Ceroid-lipofuscinosis neuronal protein 5
Function
Bis(monoacylglycero)phosphate synthase CLN5, secreted form
Catalyzes the synthesis of bis(monoacylglycero)phosphate (BMP) via transacylation of 2 molecules of lysophosphatidylglycerol (LPG) (PubMed:37708259). BMP also known as lysobisphosphatidic acid plays a key role in the formation of intraluminal vesicles and in maintaining intracellular cholesterol homeostasis (PubMed:37708259). Can use only LPG as the exclusive lysophospholipid acyl donor for base exchange and displays BMP synthase activity towards various LPGs (LPG 14:0, LPG 16:0, LPG 18:0, LPG 18:1) with a higher preference for longer chain lengths (PubMed:37708259). Plays a role in influencing the retrograde trafficking of lysosomal sorting receptors SORT1 and IGF2R from the endosomes to the trans-Golgi network by controlling the recruitment of retromer complex to the endosomal membrane (PubMed:22431521). Regulates the localization and activation of RAB7A which is required to recruit the retromer complex to the endosomal membrane (PubMed:22431521).
Exhibits palmitoyl protein thioesterase (S-depalmitoylation) activity in vitro and most likely plays a role in protein S-depalmitoylation.
Involvement in disease
Ceroid lipofuscinosis, neuronal, 5
CLN5
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 lipopigment patterns observed most often in neuronal ceroid lipofuscinosis type 5 comprise mixed combinations of granular, curvilinear, and fingerprint profiles.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
N-glycosylated with both high mannose and complex type sugars. Glycosylation is important for proper folding and trafficking to the lysosomes.
Bis(monoacylglycero)phosphate synthase CLN5
The type II membrane signal anchor is proteolytically cleaved to produce a mature form that is transported to the lysosomes (Bis(monoacylglycero)phosphate synthase CLN5, secreted form) (PubMed:20052765, PubMed:24038957, PubMed:28442266).
Can undergo proteolytic cleavage at the C-terminus, probably by a cysteine protease and may involve the removal of approximately 10-15 residues from the C-terminal end (PubMed:26342652).
Sequence Similarities
Belongs to the CLN5 family.
Tissue Specificity
Ubiquitous.
Cellular localization
- Bis(monoacylglycero)phosphate synthase CLN5, secreted form
- Lysosome
- Bis(monoacylglycero)phosphate synthase CLN5
- Membrane
- Single-pass type II membrane protein
- An amphipathic anchor region facilitates its association with the membrane.
Alternative names
BMPS, CLN5, Bis(monoacylglycero)phosphate synthase CLN5, BMP synthase CLN5, Ceroid-lipofuscinosis neuronal protein 5, Palmitoyl protein thioesterase CLN5, S-depalmitoylase CLN5, Protein CLN5