AQP4
This gene encodes a member of the aquaporin family of intrinsic membrane proteins that function as water-selective channels in the plasma membranes of many cells. This protein is the predominant aquaporin found in brain and has an important role in brain water homeostasis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. A recent study provided evidence for translational readthrough in this gene, and expression of an additional C-terminally extended isoform via the use of an alternative in-frame translation termination codon.
Alternative Names
Aquaporin 4; Mercurial-Insensitive Water Channel; MIWC; WCH4; Aquaporin Type4; Aquaporin-4; AQP-4;
Function
Forms a water-specific channel (PubMed:7559426, PubMed:8601457, PubMed:19383790).
Plays an important role in brain water homeostasis and in glymphatic solute transport. Required for a normal rate of water exchange across the blood brain interface. Required for normal levels of cerebrospinal fluid influx into the brain cortex and parenchyma along paravascular spaces that surround penetrating arteries, and for normal drainage of interstitial fluid along paravenous drainage pathways. Thereby, it is required for normal clearance of solutes from the brain interstitial fluid, including soluble beta-amyloid peptides derived from APP. Plays a redundant role in urinary water homeostasis and urinary concentrating ability (By similarity).
Biological Process
Cellular response to interferon-gamma Source: UniProtKB
Cellular water homeostasis Source: UniProtKB
Cerebrospinal fluid circulation Source: UniProtKB
Multicellular organismal water homeostasis Source: UniProtKB
Protein homotetramerization Source: UniProtKB
Renal water homeostasis Source: Reactome
Water homeostasis Source: UniProtKB
Water transport Source: UniProtKB
Cellular Location
Endosome membrane; Cell membrane; Basolateral cell membrane; Sarcolemma; Cell projection. Activation of the vasopressin receptor AVPR1A triggers AQP4 phosphorylation at Ser-180 and promotes its internalization from the cell membrane. Detected on brain astrocyte processes and astrocyte endfeet close to capillaries.
Topology
Cytoplasmic: 1-36 aa
Helical: 37-57 aa
Extracellular: 58-69 aa
Helical: 70-89 aa
Cytoplasmic: 90-93 aa
Discontinuously helical: 94-101 aa
Cytoplasmic: 102-115 aa
Helical: 116-136 aa
Extracellular: 137-155 aa
Helical: 156-176 aa
Cytoplasmic: 177-184 aa
Helical: 185-205 aa
Extracellular: 206-208 aa
Discontinuously helical: 209-222 aa
Extracellular: 223-231 aa
Helical: 232-252 aa
Cytoplasmic: 253-323 aa
PTM
Phosphorylation by PKC at Ser-180 reduces conductance by 50%. Phosphorylation by PKG at Ser-111 in response to glutamate increases conductance by 40% (By similarity).
Isoform 2: Palmitoylated on its N-terminal region. Isoform 1: Not palmitoylated.