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FLASH GENE

Symbol

SLC1A3

contributors: mct - updated : 22-05-2014

HGNC name	solute carrier family 1 (glial high affinity glutamate transporter), member 3
HGNC id	10941

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive esophagus       highly Nervous brain forebrain cerebral cortex   highly Homo sapiens   nerve cranial nerve     highly   spinal cord

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous central

cells

System Cell Pubmed Species Stage Rna symbol Nervous astrocyte Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	ten transmembrane spanning segments (mutations in transmembrane domains 5 and 7 affect the substrate-activated anion), and some AAs of TM5 take part in the transport pathway during the transport cycle
	a type I PDZ domain-binding motif
	six N terminal and cytoplasmic N and C termini

HOMOLOGY

Homologene

FAMILY	sodium:dicarboxylate (SDF) symporter (TC 2.A.23) family
	SLC1A3 subfamily

CATEGORY

transport channel

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,mitochondria,inner
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endosome
text	is expressed in myocardial mitochondria, and functions in the malate/aspartate shuttle
	co-localized with SLC9A3R2 in ER–Golgi intermediate compartments (ERGICs), at the plasma membrane and in early endosomes, but not in the ER

basic FUNCTION	Na+ (and K+) dependent glutamate transporter, involved in development and neonatal hypoxic-ischemic damage
	glial high affinity glutamate/aspartate transporter in the cerebellum
	playing an essential role for terminating the postsynaptic action of glutamate by rapidly removing released glutamate from the synaptic cleft
	may be playing a role in myocardial glutamate metabolism
	playing a necessary role for brain development through regulation of extracellular glutamate concentration
	major role, both in protecting the synapse from exposure to excess extracellular glutamate and in attenuating hearing loss due to acoustic overstimulation
	allows significant passive and active water transport, which suggests that water permeation through glutamate transporters may play an important role in glial cell homoeostasis
	does not only mediate secondary-active glutamate transport, but also functions as an ion channel

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	SLC9A3R1 interacts with SLC1A3 during ER export, while SLC9A3R2 interacts with SLC1A3 in the secretory pathway from the ERGIC to the plasma membrane, thereby modulating the cell surface expression of SLC1A3
	TNR is likely expressed in a subset of astrocytes and contributes to glutamate homeostasis by regulating astrocytic SLC1A3 expression
	CAV1 is a powerful negative regulator of the excitatory glutamate transporters SLC1A1, SLC1A2, SLC1A3, SLC1A6

cell & other

REGULATION

activated by

KL that up-regulates the excitatory glutamate transporters SLC1A3 and SLC1A2 and thus participates in the regulation of neuronal excitation

ASSOCIATED DISORDERS

corresponding disease(s)

EA6

related resource

MITOP database

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in motor neuron disease constitutional     --low   may be an adaptive response to neuronal death or it may be a causative event contributing to neuronal death constitutional     --low   reduced SLC16A4 and SLC1A3 expression by astrocytes may lead to neuronal hyperexcitability and epileptogenesis in the temporal lobe by reducing the supply of metabolic intermediates and by allowing accumulation of extracellular glutamate

Susceptibility

Variant & Polymorphism

Candidate gene	its expression is exceptionally rare in non-neoplastic choroid plexus and is a helpful diagnostic tool in choroid plexus tumors
Marker
Therapy target

ANIMAL & CELL MODELS