Gunn Teresa M, Azarani Arezou, Kim Philip H, Hyman Richard W, Davis Ronald W, Barsh Gregory S
Department of Pediatrics, and the Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA.
BMC Genet. 2002;3:2. doi: 10.1186/1471-2156-3-2. Epub 2002 Feb 13.
The metalloprotease-disintegrin family, or ADAM, proteins, are implicated in cell-cell interactions, cell fusion, and cell signaling, and are widely distributed among metazoan phyla. Orthologous relationships have been defined for a few ADAM proteins including ADAM10 (Kuzbanian), and ADAM17 (TACE), but evolutionary relationships are not clear for the majority of family members. Human ADAM33 refers to a testis cDNA clone that does not contain a complete open reading frame, but portions of the predicted protein are similar to Xenopus laevis ADAM13.
In a 48 kb region of mouse DNA adjacent to the Attractin gene on mouse chromosome 2, we identified sequences very similar to human ADAM33. A full-length mouse cDNA was identified by a combination of gene prediction programs and RT-PCR, and the probable full-length human cDNA was identified by comparison to human genomic sequence in the homologous region on chromosome 20p13. Mouse ADAM33 is 44% identical to Xenopus laevis ADAM13, however a phylogenetic alignment and consideration of functional domains suggests that the two genes are not orthologous. Mouse Adam33 is widely expressed, most highly in the adult brain, heart, kidney, lung and testis.
While mouse ADAM33 is similar to Xenopus ADAM13 in sequence, further examination of its embryonic expression pattern, catalytic activity and protein interactions will be required to assess the functional relationship between these two proteins. Adam33 is expressed in the mouse adult brain and could play a role in complex processes that require cell-cell communication.
金属蛋白酶-解整合素家族，即ADAM蛋白，参与细胞间相互作用、细胞融合及细胞信号传导，广泛分布于后生动物门。已确定了包括ADAM10（库兹班尼亚蛋白）和ADAM17（肿瘤坏死因子-α转换酶）在内的一些ADAM蛋白的直系同源关系，但大多数家族成员的进化关系尚不清楚。人类ADAM33指的是一个睾丸cDNA克隆，它不包含完整的开放阅读框，但预测蛋白的部分区域与非洲爪蟾的ADAM13相似。
在小鼠2号染色体上与吸引素基因相邻的48 kb区域的小鼠DNA中，我们鉴定出与人类ADAM33非常相似的序列。通过基因预测程序和逆转录-聚合酶链反应相结合的方法鉴定出了全长小鼠cDNA，并通过与20号染色体p13同源区域的人类基因组序列进行比较，鉴定出了可能的全长人类cDNA。小鼠ADAM33与非洲爪蟾ADAM13的同源性为44%，然而系统发育比对和功能域分析表明这两个基因并非直系同源。小鼠Adam33广泛表达，在成年脑、心脏、肾脏、肺和睾丸中表达量最高。
虽然小鼠ADAM33在序列上与非洲爪蟾ADAM13相似，但需要进一步研究其胚胎表达模式、催化活性和蛋白质相互作用，以评估这两种蛋白质之间的功能关系。Adam33在小鼠成年脑中表达，可能在需要细胞间通讯的复杂过程中发挥作用。
