Detail Information of Post-Translational Modifications

General Information of Drug Transporter (DT)
DT ID	DTD0262 Transporter Info
Gene Name	SLC2A4
Transporter Name	Glucose transporter type 4, insulin-responsive
Gene ID	6517
UniProt ID	P14672

Post-Translational Modification of This DT
Overview ofSLC2A4 Modification Sites with Functional and Structural Information
Sequence	M P S G F Q Q I G S E D G E P P Q Q R V T G T L V L A V F S A V L G S L Q F G Y N I G V I N A P Q K V I E Q S Y N E T W L G R Q G P E G P S S I P P G T L T T L W A L S V A I F S V G G M I S S F L I G I I S Q W L G R K R A M L V N N V L A V L G G S L M G L A N A A A S Y E M L I L G R F L I G A Y S G L T S G L V P M Y V G E I A P T H L R G A L G T L N Q L A I V I G I L I A Q V L G L E S L L G T A S L W P L L L G L T V L P A L L Q L V L L P F C P E S P R Y L Y I I Q N L E G P A R K S L K R L T G W A D V S G V L A E L K D E K R K L E R E R P L S L L Q L L G S R T H R Q P L I I A V V L Q L S Q Q L S G I N A V F Y Y S T S I F E T A G V G Q P A Y A T I G A G V V N T V F T L V S V L L V E R A G R R T L H L L G L A G M C G C A I L M T V A L L L L E R V P A M S Y V S I V A I F G F V A F F E I G P G P I P W F I V A E L F S Q G P R P A A M A V A G F S N W T S N F I I G M G F Q Y V A E A M G P Y V F L L F A V L L L G F F I F T F L R V P E T R G R T F D Q I S A A F H R T P S L L E Q E V K P S T E L E Y L G P D E N D
PTM type	X-Deubiquitination X-N-glycosylation X-Palmitoylation X-Phosphorylation X-S-palmitoylation X-SUMOylation X: Amino Acid

Deubiquitination
Unclear Residue	1 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Increasing cell surface expression of SLC2A4			[1]
Role of PTM	Surface Expression Modulation
Related Enzyme	Serine/threonine-protein kinase SGK1 (SGK1)
Experimental Method	Co-Immunoprecipitation
Detailed Description	Deubiquitination at SLC2A4 have been reported to increase its cell surface expression.
N-glycosylation
Asparagine	1 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Critically important for the protein stability of SLC2A4			[2]
Role of PTM	Protein Stability
Modified Residue	Asparagine	Modified Location	57
Experimental Method	Co-Immunoprecipitation
Detailed Description	Glycosylation at SLC2A4 Asparagine 57 have been reported to be critically important for its protein stability.
Palmitoylation
Cysteine	1 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Enhancing the insulin-dependent translocation of SLC2A4 to the plasma membrane			[3]
Role of PTM	Surface Expression Modulation
Modified Residue	Cysteine	Modified Location	223
Related Enzyme	Palmitoyltransferase ZDHHC7 (ZDHHC7)
Experimental Method	Co-Immunoprecipitation
Detailed Description	Palmitoylation at SLC2A4 Cysteine 223 have been reported to enhance its insulin-dependent translocation to the plasma membrane.
Phosphorylation
Serine	3 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC2A4			[4], [5]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	274
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC2A4 Serine 274 has the potential to affect its expression or activity.
PTM Phenomenon2	Have the potential to influence SLC2A4			[6], [7]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	488
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC2A4 Serine 488 has the potential to affect its expression or activity.
PTM Phenomenon3	Have the potential to influence SLC2A4			[8], [9]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	497
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC2A4 Serine 497 has the potential to affect its expression or activity.
Threonine	2 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC2A4			[6], [10]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	486
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC2A4 Threonine 486 has the potential to affect its expression or activity.
PTM Phenomenon2	Have the potential to influence SLC2A4			[8], [9]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	498
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC2A4 Threonine 498 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 SLC2A4			[5], [11]
Role of PTM	Potential impacts
Modified Residue	Tyrosine	Modified Location	56
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC2A4 Tyrosine 56 has the potential to affect its expression or activity.
PTM Phenomenon2	Have the potential to influence SLC2A4			[12]
Role of PTM	Potential impacts
Modified Residue	Tyrosine	Modified Location	229
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC2A4 Tyrosine 229 has the potential to affect its expression or activity.
PTM Phenomenon3	Have the potential to influence SLC2A4			[8], [13]
Role of PTM	Potential impacts
Modified Residue	Tyrosine	Modified Location	502
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC2A4 Tyrosine 502 has the potential to affect its expression or activity.
Unclear Residue	1 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Increasing cell surface expression of SLC2A4			[1]
Role of PTM	Surface Expression Modulation
Related Enzyme	Serine/threonine-protein kinase SGK1 (SGK1)
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC2A4 have been reported to increase its cell surface expression.
S-palmitoylation
Cystine	1 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC2A4			[14]
Role of PTM	Potential impacts
Modified Residue	Cystine	Modified Location	223
Experimental Method	Co-Immunoprecipitation
Detailed Description	S-palmitoylation at SLC2A4 Cystine 223 has the potential to affect its expression or activity.
SUMOylation
Unclear Residue	1 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Potentially improving the stability of the transporter, as well as increasing the overall level of the transporter			[2]
Role of PTM	Protein Stability
Related Enzyme	SUMO-conjugating enzyme UBC9 (UBE2I)
Experimental Method	Co-Immunoprecipitation
Detailed Description	SUMOylation at SLC2A4 have been reported to potentially improve its stability, as well as increase its overall level.

References
1	Proline Absorption and SGK1 Expression are Inhibited in Intestinal Tis7 Transgenic Mice. Cell Physiol Biochem. 2016;38(4):1532-43.
2	Posttranslational modifications of GLUT4 affect its subcellular localization and translocation. Int J Mol Sci. 2013 May 10;14(5):9963-78.
3	DHHC7 Palmitoylates Glucose Transporter 4 (Glut4) and Regulates Glut4 Membrane Translocation. J Biol Chem. 2017 Feb 17;292(7):2979-2991.
4	UniProt: a worldwide hub of protein knowledge. Nucleic Acids Res. 2019 Jan 8;47(D1):D506-D515.
5	Systematic functional prioritization of protein posttranslational modifications. Cell. 2012 Jul 20;150(2):413-25.
6	Phosphoproteomic and Functional Analyses Reveal Sperm-specific Protein Changes Downstream of Kappa Opioid Receptor in Human Spermatozoa. Mol Cell Proteomics. 2019 Mar 15;18(Suppl 1):S118-S131.
7	Modulation of Cl- signaling and ion transport by recruitment of kinases and phosphatases mediated by the regulatory protein IRBIT. Sci Signal. 2018 Oct 30;11(554):eaat5018.
8	Deep Coverage of Global Protein Expression and Phosphorylation in Breast Tumor Cell Lines Using TMT 10-plex Isobaric Labeling. J Proteome Res. 2017 Mar 3;16(3):1121-1132.
9	An integrated strategy for highly sensitive phosphoproteome analysis from low micrograms of protein samples. Analyst. 2018 Jul 23;143(15):3693-3701.
10	Robust, Reproducible, and Economical Phosphopeptide Enrichment Using Calcium Titanate. J Proteome Res. 2019 Mar 1;18(3):1411-1417.
11	Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell. 2007 Dec 14;131(6):1190-203.
12	Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels. Mol Cell Proteomics. 2014 Jul;13(7):1690-704.
13	Ultra-deep tyrosine phosphoproteomics enabled by a phosphotyrosine superbinder. Nat Chem Biol. 2016 Nov;12(11):959-966.
14	Glut4 palmitoylation at Cys223 plays a critical role in Glut4 membrane trafficking. Biochem Biophys Res Commun. 2015 May 8;460(3):709-14.

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Detail Information of Post-Translational Modifications

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