Myopalladin

Myopalladin is a 145.2 kDa protein composed of 1320 amino acids.^[8][9] Myopalladin has five Ig-like repeats within the protein, and a proline-rich domain. Myopalladin binds the Src homology domain of nebulette and nebulin and tethers it to alpha-actinin via its C-terminal domain binding to the EF hand domains of alpha-actinin. The N-terminal region of myopalladin binds to the nuclear protein CARP, known to regulate gene expression in muscle.^[5] It also has been shown to bind ANKRD23.^[10]

Myopalladin has dual subcellular localization, residing in both the nucleus and sarcomere/I-bands in muscle. Accordingly, myopalladin has functions in both sarcomere assembly and in control of gene expression.^[5] Specifics of these functions were gleaned from studies involving MYPN mutants associated with various cardiomyopathies. The Q529X myopalladin mutant demonstrated incompetence in recruiting key binding partners such as desmin, alpha-actinin and CARP to the Z-disc during myofibrilogenesis. In contrast, the Y20C mutant resulted in decreased expression of binding partners.^[11]

Mutations in MYPN have been linked to nemaline myopathy, dilated cardiomyopathy, hypertrophic cardiomyopathy and restrictive cardiomyopathy.^{[11][12] [13]}