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aquaporin-4; AQP-4; WCH4; mercurial-insensitive water channel; MIWC (AQP4)
Function:
- forms a water-specific channel
- osmoreceptor which regulates body water balance & mediates water flow within the central nervous system
- phosphorylation by PKC at Ser-180 reduces conductance by 50%
- phosphorylation by PKG at Ser-111 in response to glutamate increases conductance by 40% (putative)
- part of a complex containing MLC1, TRPV4, HEPACAM & ATP1B1
Structure:
- homotetramer
- aquaporins contain two tandem repeats each containing 3 membrane-spanning domains & a pore-forming loop with the signature motif Asn-Pro-Ala (NPA)
- belongs to the MIP/aquaporin (TC 1.A.8) family
Compartment:
- membrane, primarily on astrocyte end foot processes [5]
Alternative splicing: named isoforms=2
Expression:
- brain - muscle >> heart, kidney, lung, & trachea
Pathology:
- autoantibody of Devic's disease (neuromyelitis optica) [2]
Pharmacology:
- inebilizumab-cdon (Uplizna) a CD19 monoclonal antibody is FDA-approved for treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults with aquaporin-4 (AQP4) autoantibodies
Comparative biology:
- contact of aquaporin-4 containing astrocyte end-feet with microvasculature of brain (mice) [4]
General
aquaporin
glycoprotein
phosphoprotein
transmembrane 6 protein
Properties
SIZE: entity length = 323 aa
MW = 35 kD
COMPARTMENT: plasma membrane
MOTIF: cytoplasmic domain {1-36}
transmembrane domain {37-57}
exoplasmic loop {58-64}
transmembrane domain {65-85}
cytoplasmic loop {86-115}
MOTIF: peptide motif {97-99}
transmembrane domain {116-136}
exoplasmic loop {137-155}
MOTIF: N-glycosylation site {N153}
transmembrane domain {156-176}
cytoplasmic loop {177-184}
transmembrane domain {185-205}
exoplasmic loop {206-231}
MOTIF: N-glycosylation site {N206}
peptide motif {213-215}
transmembrane domain {232-252}
cytoplasmic domain {253-323}
MOTIF: Ser phosphorylation site {S285}
Ser phosphorylation site {S321}
Database Correlations
OMIM 600308
UniProt P55087
Pfam PF00230
Entrez Gene 361
Kegg hsa:361
References
- UniProt :accession P55087
- Medical Knowledge Self Assessment Program (MKSAP) 17,
American College of Physicians, Philadelphia 2015
- Atlas of Genetics & Cytogenetics in Oncology & Haematology
http://atlasgeneticsoncology.org/genes/AQP4ID684ch18q11.html
- Yamazaki Y, Baker DJ, Tachibana M et al
Vascular Cell Senescence Contributes to Blood-Brain Barrier
Breakdown.
Stroke. 2016 Feb 16.
PMID: 26883501
- Kleiter I, Traboulsee A, Palace J et al
Long-term Efficacy of Satralizumab in AQP4-IgG-Seropositive Neuromyelitis Optica
Spectrum Disorder From SAkuraSky and SAkuraStar.
Neurology Neuroimmunology & Neuroimflammation. 2022. Dec 8.
PMID: 36724181 PMCID: PMC9756307 Free PMC article
https://nn.neurology.org/content/10/1/e200071