Organization of the human /alpha//sub 2/-plasmin inhibitor gene
The authors have isolated overlapping phage genomic clones covering an area of 26 kilobases that encodes the human /alpha//sub 2/-plasmin inhibitor. The /alpha//sub 2/-plasmin inhibitor gene contains 10 exons and 9 introns distributed over /approx/16 kilobases of DNA. To our knowledge, the number of introns is the highest yet reported for a member of the serine protease inhibitor (serpin) superfamily. All introns are located in the 5'-half of the corresponding mRNA. The 5'-untranslated region and the leader sequence are interrupted by 3 introns totaling /approx/6 kilobases. A TATA box sequence is located 17 nucleotides upstream from the proposed transcription initiation site. Multiple GC box sequences, G+C-rich sequences, and CCAAT box-like sequence, the hepatitis B virus enhancer element-like sequence and the human immunodeficiency virus enhancer-like sequence appear in the 5'-flanking region. The NH/sub 2/-terminal region, which implements factor XIII-catalyzed cross-linking of /alpha//sub 2/-plasmin inhibitor to fibrin, is encoded by the 4th exon. The reactive site and plasminogen-binding site, both located in the COOH-terminal region, are encoded by the 10th exon. When similar amino acids of /alpha//sub 2/-plasmin inhibitor and other members of the serpin gene superfamily are aligned, the position of the 7th intron of the /alpha//sub 2/-plasmin inhibitor gene aligns precisely with that of the second intron of the genes for rat angiotensinogen and human /alpha//sub 1/-antitrypsin genes and is misaligned by only one nucleotide with that of the third intron of antithrombin III, suggesting that the /alpha//sub 2/-plasmin inhibitor gene originates from the common ancestor of these serine protease inhibitors.
- Research Organization:
- Tokyo Medical and Dental Univ. (Japan)
- OSTI ID:
- 5822121
- Journal Information:
- Proc. Natl. Acad. Sci. USA; (United States), Journal Name: Proc. Natl. Acad. Sci. USA; (United States) Vol. 85:18; ISSN PNASA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
AMINO ACID SEQUENCE
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CLONING
DAYS LIVING RADIOISOTOPES
DNA
DNA HYBRIDIZATION
DNA SEQUENCING
DNA-CLONING
DRUGS
ENZYME INHIBITORS
ENZYMES
FIBRINOLYSIN
FIBRINOLYTIC AGENTS
GENES
GENETIC MAPPING
HEMATOLOGIC AGENTS
HYBRIDIZATION
HYDROLASES
ISOTOPES
LIGHT NUCLEI
MAPPING
MESSENGER-RNA
MOLECULAR STRUCTURE
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PEPTIDE HYDROLASES
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
RADIOISOTOPES
RECOMBINANT DNA
RNA
SERINE PROTEINASES
STRUCTURAL CHEMICAL ANALYSIS