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2.A.3.8.5
Cystine/glutamate antiporter, xCT (requires the 4F2hc protein (TC #8.A.9.2.1)). Functions in the generation of glutathione and plays a role in the oxidative stress response (Wang et al. 2015). xCT is involved in the export of intracellular glutamate in exchange for extracellular cystine. Glutamate is the main neurotransmitter in the retina and plays a key metabolic role as a major anaplerotic substrate in the tricarboxylic acid cycle to generate adenosine triphosphate (ATP) (Knight et al. 2023). Glutamate is also involved in the outer plexiform glutamate-glutamine cycle, which links photoreceptors and supporting Müller cells and assists in maintaining photoreceptor neurotransmitter supply. Knight et al. 2023 investigated the role of xCT, the light chain subunit responsible for antiporter function, in glutamate pathways in the mouse retina using an xCT knockout mouse. As xCT is a glutamate exporter, loss of xCT function could influence the presynaptic metabolism of photoreceptors and postsynaptic levels of glutamate, and this proved to be true. Loss of xCT function resulted in glutamate metabolic disruption through the accumulation of glutamate in photoreceptors and a reduced uptake of glutamate by Müller cells, which in turn decreases glutamine production. These findings support the idea that xCT plays a role in the presynaptic metabolism of photoreceptors and postsynaptic levels of glutamate and derived neurotransmitters in the retina. (Knight et al. 2023).  Loss of xCT function results in glutamate metabolic disruption through the accumulation of glutamate in photoreceptors and a reduced uptake of glutamate by Müller cells, which in turn decreases glutamine production.

Accession Number:Q9WTR6
Protein Name:xCT aka SLC7A11
Length:502
Molecular Weight:55456.00
Species:Mus musculus (Mouse) [10090]
Number of TMSs:12
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate cystine, glutamate(2-)

Cross database links:

RefSeq: NP_036120.1   
Entrez Gene ID: 26570   
Pfam: PF00324   
KEGG: mmu:26570   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0015171 F:amino acid transmembrane transporter activity
GO:0006865 P:amino acid transport
GO:0055085 P:transmembrane transport

References (3)

[1] “Cloning and expression of a plasma membrane cystine/glutamate exchange transporter composed of two distinct proteins.”  Sato H.et.al.   10206947
[2] “Electrophile response element-mediated induction of the cystine/glutamate exchange transporter gene expression.”  Sasaki H.et.al.   12235164
[3] “The phagosomal proteome in interferon-gamma-activated macrophages.”  Trost M.et.al.   19144319

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MVRKPVVATI SKGGYLQGNM SGRLPSMGDQ EPPGQEKVVL KKKITLLRGV SIIIGTVIGS 
61:	GIFISPKGIL QNTGSVGMSL VFWSACGVLS LFGALSYAEL GTSIKKSGGH YTYILEVFGP 
121:	LLAFVRVWVE LLVIRPGATA VISLAFGRYI LEPFFIQCEI PELAIKLVTA VGITVVMVLN 
181:	STSVSWSARI QIFLTFCKLT AILIIIVPGV IQLIKGQTHH FKDAFSGRDT SLMGLPLAFY 
241:	YGMYAYAGWF YLNFITEEVD NPEKTIPLAI CISMAIITVG YVLTNVAYFT TISAEELLQS 
301:	SAVAVTFSER LLGKFSLAVP IFVALSCFGS MNGGVFAVSR LFYVASREGH LPEILSMIHV 
361:	HKHTPLPAVI VLHPLTMVML FSGDLYSLLN FLSFARWLFM GLAVAGLIYL RYKRPDMHRP 
421:	FKVPLFIPAL FSFTCLFMVV LSLYSDPFST GVGFLITLTG VPAYYLFIVW DKKPKWFRRL 
481:	SDRITRTLQI ILEVVPEDSK EL