THE GENE FOR THE HUMAN SRC-LIKE ADAPTER PROTEIN (HSLAP) IS LOCATED WITHIN THE 64-KB INTRON OF THE THYROGLOBULIN GENE

In this study, we describe the molecular cloning and characterization of a Src-like adaptor protein gene embedded within the genomic organiz ation of the human thyroglobulin (Tg) gene. This gene was identified b y exon trapping on overlapping cosmids encompassing the largest Tg int ron. A 2.6-kb transcript, with the highest levels of expression in fet al brain and lung, was detected on Northern blots. Two full-length cDN As tone alternatively spliced) were isolated from a fetal brain librar y, both containing an open reading frame of 276 amino acids, but lacki ng a catalytic tyrosine kinase domain. The gene shows a high degree of cross-species similarity and appears to be transcribed in the directi on opposite to Tg. This gene, designated hslap, appears to be the huma n ortholog of the recently described gene for the murine Src-like adap tor protein (mSLAP), a candidate intermediate in the signal-transducti on pathway of the Eck receptor tyrosine kinase. Human slap is located in the candidate region for a recessive demyelinating neuropathy on ch romosome 8q24, but sequence analysis failed to identify mutations, sug gesting that it is not the gene for this disease.