HACS1 encodes a novel SM-SAM adaptor protein differentially expressed in normal and malignant hematopoietic cells

SH3 and SAM domains are protein interaction motifs that are predominantly s een in signaling molecules, adaptors, and scaffold proteins. We have identi fied a novel family of putative adaptor genes that includes HACS1. HACS1 en codes a 441 amino acid protein that is differentially expressed in hematopo ietic cells and has restricted expression in human tissues. Its SH3 domain is most similar to the same motif in Crk and its SAM domain shares homology with a family of uncharacterized putative scaffold and adaptor proteins. H ACS1 maps to human chromosome 21q11.2 in a region that is frequently disrup ted by translocation events in hematopoietic malignancies. Polyclonal antib odies against HACS1 recognized a 49.5 kDa protein whose mRNA is expressed i n human immune tissues, bone marrow, heart, lung, placenta and brain. Cell lines and primary cells from acute myeloid leukemias and multiple myeloma p atients express HACS1. Immunostaining and cellular fractionation studies lo calized the HACS1 protein predominantly to the cytoplasm.