoprotein Mitochondrion Oxidoreductase Polymorphism Transit peptide E A L R N S R A MWCLLRGLGRPGALARGALGQQQSLGARALASAGSESRDEYSYVVVGAGSAGCVLAGRLT EDPAERVLLLEAGPKDVLAGSKRLSWKIHMPAALVANLCDDRYNWCYHTEVQRGLDGRVL YWPRGRVWGGSSSLNAMVYVRGHAEDYERWQRQGARGWDYAHCLPYFRKAQGHELGASRY RGADGPLRVSRGKTNHPLHCAFLEATQQAGYPLTEDMNGFQQEGFGWMDMTIHEGKRWSA ACAYLHPALSRTNLKAEAETLVSRVLFEGTRAVGVEYVKNGQSHRAYASKEVILSGGAIN SPQLLMLSGIGNADDLKKLGIPVVCHLPGVGQNLQDHLEIYIQQACTRPITLHSAQKPLR KVCIGLEWLWKFTGEGATAHLETGGFIRSQPGVPHPDIQFHFLPSQVIDHGRVPTQQEAY QVHVGPMRGTSVGWLKLRSANPQDHPVIQPNYLSTETDIEDFRLCVKLTREIFAQEALAP FRGKELQPGSHIQSDKEIDAFVRAKADSAYHPSCTCKMGQPSDPTAVVDPQTRVLGVENL RVVDASIMPSMVSGNLNAPTIMIAEKAADIIKGQPALWDKDVPVYKPRTLATQR P00981 Q91351 IVBKI_DENPO Dendrotoxin-K DTX-K Venom basic protease inhibitor K Dendroaspis polylepis polylepis Black mamba Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Lepidosauria Squamata Scleroglossa Serpentes Colubroidea Elapidae Elapinae Dendroaspis NUCLEOTIDE SEQUENCE [MRNA] PROTEIN SEQUENCE OF 23-39 PROTEIN SEQUENCE OF 23-79 Venom STRUCTURE BY NMR OF 23-79 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. Secreted Expressed by the venom gland. LD(50) is 30 mg/kg by intravenous injection. Contains 1 BPTI/Kunitz inhibitor domain. 3D-structure Direct protein sequencing Disulfide bond Ionic channel inhibitor Neurotoxin Potassium channel inhibitor Protease inhibitor Secreted Serine protease inhibitor Signal Toxin SGHLLLLLGLLTLWAELTPVSGAAKYCKLPLRIGPCKRKIPSFYYKWKAKQCLPFDYSGC GGNANRFKTIEECRRTCVG P28799 P23781 P23782 P23783 P23784 Q53Y88 Q540U8 Q9BWE7 Q9UCH0 GRN_HUMAN Granulins Proepithelin PEPI Acrogranin Paragranulin Granulin-1 Granulin G Granulin-2 Granulin F Granulin-3 Granulin B Granulin-4 Granulin A Granulin-5 Granulin C Granulin-6 Granulin D Granulin-7 Granulin E GRN Homo sapiens Human Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Primates Haplorrhini Catarrhini Hominidae Homo NUCLEOTIDE SEQUENCE [MRNA] SEQUENCE REVISION NUCLEOTIDE SEQUENCE [MRNA] Kidney NUCLEOTIDE SEQUENCE [MRNA] PARTIAL PROTEIN SEQUENCE Bone marrow NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1) NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] Brain NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2) NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2) Cervix Lung PROTEIN SEQUENCE OF 206-233; 281-336; 364-396 AND 442-447 Leukocyte PROTEIN SEQUENCE OF 281-295 GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-265 MASS SPECTROMETRY Liver STRUCTURE BY NMR OF 284-311 INVOLVEMENT IN UP-FTD VARIANT UP-FTD ASP-9 CHARACTERIZATION OF VARIANT UP-FTD ASP-9 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. Secreted P28799-1 1 P28799-2 2 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. Granulins are disulfide bridged. 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. Belongs to the granulin family. 3D-structure Alternative splicing Complete proteome Cytokine Direct protein sequencing Disulfide bond Glycoprotein Polymorphism Repeat Secreted Signal A D G A S H C S W H Q G MWTLVSWVALTAGLVAGTRCPDGQFCPVACCLDPGGASYSCCRPLLDKWPTTLSRHLGGP CQVDAHCSAGHSCIFTVSGTSSCCPFPEAVACGDGHHCCPRGFHCSADGRSCFQRSGNNS VGAIQCPDSQFECPDFSTCCVMVDGSWGCCPMPQASCCEDRVHCCPHGAFCDLVHTRCIT PTGTHPLAKKLPAQRTNRAVALSSSVMCPDARSRCPDGSTCCELPSGKYGCCPMPNATCC SDHLHCCPQDTVCDLIQSKCLSKENATTDLLTKLPAHTVGDVKCDMEVSCPDGYTCCRLQ SGAWGCCPFTQAVCCEDHIHCCPAGFTCDTQKGTCEQGPHQVPWMEKAPAHLSLPDPQAL KRDVPCDNVSSCPSSDTCCQLTSGEWGCCPIPEAVCCSDHQHCCPQGYTCVAEGQCQRGS EIVAGLEKMPARRASLSHPRDIGCDQHTSCPVGQTCCPSLGGSWACCQLPHAVCCEDRQH CCPAGYTCNVKARSCEKEVVSAQPATFLARSPHVGVKDVECGEGHFCHDNQTCCRDNRQG WACCPYRQGVCCADRRHCCPAGFRCAARGTKCLRREAPRWDAPLRDPALRQLL Q01436 CEF_BPT4 Protein cef cef mb Enterobacteria phage T4 Bacteriophage T4 Viruses dsDNA viruses, no RNA stage Caudovirales Myoviridae T4-like viruses Escherichia coli Bacteria Proteobacteria Gammaproteobacteria Enterobacteriales Enterobacteriaceae Escherichia NUCLEOTIDE SEQUENCE [GENOMIC DNA] NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] Virus reference strain MKRKIVQNCTNDEFEDVLFDPNLVVVQKEHTSKFTHLTSVYVYEKVGDKQPIYGVFREIT EDGTTYWKEIY Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms Distributed under the Creative Commons Attribution-NoDerivs License