Leucine-rich repeats and calponin homology domain-containing protein 3 (LRCH3)

Leucine-rich repeats and calponin homology domain-containing protein 3 (LRCH3) is a protein expressed in humans and belongs to a family of proteins characterized by an N-terminal leucine-rich repeat (LRR) domain and a C-terminal calponin homology (CH) domain[1][5]. The LRR domain, often implicated in protein-protein interactions, typically consists of ten LRRs in LRCH3 and is thought to facilitate diverse scaffolding roles. The CH domain, a single type found at the C-terminus, is usually involved in cytoskeletal regulation, although the direct actin-binding function for LRCH3 remains uncertain[1]. Functionally, LRCH3 is implicated in the regulation of cytoskeletal organization, particularly in mediating the association of septins with actin and thus modulating the actin cytoskeleton[5]. It acts as a part of a protein complex known as DISP, with scaffold and potential regulatory roles in cell division and cytoskeletal dynamics. Knockdown studies in HeLa cells demonstrate that LRCH3 is essential for proper chromosome segregation and mitotic progression[1]. In immune cells, the broader LRCH family regulates immune responses, cell migration, and proliferation, with LRCH3 binding to key proteins like DOCK7 (a guanine nucleotide exchange factor), myosin-6, and actin-stabilizing septin proteins[1]. LRCH3 has no known direct link to specific diseases, though it is associated with familial hypertrophic cardiomyopathy and may have as-yet-unclear roles in immunity and possibly aging, supported by bioinformatics and gene association data[5][3]. No drugs or inhibitors currently target LRCH3, and it is not considered a therapeutic target at this time. To summarize, LRCH3 is a structurally and functionally conserved cytoskeletal regulator and scaffold protein, essential for the coordination of cell division and possibly immune cell activity[1][5]. Its biological and pathophysiological relevance is still under investigation.

Other names

DISP complex protein LRCH3MGC4126LRCH3