InterPro domain: IPR036609

The LCCL domain has been named after the best characterised proteins that were found to contain it, namely Limulus factor C, Coch-5b2 and Lgl1. It is an about 100 amino acids domain whose C-terminal part contains a highly conserved histidine in a conserved motif YxxxSxxCxAAVHxGVI. The LCCL module is thought to be an autonomously folding domain that has been used for the construction of various modular proteins through exon-shuffling. It has been found in various metazoan proteins in association with complement B-type domains, C-type lectin domains, von Willebrand type A domains, CUB domains, discoidin lectin domains or CAP domains. It has been proposed that the LCCL domain could be involved in lipopolysaccharide (LPS) binding [ 1 , 2 ]. Secondary structure prediction suggests that the LCCL domain contains six beta strands and two alpha helices [ 3 ]. The structure of the LCCL domain from human Coch-5b2 has been solved. It has an unusual fold, where a centrally located helix is wrapped by extended polypeptide segments of mostly irregular secondary structure [ 3 ].

Some proteins known to contain a LCCL domain include Limulus factor C, a LPS endotoxin-sensitive trypsin type serine protease which serves to protect the organism from bacterial infection; vertebrate cochlear protein cochlin or coch-5b2 (Cochlin is probably a secreted protein, mutations affecting the LCCL domain of coch-5b2 cause the deafness disorder DFNA9 in humans); and mammalian late gestation lung protein Lgl1, contains two tandem copies of the LCCL domain [ 4 ].

1. The LCCL module. Eur. J. Biochem. 267, 5751-7
2. Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction. Nat. Genet. 20, 299-303
3. NMR structure of the LCCL domain and implications for DFNA9 deafness disorder. EMBO J. 20, 5347-53
4. A novel developmentally regulated gene in lung mesenchyme: homology to a tumor-derived trypsin inhibitor. Am. J. Physiol. 276, L1027-36