SLC5A7
Domain
The C-terminal dileucine-like motif (DKTILV) controls SLC5A7/CHT1 internalization in clathrin-coated vesicles to early endosomes as well as choline transporter activity.
Function
High-affinity Na(+)-coupled choline transmembrane symporter (PubMed:11027560, PubMed:11068039, PubMed:12237312, PubMed:12969261, PubMed:17005849, PubMed:23132865, PubMed:23141292, PubMed:27569547). Functions as an electrogenic, voltage-dependent transporter with variable charge/choline stoichiometry (PubMed:17005849). Choline uptake and choline-induced current is also Cl(-)-dependent where Cl(-) is likely a regulatory ion rather than cotransported ion (PubMed:11068039, PubMed:12237312, PubMed:17005849). Plays a critical role in acetylcholine (ACh) synthesis by taking up the substrate choline from the synaptic cleft into the presynaptic nerve terminals after neurotransmitter release (PubMed:27569547). SLC5A7/CHT1-mediated choline high-affinity transport in cholinergic neurons is the rate-limiting step for production of ACh, thereby facilitating communication by subsequent action potentials (PubMed:11027560). Localized predominantly in presynaptic terminal intracellular organelles, and translocated to the plasma membrane in active form in response to neuronal activity (PubMed:12969261, PubMed:15953352).
Involvement in disease
Neuronopathy, distal hereditary motor, autosomal dominant 7
HMND7
A form of distal hereditary motor neuronopathy, a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. HMND7 is characterized by onset in the second decade of progressive distal muscle wasting and weakness affecting the upper and lower limbs and resulting in walking difficulties and hand grip. There is significant muscle atrophy of the hands and lower limbs. The disorder is associated with vocal cord paresis due to involvement of the tenth cranial nerve.
None
The disease is caused by variants affecting the gene represented in this entry.
Myasthenic syndrome, congenital, 20, presynaptic
CMS20
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness. CMS20 is an autosomal recessive, pre-synaptic form characterized by severe hypotonia and episodic apnea soon after birth, generalized limb fatigability and weakness, delayed walking, ptosis, poor sucking and swallowing.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylated.
Sequence Similarities
Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.
Tissue Specificity
Expressed in putamen, spinal cord and medulla (PubMed:11027560, PubMed:11068039). Expressed in cholinergic neurons (PubMed:27569547).
Cellular localization
- Presynaptic cell membrane
- Multi-pass membrane protein
- Cell projection
- Axon
- Early endosome membrane
- Multi-pass membrane protein
- Cytoplasmic vesicle
- Secretory vesicle
- Synaptic vesicle membrane
- Multi-pass membrane protein
- Localized at the neuromuscular junction (PubMed:27569547). Localization at the plasma membrane is transient due to the rapid endocytosis of SLC5A7/CHT1 via the clathrin-mediated pathway, where it localizes to early endosomes (PubMed:12969261, PubMed:15953352). Also localized to synaptic vesicles where it is likely mobilized to the cell surface by exocytosis (PubMed:12969261).
Alternative names
CHT1, SLC5A7, High affinity choline transporter 1, hCHT1, Hemicholinium-3-sensitive choline transporter, Solute carrier family 5 member 7, CHT