MACF1-4 Background Information MACF1-4 (Microtubule-Actin cross-linking factor 1, isoform 4) is a 5,327 amino acid protein that is encoded by the human gene MACF1. MACF1-4 belongs to the plakin or cytolinker family and contains one Actin-binding domain, two CH (calponin-homology) domains, two EF-hand domains, nineteen plectin repeats and thirty-seven spectrin repeats. MACF1-4 is an F-Actin-binding protein which may play a role in cross-linking cytoskeletal proteins by binding intermediate filaments to the N-terminal plectin repeats and microtubules to the C-terminus. The spectrin repeats, an important feature found in many proteins involved in cytoskeletal structure, forms a three helix bundle with the second helix (with proline interrupts in some sequences). MACF1-4 is a cytoplasmic protein ex-pressed mainly in heart, lung, pituitary and placenta; however, it is not found in brain, kidney, liver, pancreas or skeletal muscle.