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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:P10852
Protein Name:4F2 cell-surface antigen heavy chain
Length:526
Molecular Weight:58337.00
Species:Mus musculus (Mouse) [10090]
Number of TMSs:1
Location1 / Topology2 / Orientation3: Apical cell membrane1
Substrate cystine, glutamate(2-)

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FASTA formatted sequence
1:	MSQDTEVDMK DVELNELEPE KQPMNAADGA AAGEKNGLVK IKVAEDETEA GVKFTGLSKE 
61:	ELLKVAGSPG WVRTRWALLL LFWLGWLGML AGAVVIIVRA PRCRELPVQR WWHKGALYRI 
121:	GDLQAFVGRD AGGIAGLKSH LEYLSTLKVK GLVLGPIHKN QKDEINETDL KQINPTLGSQ 
181:	EDFKDLLQSA KKKSIHIILD LTPNYQGQNA WFLPAQADIV ATKMKEALSS WLQDGVDGFQ 
241:	FRDVGKLMNA PLYLAEWQNI TKNLSEDRLL IAGTESSDLQ QIVNILESTS DLLLTSSYLS 
301:	NSTFTGERTE SLVTRFLNAT GSQWCSWSVS QAGLLADFIP DHLLRLYQLL LFTLPGTPVF 
361:	SYGDELGLQG ALPGQPAKAP LMPWNESSIF HIPRPVSLNM TVKGQNEDPG SLLTQFRRLS 
421:	DLRGKERSLL HGDFHALSSS PDLFSYIRHW DQNERYLVVL NFRDSGRSAR LGASNLPAGI 
481:	SLPASAKLLL STDSARQSRE EDTSLKLENL SLNPYEGLLL QFPFVA