Ferroptosis Target Information
General Information of the Ferroptosis Target (ID: TAR10046)
Target Name | Neutral amino acid transporter B(0) (SLC1A5) | ||||
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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 Click to Show/Hide
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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 | |||||
Target Type | Driver Suppressor Marker | ||||
Mechanism Diagram | Click to View the Original Diagram | ||||
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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).
Click to Show/Hide
|
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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