Aqp2
Domain
Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA).
Function
Forms a water-specific channel that provides the plasma membranes of renal collecting duct with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient (PubMed:10191086). Plays an essential role in renal water homeostasis (PubMed:16641094). Could also be permeable to glycerol (By similarity).
Involvement in disease
Defects in Aqp2 are a cause of congenital progressive hydronephrosis (cph). Homozygous mice appear grossly normal at birth, but grow slowly, and 90% die between 2 and 4 weeks after birth. They display symptoms reminiscent of diabetes insipidus, with excessive water drinking (polydipsia), excessive urine excretion (polyuria), and persistent hypotonic urine. When older than 14 days, they nearly always display severe bilateral hydronephrosis resulting from impaired downward urine transport, in spite of the absence of physical blockage of the urinary tract. Surviving adults have a shortened lifespan and die at the latest at an age of 10 months. They display reduced fertility or are infertile.
Post-translational modifications
Ser-256 phosphorylation is necessary and sufficient for expression at the apical membrane (PubMed:16641094). Endocytosis is not phosphorylation-dependent (By similarity).
N-glycosylated.
Sequence Similarities
Belongs to the MIP/aquaporin (TC 1.A.8) family.
Tissue Specificity
Detected in principal cells in the collecting duct in kidney medulla and cortex (at protein level) (PubMed:10191086, PubMed:16641094, PubMed:16735444, PubMed:31605441). Expressed in a radial pattern from the cortex through the outer medulla into the inner medulla (PubMed:12426236). Higher levels in the inner medulla (PubMed:12426236).
Cellular localization
- Apical cell membrane
- Multi-pass membrane protein
- Basolateral cell membrane
- Multi-pass membrane protein
- Cell membrane
- Multi-pass membrane protein
- Cytoplasmic vesicle membrane
- Multi-pass membrane protein
- Golgi apparatus
- trans-Golgi network membrane
- Multi-pass membrane protein
- Shuttles from vesicles to the apical membrane. Vasopressin-regulated phosphorylation is required for translocation to the apical cell membrane (PubMed:16735444). PLEKHA8/FAPP2 is required to transport AQP2 from the TGN to sites where AQP2 is phosphorylated.
Alternative names
cph, Aqp2, Aquaporin-2, AQP-2, ADH water channel, Aquaporin-CD, Collecting duct water channel protein, WCH-CD, Water channel protein for renal collecting duct, AQP-CD