Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00035024.xml
Download PDF
Thromb Haemost 1998; 79(02): 310-316
DOI: 10.1055/s-0037-1615006
DOI: 10.1055/s-0037-1615006
Scientific and Standardization Committee Communication
Nucleotide Structure and Characterization of the Murine Gene Encoding Anticoagulant Protein C
Further Information
Publication History
Received
02 July 1997
Accepted after revision
23 September 1997
Publication Date:
08 December 2017 (online)
Summary
The 15,160 bp murine gene encoding anticoagulation protein C (PC) was cloned and sequenced, including 414 bp upstream of exon 1 and 80 bp downstream of the translation stop codon. Nine exons and eight introns were identified. The first exon was untranslated and contained the major transcriptional start site, the surrounding nucleotide sequence of which matched reasonably well with the consensus eukaryotic Cap element sequence. The translational initiator methio-nine residue was located in exon 2. The other introns were positioned as splices between the major domain units of the protein. The 5’ untranslated region contained two possible CCAAT sequences and GC boxes, but no TATA box was obvious within the optimal range of distances from the transcription start site. The 3’-flanking nucleotides included a probable polyadenylation site (ATTAAA), beginning 80 nucleotides downstream of the translation stop codon, and a downstream consensus sequence (AGTGTTTC) required for the efficient formation of a 3’ terminus of mRNA. Several high probability transcription factor recognition sequences, including proteins that are enriched in, or specific to, the liver, such as C/EBP, C/EBP, HNF1, and HNF3, have been located in the 5’ region of the gene. These results indicate that all elements are present for liver-based transcription of the gene for murine PC.
-
References
- 1 Tanabe S, Sugo T, Matsuda M. Synthesis of protein C in human umbilical vein endothelial cells. J Biochem 1991; 109: 924-8.
- 2 He XH, Shen L, Bjartell A, Malm J, Lilja H, Dahlbäck B. The gene encod ing vitamin K-dependent anticoagulant protein C is expressed in human male reproductive tissues. J Histochem Cytochem 1995; 43: 563-70.
- 3 Foster DC, Davie EW. Characterization of a cDNA coding for human protein C. Proc Natl Acad Sci USA 1984; 81: 4766-70.
- 4 Foster DC, Yoshitake S, Davie EW. The nucleotide sequence of the gene for human protein C. Proc Natl Acad Sci USA 1985; 82: 4673-7.
- 5 Yoshitake S, Schach BG, Foster DC, Davie EW, Kurachi K. Nucleotide sequence of the gene for human factor IX (antihemophilic factor B). Biochemistry 1985; 24: 3736-50.
- 6 Leytus SP, Foster DC, Kurachi K, Davie EW. Gene for human factor X: A blood coagulation factor whose gene organization is essentially identical with that of factor IX and protein C. Biochemistry 1986; 25: 5098-102.
- 7 O’Hara PJ, Grant FJ, Haldeman BA, Gray CL, Insley MY, Hagen FS, Murray MJ. Nucleotide sequence of the gene coding for human factor VII, a vitamin K-dependent protein participating in blood coagulation. Proc Natl Acad Sci USA 1987; 84: 5158-62.
- 8 Kisiel W, Canfield WM, Ericsson LH, Davie EW. Anticoagulant properties of bovine plasma protein C following activation by thrombin. Biochemistry 1977; 16: 5824-31.
- 9 Amphlett GW, Kisiel W, Castellino FJ. Interaction of calcium with bovine plasma protein C. Biochemistry 1981; 20: 2156-61.
- 10 Stenflo J, Fernlund P. Amino acid sequence of the heavy chain of bovine protein C. J Biol Chem 1982; 257: 12180-90.
- 11 Vehar GA, Davie EW. Preparation and properties of bovine factor VIII (antihemophilic factor). Biochemistry 1980; 19: 401-10.
- 12 Taylor FB, Lockhart MS. A new function for activated protein C: Activated protein C prevents inhibition of plasminogen activators by releasate from mononuclear leukocytes-platelet suspensions stimulated by phorbol diester. Thromb Res 1985; 37: 639-49.
- 13 van Hinsberg VWM, Bertina RM, van Wijngaarden A, van Tilburg JH, Emeis JJ, Haverkate F. Activated protein C decreases plasminogen activator-inhibitor activity in endothelial cell-conditioned medium. Blood 1985; 65: 444-51.
- 14 Bajzar L, Morser J, Nesheim M. TAFI, or plasma procarboxypeptidase B, couples the coagulation and fibrinolytic cascades through the thrombinthrombomodulin complex. J Biol Chem 1996; 271: 16603-8.
- 15 Bajzar L, Kalafatis M, Simioni P, Tracy PB. An antifibrinolytic mechanism describing the prothrombotic effect associated with factor V-Leiden. J Biol Chem 1996; 271: 22949-52.
- 16 Seligsohn U, Berger A, Abend M, Rubin L, Attias D, Zivelin A, Rapoport SI. Homozygous protein C deficiency manifested by massive venous thrombosis in the newborn. New Engl J Med 1984; 310: 559-62.
- 17 Marlar RA, Montgomery RR, Broekmans AW. Diagnosis and treatment of homozygous protein C deficiency. Report of the Working Party on Homo-zygous Protein C Deficiency of the Subcommittee on Protein C and Protein S. International Committee on Thrombosis and Haemostasis. J Pediatr 1989; 114: 528-34.
- 18 Marlar RA, Adcock DM. Clinical evaluation of protein C: a comparative review of antigenic and functional assays. Hum Pathol 1989; 20: 1040-7.
- 19 Marlar RA, Neumann A. Neonatal purpura fulminans due to homozygous protein C or protein S deficiencies. Semin Thromb Hemost 1990; 16: 299-309.
- 20 Taylor FB, Chang A, Esmon CT, D’Angelo A, Vigano-D’Angelo S, Blick KE. Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon. J Clin Invest 1987; 79: 918-25.
- 21 Benton WD, Davis RW. Screening lgt recombinant clones by hybridization to single plaques in situ. Science 1977; 196: 180-2.
- 22 Quandt K, Frech K, Karas H, Wingender E, Werner T. MatInd and MatIn-spector: new fast versatile tools for detection of consensus matches in nucleotide sequence data. Nucl Acids Res 1995; 23: 4878-84.
- 23 Breathnach R, Chambon P. Organization and expression of eukaryotic split genes coding for proteins. Annu Rev Biochem 1981; 50: 349-83.
- 24 Tada N, Soto M, Tsujimura A, Iwase R, Hashimoto-Gotoh T. Isolation and characterization of a mouse protein C cDNA. J Biochem 1992; 111: 491-5.
- 25 Plutzky J, Hoskins JA, Long GL, Crabtree GR. Evolution and organization of the human protein C gene. Proc Natl Acad Sci USA 1986; 83: 546-50.
- 26 Miao CH, Ho WT, Greenberg DL, Davie EW. Transcriptional regulation of the gene coding for human protein C. J Biol Chem 1996; 271: 9587-94.
- 27 Ploos van Amstel HK, Reitsma PH, van der Logt CPE, Bertina RM. Intronexon organization of the active human protein S gene PS and its pseudo-gene PSß: Duplication and silencing during primate evlution. Biochemistry 1990; 29: 7853-61.
- 28 Bucher P. Weight matrix descriptions of four eukaryotic RNA polymerase II elements derived from 502 unrelated promoter sequences. J Mol Biol 1990; 212: 563-78.
- 29 Pollak ES, Hung HL, Godin W, Overton GC, High KA. Functional characterization of the human factor VII 5’-flanking region. J Biol Chem 1996; 271: 1738-47.
- 30 Huang N-M, Hung H-L, Stanfield-Oakley SA, High KA. Characterization of the human blood coagulation factor X promoter. J Biol Chem 1992; 267: 15440-8.
- 31 Hirosawa S, Fahner JB, Salier JP, Wu CT, Lovrien EW, Kurachi K. Structural and functional basis of the developmental regulation of human coagulation factor IX gene: factor IX Leyden. Proc Natl Acad Sci USA 1990; 87: 4421-5.
- 32 Bucher P, Trifonov EN. CCAAT box revisited: bidirectionality, location and context. J Biomol Struct Dyn 1988; 5: 1231-6.
- 33 Idusogie E, Rosen ED, Carmeliet P, Collen D, Castellino FJ. Nucleotide structure and characterization of the murine blood coagulation factor VII gene. Thromb Haemost 1996; 76: 957-64.
- 34 Miao CH, Leytus SP, Chung DW, Davie EW. Liver-specific expression of the gene coding for human factor X, a blood coagulation factor. J Biol Chem 1992; 267: 7395-401.
- 35 McLauchlan J, Gaffney D, Whitton JL, Clements JB. The consensus sequence YGTGTTYY located downstream from the AATAAA signal is required for efficient formation of mRNA 3U termini. Nucl Acids Res 1985; 13: 1347-68.
- 36 Greenberg D, Miao CH, Ho WT, Chung DW, Davie EW. Liver-specific expression of the human factor VII gene. Proc Natl Acad Sci USA 1995; 92: 12347-51.
- 37 Salier J-P, Hirosawa S, Kurachi K. Functional characterization of the 5’-regulatory region of human factor IX gene. J Biol Chem 1990; 265: 7062-8.
- 38 Hardon EM, Frain M, Paonessa G, Cortese R. Two distinct factors interact with the promoter regions of several liver-specific genes. EMBO J 1988; 7: 1711-9.
- 39 Crossley M, Brownlee GG. Disruption of a C/EBP binding site in the factor IX promoter is associated with hemophilia B. Nature 1990; 345: 444-6.
- 40 Spek CA, Greengard JS, Griffin JH, Bertina RM, Reitsma PH. Two mutations in the promoter region of the human protein C gene both cause type I protein C deficiency by disruption of two HNF-3 binding sites. J Biol Chem 1995; 270: 24216-21.
- 41 Arbini AA, Pollak ES, Bayleran JK, High KA, Bauer KA. Severe factor VII deficiency due to a mutation disrupting a hepatocyte nuclear factor 4 binding site in the factor VII promoter. Blood 1997; 89: 176-82.