A testis-specific gene, TPTE, encodes a putative transmembrane tyrosine phosphatase and maps to the pericentromeric region of human chromosomes 21 and 13, and to chromosomes 15, 22, and Y
A testis-specific gene, TPTE, encodes a putative transmembrane tyrosine phosphatase and maps to the pericentromeric region of human chromosomes 21 and 13, and to chromosomes 15, 22, and Y
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DOI：
10.1007/s004390051122
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发表时间：
1999-11-01
期刊：
影响因子：
5.3
通讯作者：
Antonarakis, SE
中科院分区：
文献类型：
--
作者：
Chen, HM;Rossier, C;Antonarakis, SE
为了有助于创建人类21号染色体（HC 21）的转录图谱和鉴定可能参与唐氏综合征发病机制的基因，从覆盖整个染色体的HC 21特异性cosplay进行外显子捕获。到目前为止，已经确定了700多个外显子。一个这样的外显子hmc 01 a06，映射到YAC 831 B6，其包含标记D21 Z1（α重复），并且先前已定位于HC 21的着丝粒周围区域。Northern-blot分析显示，一个2.5 kb的mRNA物种强烈和专门在睾丸中表达。我们克隆了相应的全长cDNA，其编码预测的551个氨基酸的多肽，具有至少两个潜在的跨膜结构域和酪氨酸磷酸酶基序。该cDNA与鸡张力蛋白、牛生长素和大鼠细胞周期蛋白G相关激酶（GAK）具有同源性。整个多肽序列也与肿瘤抑制因子PTEN/MMAC 1蛋白具有显著的同源性。我们将这种新的基因/蛋白质称为TPTE（transmembrane phosphatase with tensin homology）。聚合酶链反应扩增、荧光原位杂交、Southern-blot和单染色体体细胞杂交的序列分析表明，该基因除了其HC 21拷贝或拷贝外，在HC 13、15、22和Y上具有高度同源拷贝。在单倍体人类基因组中，TPTE基因的估计最小拷贝数在男性中为7，在女性中为6。Zoo-blot分析表明，TPTE在人类和其他物种之间是保守的。TPTE基因的生物学功能目前尚不清楚;然而，其表达模式、序列同源性和潜在的酪氨酸磷酸酶结构域的存在表明其可能参与睾丸内分泌或精子发生功能的信号转导途径。也不知道TPTE的所有拷贝是否都是功能性的，或者是否有些是假基因。据我们所知，TPTE是最接近人类着丝粒序列的基因。
To contribute to the creation of a transcription map of human chromosome 21 (HC21) and to the identification of genes that may be involved in the pathogenesis of Down syndrome, exon trapping was performed from HC21-specific cosmids covering the entire chromosome. More than 700 exons have been identified to date. One such exon, hmc01a06, maps to YAC 831B6 which contains marker D21Z1 (alphoid repeats) and had previously been localized to the pericentromeric region of HC21. Northern-blot analysis revealed a 2.5-kb mRNA species strongly and exclusively expressed in the testis. We cloned the corresponding full-length cDNA, which encodes a predicted polypeptide of 551 amino acids with at least two potential transmembrane domains and a tyrosine phosphatase motif. The cDNA has sequence homology to chicken tensin, bovine auxilin and rat cyclin-G associated kinase (GAK). The entire polypeptide sequence also has significant homology to tumor suppressor PTEN/MMAC1 protein. We termed this novel gene/protein TPTE (transmembrane phosphatase with tensin homology). Polymerase chain reaction amplification, fluorescent in situ hybridization, Southern-blot and sequence analysis using monochromosomal somatic cell hybrids showed that this gene has highly homologous copies on HC13, 15, 22, and Y, in addition to its HC21 copy or copies. The estimated minimum number of copies of the TPTE gene in the haploid human genome is 7 in male and 6 in female. Zoo-blot analysis showed that TPTE is conserved between humans and other species. The biological function of the TPTE gene is presently unknown; however, its expression pattern, sequence homologies, and the presence of a potential tyrosine phosphatase domain suggest that it may be involved in signal transduction pathways of the endocrine or spermatogenetic function of the testis. It is also unknown whether all copies of TPTE are functional or whether some are pseudogenes. TPTE is, to our knowledge, the gene located closest to the human centromeric sequences.