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.
Blackshear
P J
PJ
Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Tuttle
J S
JS
Oakey
R J
RJ
Seldin
M F
MF
Chery
M
M
Philippe
C
C
Stumpo
D J
DJ
D000818:Animals; D001287:Attachment Sites, Microbiological; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D003001:Cloning, Molecular; D008040:Genetic Linkage; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009115:Muridae; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D011401:Promoter Regions, Genetic / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051076:Proto-Oncogene Proteins c-fyn; D020598:Proto-Oncogene Proteins c-myb; D019908:Proto-Oncogene Proteins c-raf; D017385:Sequence Homology
D047908:Intracellular Signaling Peptides and Proteins; C000619710:MARCKS protein, human; C000619711:Marcks protein, mouse; D008565:Membrane Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; C494957:FYN protein, human; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D019908:Proto-Oncogene Proteins c-raf