CLN3
Domain
The C-terminal (153-438) mediates KCNIP3 interaction and the cytoprotective activity (PubMed:17189291). the dileucine motif mediates AP1G1 and AP3D1 interaction (PubMed:15598649).
Function
Mediates microtubule-dependent, anterograde transport connecting the Golgi network, endosomes, autophagosomes, lysosomes and plasma membrane, and participates in several cellular processes such as regulation of lysosomal pH, lysosome protein degradation, receptor-mediated endocytosis, autophagy, transport of proteins and lipids from the TGN, apoptosis and synaptic transmission (PubMed:10924275, PubMed:15471887, PubMed:18317235, PubMed:18817525, PubMed:20850431, PubMed:22261744). Facilitates the proteins transport from trans-Golgi network (TGN)-to other membrane compartments such as transport of microdomain-associated proteins to the plasma membrane, IGF2R transport to the lysosome where it regulates the CTSD release leading to regulation of CTSD maturation and thereby APP intracellular processing (PubMed:10924275, PubMed:18817525). Moreover regulates CTSD activity in response to osmotic stress (PubMed:23840424, PubMed:28390177). Also binds galactosylceramide and transports it from the trans Golgi to the rafts, which may have immediate and downstream effects on cell survival by modulating ceramide synthesis (PubMed:18317235). At the plasma membrane, regulates actin-dependent events including filopodia formation, cell migration, and pinocytosis through ARF1-CDC42 pathway and also the cytoskeleton organization through interaction with MYH10 and fodrin leading to the regulation of the plasma membrane association of Na+, K+ ATPase complex (PubMed:20850431). Regulates synaptic transmission in the amygdala, hippocampus, and cerebellum through regulation of synaptic vesicles density and their proximity to active zones leading to modulation of short-term plasticity and age-dependent anxious behavior, learning and memory (By similarity). Regulates autophagic vacuoles (AVs) maturation by modulating the trafficking between endocytic and autophagolysosomal/lysosomal compartments, which involves vesicle fusion leading to regulation of degradation process (By similarity). Participates also in cellular homeostasis of compounds such as, water, ions, amino acids, proteins and lipids in several tissue namely in brain and kidney through regulation of their transport and synthesis (PubMed:17482562).
Involvement in disease
Ceroid lipofuscinosis, neuronal, 3
CLN3
A form of neuronal ceroid lipofuscinosis. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. The hallmark of CLN3 is the ultrastructural pattern of lipopigment with a fingerprint profile, which can have 3 different appearances: pure within a lysosomal residual body; in conjunction with curvilinear or rectilinear profiles; and as a small component within large membrane-bound lysosomal vacuoles. The combination of fingerprint profiles within lysosomal vacuoles is a regular feature of blood lymphocytes from patients with neuronal ceroid lipofuscinosis type 3.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Highly glycosylated.
Farnesylation is important for trafficking to lysosomes.
Phosphorylated on both serine and threonine residues by PKA, PKG and CK2.
Sequence Similarities
Belongs to the battenin family.
Tissue Specificity
Expressed in the cortical brain, pancreas, spleen, and testis with weaker expression in the peripheral nerve (at protein level). Highly expressed in gray matter (at protein level).
Cellular localization
- Lysosome membrane
- Multi-pass membrane protein
- Late endosome
- Lysosome
- Golgi apparatus
- Golgi apparatus membrane
- Golgi apparatus
- Golgi stack
- Golgi apparatus
- trans-Golgi network
- Cell membrane
- Recycling endosome
- Membrane raft
- Membrane
- Caveola
- Early endosome membrane
- Synapse
- Synaptosome
- Late endosome membrane
- Cytoplasmic vesicle
- Autophagosome
- CLN3 is not present in late endosomes/lysosomes in fibroblasts and neurons (PubMed:15240864). Trafficks from cell membrane to Golgi via endosomes (PubMed:15240864). Osmotic stress changes the subcellular localization of CLN3 (PubMed:23840424). Trafficks to intracellular compartments via the plasma membranet through AP3M1-dependent mechanisms (PubMed:14644441). Excluded from the synaptic vesicles (By similarity).
Alternative names
BTS, CLN3, Battenin, Batten disease protein, Protein CLN3