DNAJC5

Function

Acts as a general chaperone in regulated exocytosis (By similarity). Acts as a co-chaperone for the SNARE protein SNAP-25 (By similarity). Involved in the calcium-mediated control of a late stage of exocytosis (By similarity). May have an important role in presynaptic function. May be involved in calcium-dependent neurotransmitter release at nerve endings (By similarity).

Involvement in disease

Ceroid lipofuscinosis, neuronal, 4B (Kufs type), autosomal dominant

CLN4B

An adult-onset 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. CLN4B has no visual involvement and is characterized by seizures and other neurologic symptoms.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Ser-10 phosphorylation induces an order-to-disorder transition triggering the interaction with Lys-58 (PubMed:27452402). This conformational switch modulates DNAJC5's cellular functions by reducing binding to syntaxin and synaptogamin without altering HSC70 interactions (PubMed:27452402).

Palmitoylated. Could be palmitoylated by DHHC3, DHHC7, DHHC15 and DHHC17. Palmitoylation occurs probably in the cysteine-rich domain and regulates DNAJC5 membrane attachment.

Tissue Specificity

Expressed in pancreas, kidney, skeletal muscle, liver, lung, placenta, brain and heart.

Cellular localization

• Cytoplasm
• Cytosol
• Membrane
• Lipid-anchor
• Cytoplasmic vesicle
• Secretory vesicle
• Chromaffin granule membrane
• Melanosome
• Cell membrane
• The association with membranes is regulated by palmitoylation (By similarity). Identified by mass spectrometry in melanosome fractions from stage I to stage IV (PubMed:17081065).

Alternative names

CLN4, DNAJC5, DnaJ homolog subfamily C member 5, Ceroid-lipofuscinosis neuronal protein 4, Cysteine string protein, CSP

Database links

swissprot:Q9H3Z4 omim:611203 genbank:NM_033105 entrezGene:80331 swissprot:Q9UF47 entrezGene:85479