OBSCN
Description
The OBSCN (obscurin, cytoskeletal calmodulin and titin-interacting RhoGEF) is a protein-coding gene located on chromosome 1.
Obscurin is a protein encoded by the OBSCN gene in humans. It belongs to the family of giant sarcomeric signaling proteins that includes titin and nebulin. Obscurin is found in cardiac and skeletal muscle, playing a role in organizing myofibrils during sarcomere assembly. Mutations in the OBSCN gene have been linked to hypertrophic cardiomyopathy, and altered obscurin protein properties have been associated with other muscle diseases. Human obscurin may exist as multiple splice variants, with a molecular weight of approximately 720 kDa. However, the complete sequence of only one variant has been described to date. The OBSCN gene spans over 150 kb and comprises more than 80 exons. The encoded protein contains 68 Ig domains, 2 fibronectin domains, 1 IQ calmodulin-binding motif, 1 RhoGEF domain with an associated PH domain, and 2 serine-threonine kinase domains. In mature myofibrils, obscurin is primarily located at the sarcomeric M-band. Titin, obscurin, obscurin-like-1, and myomesin form a ternary complex at sarcomeric M-bands, which is crucial for sarcomere mechanics.
Obscurin is a structural component of striated muscles, playing a role in myofibrillogenesis, the process of assembling myofibrils. It is believed to be involved in the assembly of myosin into sarcomeric A bands in striated muscle. Obscurin possesses serine/threonine protein kinase activity and has been shown to phosphorylate N-cadherin (CDH2) and sodium/potassium-transporting ATPase subunit ATP1B1. It binds strongly to phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) via its PH domain, and exhibits weaker interactions with phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 4-phosphate (PtdIns(4)P), phosphatidylinositol 5-phosphate (PtdIns(5)P), and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3).
OBSCN is also known as ARHGEF30, RHABDO1, UNC89.
