Detail Information of Post-Translational Modifications

General Information of Drug Transporter (DT)
DT ID	DTD0483 Transporter Info
Gene Name	SLC9A3
Transporter Name	Sodium/hydrogen exchanger 3
Gene ID	6550
UniProt ID	P48764

Post-Translational Modification of This DT
Overview ofSLC9A3 Modification Sites with Functional and Structural Information
Sequence	M W G L G A R G P D R G L L L A L A L G G L A R A G G V E V E P G G A H G E S G G F Q V V T F E W A H V Q D P Y V I A L W I L V A S L A K I G F H L S H K V T S V V P E S A L L I V L G L V L G G I V W A A D H I A S F T L T P T V F F F Y L L P P I V L D A G Y F M P N R L F F G N L G T I L L Y A V V G T V W N A A T T G L S L Y G V F L S G L M G D L Q I G L L D F L L F G S L M A A V D P V A V L A V F E E V H V N E V L F I I V F G E S L L N D A V T V V L Y N V F E S F V A L G G D N V T G V D C V K G I V S F F V V S L G G T L V G V V F A F L L S L V T R F T K H V R I I E P G F V F I I S Y L S Y L T S E M L S L S A I L A I T F C G I C C Q K Y V K A N I S E Q S A T T V R Y T M K M L A S S A E T I I F M F L G I S A V N P F I W T W N T A F V L L T L V F I S V Y R A I G V V L Q T W L L N R Y R M V Q L E P I D Q V V L S Y G G L R G A V A F A L V V L L D G D K V K E K N L F V S T T I I V V F F T V I F Q G L T I K P L V Q W L K V K R S E H R E P R L N E K L H G R A F D H I L S A I E D I S G Q I G H N Y L R D K W S H F D R K F L S R V L M R R S A Q K S R D R I L N V F H E L N L K D A I S Y V A E G E R R G S L A F I R S P S T D N V V N V D F T P R S S T V E A S V S Y L L R E N V S A V C L D M Q S L E Q R R R S I R D A E D M V T H H T L Q Q Y L Y K P R Q E Y K H L Y S R H E L T P T E D E K Q D R E I F H R T M R K R L E S F K S T K L G L N Q N K K A A K L Y K R E R A Q K R R N S S I P N G K L P M E S P A Q N F T I K E K D L E L S D T E E P P N Y D E E M S G G I E F L A S V T K D T A S D S P A G I D N P V F S P D E A L D R S L L A R L P P W L S P G E T V V P S Q R A R T Q I P Y S P G T F C R L M P F R L S S K S V D S F L Q A D G P E E R P P A A L P E S T H M
PTM type	X-Acetylation X-Deubiquitination X-N-glycosylation X-Oxidation X-Phosphorylation X-Phosphorylation X-Ubiquitination X: Amino Acid

Acetylation
Lysine	1 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC9A3			[1]
Role of PTM	Potential impacts
Modified Residue	Lysine	Modified Location	682
Experimental Method	Co-Immunoprecipitation
Detailed Description	Acetylation at SLC9A3 Lysine 682 has the potential to affect its expression or activity.
Deubiquitination
Unclear Residue	1 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Increasing SLC9A3 expression at the surface membrane and cellular level.			[2]
Role of PTM	Surface Expression Modulation
Related Enzyme	Ubiquitin carboxyl-terminal hydrolase 10 (USP10)
Experimental Material(s)	Human intestine epithelial cell lines (Caco-2bbe and SK-CO15)
Experimental Method	Co-Immunoprecipitation
Detailed Description	Deubiquitination at SLC9A3 have been reported to increase its expression at the surface membrane and cellular level.
N-glycosylation
Asparagine	2 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC9A3			[3]
Role of PTM	Potential impacts
Modified Residue	Asparagine	Modified Location	241
Experimental Method	Co-Immunoprecipitation
Detailed Description	N-linked Glycosylation at SLC9A3 Asparagine 241 has the potential to affect its expression or activity.
PTM Phenomenon2	Have the potential to influence SLC9A3			[3]
Role of PTM	Potential impacts
Modified Residue	Asparagine	Modified Location	326
Experimental Method	Co-Immunoprecipitation
Detailed Description	N-linked Glycosylation at SLC9A3 Asparagine 326 has the potential to affect its expression or activity.
Oxidation
Cystine	1 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC9A3			[4]
Role of PTM	Potential impacts
Modified Residue	Cystine	Modified Location	595
Experimental Method	Co-Immunoprecipitation
Detailed Description	Oxidation at SLC9A3 Cystine 595 has the potential to affect its expression or activity.
Phosphorylation
Serine	19 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Relating to increased abundance of the transporter on the cell membrane			[5]
Role of PTM	Surface Expression Modulation
Modified Residue	Serine	Modified Location	663
Related Enzyme	Serine/threonine-protein kinase SGK1 (SGK1)
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Serine 663 have been reported to be associated with increased abundance on its cell membrane.
PTM Phenomenon2	Have the potential to influence SLC9A3			[6], [7]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	545
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Serine 545 has the potential to affect its expression or activity.
PTM Phenomenon3	Have the potential to influence SLC9A3			[7], [8]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	555
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Serine 555 has the potential to affect its expression or activity.
PTM Phenomenon4	Have the potential to influence SLC9A3			[7], [9]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	561
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Serine 561 has the potential to affect its expression or activity.
PTM Phenomenon5	Have the potential to influence SLC9A3			[7], [10]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	563
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Serine 563 has the potential to affect its expression or activity.
PTM Phenomenon6	Have the potential to influence SLC9A3			[7]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	576
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Serine 576 has the potential to affect its expression or activity.
PTM Phenomenon7	Have the potential to influence SLC9A3			[7], [8]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	577
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Serine 577 has the potential to affect its expression or activity.
PTM Phenomenon8	Have the potential to influence SLC9A3			[7], [8]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	592
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Serine 592 has the potential to affect its expression or activity.
PTM Phenomenon9	Have the potential to influence SLC9A3			[11]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	600
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Serine 600 has the potential to affect its expression or activity.
PTM Phenomenon10	.			[12]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	607
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Serine 607 has the potential to affect its expression or activity.
PTM Phenomenon11	Have the potential to influence SLC9A3			[11]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	636
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Serine 636 has the potential to affect its expression or activity.
PTM Phenomenon12	Have the potential to influence SLC9A3			[13]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	693
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Serine 693 has the potential to affect its expression or activity.
PTM Phenomenon13	Have the potential to influence SLC9A3			[8]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	748
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Serine 748 has the potential to affect its expression or activity.
PTM Phenomenon14	Have the potential to influence SLC9A3			[6]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	794
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Serine 794 has the potential to affect its expression or activity.
PTM Phenomenon15	Have the potential to influence SLC9A3			[7]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	807
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Serine 807 has the potential to affect its expression or activity.
PTM Phenomenon16	Have the potential to influence SLC9A3			[7]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	808
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Serine 808 has the potential to affect its expression or activity.
PTM Phenomenon17	Have the potential to influence SLC9A3			[6]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	810
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Serine 810 has the potential to affect its expression or activity.
PTM Phenomenon18	Have the potential to influence SLC9A3			[6]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	813
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Serine 813 has the potential to affect its expression or activity.
PTM Phenomenon19	Have the potential to influence SLC9A3			[6]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	831
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Serine 831 has the potential to affect its expression or activity.
Threonine	6 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC9A3			[7], [9]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	564
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Threonine 564 has the potential to affect its expression or activity.
PTM Phenomenon2	Have the potential to influence SLC9A3			[7]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	578
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Threonine 578 has the potential to affect its expression or activity.
PTM Phenomenon3	Have the potential to influence SLC9A3			[6]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	641
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Threonine 641 has the potential to affect its expression or activity.
PTM Phenomenon4	Have the potential to influence SLC9A3			[6]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	643
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Threonine 643 has the potential to affect its expression or activity.
PTM Phenomenon5	Have the potential to influence SLC9A3			[6]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	797
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Threonine 797 has the potential to affect its expression or activity.
PTM Phenomenon6	Have the potential to influence SLC9A3			[6]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	832
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Threonine 832 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 SLC9A3			[14], [15]
Role of PTM	Potential impacts
Modified Residue	Tyrosine	Modified Location	502
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Tyrosine 502 has the potential to affect its expression or activity.
PTM Phenomenon2	Have the potential to influence SLC9A3			[6]
Role of PTM	Potential impacts
Modified Residue	Tyrosine	Modified Location	546
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Tyrosine 546 has the potential to affect its expression or activity.
PTM Phenomenon3	Have the potential to influence SLC9A3			[6]
Role of PTM	Potential impacts
Modified Residue	Tyrosine	Modified Location	793
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC9A3 Tyrosine 793 has the potential to affect its expression or activity.
Ubiquitination
Unclear Residue	1 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Inhibiting the activity of SLC9A3			[16]
Role of PTM	Protein Activity Modulation
Related Enzyme	E3 ubiquitin-protein ligase NEDD4-like (NEDD4L)
Experimental Material(s)	Humanized mice expressing hNHE3 in the intestine (hNHE3int)
Experimental Method	Co-Immunoprecipitation
Detailed Description	Ubiquitination at SLC9A3 have been reported to inhibit its transport activity.

References
1	Effect of temperature acclimation on plasma high density lipoprotein in rats (author's transl). Hokkaido Igaku Zasshi. 1981 Nov;56(6):675-7.
2	Ubiquitin-specific peptidase 7 (USP7) and USP10 mediate deubiquitination of human NHE3 regulating its expression and activity. FASEB J. 2020 Dec;34(12):16476-16488.
3	dbPTM in 2022: an updated database for exploring regulatory networks and functional associations of protein post-translational modifications. Nucleic Acids Res. 2022 Jan 7;50(D1):D471-D479. (ID: SL9A3_HUMAN)
4	A Quantitative Tissue-Specific Landscape of Protein Redox Regulation during Aging. Cell. 2020 Mar 5;180(5):968-983.e24.
5	UniProt: the Universal Protein Knowledgebase in 2023. Nucleic Acids Res. 2023 Jan 6;51(D1):D523-D531. (ID: P48764)
6	Identification of missing proteins in the neXtProt database and unregistered phosphopeptides in the PhosphoSitePlus database as part of the Chromosome-centric Human Proteome Project. J Proteome Res. 2013 Jun 7;12(6):2414-21.
7	Identification of Missing Proteins in the Phosphoproteome of Kidney Cancer. J Proteome Res. 2017 Dec 1;16(12):4364-4373.
8	Integrated analysis of global proteome, phosphoproteome, and glycoproteome enables complementary interpretation of disease-related protein networks. Sci Rep. 2015 Dec 11;5:18189.
9	Phosphoproteomic screening identifies Rab GTPases as novel downstream targets of PINK1. EMBO J. 2015 Nov 12;34(22):2840-61.
10	Time-resolved Phosphoproteome Analysis of Paradoxical RAF Activation Reveals Novel Targets of ERK. Mol Cell Proteomics. 2017 Apr;16(4):663-679.
11	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.
12	BioMuta and BioXpress: mutation and expression knowledgebases for cancer biomarker discovery. Nucleic Acids Res. 2018;46(D1):D1128-D1136.
13	Robust, Reproducible, and Economical Phosphopeptide Enrichment Using Calcium Titanate. J Proteome Res. 2019 Mar 1;18(3):1411-1417.
14	Systematic functional prioritization of protein posttranslational modifications. Cell. 2012 Jul 20;150(2):413-25.
15	Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell. 2007 Dec 14;131(6):1190-203.
16	Nedd4-2-dependent Ubiquitination Potentiates the Inhibition of Human NHE3 by Cholera Toxin and Enteropathogenic Escherichia coli. Cell Mol Gastroenterol Hepatol. 2022;13(3):695-716.

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Detail Information of Post-Translational Modifications

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