Thr58
Javascript is not enabled on this browser. This site will not work properly without Javascript.
PhosphoSitePlus Homepage PhosphoSitePlus® v6.5.9.3
Powered by Cell Signaling Technology
Home > Phosphorylation Site Page: > Thr58  -  NCCT (mouse)

Site Information
MRtFGYNtIDVVPAY   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 469617

In vivo Characterization
Methods used to characterize site in vivo:
immunoassay ( 10 ) , mass spectrometry ( 11 ) , mutation of modification site ( 4 , 7 , 9 , 12 ) , phospho-antibody ( 1 , 2 , 3 , 5 , 6 , 7 , 8 , 10 , 13 , 14 ) , western blotting ( 1 , 2 , 3 , 4 , 5 , 7 , 8 , 10 , 13 )
Relevant cell line - cell type - tissue:
'kidney, cortex' ( 6 ) , 'kidney, tubule' ( 1 ) , COS (fibroblast) ( 4 ) , COS7 (fibroblast) ( 9 ) , kidney ( 2 , 3 , 7 , 8 , 10 , 11 , 13 ) , kidney [ADCY6 (mouse), homozygous knockout] ( 8 ) , MDCK (epithelial) ( 7 ) , mpkCCD (renal) ( 14 ) , oocyte ( 12 ) , renal ( 7 )

Upstream Regulation
Regulatory protein:
ADCY6 (mouse) ( 8 ) , WNK4 (mouse) ( 7 , 10 )
Putative in vivo kinases:
STLK3 (mouse) ( 7 )
Putative upstream phosphatases:
PPP4C (human) ( 12 )
Treatments:
angiotensin_2 ( 10 ) , desmopressin ( 8 ) , fostriecin ( 12 ) , HET0016 ( 3 ) , high-potassium diet ( 13 ) , high-salt diet ( 13 ) , hypertonic_buffer ( 1 ) , hypotonic_buffer ( 14 ) , low Na ( 1 ) , low-potassium diet ( 5 , 13 ) , low-salt diet ( 7 , 10 , 13 ) , spironolactone ( 10 ) , water_loading_ ( 8 )

Downstream Regulation
Effects of modification on NCCT:
activity, induced ( 12 ) , intracellular localization ( 7 ) , phosphorylation ( 7 ) , protein stabilization ( 7 ) , ubiquitination ( 9 )

Disease / Diagnostics Relevance
Relevant diseases:
GS ( 7 )

References 

1

Fenton RA, et al. (2017) Renal tubular NHE3 is required in the maintenance of water and sodium chloride homeostasis. Kidney Int 92, 397-414
28385297   Curated Info

2

Tutakhel OAZ, et al. (2017) NaCl cotransporter abundance in urinary vesicles is increased by calcineurin inhibitors and predicts thiazide sensitivity. PLoS One 12, e0176220
28430812   Curated Info

3

Savas Ü, et al. (2016) 20-Hydroxyeicosatetraenoic Acid (HETE)-dependent Hypertension in Human Cytochrome P450 (CYP) 4A11 Transgenic Mice: NORMALIZATION OF BLOOD PRESSURE BY SODIUM RESTRICTION, HYDROCHLOROTHIAZIDE, OR BLOCKADE OF THE TYPE 1 ANGIOTENSIN II RECEPTOR. J Biol Chem 291, 16904-19
27298316   Curated Info

4

Wang J, et al. (2015) Interleukin 18 function in atherosclerosis is mediated by the interleukin 18 receptor and the Na-Cl co-transporter. Nat Med 21, 820-6
26099046   Curated Info

5

Wade JB, et al. (2015) SPAK-mediated NCC regulation in response to low-K+ diet. Am J Physiol Renal Physiol 308, F923-31
25651563   Curated Info

6

Davies M, et al. (2014) Novel mechanisms of Na+ retention in obesity: phosphorylation of NKCC2 and regulation of SPAK/OSR1 by AMPK. Am J Physiol Renal Physiol 307, F96-F106
24808538   Curated Info

7

Yang SS, et al. (2013) Phosphorylation regulates NCC stability and transporter activity in vivo. J Am Soc Nephrol 24, 1587-97
23833262   Curated Info

8

Rieg T, et al. (2013) Adenylyl Cyclase 6 Enhances NKCC2 Expression and Mediates Vasopressin-Induced Phosphorylation of NKCC2 and NCC. Am J Pathol 182, 96-106
23123217   Curated Info

9

Hossain Khan MZ, et al. (2012) Phosphorylation of Na-Cl cotransporter by OSR1 and SPAK kinases regulates its ubiquitination. Biochem Biophys Res Commun 425, 456-61
22846565   Curated Info

10

Castañeda-Bueno M, et al. (2012) Activation of the renal Na+:Cl- cotransporter by angiotensin II is a WNK4-dependent process. Proc Natl Acad Sci U S A 109, 7929-34
22550170   Curated Info

11

Huttlin EL, et al. (2010) A tissue-specific atlas of mouse protein phosphorylation and expression. Cell 143, 1174-89
21183079   Curated Info

12

Glover M, Mercier Zuber A, Figg N, O'Shaughnessy KM (2010) The activity of the thiazide-sensitive Na(+)-Cl⁻ cotransporter is regulated by protein phosphatase PP4. Can J Physiol Pharmacol 88, 986-95
20962898   Curated Info

13

Vallon V, et al. (2009) Expression and phosphorylation of the Na+-Cl- cotransporter NCC in vivo is regulated by dietary salt, potassium, and SGK1. Am J Physiol Renal Physiol 297, F704-12
19570885   Curated Info

14

Richardson C, et al. (2008) Activation of the thiazide-sensitive Na+-Cl- cotransporter by the WNK-regulated kinases SPAK and OSR1. J Cell Sci 121, 675-84
18270262   Curated Info