Recombinant Human Aquaporin-4(AQP4) Protein

Function

Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport and is 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)

Subcellular Location

Cell membrane (Multi-pass membrane protein); Basolateral cell membrane (Multi-pass membrane protein); Endosome membrane; Cell membrane, sarcolemma (Multi-pass membrane protein); Cell projection

Disease Association

Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting (MLC4) : An autosomal recessive disorder characterized by macrocephaly apparent in infancy, developmental delay, delayed walking, variable cognitive decline, behavioral abnormalities, and early-onset seizures. Brain imaging shows swelling of the cerebral white matter and subcortical cysts in the anterior temporal region. The severity of neurologic dysfunction and brain abnormalities tends to improve with time, indicating a remitting disease course. [The disease may be caused by variants affecting the gene represented in this entry]

Tissue Specificity

Detected in skeletal muscle (PubMed:29055082). Detected in stomach, along the glandular base region of the fundic gland (at protein level) (PubMed:8601457). Detected in brain, lung and skeletal muscle, and at much lower levels in heart and ovary (PubMed:7559426, PubMed:8601457)

Subunit

Homotetramer (PubMed:19383790). The tetramers can form oligomeric arrays in membranes. The size of the oligomers differs between tissues and is smaller in skeletal muscle than in brain. Interaction between AQP4 oligomeric arrays in close-by cells can contribute to cell-cell adhesion (By similarity). Part of a complex containing MLC1, TRPV4, HEPACAM and ATP1B1 (PubMed:22328087)

• Yang B. et al. cDNA cloning, gene organization, and chromosomal localization of a human mercurial insensitive water channel. Evidence for distinct transcriptional units. — J. Biol. Chem. (1995)
• Misaka T. et al. A water channel closely related to rat brain aquaporin 4 is expressed in acid- and pepsinogen-secretory cells of human stomach. — FEBS Lett. (1996)
• Lu M. et al. The human AQP4 gene: definition of the locus encoding two water channel polypeptides in brain. — Proc. Natl. Acad. Sci. U.S.A. (1996)
• Nusbaum C. et al. DNA sequence and analysis of human chromosome 18. — Nature (2005)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Lanciotti A. et al. Megalencephalic leukoencephalopathy with subcortical cysts protein 1 functionally cooperates with the TRPV4 cation channel to activate the response of astrocytes to osmotic stress: dysregulation by pathological mutations. — Hum. Mol. Genet. (2012)
• Rosito S. et al. Supramolecular aggregation of aquaporin-4 is different in muscle and brain: correlation with tissue susceptibility in neuromyelitis optica. — J. Cell. Mol. Med. (2018)
• Ho J.D. et al. Crystal structure of human aquaporin 4 at 1.8 A and its mechanism of conductance. — Proc. Natl. Acad. Sci. U.S.A. (2009)