Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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LCCL

SMART accession number:	SM00603
Description:
Interpro abstract (IPR004043):	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 [(PUBMED:10971586), (PUBMED:9806553)]. Secondary structure prediction suggests that the LCCL domain contains six beta strands and two alpha helices [(PUBMED:10971586)]. 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 [(PUBMED:10362728)].
Family alignment:	View or CHROMA formatCLUSTALW formatMSF formatFASTA formatPIR format

There are 323 LCCL domains in 187 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a LCCL domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with LCCL domain is also avaliable.

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  Go to specific node: Homo sapiens, Mus musculus, Rattus norvegicus, Takifugu rubripes

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Liepinsh E et al.
  • NMR structure of the LCCL domain and implications for DFNA9 deafnessdisorder.
  • EMBO J. 2001; 20: 5347-5353
  • Display abstract

  • The LCCL domain is a recently discovered, conserved protein module namedafter its presence in Limulus factor C, cochlear protein Coch-5b2 and lategestation lung protein Lgl1. The LCCL domain plays a key role in theautosomal dominant human deafness disorder DFNA9. Here we report thenuclear magnetic resonance (NMR) structure of the LCCL domain from humanCoch-5b2, where dominant mutations leading to DFNA9 deafness disorder havebeen identified. The fold is novel. Four of the five known DFNA9 mutationsare shown to involve at least partially solvent-exposed residues. Exceptfor the Trp91Arg mutant, expression of these four LCCL mutants resulted inmisfolded proteins. These results suggest that Trp91 participates in theinteraction with a binding partner. The unexpected sensitivity of the foldwith respect to mutations of solvent-accessible residues might beattributed to interference with the folding pathway of thisdisulfide-containing domain.

• Structure (3D structures containing this domain)

• 3D Structures of LCCL domains in PDB

  PDB code	Main view	Title
  1jbi		Nmr structure of the lccl domain

• Links (links to other resources describing this domain)

• INTERPRO	IPR004043

Send comments to Ivica Letunic