Slc6a4
entrez
15567
canonical
uniprot
Q60857
canonical
ensembl
ENSMUSG00000020838
resolver
ensp
ENSMUSP00000021195
resolver
ensp
ENSMUSP00000104039
resolver
enst
ENSMUST00000021195
resolver
enst
ENSMUST00000108402
resolver
genesymbol
Slc6a4
resolver
genesymbol_syn
Htt
resolver
genesymbol_syn
Sert
resolver
uniprot
O35241
resolver
uniprot
Q5NCR6
resolver
uniprot_entry
SC6A4_MOUSE
resolver
uniprot_sec
O35241
resolver
uniprot_sec
Q5NCR6
resolver
amino_acid_sequence
METTPLNSQKVLSECKDKEDCQENGVLQKGVPTPADKAGPGQISNGYSAVPSTSAGDEAPHSTPAATTTLVAEIHQGERETWGKKMDFLLSVIGYAVDLGNIWRFPYICYQNGGGAFLLPYTIMAIFGGIPLFYMELALGQYHRNGCISIWKKICPIFKGIGYAICIIAFYIASYYNTIIAWALYYLISSFTDQLPWTSCKNSWNTGNCTNYFAQDNITWTLHSTSPAEEFYLRHVLQIHQSKGLQDLGTISWQLALCIMLIFTIIYFSIWKGVKTSGKVVWVTATFPYIVLSVLLVRGATLPGAWRGVVFYLKPNWQKLLETGVWVDAAAQIFFSLGPGFGVLLAFASYNKFNNNCYQDALVTSVVNCMTSFVSGFVIFTVLGYMAEMRNEDVSEVAKDAGPSLLFITYAEAIANMPASTFFAIIFFLMLITLGLDSTFAGLEGVITAVLDEFPHIWAKRREWFVLIVVITCILGSLLTLTSGGAYVVTLLEEYATGPAVLTVALIEAVVVSWFYGITQFCSDVKEMLGFSPGWFWRICWVAISPLFLLFIICSFLMSPPQLRLFQYNYPHWSIILGYCIGTSSVICIPIYIIYRLISTPGTLKERIIKSITPETPTEIPCGDIRMNAV
uniprot
proteins
function
FUNCTION: Serotonin transporter that cotransports serotonin with one Na(+) ion in exchange for one K(+) ion and possibly one proton in an overall electroneutral transport cycle. Transports serotonin across the plasma membrane from the extracellular compartment to the cytosol thus limiting serotonin intercellular signaling (By similarity) (PubMed:9037532, PubMed:9547354). Essential for serotonin homeostasis in the central nervous system. In the developing somatosensory cortex, acts in glutamatergic neurons to control serotonin uptake and its trophic functions accounting for proper spatial organization of cortical neurons and elaboration of sensory circuits. In the mature cortex, acts primarily in brainstem raphe neurons to mediate serotonin uptake from the synaptic cleft back into the pre-synaptic terminal thus terminating serotonin signaling at the synapse (PubMed:25600870, PubMed:9547354). Modulates mucosal serotonin levels in the gastrointestinal tract through uptake and clearance of serotonin in enterocytes. Required for enteric neurogenesis and gastrointestinal reflexes (PubMed:27111230). Regulates blood serotonin levels by ensuring rapid high affinity uptake of serotonin from plasma to platelets, where it is further stored in dense granules via vesicular monoamine transporters and then released upon stimulation (PubMed:18317590). Mechanistically, the transport cycle starts with an outward-open conformation having Na1(+) and Cl(-) sites occupied. The binding of a second extracellular Na2(+) ion and serotonin substrate leads to structural changes to outward-occluded to inward-occluded to inward-open, where the Na2(+) ion and serotonin are released into the cytosol. Binding of intracellular K(+) ion induces conformational transitions to inward-occluded to outward-open and completes the cycle by releasing K(+) possibly together with a proton bound to Asp-98 into the extracellular compartment. Na1(+) and Cl(-) ions remain bound throughout the transport cycle (By similarity) (PubMed:9037532, PubMed:9547354). Additionally, displays serotonin-induced channel-like conductance for monovalent cations, mainly Na(+) ions. The channel activity is uncoupled from the transport cycle and may contribute to the membrane resting potential or excitability (By similarity). {ECO:0000250|UniProtKB:P31645, ECO:0000250|UniProtKB:P31652, ECO:0000269|PubMed:18317590, ECO:0000269|PubMed:25600870, ECO:0000269|PubMed:27111230, ECO:0000269|PubMed:9037532, ECO:0000269|PubMed:9547354}.
uniprot
proteins
mass_dalton
70048
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Thr-276 increases 5-HT uptake and is required for cGMP-mediated SERT regulation. {ECO:0000250|UniProtKB:P31645}.
uniprot
proteins
protein_family
SLC6A4 subfamily
uniprot
proteins
protein_family
Sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family
uniprot
proteins
pubmed
16803896
uniprot
proteins
pubmed
17452640
uniprot
proteins
pubmed
18317590
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
20676059
uniprot
proteins
pubmed
22572884
uniprot
proteins
pubmed
25600870
uniprot
proteins
pubmed
27111230
uniprot
proteins
pubmed
29038237
uniprot
proteins
pubmed
8507984
uniprot
proteins
pubmed
9037532
uniprot
proteins
pubmed
9073170
uniprot
proteins
pubmed
9547354
uniprot
proteins
sequence_length
630
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P31645}; Multi-pass membrane protein {ECO:0000255}. Endomembrane system {ECO:0000250|UniProtKB:P31652}; Multi-pass membrane protein {ECO:0000255}. Endosome membrane {ECO:0000250|UniProtKB:P31652}; Multi-pass membrane protein {ECO:0000255}. Synapse {ECO:0000269|PubMed:29038237}. Cell junction, focal adhesion {ECO:0000269|PubMed:29038237}. Cell projection, neuron projection {ECO:0000269|PubMed:25600870}. Note=Could be part of recycling endosomes. Density of transporter molecules on the plasma membrane is itself regulated by STX1A. Density of transporter molecules on the plasma membrane is also regulated by serotonin (By similarity). Density of transporter molecules seems to be modulated by ITGAV:ITGB3 (PubMed:29038237). {ECO:0000250|UniProtKB:P31645, ECO:0000250|UniProtKB:P31652, ECO:0000269|PubMed:29038237}.
uniprot
proteins
transmembrane_region
TRANSMEM 88..112; /note="Helical; Name=1"; /evidence="ECO:0000250|UniProtKB:P31645"; TRANSMEM 116..135; /note="Helical; Name=2"; /evidence="ECO:0000250|UniProtKB:P31645"; TRANSMEM 161..186; /note="Helical; Name=3"; /evidence="ECO:0000250|UniProtKB:P31645"; TRANSMEM 253..271; /note="Helical; Name=4"; /evidence="ECO:0000250|UniProtKB:P31645"; TRANSMEM 278..297; /note="Helical; Name=5"; /evidence="ECO:0000250|UniProtKB:P31645"; TRANSMEM 325..347; /note="Helical; Name=6"; /evidence="ECO:0000250|UniProtKB:P31645"; TRANSMEM 361..380; /note="Helical; Name=7"; /evidence="ECO:0000250|UniProtKB:P31645"; TRANSMEM 422..443; /note="Helical; Name=8"; /evidence="ECO:0000250|UniProtKB:P31645"; TRANSMEM 464..483; /note="Helical; Name=9"; /evidence="ECO:0000250|UniProtKB:P31645"; TRANSMEM 495..516; /note="Helical; Name=10"; /evidence="ECO:0000250|UniProtKB:P31645"; TRANSMEM 539..558; /note="Helical; Name=11"; /evidence="ECO:0000250|UniProtKB:P31645"; TRANSMEM 575..595; /note="Helical; Name=12"; /evidence="ECO:0000250|UniProtKB:P31645
uniprot
proteins