SLC5A7 (CHT1) is a high-affinity, sodium-dependent choline transporter that replenishes the cytosolic choline used by choline acetyltransferase in cholinergic neurons. Uptake is electrogenic and chloride dependent. The protein cycles between the presynaptic plasma membrane, early endosomes and synaptic vesicles; the intracellular pool regulates availability of active transporter at the cell surface. Human variants that impair choline uptake cause motor-neuron disease or congenital myasthenic syndrome with episodic apnea. Choline transport, rather than acetylcholine transport or acetylation, is its immediate molecular activity.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005307 choline:sodium symporter activity | EXP PMID:11027560 Molecular cloning of a human, hemicholinium-3-sensitive chol... | ACCEPT | Summary: CHT1 directly couples choline uptake to sodium-dependent transport. Reason: Human cDNA expression and uptake assays establish the reaction, while voltage clamp distinguishes electrogenic uptake from a fixed charge-to-substrate stoichiometry. The original uptake, variant and topology studies reinforce this same activity. Chloride dependence is real, but the older ion-substitution study interpreted chloride as regulatory; no fixed chloride cotransport ratio is asserted. Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0005307 choline:sodium symporter activity | EXP PMID:12969261 The hemicholinium-3 sensitive high affinity choline transpor... | ACCEPT | Summary: CHT1 directly couples choline uptake to sodium-dependent transport. Reason: Human cDNA expression and uptake assays establish the reaction, while voltage clamp distinguishes electrogenic uptake from a fixed charge-to-substrate stoichiometry. The original uptake, variant and topology studies reinforce this same activity. Chloride dependence is real, but the older ion-substitution study interpreted chloride as regulatory; no fixed chloride cotransport ratio is asserted. Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0005307 choline:sodium symporter activity | EXP PMID:23132865 Transmembrane topology and oligomeric structure of the high-... | ACCEPT | Summary: CHT1 directly couples choline uptake to sodium-dependent transport. Reason: Human cDNA expression and uptake assays establish the reaction, while voltage clamp distinguishes electrogenic uptake from a fixed charge-to-substrate stoichiometry. The original uptake, variant and topology studies reinforce this same activity. Chloride dependence is real, but the older ion-substitution study interpreted chloride as regulatory; no fixed chloride cotransport ratio is asserted. Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0005307 choline:sodium symporter activity | EXP PMID:23141292 Defective presynaptic choline transport underlies hereditary... | ACCEPT | Summary: CHT1 directly couples choline uptake to sodium-dependent transport. Reason: Human cDNA expression and uptake assays establish the reaction, while voltage clamp distinguishes electrogenic uptake from a fixed charge-to-substrate stoichiometry. The original uptake, variant and topology studies reinforce this same activity. Chloride dependence is real, but the older ion-substitution study interpreted chloride as regulatory; no fixed chloride cotransport ratio is asserted. Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0005307 choline:sodium symporter activity | EXP PMID:27569547 Impaired Presynaptic High-Affinity Choline Transporter Cause... | ACCEPT | Summary: CHT1 directly couples choline uptake to sodium-dependent transport. Reason: Human cDNA expression and uptake assays establish the reaction, while voltage clamp distinguishes electrogenic uptake from a fixed charge-to-substrate stoichiometry. The original uptake, variant and topology studies reinforce this same activity. Chloride dependence is real, but the older ion-substitution study interpreted chloride as regulatory; no fixed chloride cotransport ratio is asserted. Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0005307 choline:sodium symporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: CHT1 directly couples choline uptake to sodium-dependent transport. Reason: Human cDNA expression and uptake assays establish the reaction, while voltage clamp distinguishes electrogenic uptake from a fixed charge-to-substrate stoichiometry. The original uptake, variant and topology studies reinforce this same activity. Chloride dependence is real, but the older ion-substitution study interpreted chloride as regulatory; no fixed chloride cotransport ratio is asserted. Original ancestral source: PANTHER:PTN002913658. Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0005307 choline:sodium symporter activity | IDA PMID:11068039 Functional characterization of the human high-affinity choli... | ACCEPT | Summary: CHT1 directly couples choline uptake to sodium-dependent transport. Reason: Human cDNA expression and uptake assays establish the reaction, while voltage clamp distinguishes electrogenic uptake from a fixed charge-to-substrate stoichiometry. The original uptake, variant and topology studies reinforce this same activity. Chloride dependence is real, but the older ion-substitution study interpreted chloride as regulatory; no fixed chloride cotransport ratio is asserted. Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0005307 choline:sodium symporter activity | IDA PMID:17005849 Na+, Cl-, and pH dependence of the human choline transporter... | ACCEPT | Summary: CHT1 directly couples choline uptake to sodium-dependent transport. Reason: Human cDNA expression and uptake assays establish the reaction, while voltage clamp distinguishes electrogenic uptake from a fixed charge-to-substrate stoichiometry. The original uptake, variant and topology studies reinforce this same activity. Chloride dependence is real, but the older ion-substitution study interpreted chloride as regulatory; no fixed chloride cotransport ratio is asserted. Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0005307 choline:sodium symporter activity | IEA GO_REF:0000117 | ACCEPT | Summary: CHT1 directly couples choline uptake to sodium-dependent transport. Reason: Human cDNA expression and uptake assays establish the reaction, while voltage clamp distinguishes electrogenic uptake from a fixed charge-to-substrate stoichiometry. The original uptake, variant and topology studies reinforce this same activity. Chloride dependence is real, but the older ion-substitution study interpreted chloride as regulatory; no fixed chloride cotransport ratio is asserted. Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0005307 choline:sodium symporter activity | IMP PMID:12237312 Single nucleotide polymorphism of the human high affinity ch... | ACCEPT | Summary: CHT1 directly couples choline uptake to sodium-dependent transport. Reason: Human cDNA expression and uptake assays establish the reaction, while voltage clamp distinguishes electrogenic uptake from a fixed charge-to-substrate stoichiometry. The original uptake, variant and topology studies reinforce this same activity. Chloride dependence is real, but the older ion-substitution study interpreted chloride as regulatory; no fixed chloride cotransport ratio is asserted. Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: CHT1 has an active plasma-membrane pool. Reason: The human transporter produces cell-surface uptake, and human mutant imaging plus native neuromuscular-junction staining independently supports the surface pool. Constitutive internalization does not negate plasma-membrane localization. Reactome transport reactions refer to this uptake step rather than an intracellular-vesicle transport mechanism. Original ancestral source: PANTHER:PTN002913658. Supporting Evidence: PMID:27569547 We observed CHT membrane immunolabeling for the five investigated missense mutations file:human/SLC5A7/SLC5A7-uniprot.txt Localization at the plasma membrane is transient due CC to the rapid endocytosis of SLC5A7/CHT1 via the clathrin-mediated CC pathway |
| GO:0005886 plasma membrane | IDA PMID:12237312 Single nucleotide polymorphism of the human high affinity ch... | ACCEPT | Summary: CHT1 has an active plasma-membrane pool. Reason: The human transporter produces cell-surface uptake, and human mutant imaging plus native neuromuscular-junction staining independently supports the surface pool. Constitutive internalization does not negate plasma-membrane localization. Reactome transport reactions refer to this uptake step rather than an intracellular-vesicle transport mechanism. Supporting Evidence: PMID:27569547 We observed CHT membrane immunolabeling for the five investigated missense mutations file:human/SLC5A7/SLC5A7-uniprot.txt Localization at the plasma membrane is transient due CC to the rapid endocytosis of SLC5A7/CHT1 via the clathrin-mediated CC pathway |
| GO:0005886 plasma membrane | IEA GO_REF:0000107 | ACCEPT | Summary: CHT1 has an active plasma-membrane pool. Reason: The human transporter produces cell-surface uptake, and human mutant imaging plus native neuromuscular-junction staining independently supports the surface pool. Constitutive internalization does not negate plasma-membrane localization. Reactome transport reactions refer to this uptake step rather than an intracellular-vesicle transport mechanism. Supporting Evidence: PMID:27569547 We observed CHT membrane immunolabeling for the five investigated missense mutations file:human/SLC5A7/SLC5A7-uniprot.txt Localization at the plasma membrane is transient due CC to the rapid endocytosis of SLC5A7/CHT1 via the clathrin-mediated CC pathway |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-429594 | ACCEPT | Summary: CHT1 has an active plasma-membrane pool. Reason: The human transporter produces cell-surface uptake, and human mutant imaging plus native neuromuscular-junction staining independently supports the surface pool. Constitutive internalization does not negate plasma-membrane localization. Reactome transport reactions refer to this uptake step rather than an intracellular-vesicle transport mechanism. Supporting Evidence: PMID:27569547 We observed CHT membrane immunolabeling for the five investigated missense mutations file:human/SLC5A7/SLC5A7-uniprot.txt Localization at the plasma membrane is transient due CC to the rapid endocytosis of SLC5A7/CHT1 via the clathrin-mediated CC pathway |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5658483 | ACCEPT | Summary: CHT1 has an active plasma-membrane pool. Reason: The human transporter produces cell-surface uptake, and human mutant imaging plus native neuromuscular-junction staining independently supports the surface pool. Constitutive internalization does not negate plasma-membrane localization. Reactome transport reactions refer to this uptake step rather than an intracellular-vesicle transport mechanism. Supporting Evidence: PMID:27569547 We observed CHT membrane immunolabeling for the five investigated missense mutations file:human/SLC5A7/SLC5A7-uniprot.txt Localization at the plasma membrane is transient due CC to the rapid endocytosis of SLC5A7/CHT1 via the clathrin-mediated CC pathway |
| GO:0006836 neurotransmitter transport | TAS Reactome:R-HSA-264642 | MARK AS OVER ANNOTATED | Summary: The release-cycle pathway includes choline uptake, but CHT1 does not thereby transport acetylcholine. Reason: Reactome R-HSA-264642 includes synthesis, loading and release as well as precursor uptake. CHT1 performs choline uptake for resynthesis; the cited pathway membership does not itself establish movement of the acetylcholine transmitter specified by this cycle. Retain the actual choline-transport and cholinergic-transmission claims. This is a scope problem in the broad process projection, not evidence that the transporter lacks its established physiological contribution. Supporting Evidence: Reactome:R-HSA-264642 PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0007271 synaptic transmission, cholinergic | IBA GO_REF:0000033 | ACCEPT | Summary: Choline replenishment is a performed step in cholinergic synaptic transmission. Reason: SLC5A7 transports the precursor into presynaptic terminals for repeated acetylcholine synthesis. Human congenital myasthenic physiology is paired with direct mutant uptake measurements, so participation is grounded in a transport step and not solely a loss-of-function phenotype. Neuromuscular transmission is one demonstrated context of this conserved cholinergic role. Original ancestral source: PANTHER:PTN002913667. Supporting Evidence: PMID:27569547 Specific CHT-mediated choline uptake was severely impaired for all mutants tested PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0007274 neuromuscular synaptic transmission | IBA GO_REF:0000033 | ACCEPT | Summary: Choline replenishment is a performed step in cholinergic synaptic transmission. Reason: SLC5A7 transports the precursor into presynaptic terminals for repeated acetylcholine synthesis. Human congenital myasthenic physiology is paired with direct mutant uptake measurements, so participation is grounded in a transport step and not solely a loss-of-function phenotype. Neuromuscular transmission is one demonstrated context of this conserved cholinergic role. Original ancestral source: PANTHER:PTN002913667. Supporting Evidence: PMID:27569547 Specific CHT-mediated choline uptake was severely impaired for all mutants tested PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0008292 acetylcholine biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: CHT1 supplies choline through the uptake step of acetylcholine biosynthesis. Reason: The transporter itself performs substrate delivery into the presynaptic biosynthetic compartment. This established upstream transport contribution supports involvement in the multistep biosynthetic process even though CHAT, rather than CHT1, catalyses acetyl transfer. The original human expression studies and neuromuscular disease experiments corroborate the role. Original ancestral source: PANTHER:PTN000929655. Supporting Evidence: PMID:11068039 Na(+)-dependent, high-affinity choline uptake in cholinergic neurons is the rate-limiting step in acetylcholine synthesis. |
| GO:0008292 acetylcholine biosynthetic process | IDA PMID:11027560 Molecular cloning of a human, hemicholinium-3-sensitive chol... | ACCEPT | Summary: CHT1 supplies choline through the uptake step of acetylcholine biosynthesis. Reason: The transporter itself performs substrate delivery into the presynaptic biosynthetic compartment. This established upstream transport contribution supports involvement in the multistep biosynthetic process even though CHAT, rather than CHT1, catalyses acetyl transfer. The original human expression studies and neuromuscular disease experiments corroborate the role. Supporting Evidence: PMID:11068039 Na(+)-dependent, high-affinity choline uptake in cholinergic neurons is the rate-limiting step in acetylcholine synthesis. |
| GO:0008292 acetylcholine biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: CHT1 supplies choline through the uptake step of acetylcholine biosynthesis. Reason: The transporter itself performs substrate delivery into the presynaptic biosynthetic compartment. This established upstream transport contribution supports involvement in the multistep biosynthetic process even though CHAT, rather than CHT1, catalyses acetyl transfer. The original human expression studies and neuromuscular disease experiments corroborate the role. Supporting Evidence: PMID:11068039 Na(+)-dependent, high-affinity choline uptake in cholinergic neurons is the rate-limiting step in acetylcholine synthesis. |
| GO:0008292 acetylcholine biosynthetic process | IMP PMID:11068039 Functional characterization of the human high-affinity choli... | ACCEPT | Summary: CHT1 supplies choline through the uptake step of acetylcholine biosynthesis. Reason: The transporter itself performs substrate delivery into the presynaptic biosynthetic compartment. This established upstream transport contribution supports involvement in the multistep biosynthetic process even though CHAT, rather than CHT1, catalyses acetyl transfer. The original human expression studies and neuromuscular disease experiments corroborate the role. Supporting Evidence: PMID:11068039 Na(+)-dependent, high-affinity choline uptake in cholinergic neurons is the rate-limiting step in acetylcholine synthesis. |
| GO:0015220 choline transmembrane transporter activity | IDA PMID:11027560 Molecular cloning of a human, hemicholinium-3-sensitive chol... | MODIFY | Summary: The supported choline transporter is specifically a sodium-coupled symporter. Reason: The broad choline-transporter term is correct, but direct human ion-dependence and uptake experiments warrant the already-present choline:sodium symporter activity. The 2025 comparative transport study additionally confirms SLC5A7 uptake capacity; its cell-system kinetic estimates need not equal older estimates in different preparations. Proposed replacements: choline:sodium symporter activity Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent PMID:40972734 SLC5A7 displayed over tenfold higher intrinsic clearance than any of the others. |
| GO:0015220 choline transmembrane transporter activity | IDA PMID:11068039 Functional characterization of the human high-affinity choli... | MODIFY | Summary: The supported choline transporter is specifically a sodium-coupled symporter. Reason: The broad choline-transporter term is correct, but direct human ion-dependence and uptake experiments warrant the already-present choline:sodium symporter activity. The 2025 comparative transport study additionally confirms SLC5A7 uptake capacity; its cell-system kinetic estimates need not equal older estimates in different preparations. Proposed replacements: choline:sodium symporter activity Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent PMID:40972734 SLC5A7 displayed over tenfold higher intrinsic clearance than any of the others. |
| GO:0015220 choline transmembrane transporter activity | IDA PMID:12969261 The hemicholinium-3 sensitive high affinity choline transpor... | MODIFY | Summary: The supported choline transporter is specifically a sodium-coupled symporter. Reason: The broad choline-transporter term is correct, but direct human ion-dependence and uptake experiments warrant the already-present choline:sodium symporter activity. The 2025 comparative transport study additionally confirms SLC5A7 uptake capacity; its cell-system kinetic estimates need not equal older estimates in different preparations. Proposed replacements: choline:sodium symporter activity Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent PMID:40972734 SLC5A7 displayed over tenfold higher intrinsic clearance than any of the others. |
| GO:0015220 choline transmembrane transporter activity | IDA PMID:17005849 Na+, Cl-, and pH dependence of the human choline transporter... | MODIFY | Summary: The supported choline transporter is specifically a sodium-coupled symporter. Reason: The broad choline-transporter term is correct, but direct human ion-dependence and uptake experiments warrant the already-present choline:sodium symporter activity. The 2025 comparative transport study additionally confirms SLC5A7 uptake capacity; its cell-system kinetic estimates need not equal older estimates in different preparations. Proposed replacements: choline:sodium symporter activity Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent PMID:40972734 SLC5A7 displayed over tenfold higher intrinsic clearance than any of the others. |
| GO:0015220 choline transmembrane transporter activity | IDA PMID:23141292 Defective presynaptic choline transport underlies hereditary... | MODIFY | Summary: The supported choline transporter is specifically a sodium-coupled symporter. Reason: The broad choline-transporter term is correct, but direct human ion-dependence and uptake experiments warrant the already-present choline:sodium symporter activity. The 2025 comparative transport study additionally confirms SLC5A7 uptake capacity; its cell-system kinetic estimates need not equal older estimates in different preparations. Proposed replacements: choline:sodium symporter activity Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent PMID:40972734 SLC5A7 displayed over tenfold higher intrinsic clearance than any of the others. |
| GO:0015220 choline transmembrane transporter activity | IDA PMID:40972734 Diversity of human choline transporters: substrate specifici... | MODIFY | Summary: The supported choline transporter is specifically a sodium-coupled symporter. Reason: The broad choline-transporter term is correct, but direct human ion-dependence and uptake experiments warrant the already-present choline:sodium symporter activity. The 2025 comparative transport study additionally confirms SLC5A7 uptake capacity; its cell-system kinetic estimates need not equal older estimates in different preparations. Proposed replacements: choline:sodium symporter activity Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent PMID:40972734 SLC5A7 displayed over tenfold higher intrinsic clearance than any of the others. |
| GO:0015220 choline transmembrane transporter activity | IEA GO_REF:0000107 | MODIFY | Summary: The supported choline transporter is specifically a sodium-coupled symporter. Reason: The broad choline-transporter term is correct, but direct human ion-dependence and uptake experiments warrant the already-present choline:sodium symporter activity. The 2025 comparative transport study additionally confirms SLC5A7 uptake capacity; its cell-system kinetic estimates need not equal older estimates in different preparations. Proposed replacements: choline:sodium symporter activity Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent PMID:40972734 SLC5A7 displayed over tenfold higher intrinsic clearance than any of the others. |
| GO:0015220 choline transmembrane transporter activity | IMP PMID:11068039 Functional characterization of the human high-affinity choli... | MODIFY | Summary: The supported choline transporter is specifically a sodium-coupled symporter. Reason: The broad choline-transporter term is correct, but direct human ion-dependence and uptake experiments warrant the already-present choline:sodium symporter activity. The 2025 comparative transport study additionally confirms SLC5A7 uptake capacity; its cell-system kinetic estimates need not equal older estimates in different preparations. Proposed replacements: choline:sodium symporter activity Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent PMID:40972734 SLC5A7 displayed over tenfold higher intrinsic clearance than any of the others. |
| GO:0015220 choline transmembrane transporter activity | IMP PMID:12237312 Single nucleotide polymorphism of the human high affinity ch... | MODIFY | Summary: The supported choline transporter is specifically a sodium-coupled symporter. Reason: The broad choline-transporter term is correct, but direct human ion-dependence and uptake experiments warrant the already-present choline:sodium symporter activity. The 2025 comparative transport study additionally confirms SLC5A7 uptake capacity; its cell-system kinetic estimates need not equal older estimates in different preparations. Proposed replacements: choline:sodium symporter activity Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent PMID:40972734 SLC5A7 displayed over tenfold higher intrinsic clearance than any of the others. |
| GO:0015220 choline transmembrane transporter activity | IMP PMID:23132865 Transmembrane topology and oligomeric structure of the high-... | MODIFY | Summary: The supported choline transporter is specifically a sodium-coupled symporter. Reason: The broad choline-transporter term is correct, but direct human ion-dependence and uptake experiments warrant the already-present choline:sodium symporter activity. The 2025 comparative transport study additionally confirms SLC5A7 uptake capacity; its cell-system kinetic estimates need not equal older estimates in different preparations. Proposed replacements: choline:sodium symporter activity Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent PMID:40972734 SLC5A7 displayed over tenfold higher intrinsic clearance than any of the others. |
| GO:0015220 choline transmembrane transporter activity | IMP PMID:27569547 Impaired Presynaptic High-Affinity Choline Transporter Cause... | MODIFY | Summary: The supported choline transporter is specifically a sodium-coupled symporter. Reason: The broad choline-transporter term is correct, but direct human ion-dependence and uptake experiments warrant the already-present choline:sodium symporter activity. The 2025 comparative transport study additionally confirms SLC5A7 uptake capacity; its cell-system kinetic estimates need not equal older estimates in different preparations. Proposed replacements: choline:sodium symporter activity Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent PMID:40972734 SLC5A7 displayed over tenfold higher intrinsic clearance than any of the others. |
| GO:0015220 choline transmembrane transporter activity | TAS Reactome:R-HSA-429594 | MODIFY | Summary: The supported choline transporter is specifically a sodium-coupled symporter. Reason: The broad choline-transporter term is correct, but direct human ion-dependence and uptake experiments warrant the already-present choline:sodium symporter activity. The 2025 comparative transport study additionally confirms SLC5A7 uptake capacity; its cell-system kinetic estimates need not equal older estimates in different preparations. Proposed replacements: choline:sodium symporter activity Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent PMID:40972734 SLC5A7 displayed over tenfold higher intrinsic clearance than any of the others. |
| GO:0015220 choline transmembrane transporter activity | TAS Reactome:R-HSA-5658483 | MODIFY | Summary: The supported choline transporter is specifically a sodium-coupled symporter. Reason: The broad choline-transporter term is correct, but direct human ion-dependence and uptake experiments warrant the already-present choline:sodium symporter activity. The 2025 comparative transport study additionally confirms SLC5A7 uptake capacity; its cell-system kinetic estimates need not equal older estimates in different preparations. Proposed replacements: choline:sodium symporter activity Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent PMID:40972734 SLC5A7 displayed over tenfold higher intrinsic clearance than any of the others. |
| GO:0015721 bile acid and bile salt transport | TAS Reactome:R-HSA-9958517 | MARK AS OVER ANNOTATED | Summary: The bile-acid pathway grouping does not establish bile-acid transport by CHT1. Reason: The original Reactome parent is a collection labelled SLC-mediated bile acid transport, but its linked SLC5A7 reaction is uptake of choline. The directly measured substrate and curated reaction support choline transport; grouping a sodium-solute-family reaction under this parent does not demonstrate movement of a bile acid or bile salt. This assessment does not claim that an untested bile-acid transport assay was negative. Supporting Evidence: Reactome:R-HSA-9958517 Reactome:R-HSA-429594 PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0015871 choline transport | IBA GO_REF:0000033 | ACCEPT | Summary: SLC5A7 directly transports choline. Reason: The process names the measured substrate movement itself. Human expression, variant and pharmacological uptake experiments directly support choline transport; the conserved PAINT process and electronic reaction mappings agree with these independent results. Original ancestral source: PANTHER:PTN000929655. Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0015871 choline transport | IDA PMID:11027560 Molecular cloning of a human, hemicholinium-3-sensitive chol... | ACCEPT | Summary: SLC5A7 directly transports choline. Reason: The process names the measured substrate movement itself. Human expression, variant and pharmacological uptake experiments directly support choline transport; the conserved PAINT process and electronic reaction mappings agree with these independent results. Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0015871 choline transport | IDA PMID:11068039 Functional characterization of the human high-affinity choli... | ACCEPT | Summary: SLC5A7 directly transports choline. Reason: The process names the measured substrate movement itself. Human expression, variant and pharmacological uptake experiments directly support choline transport; the conserved PAINT process and electronic reaction mappings agree with these independent results. Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0015871 choline transport | IDA PMID:12969261 The hemicholinium-3 sensitive high affinity choline transpor... | ACCEPT | Summary: SLC5A7 directly transports choline. Reason: The process names the measured substrate movement itself. Human expression, variant and pharmacological uptake experiments directly support choline transport; the conserved PAINT process and electronic reaction mappings agree with these independent results. Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0015871 choline transport | IDA PMID:17005849 Na+, Cl-, and pH dependence of the human choline transporter... | ACCEPT | Summary: SLC5A7 directly transports choline. Reason: The process names the measured substrate movement itself. Human expression, variant and pharmacological uptake experiments directly support choline transport; the conserved PAINT process and electronic reaction mappings agree with these independent results. Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0015871 choline transport | IDA PMID:23141292 Defective presynaptic choline transport underlies hereditary... | ACCEPT | Summary: SLC5A7 directly transports choline. Reason: The process names the measured substrate movement itself. Human expression, variant and pharmacological uptake experiments directly support choline transport; the conserved PAINT process and electronic reaction mappings agree with these independent results. Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0015871 choline transport | IDA PMID:40972734 Diversity of human choline transporters: substrate specifici... | ACCEPT | Summary: SLC5A7 directly transports choline. Reason: The process names the measured substrate movement itself. Human expression, variant and pharmacological uptake experiments directly support choline transport; the conserved PAINT process and electronic reaction mappings agree with these independent results. Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0015871 choline transport | IMP PMID:12237312 Single nucleotide polymorphism of the human high affinity ch... | ACCEPT | Summary: SLC5A7 directly transports choline. Reason: The process names the measured substrate movement itself. Human expression, variant and pharmacological uptake experiments directly support choline transport; the conserved PAINT process and electronic reaction mappings agree with these independent results. Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0015871 choline transport | IMP PMID:23132865 Transmembrane topology and oligomeric structure of the high-... | ACCEPT | Summary: SLC5A7 directly transports choline. Reason: The process names the measured substrate movement itself. Human expression, variant and pharmacological uptake experiments directly support choline transport; the conserved PAINT process and electronic reaction mappings agree with these independent results. Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0015871 choline transport | IMP PMID:27569547 Impaired Presynaptic High-Affinity Choline Transporter Cause... | ACCEPT | Summary: SLC5A7 directly transports choline. Reason: The process names the measured substrate movement itself. Human expression, variant and pharmacological uptake experiments directly support choline transport; the conserved PAINT process and electronic reaction mappings agree with these independent results. Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0016020 membrane | IDA PMID:11027560 Molecular cloning of a human, hemicholinium-3-sensitive chol... | MODIFY | Summary: CHT1 occupies defined surface and intracellular vesicle membranes. Reason: Membrane is correct but less precise than the independently supported plasma membrane, early endosome membrane and synaptic vesicle membrane. Preserve all three established pools rather than refining the broad term only to the active surface pool. |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: CHT1 occupies defined surface and intracellular vesicle membranes. Reason: Membrane is correct but less precise than the independently supported plasma membrane, early endosome membrane and synaptic vesicle membrane. Preserve all three established pools rather than refining the broad term only to the active surface pool. |
| GO:0022857 transmembrane transporter activity | IEA GO_REF:0000002 | MODIFY | Summary: The general transporter activity resolves to sodium-coupled choline uptake. Reason: Direct substrate and ion-dependence assays justify the same specific symporter activity already asserted elsewhere; this is a refinement of a true broad function, not exclusion of the electronic family assignment. Proposed replacements: choline:sodium symporter activity Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0030424 axon | IBA GO_REF:0000033 | ACCEPT | Summary: CHT1 is present in the axonal compartment of cholinergic neurons. Reason: The ancestral neuronal-localization inference agrees with the curated axonal localization and the presynaptic choline-replenishment role. This does not assign an axon-restricted distribution to every intracellular transporter molecule. Original ancestral source: PANTHER:PTN002913667. Supporting Evidence: file:human/SLC5A7/SLC5A7-uniprot.txt Cell projection, axon {ECO:0000250|UniProtKB:Q8BGY9}. |
| GO:0030424 axon | IEA GO_REF:0000044 | ACCEPT | Summary: CHT1 is present in the axonal compartment of cholinergic neurons. Reason: The ancestral neuronal-localization inference agrees with the curated axonal localization and the presynaptic choline-replenishment role. This does not assign an axon-restricted distribution to every intracellular transporter molecule. Supporting Evidence: file:human/SLC5A7/SLC5A7-uniprot.txt Cell projection, axon {ECO:0000250|UniProtKB:Q8BGY9}. |
| GO:0030425 dendrite | IBA GO_REF:0000033 | ACCEPT | Summary: CHT1 has a conserved somatodendritic pool in addition to terminal enrichment. Reason: The rat motor-unit study explicitly localizes CHT1 to perikaryon, dendrites and axon by immunohistochemistry. This provides independent experimental grounding for the inherited neuronal-compartment assertion; human uptake and terminal staining corroborate conserved CHT1 function without being presented as direct human dendrite imaging. Presynaptic enrichment is compatible with these additional pools. Original ancestral source: PANTHER:PTN002913667. Supporting Evidence: PMID:11904763 CHT1 immunoreativity is principally found at all segments (perikaryon, dendrites, axon) of the motoneuron but is enriched at neuro-neuronal and neuro-muscular synapses. |
| GO:0030672 synaptic vesicle membrane | IDA PMID:12969261 The hemicholinium-3 sensitive high affinity choline transpor... | ACCEPT | Summary: CHT1 has a synaptic-vesicle membrane reservoir. Reason: The original trafficking study combines tagged transporter imaging with rat-brain fractionation and vesicle immunoisolation. Together with curated human localization, this supports the vesicle pool. It does not mean that CHT1 loads acetylcholine into the vesicle: VAChT performs that activity, and acidic-pH suppression of CHT1 is a mechanistic hypothesis for its intracellular silence. Supporting Evidence: PMID:12969261 Subcellular fractionation and immunoisolation of organelles from rat brain indicate that CHT1 is present in synaptic vesicles. |
| GO:0030672 synaptic vesicle membrane | IEA GO_REF:0000044 | ACCEPT | Summary: CHT1 has a synaptic-vesicle membrane reservoir. Reason: The original trafficking study combines tagged transporter imaging with rat-brain fractionation and vesicle immunoisolation. Together with curated human localization, this supports the vesicle pool. It does not mean that CHT1 loads acetylcholine into the vesicle: VAChT performs that activity, and acidic-pH suppression of CHT1 is a mechanistic hypothesis for its intracellular silence. Supporting Evidence: PMID:12969261 Subcellular fractionation and immunoisolation of organelles from rat brain indicate that CHT1 is present in synaptic vesicles. |
| GO:0031594 neuromuscular junction | IDA PMID:27569547 Impaired Presynaptic High-Affinity Choline Transporter Cause... | ACCEPT | Summary: Human CHT1 is localized at the neuromuscular junction. Reason: The source includes native human muscle biopsies, not only heterologous mutant uptake. Junctional CHT staining in affected individuals and a control supports this location despite transport-defective variants retaining detectable protein. Supporting Evidence: PMID:27569547 CHT was immunostained at the NMJ in the muscle biopsies of the two individuals at a level similar to the control muscle biopsy |
| GO:0031901 early endosome membrane | IDA PMID:12969261 The hemicholinium-3 sensitive high affinity choline transpor... | ACCEPT | Summary: CHT1 cycles through early-endosomal membranes. Reason: Tagged-transporter colocalization with Rab5 and disruption of the cytoplasmic internalization motif identify the endosomal pool. Increased surface expression after inhibition of internalization connects this trafficking to uptake availability without making CHT1 an endocytosis catalyst. Supporting Evidence: PMID:15953352 CHT1 is rapidly and constitutively internalized in clathrin-coated vesicles to Rab5-positive early endosomes. |
| GO:0031901 early endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: CHT1 cycles through early-endosomal membranes. Reason: Tagged-transporter colocalization with Rab5 and disruption of the cytoplasmic internalization motif identify the endosomal pool. Increased surface expression after inhibition of internalization connects this trafficking to uptake availability without making CHT1 an endocytosis catalyst. Supporting Evidence: PMID:15953352 CHT1 is rapidly and constitutively internalized in clathrin-coated vesicles to Rab5-positive early endosomes. |
| GO:0031901 early endosome membrane | IMP PMID:15953352 Constitutive high-affinity choline transporter endocytosis i... | ACCEPT | Summary: CHT1 cycles through early-endosomal membranes. Reason: Tagged-transporter colocalization with Rab5 and disruption of the cytoplasmic internalization motif identify the endosomal pool. Increased surface expression after inhibition of internalization connects this trafficking to uptake availability without making CHT1 an endocytosis catalyst. Supporting Evidence: PMID:15953352 CHT1 is rapidly and constitutively internalized in clathrin-coated vesicles to Rab5-positive early endosomes. |
| GO:0033265 choline binding | IEA GO_REF:0000107 | ACCEPT | Summary: Choline recognition is integral to the transporter mechanism. Reason: Saturable human choline uptake and substrate/ion structural evidence support binding of its transported substrate. This is a core biochemical property, not a peripheral association or a claim that binding alone establishes transport. Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0042734 presynaptic membrane | EXP PMID:11027560 Molecular cloning of a human, hemicholinium-3-sensitive chol... | ACCEPT | Summary: The presynaptic membrane contains the active CHT1 uptake pool. Reason: Native human neuromuscular localization and publication-linked curated targeting support the presynaptic surface assignment. The surface population is regulated by internalization and replenishment from intracellular vesicles. Supporting Evidence: file:human/SLC5A7/SLC5A7-uniprot.txt Presynaptic cell membrane |
| GO:0042734 presynaptic membrane | IDA PMID:12969261 The hemicholinium-3 sensitive high affinity choline transpor... | ACCEPT | Summary: The presynaptic membrane contains the active CHT1 uptake pool. Reason: Native human neuromuscular localization and publication-linked curated targeting support the presynaptic surface assignment. The surface population is regulated by internalization and replenishment from intracellular vesicles. Supporting Evidence: file:human/SLC5A7/SLC5A7-uniprot.txt Presynaptic cell membrane |
| GO:0042734 presynaptic membrane | IDA PMID:27569547 Impaired Presynaptic High-Affinity Choline Transporter Cause... | ACCEPT | Summary: The presynaptic membrane contains the active CHT1 uptake pool. Reason: Native human neuromuscular localization and publication-linked curated targeting support the presynaptic surface assignment. The surface population is regulated by internalization and replenishment from intracellular vesicles. Supporting Evidence: file:human/SLC5A7/SLC5A7-uniprot.txt Presynaptic cell membrane |
| GO:0042734 presynaptic membrane | IEA GO_REF:0000120 | ACCEPT | Summary: The presynaptic membrane contains the active CHT1 uptake pool. Reason: Native human neuromuscular localization and publication-linked curated targeting support the presynaptic surface assignment. The surface population is regulated by internalization and replenishment from intracellular vesicles. Supporting Evidence: file:human/SLC5A7/SLC5A7-uniprot.txt Presynaptic cell membrane |
| GO:0043025 neuronal cell body | IEA GO_REF:0000107 | ACCEPT | Summary: CHT1 has a conserved somatodendritic pool in addition to terminal enrichment. Reason: The rat motor-unit study explicitly localizes CHT1 to perikaryon, dendrites and axon by immunohistochemistry. This provides independent experimental grounding for the inherited neuronal-compartment assertion; human uptake and terminal staining corroborate conserved CHT1 function without being presented as direct human dendrite imaging. Presynaptic enrichment is compatible with these additional pools. Supporting Evidence: PMID:11904763 CHT1 immunoreativity is principally found at all segments (perikaryon, dendrites, axon) of the motoneuron but is enriched at neuro-neuronal and neuro-muscular synapses. |
| GO:0043204 perikaryon | IBA GO_REF:0000033 | ACCEPT | Summary: CHT1 has a conserved somatodendritic pool in addition to terminal enrichment. Reason: The rat motor-unit study explicitly localizes CHT1 to perikaryon, dendrites and axon by immunohistochemistry. This provides independent experimental grounding for the inherited neuronal-compartment assertion; human uptake and terminal staining corroborate conserved CHT1 function without being presented as direct human dendrite imaging. Presynaptic enrichment is compatible with these additional pools. Original ancestral source: PANTHER:PTN002913667. Supporting Evidence: PMID:11904763 CHT1 immunoreativity is principally found at all segments (perikaryon, dendrites, axon) of the motoneuron but is enriched at neuro-neuronal and neuro-muscular synapses. |
| GO:0045202 synapse | IBA GO_REF:0000033 | ACCEPT | Summary: CHT1 is a synaptic protein with a demonstrated presynaptic role. Reason: Human junctional staining and uptake physiology independently corroborate the inherited synapse localization. The synapse term is retained as an informative compartment-level assertion alongside the more specific membrane and vesicle pools. Original ancestral source: PANTHER:PTN002913667. |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | MODIFY | Summary: The measured transmembrane process is choline transport. Reason: The transporter moves choline across the membrane through its sodium-dependent cycle; refine the broad transport process to the already-supported substrate-specific process. Proposed replacements: choline transport Supporting Evidence: PMID:11027560 Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake PMID:17005849 the choline uptake and choline-induced current are Na+ and Cl- dependent |
| GO:0098793 presynapse | IEA GO_REF:0000117 | ACCEPT | Summary: CHT1 acts in the presynaptic compartment. Reason: The precursor-uptake role and native neuromuscular-junction localization support this synaptic side. Neither a postsynaptic acetylcholine-receptor activity nor acetylcholine vesicle loading is assigned to CHT1. |
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