The domain within your query sequence starts at position 37 and ends at position 76; the E-value for the CLN3 domain shown below is 1.2e-17.



PFAM accession number:PF02487
Interpro abstract (IPR003492):

Batten's disease, the juvenile variant of neuronal ceroid lipofuscionosis (NCL), is a recessively inherited disorder affecting children of 5-10 years of age. The disease is characterised by progressive loss of vision, seizures and psychomotor disturbances. Biochemically, the disease is characterised by lysosomal accumulation of hydrophobic material, mainly ATP synthase subunit C, largely in the brain but also in other tissues. The disease is fatal within a decade [ (PUBMED:7553855) ].

Mutations in the CLN3 gene are believed to cause Batten's disease [ (PUBMED:7553855) ]. The CLN3 gene, with a predicted 438-residue product, maps to chromosome p16p12.1. The gene contains at least 15 exons spanning 15kb and is highly conserved in mammals [ (PUBMED:2142158) ]. A 1.02kb deletion in the CLN3 gene, occurring in either one or both alleles, is found in 85% of Batten disease chromosomes causing a frameshift generating a predicted translated product of 181 amino acid residues [ (PUBMED:7553855) (PUBMED:10191115) ]. 22 other mutations, including deletions, insertions and point mutations, have been reported. It has been suggested that such mutations result in severely truncated CLN3 proteins, or affect its structure/conformation [ (PUBMED:7553855) (PUBMED:9311735) ].

CLN3 proteins, which are believed to associate in complexes, are heavily glycosylated lysosomal membrane proteins [ (PUBMED:10191115) ], containing complex Asn-linked oligosaccharides [ (PUBMED:2142158) ]. Extensive glycosylation is important for the stability of these lysosomal proteins in the highly hydrolytic lysosomal lumen. Lysosomal sequestration of active lysosomal enzymes, transport of degraded molecules from the lysosomes, and fusion and fission between lysosomes and other organelles. The CLN3 protein is a 43kDa, highly hydrophobic, multi-transmembrane (TM), phosphorylated protein [ (PUBMED:10191115) ]. Hydrophobicity analysis predicts 6-9 TM segments, suggesting that CLN3 is a TM protein that may function as a chaperone or signal transducer. The majority of putative phosphorylation sites are found in the N-terminal domain, encompassing 150 residues [ (PUBMED:10191114) ]. Phosphorylation is believed to be important for membrane compartment interaction, in the formation of functional complexes, and in regulation and interactions with other proteins [ (PUBMED:1482112) ].

CLN3 contains several motifs that may undergo lipid post-translational modifications (PTMs). PTMs contribute to targeting and anchoring of modified proteins to distinct biological membranes [ (PUBMED:7716512) ]. There are three general classes of lipid modification: N-terminal myristoylation, C-terminal prenylation, and palmitoylation of cysteine residues. Such modifications are believed to be a common form of PTM occurring in 0.5% of all cellular proteins, including brain tissue [ (PUBMED:10191112) ]. The C terminus of the CLN3 contains various lipid modification sites: C435, target for prenylation; G419, target for myristoylation; and C414, target for palmitoylation [ (PUBMED:9384607) ]. Prenylation results in protein hydrophobicity, influences interaction with upstream regulatory proteins and downstream effectors, facilitates protein-protein interaction (multisubunit assembly) and promotes anchoring to membrane lipids. The prenylation motif, Cys-A-A-X, is highly conserved within CLN3 protein sequences of different species [ (PUBMED:10191112) ]. Species with known CLN3 protein homologues include: Homo sapiens, Canis familiaris, Mus musculus, Saccharomyces cerevisiae and Drosophila melanogaster.

GO component:membrane (GO:0016020)

This is a PFAM domain. For full annotation and more information, please see the PFAM entry CLN3