General Information of the Ferroptosis Target (ID: TAR10046)
Target Name Neutral amino acid transporter B(0) (SLC1A5)
Synonyms
Baboon M7 virus receptor; RD114/simian type D retrovirus receptor; Sodium-dependent neutral amino acid transporter type 2; Solute carrier family 1 member 5
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Gene Name SLC1A5
Sequence
MVADPPRDSKGLAAAEPTANGGLALASIEDQGAAAGGYCGSRDQVRRCLRANLLVLLTVV
AVVAGVALGLGVSGAGGALALGPERLSAFVFPGELLLRLLRMIILPLVVCSLIGGAASLD
PGALGRLGAWALLFFLVTTLLASALGVGLALALQPGAASAAINASVGAAGSAENAPSKEV
LDSFLDLARNIFPSNLVSAAFRSYSTTYEERNITGTRVKVPVGQEVEGMNILGLVVFAIV
FGVALRKLGPEGELLIRFFNSFNEATMVLVSWIMWYAPVGIMFLVAGKIVEMEDVGLLFA
RLGKYILCCLLGHAIHGLLVLPLIYFLFTRKNPYRFLWGIVTPLATAFGTSSSSATLPLM
MKCVEENNGVAKHISRFILPIGATVNMDGAALFQCVAAVFIAQLSQQSLDFVKIITILVT
ATASSVGAAGIPAGGVLTLAIILEAVNLPVDHISLILAVDWLVDRSCTVLNVEGDALGAG
LLQNYVDRTESRSTEPELIQVKSELPLDPLPVPTEEGNPLLKHYRGPAGDATVASEKESV
M

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Family Dicarboxylate/amino acid:cation symporte
Function
Sodium-coupled antiporter of neutral amino acids. In a tri- substrate transport cycle, exchanges neutral amino acids between the extracellular and intracellular compartments, coupled to the inward cotransport of at least one sodium ion. The preferred substrate is the essential amino acid L- glutamine, a precursor for biosynthesis of proteins, nucleotides and amine sugars as well as an alternative fuel for mitochondrial oxidative phosphorylation. Exchanges L-glutamine with other neutral amino acids such as L-serine, L-threonine and L-asparagine in a bidirectional way. Provides L-glutamine to proliferating stem and activated cells driving the metabolic switch toward cell differentiation . The transport cycle is usually pH-independent, with the exception of L-glutamate. Transports extracellular L-glutamate coupled to the cotransport of one proton and one sodium ion in exchange for intracellular L-glutamine counter-ion. May provide for L-glutamate uptake in glial cells regulating glutamine/glutamate cycle in the nervous system. Can transport D-amino acids. Mediates D-serine release from the retinal glia potentially affecting NMDA receptor function in retinal neurons. Displays sodium- and amino acid-dependent but uncoupled channel-like anion conductance with a preference SCN(-) >> NO3(-) > I(-) > Cl(-). Through binding of the fusogenic protein syncytin-1/ERVW-1 may mediate trophoblasts syncytialization, the spontaneous fusion of their plasma membranes, an essential process in placental development .

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Gene ID 6510
Uniprot ID
Q15758
Target Type Driver Suppressor Marker
Mechanism Diagram Click to View the Original Diagram
Tissue Relative Abundances of This Target
Full List of Regulator(s) of This Ferroptosis Target and Corresponding Disease/Drug Response(s)
SLC1A5 can be involved in and affect the ferroptosis by the following regulators, and result in corresponding disease/drug response(s). You can browse corresponding disease or drug response(s) resulting from the regulation of certain regulators.
Browse Regulator related Disease
Browse Regulator related Drug
hsa-mir-137 (Precursor RNA)
Melanoma [ICD-11: 2C30]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [1]
Regulator for Ferroptosis Suppressor
Responsed Drug Antagomir Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Glutamate metabolism hsa00250
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
A-375 cells Amelanotic melanoma Homo sapiens CVCL_0132
G-361 cells Melanoma Homo sapiens CVCL_1220
In Vivo Model
To generate murine subcutaneous tumors, melanoma cells (5 x 106 cells per mouse) were injected subcutaneously into the right posterior flanks of 7-week-old immunodeficient nude mice. When tumors reached a volume of approximately 50 mm3, mice were randomly allocated into groups and treated with erastin for 20 days. The erastin was dissolved in 5% dimethylsulfoxide (DMSO) + corn oil (C8267, Sigma).

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Response Description MiR-137 negatively regulates ferroptosis by directly targeting glutamine transporter SLC1A5 in melanoma cells. Ectopic expression of miR-137 suppressed SLC1A5, resulting in decreased glutamine uptake and malondialdehyde (MDA) accumulation. Meanwhile, antagomir-mediated inactivation of endogenous miR-137 increased the sensitivity of melanoma cells to erastin- and RSL3-induced ferroptosis.
hsa-miR-338-3p (miRNA)
Retinopathy [ICD-11: 9B71]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [2]
Regulator for Ferroptosis Suppressor
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
ARPE-19 cells Normal Homo sapiens CVCL_0145
Response Description High glucose upregulated miR-338-3p to cause SLC1A5-deficiency in RPE cells, resulting in oxidative stress mediated cell ferroptosis, which further caused RPE cell death and aggravate diabetic retinopathy (DR) progression.
Unspecific Regulator
Neurotoxicity [ICD-11: NE61]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [3]
Responsed Drug Formaldehyde Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
Sprague-Dawley (SD, weight: 200-220 g) rats were obtained from Hunan SJA laboratory animal company (Changsha, Hunan, China). SD rats were anaesthetized by sodium pentobarbital (45 mg/kg, i.p.) and secured in a stereotaxic frame. The aseptically cannula was implanted into lateral ventricle according to the following coordinates: AP: -1mm; ML: 2 mm; DV: 4 mm. During experiment, the unilateral ventricle of rats was received 2.5 ul FA (0.1, 1, 10 umol) according to the experiment scheme in vivo.

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Response Description Formaldehyde (FA)-induced neurotoxicity is implicated in neuronal ferroptosis. FA induced cell death in HT22 cells, and upregulated the ferroptosis-associated genes, including Ptgs2 (prostaglandin-endoperoxide synthase 2), GLS2 (glutaminase 2), solute carrier family 1 member 5 (SLC1A5), and solute carrier family 38 member 1 (SLC38A1) in HT22 cells, indicating the inductive role of FA in the ferroptosis of HT22 cells for the formaldehyde-induced neurotoxicity.
hsa-mir-137 (Precursor RNA)
Antagomir [Investigative]
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [1]
Regulator for Ferroptosis Suppressor
Responsed Disease Melanoma [ICD-11: 2C30]
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Glutamate metabolism hsa00250
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model A-375 cells Amelanotic melanoma Homo sapiens CVCL_0132
G-361 cells Melanoma Homo sapiens CVCL_1220
In Vivo Model
To generate murine subcutaneous tumors, melanoma cells (5 x 106 cells per mouse) were injected subcutaneously into the right posterior flanks of 7-week-old immunodeficient nude mice. When tumors reached a volume of approximately 50 mm3, mice were randomly allocated into groups and treated with erastin for 20 days. The erastin was dissolved in 5% dimethylsulfoxide (DMSO) + corn oil (C8267, Sigma).

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Response Description MiR-137 negatively regulates ferroptosis by directly targeting glutamine transporter SLC1A5 in melanoma cells. Ectopic expression of miR-137 suppressed SLC1A5, resulting in decreased glutamine uptake and malondialdehyde (MDA) accumulation. Meanwhile, antagomir-mediated inactivation of endogenous miR-137 increased the sensitivity of melanoma cells to erastin- and RSL3-induced ferroptosis.
Unspecific Regulator
Formaldehyde [Investigative]
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [3]
Responsed Disease Neurotoxicity [ICD-11: NE61]
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
Sprague-Dawley (SD, weight: 200-220 g) rats were obtained from Hunan SJA laboratory animal company (Changsha, Hunan, China). SD rats were anaesthetized by sodium pentobarbital (45 mg/kg, i.p.) and secured in a stereotaxic frame. The aseptically cannula was implanted into lateral ventricle according to the following coordinates: AP: -1mm; ML: 2 mm; DV: 4 mm. During experiment, the unilateral ventricle of rats was received 2.5 ul FA (0.1, 1, 10 umol) according to the experiment scheme in vivo.

    Click to Show/Hide
Response Description Formaldehyde (FA)-induced neurotoxicity is implicated in neuronal ferroptosis. FA induced cell death in HT22 cells, and upregulated the ferroptosis-associated genes, including Ptgs2 (prostaglandin-endoperoxide synthase 2), GLS2 (glutaminase 2), solute carrier family 1 member 5 (SLC1A5), and solute carrier family 38 member 1 (SLC38A1) in HT22 cells, indicating the inductive role of FA in the ferroptosis of HT22 cells for the formaldehyde-induced neurotoxicity.
References
Ref 1 miR-137 regulates ferroptosis by targeting glutamine transporter SLC1A5 in melanoma. Cell Death Differ. 2018 Aug;25(8):1457-1472. doi: 10.1038/s41418-017-0053-8. Epub 2018 Jan 18.
Ref 2 A novel miR-338-3p/SLC1A5 axis reprograms retinal pigment epithelium to increases its resistance to high glucose-induced cell ferroptosis. J Mol Histol. 2022 Jun;53(3):561-571. doi: 10.1007/s10735-022-10070-0. Epub 2022 Mar 23.
Ref 3 Formaldehyde induces ferroptosis in hippocampal neuronal cells by upregulation of the Warburg effect. Toxicology. 2021 Jan 30;448:152650. doi: 10.1016/j.tox.2020.152650. Epub 2020 Nov 28.