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

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:
[32P] bio-synthetic labeling ( 18 , 19 ) , electrophoretic mobility shift ( 7 ) , immunoassay ( 7 ) , immunoprecipitation ( 3 , 6 , 19 ) , mass spectrometry ( 1 , 4 ) , microscopy-colocalization with upstream kinase ( 15 , 21 ) , mutation of modification site ( 3 , 4 , 5 , 7 , 9 , 11 , 12 , 14 , 15 , 16 , 17 , 18 , 19 , 21 ) , phospho-antibody ( 1 , 2 , 3 , 6 , 7 , 13 , 15 , 16 , 18 ) , western blotting ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 13 , 15 , 19 , 21 )
Disease tissue studied:
kidney cancer ( 12 ) , leukemia ( 3 )
Relevant cell line - cell type - tissue:
'kidney, cortex' ( 6 ) , 'kidney, inner medulla' ( 6 , 13 ) , 'kidney, outer medulla' ( 6 ) , 3T3 (fibroblast) [SHP-2 (mouse), homozygous knockout] ( 14 ) , 3T3 (fibroblast) ( 11 ) , BEAS-2B (epithelial) ( 11 ) , COS (fibroblast) ( 12 ) , E.coli (bacterial) ( 4 ) , kidney ( 12 ) , LLC-PK1 (renal) ( 9 , 17 , 21 ) , M1 (myeloid) ( 3 ) , MCD4 (renal) ( 2 , 3 ) , MDCK (epithelial) ( 5 , 6 , 7 , 9 , 15 , 16 , 18 ) , mpkCCD (renal) ( 7 ) , oocyte ( 15 ) , oocyte [CPEB (mouse)] ( 19 ) , Pichia pastoris (yeast cell) ( 4 ) , RC.SV3 (renal tubule cell) ( 13 ) , urine ( 1 )

Upstream Regulation
Regulatory protein:
AVPR2 (human) ( 2 ) , CHIP (human) ( 3 ) , PKD1 (human) ( 6 ) , PPP2CA (human) ( 6 )
Putative in vivo kinases:
PKACA (human) ( 11 )
Kinases, in vitro:
CK1A (rat) ( 20 )
Treatments:
calyculin_A ( 6 ) , cAMP_analog ( 19 ) , colforsin ( 5 , 10 , 15 , 18 ) , dDAVP ( 6 ) , H-89 ( 19 , 21 ) , hypotonic_buffer ( 13 ) , indometacin ( 15 ) , NKH_477 ( 6 , 7 ) , seliciclib ( 6 ) , SNP ( 21 ) , vasopressin ( 1 , 7 )

Downstream Regulation
Effects of modification on AQP2:
intracellular localization ( 2 , 5 , 6 , 7 , 9 , 11 , 12 , 14 , 15 , 16 , 17 , 18 , 19 , 21 ) , molecular association, regulation ( 3 , 4 , 12 , 19 )
Effects of modification on biological processes:
exocytosis, induced ( 1 )
Induce interaction with:
AQP2 (human) ( 19 ) , TIRAP (human) ( 12 )
Inhibit interaction with:
HSP70 (human) ( 3 ) , VTA1 (mouse) ( 4 )

Disease / Diagnostics Relevance
Relevant diseases:
nephrogenic diabetes insipidus ( 15 )

References 

1

Sakai M, et al. (2020) Phosphorylation profile of human AQP2 in urinary exosomes by LC-MS/MS phosphoproteomic analysis. Clin Exp Nephrol
32529500   Curated Info

2

Ranieri M, et al. (2020) The Vasopressin Receptor 2 Mutant R137L Linked to the Nephrogenic Syndrome of Inappropriate Antidiuresis (NSIAD) Signals through an Alternative Pathway that Increases AQP2 Membrane Targeting Independently of S256 Phosphorylation. Cells 9
32486031   Curated Info

3

Centrone M, et al. (2017) AQP2 Abundance is Regulated by the E3-Ligase CHIP Via HSP70. Cell Physiol Biochem 44, 515-531
29145196   Curated Info

4

Roche JV, et al. (2017) Phosphorylation of human aquaporin 2 (AQP2) allosterically controls its interaction with the lysosomal trafficking protein LIP5. J Biol Chem 292, 14636-14648
28710278   Curated Info

5

Dollerup P, et al. (2015) Partial nephrogenic diabetes insipidus caused by a novel AQP2 variation impairing trafficking of the aquaporin-2 water channel. BMC Nephrol 16, 217
26714855   Curated Info

6

Tamma G, et al. (2014) A protein kinase A-independent pathway controlling aquaporin 2 trafficking as a possible cause for the syndrome of inappropriate antidiuresis associated with polycystic kidney disease 1 haploinsufficiency. J Am Soc Nephrol 25, 2241-53
24700872   Curated Info

7

Trimpert C, et al. (2012) Vasopressin increases S261 phosphorylation in AQP2-P262L, a mutant in recessive nephrogenic diabetes insipidus. Nephrol Dial Transplant 27, 4389-97
22778181   Curated Info

8

van Balkom BW, et al. (2009) LIP5 interacts with aquaporin 2 and facilitates its lysosomal degradation. J Am Soc Nephrol 20, 990-1001
19357255   Curated Info

9

Hasler U, et al. (2008) Acute hypertonicity alters aquaporin-2 trafficking and induces a MAPK-dependent accumulation at the plasma membrane of renal epithelial cells. J Biol Chem 283, 26643-61
18664568   Curated Info

10

Kamsteeg EJ, et al. (2008) Missorting of the Aquaporin-2 mutant E258K to multivesicular bodies/lysosomes in dominant NDI is associated with its monoubiquitination and increased phosphorylation by PKC but is due to the loss of E258. Pflugers Arch 455, 1041-54
17965877   Curated Info

11

Woo J, et al. (2008) Membrane trafficking of AQP5 and cAMP dependent phosphorylation in bronchial epithelium. Biochem Biophys Res Commun 366, 321-7
18042467   Curated Info

12

Kamsteeg EJ, et al. (2007) MAL decreases the internalization of the aquaporin-2 water channel. Proc Natl Acad Sci U S A 104, 16696-701
17940053   Curated Info

13

Tamma G, et al. (2007) Hypotonicity induces aquaporin-2 internalization and cytosol-to-membrane translocation of ICln in renal cells. Endocrinology 148, 1118-30
17138647   Curated Info

14

Procino G, Caces DB, Valenti G, Pessin JE (2006) Adipocytes support cAMP-dependent translocation of aquaporin-2 from intracellular sites distinct from the insulin-responsive GLUT4 storage compartment. Am J Physiol Renal Physiol 290, F985-94
16303856   Curated Info

15

de Mattia F, et al. (2005) Lack of arginine vasopressin-induced phosphorylation of aquaporin-2 mutant AQP2-R254L explains dominant nephrogenic diabetes insipidus. J Am Soc Nephrol 16, 2872-80
16120822   Curated Info

16

Nejsum LN, et al. (2005) Bidirectional regulation of AQP2 trafficking and recycling: involvement of AQP2-S256 phosphorylation. Am J Physiol Renal Physiol 288, F930-8
15625084   Curated Info

17

Lu H, et al. (2004) Inhibition of endocytosis causes phosphorylation (S256)-independent plasma membrane accumulation of AQP2. Am J Physiol Renal Physiol 286, F233-43
14519593   Curated Info

18

van Balkom BW, et al. (2002) The role of putative phosphorylation sites in the targeting and shuttling of the aquaporin-2 water channel. J Biol Chem 277, 41473-9
12194985   Curated Info

19

Kamsteeg EJ, Heijnen I, van Os CH, Deen PM (2000) The subcellular localization of an aquaporin-2 tetramer depends on the stoichiometry of phosphorylated and nonphosphorylated monomers. J Cell Biol 151, 919-30
11076974   Curated Info

20

Brunati AM, et al. (2000) Novel consensus sequence for the Golgi apparatus casein kinase, revealed using proline-rich protein-1 (PRP1)-derived peptide substrates. Biochem J 351 Pt 3, 765-8
11042132   Curated Info

21

Bouley R, et al. (2000) Nitric oxide and atrial natriuretic factor stimulate cGMP-dependent membrane insertion of aquaporin 2 in renal epithelial cells. J Clin Invest 106, 1115-26
11067864   Curated Info