MOLECULAR-CLONING OF THE HUMAN HOMOLOG OF A STRIATUM-ENRICHED PHOSPHATASE (STEP) GENE AND CHROMOSOMAL MAPPING OF THE HUMAN AND MURINE LOCI

A gene for a protein tyrosine phosphatase (PTPase) was isolated from a human fetal brain cDNA library by PCR amplification. Sequence analysi s revealed that the PTPase has a single phosphatase catalytic domain l ocated 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 putativ e Src homology domain 3 (SH3) binding moths. Comparison of the PTPase with a previously cloned striatum enriched phosphatase (STEP) from rat and from mouse exhibited a high degree of identity (similar to 85-90% ) at both the nucleotide and the amino acid levels, indicating that th e human PTPase is the homolog of the rat and murine STEP gene. By usin g a combination of somatic cell hybrid analysis and fluorescence in si tu hybridization, we have mapped the human STEP locus to chromosome 11 p15.2-p15.1 and the murine STEP gene to chromosome 7B3-B5. These are t wo regions of known conserved synteny, providing further evidence that the human STEP is a true homolog of the murine STEP gene. Candidate d isease genes in the vicinity include Usher syndrome type 1C in human a nd a mouse mutant locus, twister (twt). (C) 1995 Academic Press, Inc.