Ser256
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Home > Phosphorylation Site Page: > Ser256  -  AQP2 (mouse)

Site Information
REVRRRQsVELHsPQ   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 449854

In vivo Characterization
Methods used to characterize site in vivo:
immunoassay ( 2 ) , immunoprecipitation ( 5 ) , mass spectrometry ( 11 , 13 ) , mutation of modification site ( 1 , 2 , 6 , 7 , 8 , 14 , 16 , 17 , 19 ) , phospho-antibody ( 2 , 3 , 4 , 5 , 6 , 9 , 10 , 12 , 15 , 16 , 17 , 19 ) , western blotting ( 2 , 3 , 4 , 5 , 6 , 8 , 9 , 10 , 12 , 14 , 15 , 16 )
Disease tissue studied:
kidney cancer ( 15 ) , congenital progressive hydronephrosis ( 19 )
Relevant cell line - cell type - tissue:
'kidney, cortex' ( 2 ) , 'kidney, inner medulla' ( 2 , 10 ) , 'kidney, tubule' ( 4 ) , Flp-In-T-REx-293 ( 1 ) , HEK293T (epithelial) ( 7 ) , kidney ( 3 , 11 , 15 , 17 , 19 ) , LLC-PK1 (renal) ( 6 ) , MDCK (epithelial) ( 2 , 8 , 9 , 14 , 17 ) , MDCK-FTM ( 1 ) , mpkCCD (renal) ( 12 , 13 ) , oocyte ( 16 )

Upstream Regulation
Regulatory protein:
ADCY6 (mouse) ( 10 ) , GJA4 (human) ( 3 )
Treatments:
dDAVP ( 3 ) , desmopressin ( 5 , 10 ) , EGF ( 6 ) , erlotinib ( 6 ) , NH4Cl ( 15 ) , NKH_477 ( 2 ) , vasopressin ( 6 ) , Whole cell lysate ( 2 )

Downstream Regulation
Effects of modification on AQP2:
activity, induced ( 16 ) , intracellular localization ( 8 , 16 , 19 ) , molecular association, regulation ( 7 , 14 ) , phosphorylation ( 16 , 17 ) , protein stabilization ( 14 ) , receptor internalization, inhibited ( 8 )
Effects of modification on biological processes:
endocytosis, altered ( 14 ) , exocytosis, altered ( 14 )
Induce interaction with:
14-3-3 theta (human) ( 7 ) , 14-3-3 zeta (human) ( 7 )
Inhibit interaction with:
ACTG1 (human) ( 14 ) , ANXA2 (dog) ( 14 ) , HSC70 (human) ( 14 )

Disease / Diagnostics Relevance
Relevant diseases:
congenital progressive hydronephrosis ( 19 )

References 

1

Venneri M, et al. (2023) Novel signalling pathways in nephrogenic syndrome of inappropriate antidiuresis: functional implication of site-specific AQP2 phosphorylation. J Physiol
36823952   Curated Info

2

Ernstsen CV, et al. (2022) Acute pyelonephritis: Increased plasma membrane targeting of renal aquaporin-2. Acta Physiol (Oxf) 234, e13760
34978750   Curated Info

3

Xue J, et al. (2020) Genetic deletion of connexin 37 causes polyuria and polydipsia. PLoS One
33332450   Curated Info

4

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

5

Yui N, Sasaki S, Uchida S (2017) Aquaporin-2 Ser-261 phosphorylation is regulated in combination with Ser-256 and Ser-269 phosphorylation. Biochem Biophys Res Commun 482, 524-529
27889609   Curated Info

6

Cheung PW, et al. (2016) EGF Receptor Inhibition by Erlotinib Increases Aquaporin 2-Mediated Renal Water Reabsorption. J Am Soc Nephrol 27, 3105-3116
27694161   Curated Info

7

Moeller HB, et al. (2016) Regulation of the Water Channel Aquaporin-2 via 14-3-3θ and -ζ. J Biol Chem 291, 2469-84
26645691   Curated Info

8

Moeller HB, et al. (2014) Phosphorylation and ubiquitylation are opposing processes that regulate endocytosis of the water channel aquaporin-2. J Cell Sci 127, 3174-83
24876223   Curated Info

9

Feinstein TN, et al. (2013) Noncanonical control of vasopressin receptor type 2 signaling by retromer and arrestin. J Biol Chem 288, 27849-60
23935101   Curated Info

10

Rieg T, et al. (2010) Adenylate cyclase 6 determines cAMP formation and aquaporin-2 phosphorylation and trafficking in inner medulla. J Am Soc Nephrol 21, 2059-68
20864687   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

Xie L, et al. (2010) Quantitative analysis of aquaporin-2 phosphorylation. Am J Physiol Renal Physiol 298, F1018-23
20089674   Curated Info

13

Rinschen MM, et al. (2010) Quantitative phosphoproteomic analysis reveals vasopressin V2-receptor-dependent signaling pathways in renal collecting duct cells. Proc Natl Acad Sci U S A 107, 3882-7
20139300   Curated Info

14

Moeller HB, Praetorius J, Rützler MR, Fenton RA (2010) Phosphorylation of aquaporin-2 regulates its endocytosis and protein-protein interactions. Proc Natl Acad Sci U S A 107, 424-9
19966308   Curated Info

15

Nowik M, et al. (2010) Induction of metabolic acidosis with ammonium chloride (NH4Cl) in mice and rats--species differences and technical considerations. Cell Physiol Biochem 26, 1059-72
21220937   Curated Info

16

Moeller HB, Macaulay N, Knepper MA, Fenton RA (2009) Role of multiple phosphorylation sites in the COOH-terminal tail of aquaporin-2 for water transport: evidence against channel gating. Am J Physiol Renal Physiol 296, F649-57
19144687   Curated Info

17

Hoffert JD, et al. (2008) Vasopressin-stimulated increase in phosphorylation at Ser269 potentiates plasma membrane retention of aquaporin-2. J Biol Chem 283, 24617-27
18606813   Curated Info

18

Shi PP, et al. (2007) Nephrogenic diabetes insipidus in mice caused by deleting COOH-terminal tail of aquaporin-2. Am J Physiol Renal Physiol 292, F1334-44
17229678   Curated Info

19

McDill BW, et al. (2006) Congenital progressive hydronephrosis (cph) is caused by an S256L mutation in aquaporin-2 that affects its phosphorylation and apical membrane accumulation. Proc Natl Acad Sci U S A 103, 6952-7
16641094   Curated Info

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