The cwf21 domain is involved in mRNA splicing; it binds directly to the spliceosomal protein Prp8. Mutations in the cwf21 domain prevents its binding to Prp8. The domain is composed of two alpha helices. Proteins containing the cwf21 domain include complexed with CEF1 protein 21 (CWC21) from budding yeast, complexed with cdc5 protein 21 (CWF21) from fission yeast, as well as their orthologs, serine/arginine repetitive matrix proteins (SRRM2 and SRRM3) from vertebrates. This domain family also includes U2-associated protein SR140 from Eumetazoa, protein RRC1, and similar proteins from plants.