Aquaporin-2 (254-267), pSER261, human

Product Name: Aquaporin-2 (254-267), pSER261, human

Sequence One Letter Code: RQSVELH-pS-PQSLPR

Sequence Three Letter Code: H-Arg-Gln-Ser-Val-Glu-Leu-His-pSer-Pro-Gln- Ser-Leu-Pro-Arg-OH

Molecular Weight: 1713.9

Purity: 95%

Form: Lyophilized

Storage Conditions: - 20 °C

Research Area: Metabolic Disease Research

Source / Species: human

Conjugation: Unconjugated

Code Nacres: NA.26

Application: Aquaporin-2 (254–267), pSer261 is a synthetic phosphopeptide corresponding to a C-terminal fragment of human AQP2 containing a phosphorylated serine at position 261. AQP2 is the principal vasopressin-regulated water channel in renal collecting duct cells and is essential for urine concentration. Phosphorylation at Ser261 is dynamically regulated and contributes to controlling AQP2 trafficking, endocytosis, and membrane localization. Together with other phosphorylation sites such as Ser256, this modification integrates hormonal signaling pathways that regulate water reabsorption. The phosphopeptide is widely used in kinase and phosphatase assays, antibody validation, and studies of site-specific phosphorylation. It also supports mechanistic investigations of vasopressin signaling and renal water balance disorders. This peptide is particularly relevant in research on nephrogenic diabetes insipidus and fluid homeostasis regulation.

Current Research: Aquaporin-2 (254–267), pSer261 has become an important molecular tool in renal physiology research aimed at dissecting vasopressin-dependent water reabsorption mechanisms. AQP2 is the principal water channel expressed in collecting duct principal cells, where its trafficking between intracellular vesicles and the apical membrane determines urine concentration capacity. While phosphorylation at Ser256 is classically associated with protein kinase A (PKA) activation and membrane insertion, phosphorylation at Ser261 is now recognized as a dynamically regulated modification linked to channel retrieval, degradation, and signal integration. Current research indicates that Ser261 phosphorylation decreases in response to vasopressin stimulation, coinciding with enhanced apical membrane accumulation of AQP2. Conversely, increased Ser261 phosphorylation has been associated with AQP2 internalization and turnover. Studies using phospho-specific antibodies validated with the pSer261 peptide have clarified how this residue responds to cAMP signaling, intracellular calcium flux, and alternative kinase pathways, including casein kinase and MAP kinase signaling cascades. The phosphopeptide serves as a calibration standard in Western blotting, ELISA, and mass spectrometry workflows designed to quantify site-specific phosphorylation. Emerging evidence suggests that Ser261 participates in cross-talk among multiple post-translational modifications. Investigations into ubiquitination, sumoylation, and additional phosphorylation sites (Ser264, Ser269) indicate coordinated regulation of AQP2 trafficking, stability, and recycling. The pSer261 peptide supports mechanistic studies examining how combinations of modifications alter protein–protein interactions within endocytic and recycling compartments. Pathophysiologically, altered Ser261 phosphorylation has been implicated in disorders of water balance, including nephrogenic diabetes insipidus (NDI), syndrome of inappropriate antidiuretic hormone secretion (SIADH), and lithium-induced concentrating defects. Experimental models demonstrate that dysregulated phosphorylation patterns correlate with impaired membrane targeting and reduced urinary concentrating ability. The phosphopeptide is therefore instrumental in evaluating kinase inhibitors, vasopressin analogs, and signaling modulators aimed at restoring AQP2 function. Advanced imaging approaches now integrate phosphosite-specific detection with confocal and super-resolution microscopy to map AQP2 subcellular localization in response to hormonal stimulation. Quantitative phosphoproteomics further leverages synthetic standards such as AQP2 (254–267), pSer261 to define dynamic phosphorylation kinetics under physiologic and pharmacologic conditions. Collectively, this phosphopeptide underpins mechanistic studies of AQP2 regulation at the intersection of signal transduction, membrane trafficking, and renal water homeostasis. Ongoing research continues to refine understanding of how Ser261 phosphorylation integrates hormonal cues to maintain fluid balance and how its dysregulation contributes to renal pathophysiology.