MYPN

Myopalladin is a is_associated_with::protein that in humans is encoded by the MYPN is_associated_with::gene. Myopalladin is a muscle protein responsible for tethering proteins at the Z-disc and for communicating between the is_associated_with::sarcomere and the nucleus in cardiac and is_associated_with::skeletal muscle

Structure
Myopalladin is a 145.2 kDa protein composed of 1320 amino acids. Myopalladin has five Ig-like repeats within the protein, and a is_associated_with::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 is_associated_with::EF hand domains of alpha-actinin. The N-terminal region of myopalladin binds to the nuclear protein CARP, known to regulate is_associated_with::gene expression in muscle. It also has been shown to bind is_associated_with::ANKRD23.

Function
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. 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.

Clinical significance
Mutations in MYPN have been linked to is_associated_with::dilated cardiomyopathy, is_associated_with::hypertrophic cardiomyopathy and is_associated_with::restrictive cardiomyopathy.