Detail Information of Post-Translational Modifications

General Information of Drug Transporter (DT)
DT ID	DTD0019 Transporter Info
Gene Name	SLC10A1
Transporter Name	Sodium/taurocholate cotransporting polypeptide
Gene ID	6554
UniProt ID	Q14973

Post-Translational Modification of This DT
Overview ofSLC10A1 Modification Sites with Functional and Structural Information
Sequence	M E A H N A S A P F N F T L P P N F G K R P T D L A L S V I L V F M L F F I M L S L G C T M E F S K I K A H L W K P K G L A I A L V A Q Y G I M P L T A F V L G K V F R L K N I E A L A I L V C G C S P G G N L S N V F S L A M K G D M N L S I V M T T C S T F C A L G M M P L L L Y I Y S R G I Y D G D L K D K V P Y K G I V I S L V L V L I P C T I G I V L K S K R P Q Y M R Y V I K G G M I I I L L C S V A V T V L S A I N V G K S I M F A M T P L L I A T S S L M P F I G F L L G Y V L S A L F C L N G R C R R T V S M E T G C Q N V Q L C S T I L N V A F P P E V I G P L F F F P L L Y M I F Q L G E G L L L I A I F W C Y E K F K T P K D K T K M I Y T A A T T E E T I P G A L G N G T Y K G E D C S P C T A
PTM type	X-Dephosphorylation X-N-glycosylation X-N-linked glycosylation X-Phosphorylation X-S-nitrosylation X: Amino Acid

Dephosphorylation
Serine	1 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Increasing in taurocholate uptake and SLC10A1 retention in the plasma membrane			[1]
Role of PTM	Protein Activity Modulation
Affected Drug/Substrate	Taurocholate	Results for Drug	Incerasing uptake of taurocholate
Modified Residue	Serine	Modified Location	226
Related Enzyme	Protein phosphatase 3 catalytic subunit alpha (PPP3CA)
Studied Phenotype	Liver cancer [ICD11: 2C12]
Experimental Material(s)	Human hepatoma (HuH-7) cells
Experimental Method	Co-Immunoprecipitation
Detailed Description	Dephosphorylation at SLC10A1 Serine 226 have been reported to increase in taurocholate uptake and NTCP retention in the plasma membrane.
N-glycosylation
Asparagine	4 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Affecting the function of the physiological bile acid SLC10A1			[2]
Role of PTM	Protein Activity Modulation
Affected Drug/Substrate	Bile acids	Results for Drug	Affecting the transport of bile acids
Modified Residue	Asparagine	Modified Location	5
Modified State	Asparagine to Glutamine mutation
Studied Phenotype	Liver cancer [ICD11: 2C12]
Experimental Material(s)	Human liver carcinoma (HepG11) cells
Experimental Method	Co-Immunoprecipitation
Detailed Description	Removal of the N-glycosylation at SLC10A1 Asparagine5 (i.e. Asparagine to Glutamine mutation) have been reported to affect its function of the physiological bile acid transporter.
PTM Phenomenon2	Affecting the function of the physiological bile acid SLC10A1			[2]
Role of PTM	Protein Activity Modulation
Affected Drug/Substrate	Bile acids	Results for Drug	Affecting the transport of bile acids
Modified Residue	Asparagine	Modified Location	11
Modified State	Asparagine to Glutamine mutation
Studied Phenotype	Liver cancer [ICD11: 2C12]
Experimental Material(s)	Human liver carcinoma (HepG11) cells
Experimental Method	Co-Immunoprecipitation
Detailed Description	Removal of the N-glycosylation at SLC10A1 Asparagine11 (i.e. Asparagine to Glutamine mutation) have been reported to affect its function of the physiological bile acid transporter.
PTM Phenomenon3	Have the potential to influence SLC10A1			[3]
Role of PTM	Potential impacts
Modified Residue	Asparagine	Modified Location	117
Experimental Method	Co-Immunoprecipitation
Detailed Description	N-linked Glycosylation at SLC10A1 Asparagine 117 has the potential to affect its expression or activity.
PTM Phenomenon4	Have the potential to influence SLC10A1			[3]
Role of PTM	Potential impacts
Modified Residue	Asparagine	Modified Location	336
Experimental Method	Co-Immunoprecipitation
Detailed Description	N-linked Glycosylation at SLC10A1 Asparagine 336 has the potential to affect its expression or activity.
N-linked glycosylation
Unclear Residue	1 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	.			[4]
Role of PTM	Influencing the Disease Progression
Experimental Material(s)	liver tissues
Experimental Method	Co-Immunoprecipitation
Detailed Description	Removal of the N-linked glycosylation at SLC10A1 has been reported to altered drug disposition in humans NASH.
Phosphorylation
Serine	1 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	Have the potential to influence SLC10A1			[5]
Role of PTM	Potential impacts
Modified Residue	Serine	Modified Location	142
Experimental Method	Co-Immunoprecipitation
Detailed Description	Phosphorylation at SLC10A1 Serine 142 has the potential to affect its expression or activity.
S-nitrosylation
Cysteine	1 PTM Phenomena Related to This Residue		Click to Show/Hide the Full List
PTM Phenomenon1	May contribute to the development of cholestasis by inhibiting SLC10A1 function			[6]
Role of PTM	Protein Activity Modulation
Affected Drug/Substrate	Na(+) taurocholate (TC)	Results for Drug	Decreasing uptake of Na(+) taurocholate (TC)
Modified Residue	Cysteine	Modified Location	96
Studied Phenotype	Liver cancer [ICD11: 2C12]
Experimental Material(s)	Human hepatoma (HuH-7) cells
Experimental Method	Co-Immunoprecipitation
Detailed Description	S-nitrosylation at SLC10A1 Cysteine 96 have been reported to potentially inhibit its function and thus contribute to the development of cholestasis.

References
1	Dephosphorylation of Ser-226 facilitates plasma membrane retention of Ntcp. J Biol Chem. 2005 Sep 30;280(39):33687-92.
2	N-Glycosylation of the Na+-Taurocholate Cotransporting Polypeptide (NTCP) Determines Its Trafficking and Stability and Is Required for Hepatitis B Virus Infection. PLoS One. 2017 Jan 26;12(1):e0170419.
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: NTCP_HUMAN)
4	Impaired N-linked glycosylation of uptake and efflux transporters in human non-alcoholic fatty liver disease. Liver Int. 2017 Jul;37(7):1074-1081.
5	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.
6	Cysteine 96 of Ntcp is responsible for NO-mediated inhibition of taurocholate uptake. Am J Physiol Gastrointest Liver Physiol. 2013 Oct 1;305(7):G513-9.

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Detail Information of Post-Translational Modifications

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