Jiang W M, Jenkins D, Yuan Q, Leung E, Choo K H, Watson J D, Krissansen G W
Department of Molecular Medicine, School of Medicine, University of Auckland, New Zealand.
Int Immunol. 1992 Sep;4(9):1031-40. doi: 10.1093/intimm/4.9.1031.
The integrin beta 7 subunit associates with two alternative alpha subunits termed alpha HML-1 and alpha 4 to give the lymphocyte activation and homing receptors HML-1 and LPAM-1. Overlapping genomic clones that encoded the human beta 7 subunit gene were isolated from cosmid and phage lambda libraries. The coding portion of the gene spanned approximately 10 kb and was composed of 14 exons. Exon 1 (123 bp) encoded 5' untranslated sequences; exon 2 (204 bp) encoded the initiation codon, signal peptide, and 50 amino acid residues of the N-terminus of the mature protein; 7 exons (exons 3-9), ranging in size from 90 bp to 242 bp, encoded most of the extracellular domain proximal to the four cysteine-rich repeats; the region corresponding to the beta 3 arginine-glycine-aspartic acid (RGD)-binding domain was divided amongst exons 4 and 5; the four cysteine-rich repeats were encoded by 3 exons (exons 10-12) with intron insertion into the first and third repeats; exon 13 (209 bp) provided a spacer between the cysteine-rich domains and the transmembrane domain; exon 14 (161 bp) encoded the transmembrane domain and exactly half of the cytoplasmic domain; the remainder of the cytoplasmic domain and most of the 3' untranslated region was contained in the largest 313 bp exon 15. Comparison of integrin beta subunit genes revealed that the gene organization of beta 7 was almost identical to that of beta 2, but had diverged from that of beta 3. Amplification of integrin DNAs directly from genomic DNA, using PCR primers based on beta subunit consensus sequences corresponding to the beta 3 RGD-binding domain, yielded partial gene sequences for the beta 3, beta 5, and beta 6 subunits only. Inspection of the amplified sequences revealed that, as for beta 3, the regions in beta 5 and beta 6 corresponding to the beta 3 RGD-binding domain lacked the intron present in beta 7, beta 1, and beta 2, which divides this region in beta 2 into two subdomains that contribute to subunit assembly. This study provides genetic evidence for at least two major branches to the integrin beta subunit evolutionary tree, with beta 7, beta 2, and probably beta 1 in one branch, and the cytoadhesin beta 3 and probably also beta 5 and beta 6 in the other.
整合素β7亚基与另外两个α亚基（分别称为αHML-1和α4）结合，形成淋巴细胞激活和归巢受体HML-1和LPAM-1。从黏粒文库和λ噬菌体文库中分离出了编码人β7亚基基因的重叠基因组克隆。该基因的编码部分跨度约为10 kb，由14个外显子组成。外显子1（123 bp）编码5'非翻译序列；外显子2（204 bp）编码起始密码子、信号肽以及成熟蛋白N端的50个氨基酸残基；7个外显子（外显子3 - 9），大小从90 bp到242 bp不等，编码靠近四个富含半胱氨酸重复序列的大部分细胞外结构域；对应于β3精氨酸 - 甘氨酸 - 天冬氨酸（RGD）结合结构域的区域分布在外显子4和5中；四个富含半胱氨酸的重复序列由3个外显子（外显子10 - 12）编码，内含子插入到第一个和第三个重复序列中；外显子13（209 bp）在富含半胱氨酸结构域和跨膜结构域之间提供一个间隔；外显子14（161 bp）编码跨膜结构域和细胞质结构域的正好一半；细胞质结构域的其余部分和大部分3'非翻译区域包含在最大的313 bp外显子15中。整合素β亚基基因的比较显示，β7的基因组织与β2几乎相同，但与β3的基因组织有所不同。使用基于与β3 RGD结合结构域相对应的β亚基共有序列的PCR引物，直接从基因组DNA中扩增整合素DNA，仅得到了β3、β5和β6亚基的部分基因序列。对扩增序列的检查发现，与β3一样，β5和β6中对应于β3 RGD结合结构域的区域缺少β7、β1和β2中存在的内含子，该内含子将β2中的这个区域分成两个有助于亚基组装的子结构域。这项研究为整合素β亚基进化树至少提供了两个主要分支的遗传学证据，其中一个分支包含β7、β2以及可能的β1，另一个分支包含细胞黏附素β3以及可能的β5和β6。
