TPM1

TPM1, or tropomyosin 1, is a gene in humans that encodes the alpha-tropomyosin protein, a member of the tropomyosin family that binds along actin filaments. Tropomyosins are coiled-coil dimers that align head-to-tail along actin, stabilizing filaments and regulating interactions with other actin-binding proteins. The TPM1 gene produces multiple isoforms through alternative splicing and promoter usage, with transcripts expressed in cardiac and skeletal muscle as well as in non-muscle cells.

Functionally, alpha-tropomyosin forms part of the thin filament in striated muscle and participates in the regulation of muscle contraction through the troponin-tropomyosin complex. By coating actin at regular intervals, TPM1-derived tropomyosin modulates the access of myosin to actin and influences filament stability in non-muscle cells as well. The canonical alpha isoform is typically about 284 amino acids in length, corresponding to roughly 31 kDa per monomer; dimers polymerize along actin filaments to cover multiple actin subunits.

Genetics and expression, TPM1 belongs to a conserved gene family with several tissue-specific isoforms arising from alternative splicing and promoter usage. These isoforms differ mainly at their N- and C-terminal regions, enabling distinct functional roles in muscle versus non-muscle cells.

Clinical significance, Mutations and variants in TPM1 have been associated with inherited cardiomyopathies, including hypertrophic and dilated cardiomyopathy, and may contribute to other sarcomeric or muscular phenotypes in some contexts. The precise impact of different TPM1 isoforms in disease is an area of ongoing research.

Research and notes, TPM1 is studied to understand how isoform diversity affects actin architecture, muscle mechanics, and cytoskeletal organization in non-muscle cells, as well as to elucidate its contribution to cardiomyopathic processes.