Detail Information of Post-Translational Modifications

General Information of Drug Transporter (DT)
DT ID	DTD0082 Transporter Info
Gene Name	SLC12A1
Transporter Name	Bumetanide-sensitive sodium-(potassium)-chloride cotransporter 2
Gene ID	6557
UniProt ID	Q13621

Post-Translational Modification of This DT
Overview ofSLC12A1 Modification Sites with Functional and Structural Information
Sequence	M S L N N S S N V F L D S V P S N T N R F Q V S V I N E N H E S S A A A D D N T D P P H Y E E T S F G D E A Q K R L R I S F R P G N Q E C Y D N F L Q S G E T A K T D A S F H A Y D S H T N T Y Y L Q T F G H N T M D A V P K I E Y Y R N T G S I S G P K V N R P S L L E I H E Q L A K N V A V T P S S A D R V A N G D G I P G D E Q A E N K E D D Q A G V V K F G W V K G V L V R C M L N I W G V M L F I R L S W I V G E A G I G L G V L I I L L S T M V T S I T G L S T S A I A T N G F V R G G G A Y Y L I S R S L G P E F G G S I G L I F A F A N A V A V A M Y V V G F A E T V V D L L K E S D S M M V D P T N D I R I I G S I T V V I L L G I S V A G M E W E A K A Q V I L L V I L L I A I A N F F I G T V I P S N N E K K S R G F F N Y Q A S I F A E N F G P R F T K G E G F F S V F A I F F P A A T G I L A G A N I S G D L E D P Q D A I P R G T M L A I F I T T V A Y L G V A I C V G A C V V R D A T G N M N D T I I S G M N C N G S A A C G L G Y D F S R C R H E P C Q Y G L M N N F Q V M S M V S G F G P L I T A G I F S A T L S S A L A S L V S A P K V F Q A L C K D N I Y K A L Q F F A K G Y G K N N E P L R G Y I L T F L I A M A F I L I A E L N T I A P I I S N F F L A S Y A L I N F S C F H A S Y A K S P G W R P A Y G I Y N M W V S L F G A V L C C A V M F V I N W W A A V I T Y V I E F F L Y V Y V T C K K P D V N W G S S T Q A L S Y V S A L D N A L E L T T V E D H V K N F R P Q C I V L T G G P M T R P A L L D I T H A F T K N S G L C I C C E V F V G P R K L C V K E M N S G M A K K Q A W L I K N K I K A F Y A A V A A D C F R D G V R S L L Q A S G L G R M K P N T L V I G Y K K N W R K A P L T E I E N Y V G I I H D A F D F E I G V V I V R I S Q G F D I S Q V L Q V Q E E L E R L E Q E R L A L E A T I K D N E C E E E S G G I R G L F K K A G K L N I T K T T P K K D G S I N T S Q S M H V G E F N Q K L V E A S T Q F K K K Q E K G T I D V W W L F D D G G L T L L I P Y I L T L R K K W K D C K L R I Y V G G K I N R I E E E K I V M A S L L S K F R I K F A D I H I I G D I N I R P N K E S W K V F E E M I E P Y R L H E S C K D L T T A E K L K R E T P W K I T D A E L E A V K E K S Y R Q V R L N E L L Q E H S R A A N L I V L S L P V A R K G S I S D L L Y M A W L E I L T K N L P P V L L V R G N H K N V L T F Y S
PTM type	X-N-glycosylation X-Oxidation X-Phosphorylation X-Phosphorylation 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 SLC12A1			[1]
Role of PTM	Potential impacts
Modified Residue	Asparagine	Modified Location	446
Experimental Method	Co-Immunoprecipitation
Detailed Description	N-linked Glycosylation at SLC12A1 Asparagine 446 has the potential to affect its expression or activity.
PTM Phenomenon2	Have the potential to influence SLC12A1			[1]
Role of PTM	Potential impacts
Modified Residue	Asparagine	Modified Location	456
Experimental Method	Co-Immunoprecipitation
Detailed Description	N-linked Glycosylation at SLC12A1 Asparagine 456 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 SLC12A1			[2]
Role of PTM	Potential impacts
Modified Residue	Cystine	Modified Location	69
Experimental Method	Co-Immunoprecipitation
Detailed Description	Oxidation at SLC12A1 Cystine 69 has the potential to affect its expression or activity.
PTM Phenomenon2	Have the potential to influence SLC12A1			[2]
Role of PTM	Potential impacts
Modified Residue	Cystine	Modified Location	755
Experimental Method	Co-Immunoprecipitation
Detailed Description	Oxidation at SLC12A1 Cystine 755 has the potential to affect its expression or activity.
Phosphorylation
Serine	14 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC12A1			[3], [4]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	2
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A1 Serine 2 has the potential to affect its expression or activity.
PTM Phenomenon2	Have the potential to influence SLC12A1			[3], [4]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	61
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A1 Serine 61 has the potential to affect its expression or activity.
PTM Phenomenon3	Have the potential to influence SLC12A1			[5]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	91
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A1 Serine 91 has the potential to affect its expression or activity.
PTM Phenomenon4	Have the potential to influence SLC12A1			[3], [4]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	120
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A1 Serine 120 has the potential to affect its expression or activity.
PTM Phenomenon5	Have the potential to influence SLC12A1			[3], [4]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	122
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A1 Serine 122 has the potential to affect its expression or activity.
PTM Phenomenon6	Have the potential to influence SLC12A1			[4], [6]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	130
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A1 Serine 130 has the potential to affect its expression or activity.
PTM Phenomenon7	Have the potential to influence SLC12A1			[3], [4]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	147
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A1 Serine 147 has the potential to affect its expression or activity.
PTM Phenomenon8	Have the potential to influence SLC12A1			[3], [4]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	148
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A1 Serine 148 has the potential to affect its expression or activity.
PTM Phenomenon9	Have the potential to influence SLC12A1			[7]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	290
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A1 Serine 290 has the potential to affect its expression or activity.
PTM Phenomenon10	Have the potential to influence SLC12A1			[3], [4]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	879
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A1 Serine 879 has the potential to affect its expression or activity.
PTM Phenomenon11	Have the potential to influence SLC12A1			[4]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	883
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A1 Serine 883 has the potential to affect its expression or activity.
PTM Phenomenon12	Have the potential to influence SLC12A1			[3], [4]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	885
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A1 Serine 885 has the potential to affect its expression or activity.
PTM Phenomenon13	Have the potential to influence SLC12A1			[8]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	961
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A1 Serine 961 has the potential to affect its expression or activity.
PTM Phenomenon14	Have the potential to influence SLC12A1			[4]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	1003
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A1 Serine 1003 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	.			[9]
Role of PTM	Protein Activity Modulation
Modified Residue	Threonine	Modified Location	101
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A1 Threonine 101 have been reported to be significantly reduced in pre-eclampsia, potentially contributing to impaired renal sodium reabsorption.
PTM Phenomenon2	Have the potential to influence SLC12A1			[5], [10]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	95
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A1 Threonine 95 has the potential to affect its expression or activity.
PTM Phenomenon3	Have the potential to influence SLC12A1			[5], [10]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	100
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A1 Threonine 100 has the potential to affect its expression or activity.
PTM Phenomenon4	Have the potential to influence SLC12A1			[5]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	105
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A1 Threonine 105 has the potential to affect its expression or activity.
PTM Phenomenon5	Have the potential to influence SLC12A1			[3], [4]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	118
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A1 Threonine 118 has the potential to affect its expression or activity.
PTM Phenomenon6	Have the potential to influence SLC12A1			[4], [6]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	145
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A1 Threonine 145 has the potential to affect its expression or activity.
PTM Phenomenon7	Have the potential to influence SLC12A1			[4]
Role of PTM	Potential impacts
Modified Residue	Threonine	Modified Location	882
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A1 Threonine 882 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 SLC12A1			[3]
Role of PTM	Potential impacts
Modified Residue	Tyrosine	Modified Location	70
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A1 Tyrosine 70 has the potential to affect its expression or activity.
PTM Phenomenon2	.			[11]
Role of PTM	Potential impacts
Modified Residue	Tyrosine	Modified Location	245
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A1 Tyrosine 245 has the potential to affect its expression or activity.
PTM Phenomenon3	Have the potential to influence SLC12A1			[12]
Role of PTM	Potential impacts
Modified Residue	Tyrosine	Modified Location	781
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC12A1 Tyrosine 781 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: S12A1_HUMAN)
2	A Quantitative Tissue-Specific Landscape of Protein Redox Regulation during Aging. Cell. 2020 Mar 5;180(5):968-983.e24.
3	A fast sample processing strategy for large-scale profiling of human urine phosphoproteome by mass spectrometry. Talanta. 2018 Aug 1;185:166-173.
4	Identification of Missing Proteins in the Phosphoproteome of Kidney Cancer. J Proteome Res. 2017 Dec 1;16(12):4364-4373.
5	Regulation of the NKCC2 ion cotransporter by SPAK-OSR1-dependent and -independent pathways. J Cell Sci. 2011 Mar 1;124(Pt 5):789-800.
6	iTRAQ labeling is superior to mTRAQ for quantitative global proteomics and phosphoproteomics. Mol Cell Proteomics. 2012 Jun;11(6):M111.014423.
7	Preparation of magnetic polymer material with phosphate group and its application to the enrichment of phosphopeptides. J Chromatogr A. 2011 Jun 24;1218(25):3845-53.
8	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.
9	Pre-eclampsia is associated with altered expression of the renal sodium transporters NKCC2, NCC and ENaC in urinary extracellular vesicles. PLoS One. 2018;13(9):e0204514. Published 2018 Sep 24.
10	MO25 is a master regulator of SPAK/OSR1 and MST3/MST4/YSK1 protein kinases. EMBO J. 2011 May 4;30(9):1730-41.
11	ActiveDriverDB: human disease mutations and genome variation in post-translational modification sites of proteins. Nucleic Acids Res. 2018;46(D1):D901-D910.
12	Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell. 2007 Dec 14;131(6):1190-203.

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Detail Information of Post-Translational Modifications

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