Sequence analysis of LRPPRC and its SEC1 domain interaction partners suggests roles in cytoskeletal organization, vesicular trafficking, nucleocytosolic shuttling, and chromosome activity.

LRPPRC (originally called LRP130) is an intracellular, 130-kD, leucine-rich protein that copurifies with the fibroblast growth factor receptor from liver cell extracts and has been detected in diverse multiprotein complexes from the cell membrane, cytoskeleton, and nucleus. Here we report results of a sequence homology analysis of LRPPRC and its SEC1 domain interactive partners. We found that 23 copies of tandem repeats that are similar to pentatricopeptide, tetratricopeptide, and huntingtin-elongation A subunit-TOR repeats characterize the LRPPRC sequence. The amino terminus exhibits multiple copies of leucine-rich nuclear transport signals followed by ENTH, DUF28, and SEC1 homology domains. We used the SEC1 domain to trap interactive partners expressed from a human liver cDNA library. Interactive C19ORF5 (XP_038600) exhibited a strong homology to microtubule-associated proteins and a potential arginine-rich mRNA binding motif. UXT (XP_033860) exhibited alpha-helical properties homologous to the actin-associated spectrin repeat and L/I heptad repeats in mobile transcription factors. C6ORF34 (XP_004305) was homologous to the non-DNA-binding carboxy terminus of the Escherichia coli Rob transcription factor. CECR2 (AAK15343) exhibited a transcription factor AT-hook motif next to two bromodomains and a homology to guanylatebinding protein-1. Together these features suggest a regulatory role of LRPPRC and its SEC1 domain-interactive partners in integration of cytoskeletal networks with vesicular trafficking, nucleocytosolic shuttling, transcription, chromosome remodeling, and cytokinesis.