Li X, Luna J, Lombroso P J, Francke U
Howard Hughes Medical Institute, Stanford University Medical Center, California 94305, USA.
Genomics. 1995 Aug 10;28(3):442-9. doi: 10.1006/geno.1995.1173.
A gene for a protein tyrosine phosphatase (PTPase) was isolated from a human fetal brain cDNA library by PCR amplification. Sequence analysis revealed that the PTPase has a single phosphatase catalytic domain located at the C-terminus that includes the highly conserved amino acid domain [I/V]HCXAGXXR[S/T]GX[F/Y] found in all tyrosine phosphatases. Two proline-rich regions located at the N-terminus may contain putative Src homology domain 3 (SH3) binding motifs. Comparison of the PTPase with a previously cloned striatum enriched phosphatase (STEP) from rat and from mouse exhibited a high degree of identity (approximately 85-90%) at both the nucleotide and the amino acid levels, indicating that the human PTPase is the homolog of the rat and murine STEP gene. By using a combination of somatic cell hybrid analysis and fluorescence in situ hybridization, we have mapped the human STEP locus to chromosome 11p15.2-p15.1 and the murine STEP gene to chromosome 7B3-B5. These are two regions of known conserved synteny, providing further evidence that the human STEP is a true homolog of the murine STEP gene. Candidate disease genes in the vicinity include Usher syndrome type 1C in human and a mouse mutant locus, twister (twt).
通过聚合酶链反应（PCR）扩增，从人胎儿脑cDNA文库中分离出一种蛋白质酪氨酸磷酸酶（PTPase）基因。序列分析表明，该PTPase在C末端有一个单一的磷酸酶催化结构域，其中包括在所有酪氨酸磷酸酶中都存在的高度保守的氨基酸结构域[I/V]HCXAGXXR[S/T]GX[F/Y]。位于N末端的两个富含脯氨酸的区域可能包含假定的Src同源结构域3（SH3）结合基序。将该PTPase与先前从大鼠和小鼠克隆的纹状体富集磷酸酶（STEP）进行比较，发现在核苷酸和氨基酸水平上都有高度的同一性（约85-90%），这表明人PTPase是大鼠和小鼠STEP基因的同源物。通过体细胞杂交分析和荧光原位杂交相结合的方法，我们已将人STEP基因座定位于染色体11p15.2-p15.1，将小鼠STEP基因定位于染色体7B3-B5。这是两个已知的保守同线性区域，进一步证明人STEP是小鼠STEP基因的真正同源物。附近的候选疾病基因包括人类的1C型Usher综合征和一个小鼠突变基因座twister（twt）。
