We have recently reviewed the literature on the growing number of cytoplasmic autoantigens rich in α-helical coiled-coil domains as typified from our study of Golgi autoantigens [
41]. Golgi autoantigens are generally high molecular weight proteins between 100 and 350 kDa and rich in coiled-coil domains in the central region with non-coiled-coil or globular domains at both N and C termini. Golgi autoantigens are displayed on the cytoplasmic face of the Golgi complex and are not localized to apoptotic blebs during apoptosis [
42]. Giantin, the highest molecular weight Golgi autoantigen reported, is the predominant target of human anti-Golgi complex antibodies and multiple non-cross-reactive epitopes have been mapped spanning the 350 kDa protein [
43]. Other high molecular weight autoantigens with similar features have been reported in cytoplasmic and mitotic organelles suggesting that these selected proteins become autoimmunogenic based on their subcellular association and molecular features [
41]. For example, in the endosomal compartment, the two known autoantigens are early endosomal protein EEA1 (180 kDa) [
44] and CLIP-170 (170 kDa) [
45]. There is also a series of centrosomal autoantigens identified as coiled-coil-rich proteins including pericentrin, a 220 kDa protein [
46], ninein, a protein with alternatively spliced products of 245 and 249 kDa [
47], Cep250 (250 kDa) and Cep110 (110 kDa) [
48]. Centromere autoantigens have been described but the two interesting ones related to this discussion are CENP-E [
49] and CENP-F [
50]; both are high molecular weight proteins (312 to 400 kDa) and have the same type of overall structure as discussed above. NuMA is another large coiled-coil protein located at the mitotic spindle pole and is the most common target autoantigen in sera with mitotic spindle apparatus staining [
51]. Non-muscle myosin (~200 kDa) is a cytoskeletal autoantigen [
52] that falls in the same group of high molecular weight and coiled-coil-rich autoantigens. These endosomal, centrosomal, mitotic apparatus and intracellular autoantigens are, like the golgins, proteins with high molecular weights and an overall high content of coiled-coil domains. The combination of these two physical features in autoantigens may contribute to the induction and production of autoimmune antibodies in certain disease states. Kinectin is an integral membrane protein largely confined to the endoplasmic reticulum [
28,
31] and it fits into this new category of autoantigens that are large coiled-coil rich proteins (≥100 kDa) in the cytoplasm.