Detail Information of Post-Translational Modifications

General Information of Drug Transporter (DT)
DT ID	DTD0086 Transporter Info
Gene Name	SLC12A5
Transporter Name	Electroneutral potassium-chloride cotransporter 2
Gene ID	57468
UniProt ID	Q9H2X9

Post-Translational Modification of This DT
Overview ofSLC12A5 Modification Sites with Functional and Structural Information
Sequence	M S R R F T V T S L P P A G P A R S P D P E S R R H S V A D P R H L P G E D V K G D G N P K E S S P F I N S T D T E K G K E Y D G K N M A L F E E E M D T S P M V S S L L S G L A N Y T N L P Q G S R E H E E A E N N E G G K K K P V Q A P R M G T F M G V Y L P C L Q N I F G V I L F L R L T W V V G I A G I M E S F C M V F I C C S C T M L T A I S M S A I A T N G V V P A G G S Y Y M I S R S L G P E F G G A V G L C F Y L G T T F A G A M Y I L G T I E I L L A Y L F P A M A I F K A E D A S G E A A A M L N N M R V Y G T C V L T C M A T V V F V G V K Y V N K F A L V F L G C V I L S I L A I Y A G V I K S A F D P P N F P I C L L G N R T L S R H G F D V C A K L A W E G N E T V T T R L W G L F C S S R F L N A T C D E Y F T R N N V T E I Q G I P G A A S G L I K E N L W S S Y L T K G V I V E R S G M T S V G L A D G T P I D M D H P Y V F S D M T S Y F T L L V G I Y F P S V T G I M A G S N R S G D L R D A Q K S I P T G T I L A I A T T S A V Y I S S V V L F G A C I E G V V L R D K F G E A V N G N L V V G T L A W P S P W V I V I G S F F S T C G A G L Q S L T G A P R L L Q A I S R D G I V P F L Q V F G H G K A N G E P T W A L L L T A C I C E I G I L I A S L D E V A P I L S M F F L M C Y M F V N L A C A V Q T L L R T P N W R P R F R Y Y H W T L S F L G M S L C L A L M F I C S W Y Y A L V A M L I A G L I Y K Y I E Y R G A E K E W G D G I R G L S L S A A R Y A L L R L E E G P P H T K N W R P Q L L V L V R V D Q D Q N V V H P Q L L S L T S Q L K A G K G L T I V G S V L E G T F L E N H P Q A Q R A E E S I R R L M E A E K V K G F C Q V V I S S N L R D G V S H L I Q S G G L G G L Q H N T V L V G W P R N W R Q K E D H Q T W R N F I E L V R E T T A G H L A L L V T K N V S M F P G N P E R F S E G S I D V W W I V H D G G M L M L L P F L L R H H K V W R K C K M R I F T V A Q M D D N S I Q M K K D L T T F L Y H L R I T A E V E V V E M H E S D I S A Y T Y E K T L V M E Q R S Q I L K Q M H L T K N E R E R E I Q S I T D E S R G S I R R K N P A N T R L R L N V P E E T A G D S E E K P E E E V Q L I H D Q S A P S C P S S S P S P G E E P E G E G E T D P E K V H L T W T K D K S V A E K N K G P S P V S S E G I K D F F S M K P E W E N L N Q S N V R R M H T A V R L N E V I V K K S R D A K L V L L N M P G P P R N R N G D E N Y M E F L E V L T E H L D R V M L V R G G G R E V I T I Y S
PTM type	X-N-glycosylation X-Oxidation X-Phosphorylation X-Phosphorylation X-Ubiquitination X: Amino Acid

N-glycosylation
Asparagine	2 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC12A5			[1]
Role of PTM	Potential impacts
Modified Residue	Asparagine	Modified Location	442
Experimental Method	Co-Immunoprecipitation
Detailed Description	N-linked Glycosylation at SLC12A5 Asparagine 442 has the potential to affect its expression or activity.
PTM Phenomenon2	Have the potential to influence SLC12A5			[1]
Role of PTM	Potential impacts
Modified Residue	Asparagine	Modified Location	833
Experimental Method	Co-Immunoprecipitation
Detailed Description	N-linked Glycosylation at SLC12A5 Asparagine 833 has the potential to affect its expression or activity.
Oxidation
Cystine	2 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC12A5			[2]
Role of PTM	Potential impacts
Modified Residue	Cystine	Modified Location	325
Experimental Method	Co-Immunoprecipitation
Detailed Description	Oxidation at SLC12A5 Cystine 325 has the potential to affect its expression or activity.
PTM Phenomenon2	Have the potential to influence SLC12A5			[2]
Role of PTM	Potential impacts
Modified Residue	Cystine	Modified Location	765
Experimental Method	Co-Immunoprecipitation
Detailed Description	Oxidation at SLC12A5 Cystine 765 has the potential to affect its expression or activity.
Phosphorylation
Serine	22 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC12A5			[3]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	2
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Serine 2 has the potential to affect its expression or activity.
PTM Phenomenon2	Have the potential to influence SLC12A5			[3], [4]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	9
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Serine 9 has the potential to affect its expression or activity.
PTM Phenomenon3	Have the potential to influence SLC12A5			[4]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	18
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Serine 18 has the potential to affect its expression or activity.
PTM Phenomenon4	Have the potential to influence SLC12A5			[4]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	23
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Serine 23 has the potential to affect its expression or activity.
PTM Phenomenon5	Have the potential to influence SLC12A5			[5], [6]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	27
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Serine 27 has the potential to affect its expression or activity.
PTM Phenomenon6	Have the potential to influence SLC12A5			[7], [8]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	49
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Serine 49 has the potential to affect its expression or activity.
PTM Phenomenon7	.			[9]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	78
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Serine 78 has the potential to affect its expression or activity.
PTM Phenomenon8	.			[9]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	82
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Serine 82 has the potential to affect its expression or activity.
PTM Phenomenon9	Have the potential to influence SLC12A5			[10]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	537
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Serine 537 has the potential to affect its expression or activity.
PTM Phenomenon10	Have the potential to influence SLC12A5			[11]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	672
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Serine 672 has the potential to affect its expression or activity.
PTM Phenomenon11	Have the potential to influence SLC12A5			[11]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	674
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Serine 674 has the potential to affect its expression or activity.
PTM Phenomenon12	Have the potential to influence SLC12A5			[12]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	751
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Serine 751 has the potential to affect its expression or activity.
PTM Phenomenon13	Have the potential to influence SLC12A5			[13]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	770
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Serine 770 has the potential to affect its expression or activity.
PTM Phenomenon14	Have the potential to influence SLC12A5			[14]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	936
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Serine 936 has the potential to affect its expression or activity.
PTM Phenomenon15	Have the potential to influence SLC12A5			[11]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	960
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Serine 960 has the potential to affect its expression or activity.
PTM Phenomenon16	Have the potential to influence SLC12A5			[7], [11]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	963
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Serine 963 has the potential to affect its expression or activity.
PTM Phenomenon17	Have the potential to influence SLC12A5			[15]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	1007
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Serine 1007 has the potential to affect its expression or activity.
PTM Phenomenon18	Have the potential to influence SLC12A5			[7], [16]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	1045
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Serine 1045 has the potential to affect its expression or activity.
PTM Phenomenon19	Have the potential to influence SLC12A5			[16]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	1048
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Serine 1048 has the potential to affect its expression or activity.
PTM Phenomenon20	.			[17]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	1049
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Serine 1049 has the potential to affect its expression or activity.
PTM Phenomenon21	Have the potential to influence SLC12A5			[18]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	1057
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Serine 1057 has the potential to affect its expression or activity.
PTM Phenomenon22	.			[19]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	1068
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Serine 1068 has the potential to affect its expression or activity.
Threonine	14 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC12A5			[4], [18]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	6
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Threonine 6 has the potential to affect its expression or activity.
PTM Phenomenon2	Have the potential to influence SLC12A5			[3], [4]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	8
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Threonine 8 has the potential to affect its expression or activity.
PTM Phenomenon3	.			[9]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	77
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Threonine 77 has the potential to affect its expression or activity.
PTM Phenomenon4	.			[9]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	92
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Threonine 92 has the potential to affect its expression or activity.
PTM Phenomenon5	.			[9]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	92
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Threonine 92 has the potential to affect its expression or activity.
PTM Phenomenon6	.			[9]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	92
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Threonine 92 has the potential to affect its expression or activity.
PTM Phenomenon7	Have the potential to influence SLC12A5			[20]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	335
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Threonine 335 has the potential to affect its expression or activity.
PTM Phenomenon8	Have the potential to influence SLC12A5			[20]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	337
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Threonine 337 has the potential to affect its expression or activity.
PTM Phenomenon9	Have the potential to influence SLC12A5			[20]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	338
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Threonine 338 has the potential to affect its expression or activity.
PTM Phenomenon10	.			[19]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	501
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Threonine 501 has the potential to affect its expression or activity.
PTM Phenomenon11	Have the potential to influence SLC12A5			[21]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	929
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Threonine 929 has the potential to affect its expression or activity.
PTM Phenomenon12	Have the potential to influence SLC12A5			[22]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	945
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Threonine 945 has the potential to affect its expression or activity.
PTM Phenomenon13	Have the potential to influence SLC12A5			[15], [21]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	1030
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Threonine 1030 has the potential to affect its expression or activity.
PTM Phenomenon14	.			[9]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	1032
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Threonine 1032 has the potential to affect its expression or activity.
Tyrosine	1 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC12A5			[23]
Role of PTM	Potential impacts
Modified Residue	Tyrosine	Modified Location	1110
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A5 Tyrosine 1110 has the potential to affect its expression or activity.
Ubiquitination
Arginine	1 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC12A5			[24]
Role of PTM	Potential impacts
Modified Residue	Arginine	Modified Location	702
Experimental Method	Co-Immunoprecipitation
Detailed Description	Ubiquitination at SLC12A5 Arginine 702 has the potential to affect its expression or activity.
Isoleucine	1 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC12A5			[24], [25]
Role of PTM	Potential impacts
Modified Residue	Isoleucine	Modified Location	668
Experimental Method	Co-Immunoprecipitation
Detailed Description	Ubiquitination at SLC12A5 Isoleucine 668 has the potential to affect its expression or activity.
Lysine	4 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC12A5			[24], [25]
Role of PTM	Potential impacts
Modified Residue	Lysine	Modified Location	691
Experimental Method	Co-Immunoprecipitation
Detailed Description	Ubiquitination at SLC12A5 Lysine 691 has the potential to affect its expression or activity.
PTM Phenomenon2	Have the potential to influence SLC12A5			[24]
Role of PTM	Potential impacts
Modified Residue	Lysine	Modified Location	725
Experimental Method	Co-Immunoprecipitation
Detailed Description	Ubiquitination at SLC12A5 Lysine 725 has the potential to affect its expression or activity.
PTM Phenomenon3	Have the potential to influence SLC12A5			[24]
Role of PTM	Potential impacts
Modified Residue	Lysine	Modified Location	872
Experimental Method	Co-Immunoprecipitation
Detailed Description	Ubiquitination at SLC12A5 Lysine 872 has the potential to affect its expression or activity.
PTM Phenomenon4	Have the potential to influence SLC12A5			[24]
Role of PTM	Potential impacts
Modified Residue	Lysine	Modified Location	895
Experimental Method	Co-Immunoprecipitation
Detailed Description	Ubiquitination at SLC12A5 Lysine 895 has the potential to affect its expression or activity.

References
1	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: S12A5_HUMAN)
2	A Quantitative Tissue-Specific Landscape of Protein Redox Regulation during Aging. Cell. 2020 Mar 5;180(5):968-983.e24.
3	Characterization of native protein complexes and protein isoform variation using size-fractionation-based quantitative proteomics. Mol Cell Proteomics. 2013 Dec;12(12):3851-73.
4	Phosphoproteomic screening identifies physiological substrates of the CDKL5 kinase. EMBO J. 2018 Dec 14;37(24):e99559.
5	Proteogenomic integration reveals therapeutic targets in breast cancer xenografts. Nat Commun. 2017 Mar 28;8:14864.
6	Phosphoproteome profiling revealed abnormally phosphorylated AMPK and ATF2 involved in glucose metabolism and tumorigenesis of GH-PAs. J Endocrinol Invest. 2019 Feb;42(2):137-148.
7	Quantitative phosphoproteomics of Alzheimer's disease reveals cross-talk between kinases and small heat shock proteins. Proteomics. 2015 Jan;15(2-3):508-519.
8	Defective sphingosine 1-phosphate receptor 1 (S1P1) phosphorylation exacerbates TH17-mediated autoimmune neuroinflammation. Nat Immunol. 2013 Nov;14(11):1166-72.
9	ActiveDriverDB: human disease mutations and genome variation in post-translational modification sites of proteins. Nucleic Acids Res. 2018;46(D1):D901-D910.
10	Tip-Based Fractionation of Batch-Enriched Phosphopeptides Facilitates Easy and Robust Phosphoproteome Analysis. J Proteome Res. 2018 Jan 5;17(1):46-54.
11	A Methodological Assessment and Characterization of Genetically-Driven Variation in Three Human Phosphoproteomes. Sci Rep. 2018 Aug 14;8(1):12106.
12	Global Phosphoproteomic Analysis of Human Skeletal Muscle Reveals a Network of Exercise-Regulated Kinases and AMPK Substrates. Cell Metab. 2015 Nov 3;22(5):922-35.
13	Robust, Reproducible, and Economical Phosphopeptide Enrichment Using Calcium Titanate. J Proteome Res. 2019 Mar 1;18(3):1411-1417.
14	Integrative network analysis of signaling in human CD34(+) hematopoietic progenitor cells by global phosphoproteomic profiling using TiO2 enrichment combined with 2D LC-MS/MS and pathway mapping. Proteomics. 2013 Apr;13(8):1325-33.
15	Global Landscape and Dynamics of Parkin and USP30-Dependent Ubiquitylomes in iNeurons during Mitophagic Signaling. Mol Cell. 2020 Mar 5;77(5):1124-1142.e10.
16	Refined phosphopeptide enrichment by phosphate additive and the analysis of human brain phosphoproteome. Proteomics. 2015 Jan;15(2-3):500-7.
17	BioMuta and BioXpress: mutation and expression knowledgebases for cancer biomarker discovery. Nucleic Acids Res. 2018;46(D1):D1128-D1136.
18	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.
19	15 years of PhosphoSitePlus?: integrating post-translationally modified sites, disease variants and isoforms. Nucleic Acids Res. 2019;47(D1):D433-D441.
20	Proteogenomics connects somatic mutations to signalling in breast cancer. Nature. 2016 Jun 2;534(7605):55-62.
21	Sites of regulated phosphorylation that control K-Cl cotransporter activity. Cell. 2009 Aug 7;138(3):525-36.
22	Quantitative Proteomics Reveals the Dynamics of Protein Phosphorylation in Human Bronchial Epithelial Cells during Internalization, Phagosomal Escape, and Intracellular Replication of Staphylococcus aureus. J Proteome Res. 2016 Dec 2;15(12):4369-4386.
23	Dependence of KCC2 K-Cl cotransporter activity on a conserved carboxy terminus tyrosine residue. Am J Physiol Cell Physiol. 2000 Sep;279(3):C860-7.
24	Quantitative Analysis of the Brain Ubiquitylome in Alzheimer's Disease. Proteomics. 2018 Oct;18(20):e1800108.
25	Systematic functional prioritization of protein posttranslational modifications. Cell. 2012 Jul 20;150(2):413-25.

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Detail Information of Post-Translational Modifications

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