Identification and characterization of PF4var1, a human gene variant of platelet factor 4
- SRI International, Menlo Park, CA (USA)
- Wayne State Univ., Detroit, MI (USA). Dept. of Chemistry
A synthetic DNA probe designed to detect coding sequences for platelet factor 4 and connective tissue-activating peptide III (two human platelet {alpha}-granule proteins) was used to identify several similar sequences in total human DNA. Sequence analysis of a corresponding 3,201-base-pair EcoRI fragment isolated from a human genomic library demonstrated the existence of a variant of platelet factor 4, designated PF4var1. The gene for PF4var1 consisted of three exons and two introns. Exon 1 coded for a 34-amino-acid hydrophobic leader sequence that had 70% sequence homology with the leader sequence for PF4 but, in contrast, contained a hydrophilic amino-terminal region with four arginine residues. Exon 2 coded for a 42-amino-acid segment that was 100% identical with the corresponding segment of the mature PF4 sequence containing the amino-terminal and disulfide-bonded core regions. Exon 3 coded for the 28-residue carboxy-terminal region corresponding to a domain specifying heparin-binding and cellular chemotaxis. However, PF4var1 had amino acid differences at three positions in the lysine-rich carboxy-terminal end that were all conserved among human, bovine, and rat PF4s. These differences should significantly affect the secondary structure and heparin-binding properties of the protein based on considerations of the bovine PF4 crystal structure. By comparing the PF4var 1 genomic sequence with the known human cDNA and the rat genomic PF4-coding sequences, the authors identified potential genetic regulatory regions for PF4var1. Rat PF4 and human PF4var1 genes had identical 18-base sequences 5' to the promoter region. The intron positions appeared to correspond approximately to the boundaries of the protein functional domains.
- OSTI ID:
- 5516429
- Journal Information:
- Molecular and Cellular Biology; (USA), Journal Name: Molecular and Cellular Biology; (USA) Vol. 9:4; ISSN MCEBD; ISSN 0270-7306
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
AMINO ACID SEQUENCE
BIOLOGICAL MATERIALS
BIOLOGICAL VARIABILITY
BLOOD
BLOOD CELLS
BLOOD PLATELETS
BODY FLUIDS
DESIGN
DNA SEQUENCING
GENE REGULATION
GENETIC VARIABILITY
GROWTH FACTORS
MATERIALS
MITOGENS
MOLECULAR STRUCTURE
ORGANIC COMPOUNDS
PROBES
PROTEINS
STRUCTURAL CHEMICAL ANALYSIS