The four-and-a-half-LIM domain (FHL) proteins include FHL-1 (SLIM1), FHL-2 (SLIM3), FHL-3 (SLIM2) and FHL-4. The signature "half-domain", a single zinc finger domain located in the N-terminal region, differentiates FHLs from other LIM-only proteins, which have numbers of zinc fingers. Specific combinations of FHL proteins elicit selective activation of both CREB and CREM. Skeletal and cardiac muscle express FHL-1 in high levels as compared to the low level of expression in smooth muscle of the colon, small intestine and prostate. FHL-1 localizes to the cytosol of myoblasts, myotubes, and differentiated myocytes. FHL-2 is also located in cardiac and skeletal muscle, as well as in placenta and ovary tissues. FHL-3 is found in skeletal muscle, but absent in cardiac muscle. FHL-4 is expressed exclusively by the seminiferous epithelium of the testis, which suggests that FHL-4 is involved in spermatogenesis. The genetic loci for FHLs vary considerably despite similiar amino acid sequences among the FHL group.
