Detail Information of Post-Translational Modifications

General Information of Drug Transporter (DT)
DT ID	DTD0133 Transporter Info
Gene Name	SLC1A5
Transporter Name	Alanine/serine/cysteine/threonine transporter 2
Gene ID	6510
UniProt ID	Q15758

Post-Translational Modification of This DT
Overview ofSLC1A5 Modification Sites with Functional and Structural Information
Sequence	M V A D P P R D S K G L A A A E P T A N G G L A L A S I E D Q G A A A G G Y C G S R D Q V R R C L R A N L L V L L T V V A V V A G V A L G L G V S G A G G A L A L G P E R L S A F V F P G E L L L R L L R M I I L P L V V C S L I G G A A S L D P G A L G R L G A W A L L F F L V T T L L A S A L G V G L A L A L Q P G A A S A A I N A S V G A A G S A E N A P S K E V L D S F L D L A R N I F P S N L V S A A F R S Y S T T Y E E R N I T G T R V K V P V G Q E V E G M N I L G L V V F A I V F G V A L R K L G P E G E L L I R F F N S F N E A T M V L V S W I M W Y A P V G I M F L V A G K I V E M E D V G L L F A R L G K Y I L C C L L G H A I H G L L V L P L I Y F L F T R K N P Y R F L W G I V T P L A T A F G T S S S S A T L P L M M K C V E E N N G V A K H I S R F I L P I G A T V N M D G A A L F Q C V A A V F I A Q L S Q Q S L D F V K I I T I L V T A T A S S V G A A G I P A G G V L T L A I I L E A V N L P V D H I S L I L A V D W L V D R S C T V L N V E G D A L G A G L L Q N Y V D R T E S R S T E P E L I Q V K S E L P L D P L P V P T E E G N P L L K H Y R G P A G D A T V A S E K E S V M
PTM type	X-Acetylation X-Monomethylation X-N-glycosylation X-Oxidation X-Phosphorylation X-S-nitrosylation X-S-palmitoylation X-Sulfoxidation X-Ubiquitination X: Amino Acid

Acetylation
Lysine	2 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC1A5			[1]
Role of PTM	Potential impacts
Modified Residue	Lysine	Modified Location	522
Experimental Method	Co-Immunoprecipitation
Detailed Description	Acetylation at SLC1A5 Lysine 522 has the potential to affect its expression or activity.
PTM Phenomenon2	Have the potential to influence SLC1A5			[2]
Role of PTM	Potential impacts
Affected Drug/Substrate	Glutamate	Results for Drug	Affecting the inward transport of glutamate
Modified Residue	Lysine	Modified Location	537
Experimental Method	Co-Immunoprecipitation
Detailed Description	Acetylation at SLC1A5 Lysine 537 has the potential to affect its expression or activity.
Methionine	1 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC1A5			[3], [4]
Role of PTM	Potential impacts
Modified Residue	Methionine	Modified Location	1
Experimental Method	Co-Immunoprecipitation
Detailed Description	Acetylation at SLC1A5 Methionine 1 has the potential to affect its expression or activity.
Monomethylation
Arginine	1 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC1A5			[2]
Role of PTM	Potential impacts
Affected Drug/Substrate	Glutamate	Results for Drug	Affecting the inward transport of glutamate
Modified Residue	Arginine	Modified Location	525
Experimental Method	Co-Immunoprecipitation
Detailed Description	Monomethylation at SLC1A5 Arginine 525 has the potential to affect its expression or activity.
N-glycosylation
Asparagine	2 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Impairing the trafficking to the membrane of SLC1A5			[2]
Role of PTM	Trafficking to Plasma Membrane
Affected Drug/Substrate	Glutamate	Results for Drug	no effect in the transport function
Modified Residue	Asparagine	Modified Location	163
Modified State	Asparagine to Glutamine mutation
Experimental Method	Co-Immunoprecipitation
Detailed Description	Removal of the Glycosylation at SLC1A5 Asparagine 163 (i.e. Asparagine to Glutamine mutation) have been reported to impaire its trafficking to the membrane.
PTM Phenomenon2	Impairing the trafficking to the membrane of SLC1A5			[2]
Role of PTM	Trafficking to Plasma Membrane
Affected Drug/Substrate	Glutamate	Results for Drug	no effect in the transport function
Modified Residue	Asparagine	Modified Location	212
Modified State	Asparagine to Glutamine mutation
Experimental Method	Co-Immunoprecipitation
Detailed Description	Removal of the Glycosylation at SLC1A5 Asparagine 212 (i.e. Asparagine to Glutamine mutation) have been reported to impaire its trafficking to the membrane.
Oxidation
Cystine	1 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC1A5			[5]
Role of PTM	Potential impacts
Modified Residue	Cystine	Modified Location	467
Experimental Method	Co-Immunoprecipitation
Detailed Description	Oxidation at SLC1A5 Cystine 467 has the potential to affect its expression or activity.
Phosphorylation
Serine	10 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC1A5			[2]
Role of PTM	Potential impacts
Affected Drug/Substrate	Glutamate	Results for Drug	Affecting the inward transport of glutamate
Modified Residue	Serine	Modified Location	9
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC1A5 Serine 9 has the potential to affect its expression or activity.
PTM Phenomenon2	Have the potential to influence SLC1A5			[2]
Role of PTM	Potential impacts
Affected Drug/Substrate	Glutamate	Results for Drug	Affecting the inward transport of glutamate
Modified Residue	Serine	Modified Location	27
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC1A5 Serine 27 has the potential to affect its expression or activity.
PTM Phenomenon3	Have the potential to influence SLC1A5			[2]
Role of PTM	Potential impacts
Affected Drug/Substrate	Glutamate	Results for Drug	Affecting the inward transport of glutamate
Modified Residue	Serine	Modified Location	183
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC1A5 Serine 183 has the potential to affect its expression or activity.
PTM Phenomenon4	Have the potential to influence SLC1A5			[2]
Role of PTM	Potential impacts
Affected Drug/Substrate	Glutamate	Results for Drug	Affecting the inward transport of glutamate
Modified Residue	Serine	Modified Location	194
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC1A5 Serine 194 has the potential to affect its expression or activity.
PTM Phenomenon5	Have the potential to influence SLC1A5			[2]
Role of PTM	Potential impacts
Affected Drug/Substrate	Glutamate	Results for Drug	Affecting the inward transport of glutamate
Modified Residue	Serine	Modified Location	198
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC1A5 Serine 198 has the potential to affect its expression or activity.
PTM Phenomenon6	Have the potential to influence SLC1A5			[6], [7]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	491
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC1A5 Serine 491 has the potential to affect its expression or activity.
PTM Phenomenon7	Have the potential to influence SLC1A5			[2]
Role of PTM	Potential impacts
Affected Drug/Substrate	Glutamate	Results for Drug	Affecting the inward transport of glutamate
Modified Residue	Serine	Modified Location	493
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC1A5 Serine 493 has the potential to affect its expression or activity.
PTM Phenomenon8	Have the potential to influence SLC1A5			[2]
Role of PTM	Potential impacts
Affected Drug/Substrate	Glutamate	Results for Drug	Affecting the inward transport of glutamate
Modified Residue	Serine	Modified Location	503
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC1A5 Serine 503 has the potential to affect its expression or activity.
PTM Phenomenon9	Have the potential to influence SLC1A5			[2]
Role of PTM	Potential impacts
Affected Drug/Substrate	Glutamate	Results for Drug	Affecting the inward transport of glutamate
Modified Residue	Serine	Modified Location	535
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC1A5 Serine 535 has the potential to affect its expression or activity.
PTM Phenomenon10	Have the potential to influence SLC1A5			[2]
Role of PTM	Potential impacts
Affected Drug/Substrate	Glutamate	Results for Drug	Affecting the inward transport of glutamate
Modified Residue	Serine	Modified Location	539
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC1A5 Serine 539 has the potential to affect its expression or activity.
Threonine	7 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC1A5			[8], [9]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	18
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC1A5 Threonine 18 has the potential to affect its expression or activity.
PTM Phenomenon2	Have the potential to influence SLC1A5			[10]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	206
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC1A5 Threonine 206 has the potential to affect its expression or activity.
PTM Phenomenon3	Have the potential to influence SLC1A5			[10]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	214
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC1A5 Threonine 214 has the potential to affect its expression or activity.
PTM Phenomenon4	Have the potential to influence SLC1A5			[7], [11]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	489
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC1A5 Threonine 489 has the potential to affect its expression or activity.
PTM Phenomenon5	Have the potential to influence SLC1A5			[2]
Role of PTM	Potential impacts
Affected Drug/Substrate	Glutamate	Results for Drug	Affecting the inward transport of glutamate
Modified Residue	Threonine	Modified Location	494
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC1A5 Threonine 494 has the potential to affect its expression or activity.
PTM Phenomenon6	Have the potential to influence SLC1A5			[12], [13]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	514
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC1A5 Threonine 514 has the potential to affect its expression or activity.
PTM Phenomenon7	Have the potential to influence SLC1A5			[2]
Role of PTM	Potential impacts
Affected Drug/Substrate	Glutamate	Results for Drug	Affecting the inward transport of glutamate
Modified Residue	Threonine	Modified Location	532
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC1A5 Threonine 532 has the potential to affect its expression or activity.
Tyrosine	3 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC1A5			[2]
Role of PTM	Potential impacts
Affected Drug/Substrate	Glutamate	Results for Drug	Affecting the inward transport of glutamate
Modified Residue	Tyrosine	Modified Location	38
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC1A5 Tyrosine 38 has the potential to affect its expression or activity.
PTM Phenomenon2	Have the potential to influence SLC1A5			[10]
Role of PTM	Potential impacts
Modified Residue	Tyrosine	Modified Location	204
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC1A5 Tyrosine 204 has the potential to affect its expression or activity.
PTM Phenomenon3	Have the potential to influence SLC1A5			[2]
Role of PTM	Potential impacts
Affected Drug/Substrate	Glutamate	Results for Drug	Affecting the inward transport of glutamate
Modified Residue	Tyrosine	Modified Location	524
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC1A5 Tyrosine 524 has the potential to affect its expression or activity.
S-nitrosylation
Cystine	2 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC1A5			[14]
Role of PTM	Potential impacts
Modified Residue	Cystine	Modified Location	39
Experimental Method	Co-Immunoprecipitation
Detailed Description	S-nitrosylation (-SNO) at SLC1A5 Cystine 39 has the potential to affect its expression or activity.
PTM Phenomenon2	Have the potential to influence SLC1A5			[14], [15]
Role of PTM	Potential impacts
Modified Residue	Cystine	Modified Location	467
Experimental Method	Co-Immunoprecipitation
Detailed Description	S-nitrosylation (-SNO) at SLC1A5 Cystine 467 has the potential to affect its expression or activity.
S-palmitoylation
Cystine	2 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC1A5			[16], [17]
Role of PTM	Potential impacts
Modified Residue	Cystine	Modified Location	39
Experimental Method	Co-Immunoprecipitation
Detailed Description	S-palmitoylation at SLC1A5 Cystine 39 has the potential to affect its expression or activity.
PTM Phenomenon2	Have the potential to influence SLC1A5			[16]
Role of PTM	Potential impacts
Modified Residue	Cystine	Modified Location	467
Experimental Method	Co-Immunoprecipitation
Detailed Description	S-palmitoylation at SLC1A5 Cystine 467 has the potential to affect its expression or activity.
Sulfoxidation
Methionine	1 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC1A5			[18]
Role of PTM	Potential impacts
Modified Residue	Methionine	Modified Location	541
Experimental Method	Co-Immunoprecipitation
Detailed Description	Sulfoxidation at SLC1A5 Methionine 541 has the potential to affect its expression or activity.
Ubiquitination
Alanine	1 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC1A5			[19]
Role of PTM	Potential impacts
Modified Residue	Alanine	Modified Location	300
Experimental Method	Co-Immunoprecipitation
Detailed Description	Ubiquitination at SLC1A5 Alanine 300 has the potential to affect its expression or activity.
Asparticacid	1 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC1A5			[19]
Role of PTM	Potential impacts
Modified Residue	Asparticacid	Modified Location	294
Experimental Method	Co-Immunoprecipitation
Detailed Description	Ubiquitination at SLC1A5 Asparticacid 294 has the potential to affect its expression or activity.
Lysine	7 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Decreasing cell surface expression of SLC1A5			[20]
Role of PTM	Surface Expression Modulation
Modified Residue	Lysine	Modified Location	10
Studied Phenotype	Hepatoblastoma [ICD11: 2C12.01]
Experimental Material(s)	Human hepatoblastoma (HepG2.2.15) cells
Experimental Method	Co-Immunoprecipitation
Detailed Description	Ubiquitination at SLC1A5 Lysine 10 have been reported to decrease its cell surface expression.
PTM Phenomenon2	Decreasing cell surface expression of SLC1A5			[20]
Role of PTM	Surface Expression Modulation
Modified Residue	Lysine	Modified Location	522
Studied Phenotype	Hepatoblastoma [ICD11: 2C12.01]
Experimental Material(s)	Human hepatoblastoma (HepG2.2.15) cells
Experimental Method	Co-Immunoprecipitation
Detailed Description	Ubiquitination at SLC1A5 Lysine 522 have been reported to decrease its cell surface expression.
PTM Phenomenon3	Decreasing cell surface expression of SLC1A5			[20]
Role of PTM	Surface Expression Modulation
Modified Residue	Lysine	Modified Location	537
Studied Phenotype	Hepatoblastoma [ICD11: 2C12.01]
Experimental Material(s)	Human hepatoblastoma (HepG2.2.15) cells
Experimental Method	Co-Immunoprecipitation
Detailed Description	Ubiquitination at SLC1A5 Lysine 537 have been reported to decrease its cell surface expression.
PTM Phenomenon4	Have the potential to influence SLC1A5			[2]
Role of PTM	Potential impacts
Affected Drug/Substrate	Glutamate	Results for Drug	Affecting the inward transport of glutamate
Modified Residue	Lysine	Modified Location	178
Experimental Method	Co-Immunoprecipitation
Detailed Description	Ubiquitination at SLC1A5 Lysine 178 has the potential to affect its expression or activity.
PTM Phenomenon5	Have the potential to influence SLC1A5			[2]
Role of PTM	Potential impacts
Affected Drug/Substrate	Glutamate	Results for Drug	Affecting the inward transport of glutamate
Modified Residue	Lysine	Modified Location	247
Experimental Method	Co-Immunoprecipitation
Detailed Description	Ubiquitination at SLC1A5 Lysine 247 has the potential to affect its expression or activity.
PTM Phenomenon6	Have the potential to influence SLC1A5			[2]
Role of PTM	Potential impacts
Affected Drug/Substrate	Glutamate	Results for Drug	Affecting the inward transport of glutamate
Modified Residue	Lysine	Modified Location	372
Experimental Method	Co-Immunoprecipitation
Detailed Description	Ubiquitination at SLC1A5 Lysine 372 has the potential to affect its expression or activity.
PTM Phenomenon7	Have the potential to influence SLC1A5			[2]
Role of PTM	Potential impacts
Affected Drug/Substrate	Glutamate	Results for Drug	Affecting the inward transport of glutamate
Modified Residue	Lysine	Modified Location	502
Experimental Method	Co-Immunoprecipitation
Detailed Description	Ubiquitination at SLC1A5 Lysine 502 has the potential to affect its expression or activity.
Methionine	1 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC1A5			[19]
Role of PTM	Potential impacts
Modified Residue	Methionine	Modified Location	274
Experimental Method	Co-Immunoprecipitation
Detailed Description	Ubiquitination at SLC1A5 Methionine 274 has the potential to affect its expression or activity.
Valine	1 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC1A5			[19]
Role of PTM	Potential impacts
Modified Residue	Valine	Modified Location	320
Experimental Method	Co-Immunoprecipitation
Detailed Description	Ubiquitination at SLC1A5 Valine 320 has the potential to affect its expression or activity.

References
1	Lysine Acetylation and Succinylation in HeLa Cells and their Essential Roles in Response to UV-induced Stress. Sci Rep. 2016 Jul 25;6:30212.
2	The Human SLC1A5 (ASCT2) Amino Acid Transporter: From Function to Structure and Role in Cell Biology. Front Cell Dev Biol. 2018 Sep 4;6:96.
3	Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501.
4	N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54.
5	A Quantitative Tissue-Specific Landscape of Protein Redox Regulation during Aging. Cell. 2020 Mar 5;180(5):968-983.e24.
6	Capillary Zone Electrophoresis-Tandem Mass Spectrometry for Large-Scale Phosphoproteomics with the Production of over 11,000 Phosphopeptides from the Colon Carcinoma HCT116 Cell Line. Anal Chem. 2019 Feb 5;91(3):2201-2208.
7	Defeating Major Contaminants in Fe3+- Immobilized Metal Ion Affinity Chromatography (IMAC) Phosphopeptide Enrichment. Mol Cell Proteomics. 2018 May;17(5):1028-1034.
8	An integrated strategy for highly sensitive phosphoproteome analysis from low micrograms of protein samples. Analyst. 2018 Jul 23;143(15):3693-3701.
9	Phosphoproteomic screening identifies Rab GTPases as novel downstream targets of PINK1. EMBO J. 2015 Nov 12;34(22):2840-61.
10	Improved Method for Determining Absolute Phosphorylation Stoichiometry Using Bayesian Statistics and Isobaric Labeling. J Proteome Res. 2017 Nov 3;16(11):4217-4226.
11	Tip-Based Fractionation of Batch-Enriched Phosphopeptides Facilitates Easy and Robust Phosphoproteome Analysis. J Proteome Res. 2018 Jan 5;17(1):46-54.
12	Phosphoproteomics to Characterize Host Response During Influenza A Virus Infection of Human Macrophages. Mol Cell Proteomics. 2016 Oct;15(10):3203-3219.
13	Temporal proteomic analysis of HIV infection reveals remodelling of the host phosphoproteome by lentiviral Vif variants. Elife. 2016 Sep 30;5:e18296.
14	Proteome-wide detection of S-nitrosylation targets and motifs using bioorthogonal cleavable-linker-based enrichment and switch technique. Nat Commun. 2019 May 16;10(1):2195.
15	Dual Labeling Biotin Switch Assay to Reduce Bias Derived From Different Cysteine Subpopulations: A Method to Maximize S-Nitrosylation Detection. Circ Res. 2015 Oct 23;117(10):846-57.
16	Selective Enrichment and Direct Analysis of Protein S-Palmitoylation Sites. J Proteome Res. 2018 May 4;17(5):1907-1922.
17	Proteome scale characterization of human S-acylated proteins in lipid raft-enriched and non-raft membranes. Mol Cell Proteomics. 2010 Jan;9(1):54-70.
18	Redox proteomics of protein-bound methionine oxidation. Mol Cell Proteomics. 2011 May;10(5):M110.006866.
19	A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. Mol Cell Proteomics. 2011 Oct;10(10):M111.013284.
20	Global analysis of HBV-mediated host proteome and ubiquitylome change in HepG2.2.15 human hepatoblastoma cell line. Cell Biosci. 2021 Apr 17;11(1):75.

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Detail Information of Post-Translational Modifications

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