基因的结构和功能比较人类血小板因子4和PF4alt。
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Eisman R,萨里,拉玛钱德朗B,施瓦茨E, Poncz M
基因的结构和功能比较人类血小板因子4和PF4alt。
血。1990年7月15日,76 (2):336 - 44。
- PubMed ID
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1695112 (在PubMed]
- 文摘
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血小板因子4 (PF4)是70氨基酸heparin-binding蛋白质释放的alpha-granules激活血小板。它的确切生物学功能尚不清楚,尽管PF4基因家族的成员参与趋化作用,凝固,炎症和细胞生长。我们以前从人类克隆人类PF4的互补erythroleukemic (HEL)细胞表达库。我们现在报告隔离和人类PF4基因的序列测定。这个基因包含三个外显子和横跨大约1000完全(bp)。同时,我们克隆出一个高度同源基因,称为PF4alt。我们表明,PF4 PF4alt non-allelic基因:人类PF4基因编码10 kilobasepairs EcoRI片段(kb),及其与蛋白质和DNA序列同意cDNA PF4的数据,虽然PF4alt编码在多态3或5 kb EcoRI片段。与PF4相比,这种基因有14%的DNA和信号肽氨基酸差异38%,4.3%和2.6%的DNA和氨基酸差异蛋白质编码区域的成熟。PF4alt包含三个氨基酸替换(P58——L, K66——E,和L67——H)糖基附近地区已知PF4的关键功能。引物的5 '非翻译区扩展研究显示PF4长73个基点。 A TATA box is present 30 bp 5' to the transcription start site. A 90 bp stretch of pyrimidines (including 53 consecutive thymidine residues) begins at -227 bp and is analogous to a similar region of 30 residues 5' to the rodent PF4 gene. This pyrimidine-rich region is absent from the PF4alt gene; however, DNA homology exists between the two human genes in the 5'- and 3'-flanking regions and extends for over 3.6 kb. Alternating purine/pyrimidine tracts occur both 5' and 3' to PF4 and PF4alt but do not define the endpoints of the gene duplication, which extend beyond these sequences at least at the 5' end. Northern blot analysis using gene-specific oligonucleotides and platelet RNA showed an 800 or 900 nucleotide (n) message for PF4 and PF4alt, respectively. Northern blot and primer extension studies show that steady-state platelet PF4 mRNA levels are approximately one magnitude greater than PF4alt mRNA levels. Thus, these studies demonstrate that PF4alt mRNA is expressed in platelets. Whether PF4alt protein is expressed remains to be determined, and the nature of its biologic function needs to be studied.(ABSTRACT TRUNCATED AT 400 WORDS)