Gerard N P, Bao L, Xiao-Ping H, Eddy R L, Shows T B, Gerard C
Ina Sue Perlmutter Laboratory, Children's Hospital, Boston, Massachusetts.
Biochemistry. 1993 Feb 9;32(5):1243-50. doi: 10.1021/bi00056a007.
The human C5a anaphylatoxin and formyl peptide receptor genes, as well as two genes with high sequence identity to the formyl peptide receptor, FPRH1 and FPRH2, have been mapped to chromosome 19 (Lu et al., 1992). Further analysis reveals that these genes are present in the 19q13.3 band adjacent to the 13.3-13.4 interface. MRNAs for the C5a and formyl peptide receptors, as well as for FPRH1, are expressed in cAMP differentiated U937 cells and human eosinophils, while all four transcripts are expressed in human lung. This observation opens the possibility for coordinate regulation of these genes. In order to initiate the mapping of fine structure at this locus, genomic clones have been analyzed. All four of the genes have a similar structure, with the receptor protein encoded in a single exon. Detailed characterization of the C5a receptor gene reveals a two exon structure, with the 5' untranslated sequence and initiating methionine located in the first exon. An intron of approximately 9 kb separates exon 1 from the receptor-encoding exon 2. The region of genomic DNA flanking the 5' untranslated sequence possesses promoter activity when transfected into the myeloid-derived rat basophilic leukemia RBL-1 cells, but the same region is inactive when transfected into nonmyeloid cells. Deletional analyses indicate that C5a receptor 5' flanking region contains both cell-specific suppressor and promoter regions.
人C5a过敏毒素和甲酰肽受体基因，以及与甲酰肽受体具有高度序列同一性的两个基因FPRH1和FPRH2，已被定位于19号染色体（Lu等人，1992年）。进一步分析表明，这些基因位于19q13.3带，与13.3 - 13.4界面相邻。C5a和甲酰肽受体以及FPRH1的mRNA在cAMP分化的U937细胞和人嗜酸性粒细胞中表达，而所有四种转录本在人肺中均有表达。这一观察结果为这些基因的协同调控提供了可能性。为了开始对该位点的精细结构进行定位分析，已对基因组克隆进行了研究。所有这四个基因都具有相似的结构，受体蛋白由单个外显子编码。C5a受体基因的详细特征显示其具有两个外显子结构，5'非翻译序列和起始甲硫氨酸位于第一个外显子中。一个约9 kb的内含子将外显子1与编码受体的外显子2分隔开。当转染到髓系来源的大鼠嗜碱性白血病RBL - 1细胞中时，5'非翻译序列侧翼的基因组DNA区域具有启动子活性，但当转染到非髓系细胞中时，该区域无活性。缺失分析表明，C5a受体5'侧翼区域同时包含细胞特异性抑制区和启动区。
