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FLASH GENE

Symbol

CLN3

contributors: mct/npt/pgu - updated : 25-10-2017

HGNC name	ceroid-lipofuscinosis, neuronal 3
HGNC id	2074

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001042432 15 - 1915 NP_001035897 47.6 438 - 2008 18688960 NM_000086 - - 1879 NP_000077 - 438 in normal brain, overexpressed in brains of patients with Batten disease 2006 16515873 also called CLN3L or variant 2

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)

cells

System Cell Pubmed Species Stage Rna symbol Endocrine islet cell (alpha,beta...) Nervous astrocyte Nervous neuron

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	expressed in the developing eye but is not required for its development

PROTEIN

PHYSICAL PROPERTIES		Hydrophobic
STRUCTURE

motifs/domains	five transmembrane domains
	several Alu repeats, phosphorylated on both serine and threonine residues
	four predicted N glycosylation sites
	a dileucine motif and a cluster of acidic amino acids in the second cytoplasmic domain are required for efficient lysosomal targeting
	a galactosylceramide binding domain that may be involved in its trafficking from Golgi to rafts via recycling endosomes

HOMOLOGY

interspecies

ortholog to yeast BTN1

Homologene

FAMILY

battenin family

CATEGORY

regulatory , transport

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,organelle,endosome
	intracellular,cytoplasm,organelle,lysosome
	intracellular,nucleus
text	integral transmembrane protein, localizing to membrane lipid rafts
	lysosomal protein trafficked in synapses through the ER-Golgi intermediary compartment ERGIC
	in lysosomes in non-neuronal cells and in endosomes in neuronal cells.
	localized in synaptosomes but not targetted to synaptic vesicles
	predominantly a lysosomal protein

basic FUNCTION	palmitoyl-protein Delta-9 desaturase, which converts membrane-associated palmitoylated proteins to their respective palmitoylated derivatives
	potentially protecting neurons from apoptosis mediated by ceramide
	chaperone involved in the folding/unfolding or assembly/disassembly of other proteins, regulating cell growth and apoptosis
	multimembrane-spanning protein involved in recycling of synaptic vesicles through the endosomal lysosome
	inhibitor of amyloid beta protein precursor and cathepsin
	a N terminus probably involved in protein-protein interactions and a C terminal required for movement from ER to Golgi and prenylation
	may have a role in regulating intracellular levels of arginine possibly through control of the transport of this amino acid into lysosomes
	playing a role in neuronal proteolipid trafficking and synaptic transmission
	negatively regulating cellular level of calsenilin, suppressing neuronal cell death mediated by calsenilin and dysregulation of intracellular Ca2+
	involved in the regulation of plasma membrane fodrin cytoskeleton and consequently, the plasma membrane association of Na(+), K(+) ATPase (ATP1B1)
	may traffic across the cells from the Golgi apparatus to plasma membranes via endosomes/lysosomes or synaptosomes in neuronal cells
	mediates several regulatory pathways by coupling the cell-cycle progression in G1 to physiological conditions, including nitrogen deprivation, daughter cell G1-delay and changes in glucose levels
	may be involved in the cellular response to stress
	specific role for CLN3 in the oxidative stress response, suggesting that a compromise of this response may be a fundamental defect leading to neurodegeneration in Batten disease

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

cellular trafficking transport

text	endocytic and exocytic neuronal transport processes

PATHWAY

metabolism

signaling

a component	constituent of integral lysosomal membrane protein battenin
	interacts with the plasma membrane-associated cytoskeletal and endocytic fodrin and the associated Na(+), K(+) ATPase (ATP1B1)
	may be a component of, or trafficked by, the vesicles from the perinuclear recycling compartment to the plasma membrane

INTERACTION

DNA

RNA

small molecule

protein	interacting with RAB proteins
	CLN5, CLN6, and CLN8 complement each otherwith respect to growth and apoptosis
	calsenilin-binding partner (KCNIP3)
	interacting with FLNA (CAV1-dependent target in IGF1-stimulated cancer cell migration)
	interaction with the mammalian HOOK1 protein suggests an interaction with cytoskeleton and a role in membrane trafficking, possibly by regulating vesicular transport and/or fusion
	interacting with Notch and Jun N-terminal kinase signalling pathways (potential role for the RNA splicing and localization machinery in regulating CLN3 function)
	interacts with cytoskeleton-associated nonmuscle myosin-IIB (MYH10)
	functional and physical interaction between CLN3 and myosin-IIB (MYH10)
	direct involvement of CLN3 in the regulation of CTSD activity

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

CLN3

related resource

Neuronal Ceroid Lipofuscinoses Neuronal Ceroid Lipofuscinoses

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   seems to cause neurodegeneration via a process that does not require apoptosis constitutional     --over   is sufficient to confer increased resistance to oxidative stress

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	Cln3 deficient mouse model
	canine model of juvenile Batten disease