Molecular characterization of TUB, TULP1, and TULP2, members of the novel tubby gene family and their possible relation to ocular diseases
Molecular characterization of TUB, TULP1, and TULP2, members of the novel tubby gene family and their possible relation to ocular diseases
复制标题
DOI：
10.1073/pnas.94.7.3128
复制
发表时间：
1997-04-01
影响因子：
11.1
通讯作者：
Nishina, PM
中科院分区：
文献类型：
--
作者：
North, MA;Naggert, JK;Nishina, PM
Tubby是一种常染色体隐性突变，定位于小鼠7号染色体，最近被发现是一个功能未知的新基因剪接缺陷的结果，数据库搜索显示对应于Tub蛋白C末端的序列在许多物种中高度保守，包括人、螨虫、线虫、拟南芥、水稻和玉米，该Tub是一个基因家族的成员，我们在这里描述了Tub，小鼠Tub的人类同源物，以及两个新发现的家族成员，TULP1代表Tubby样蛋白1和TULP2。这三个微弱的成员在蛋白质的N-末端半部分不同，在它们保守的C-末端区域有60%-90%的氨基酸同源性，并且有不同的组织表达模式。另一种具有5‘可变序列的剪接转录本，其中三个已被鉴定为Tubby基因，可能介导组织特异性表达，Wt还报道了Tub、TULP1和TULP2映射到人类染色体11p15.4。6p21.3和19q13.1。分别进行了分析。TULP1和TULP2在染色体6p21.3上的视网膜色素变性14和19q13.1上的视锥-杆状营养不良的最小间隔内定位。在视网膜中表达的TULP1和TULP2是这些眼部疾病的极佳候选基因，因为已知tub基因中的突变会导致早期进行性视网膜退化。
Tubby, an autosomal recessive mutation, mapping to mouse chromosome 7, was recently found to be the result of a splicing defect in a novel gene with unknown function, Database searches revealed that sequences corresponding to the C terminus of the tub protein were highly conserved across a number of species including humans, mite, Caenorhabditis elegans, Arabidopsis, rice, and maize, and that tub was a member of a gene family, We describe here, TUB, the human homolog of mouse tub, and two newly characterized family members, TULP1 for tubby like protein 1 and TULP2. These three faintly members, which differ in the N-terminal half of the protein, share 60-90% amino acid identity across their conserved C-terminal region and hale distinct tissue expression patterns. Alternatively spliced transcripts with 5' variable sequences, three of which have been identified for the tubby gene, may mediate tissue specific expression, Wt also report that TUB, TULP1, and TULP2 map to human chromosomes 11p15.4. 6p21.3, and 19q13.1. respectively. TULP1 and TULP2 map within the minimal intervals identified for retinitis pigmentosa 14 on chromosome 6p21.3 and cone-rod dystrophy on chromosome 19q13.1. TULP1 and TULP2, which are expressed in the retina, make excellent candidates for these ocular diseases as a mutation within the tub gene is known to lead to early progressive retinal degeneration.