ANKRD54 plays a crucial role in regulating intracellular signaling events, particularly those associated with erythroid terminal differentiation . This protein interacts with LYN, a member of the Src family of tyrosine kinases, through its ankyrin repeat region and the SH3-domain of LYN . This interaction is activation-independent, meaning it occurs regardless of LYN’s activation status . ANKRD54 forms a multiprotein complex with LYN and HCLS1, which is essential for its function in signaling pathways .
The ANKRD54 gene is a protein-coding gene, and its dysfunction has been associated with several diseases. Notably, it is linked to Machado-Joseph Disease and Autosomal Dominant Cerebellar Ataxia . Gene Ontology (GO) annotations related to ANKRD54 include protein-containing complex binding and protein kinase regulator activity . An important paralog of this gene is ANKRD61 .
Ankyrin repeats are highly conserved across different species, indicating their functional significance . These repeats are involved in maintaining the integrity of the cytoskeleton and cellular signaling . Ankyrins, including ANKRD54, are modular adaptor proteins that link integral membrane proteins to the spectrin cytoskeleton . This linkage is crucial for various cellular functions, including membrane transport, cellular adhesion, and maintenance of cytoskeleton structures .
Research on ANKRD54 and other ankyrin proteins has provided valuable insights into their roles in health and disease. For instance, studies have shown that ankyrins are involved in several diseases, such as hereditary spherocytosis, long QT syndrome, intellectual disability, and CRASH syndrome . Understanding the molecular mechanisms underlying these associations can lead to the development of targeted therapies and improved diagnostic tools.