RALGDS is a 115 kDa protein which was identified by its
ability to enhance guanine nucleotide
exchange for the ras family member ral. It also
binds to activated ras and rap1, and appears to
function as part of a signalling complex in downstream events
following rap1 activation. Here we
report the identification of full-length cDNA clones for human RALGDS,
isolated from a brain
cDNA library. The predicted protein has strong sequence homology to rat
and murine isoforms of
RALGDS in the N- and C-terminal regions, but an internal region
(aa 250–380) shows relatively high
divergence with only 42% identical amino acid residues. The human RALGDS
gene is contained
within a 30 kb region of 9q34, approximately 200 kb proximal to the ABO
gene, within the current
critical region for the tuberous sclerosis gene TSC1. Partial genomic
structure was determined; it
consists of at least 11 exons. Based upon analysis of Southern blots from
110 TSC patients, genomic
DNA SSCP analysis, and RT-PCR analysis which demonstrated RNA expression
of both alleles in
patients from 9q34-linked TSC families using intragenic polymorphisms,
we conclude that RALGDS is not likely to be TSC1.