THE D4 GENE FAMILY IN THE HUMAN GENOME

The d4 domain, a novel zinc finger-like structural motif, was first re vealed in the rat neuro-d4 protein. Here we demonstrate that the d4 do main is conserved in evolution and that three related genes form a d4 family in the human genome, The human neuro-d4 is very similar to rat neuro-d4 at both the amino acid and the nucleotide levels. Moreover, t he same splice variants have been detected among rat and human neuro-d 4 transcripts. This gene has been localized on chromosome is, and two other genes, members of the d4 family isolated by screening of the hum an genomic library at low stringency, have been mapped to chromosomes 11 and 14. The gene on chromosome 11 is the homolog of the ubiquitousl y expressed mouse gene ubi-d4/requiem, which is required for cell deat h after deprivation of trophic factors. A gene with a conserved d4 dom ain has been found in the genome of the nematode Caenorhabditis elegan s. The conservation of d4 proteins from nematodes to vertebrates sugge sts that they have a general importance, but a diversity of d4 protein s expressed in vertebrate nervous systems suggests that some family me mbers have special functions. (C) 1996 Academic Press, Inc.