Chromosomal mapping of the human (MACS) and mouse (Macs) genes encoding the MARCKS protein.

The myristoylated, alanine-rich C-kinase substrate, or MARCKS protein, is a major cellular substrate for protein kinase C that is also a high-affinity calmodulin-binding protein. In addition, it is the prototype of a small family of myristoylated, calmodulin-binding protein kinase C substrate proteins. We isolated a phage clone from a mouse genomic library that spanned the entire coding sequence of the mouse MARCKS protein. The first 612 bp of the putative promoter was 89% identical to a corresponding region of the human promoter, and contained at least 59 potential transcription factor binding sites in analogous locations; both human and mouse promoters lacked TATA boxes. The mouse genomic probe was used to localize the mouse gene to chromosome 10, in the middle of a linkage group that corresponds to a region on human chromosome 6q. These data strongly suggested that the human gene would localize to 6q21. This was confirmed by studies of DNA from a patient with del(6)(q21), in which expression of the human gene encoding MARCKS, MACS, was only about 50% of normal; MARCKS mRNA expression in lymphoblast RNA from this patient was only 22% of normal. These studies confirm that the mouse and human MARCKS proteins are products of the same genes in their respective species; differences in their primary sequence can therefore be attributed to species variation rather than to the existence of related genes.