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FLASH GENE
Symbol AQP4 contributors: mct/shn - updated : 05-01-2013
HGNC name aquaporin 4
HGNC id 637
Location 18q11.2      Physical location : 24.432.009 - 24.445.716
Synonym name
  • mercurial-insensitive water channel
  • aquaporin type 4 transcript variant c
  • aquaporin type4
  • aquaporin-4
  • Synonym symbol(s) MIWC, HMIWC2, MGC22454, WCH4
    DNA
    TYPE functioning gene
    STRUCTURE 13.71 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence
    MAPPING cloned Y linked N status provisional
    Map cen - D18S866 - D18S66 - AQP4 - D18S478 - D18S1151 - qter
    Physical map
    LOC91768 MGC11386 18q11.2 hypothetical protein MGC11386 RIOK3 18q11.2 RIO kinase 3 (yeast) C18orf8 18q11.2 chromosome 18 open reading frame 8 NPC1 18q11.1-q11.2 Niemann-Pick disease, type C1 LOC147463 18q11.2 hypothetical protein LOC147463 LOC390842 18 similar to 40S ribosomal protein S10 LAMA3 18q11.2 laminin, alpha 3 FLJ33761 18q11.2 hypothetical protein FLJ33761 CABYR 18q11.1 calcium-binding tyrosine-(Y)-phosphorylation regulated (fibrousheathin 2) OSBPL1A 18q11-q12 oxysterol binding protein-like 1A IMPACT 18q11.2-q12.1 hypothetical protein IMPACT HRH4 18q11.2 histamine receptor H4 LOC390843 18 similar to hypothetical protein BC005868 LOC342741 18q11.2 similar to DEAD (Asp-Glu-Ala-Asp) box polypeptide 48 LOC147468 18q11.2 similar to WW domain binding protein 2 EHZF 18q11.2 early hematopoietic zinc finger SS18 18q11.2 synovial sarcoma translocation, chromosome 18 MGC26605 18q11.2 hypothetical protein MGC26605 TAF4B 18q11.2 TAF4b RNA polymerase II, TATA box binding protein (TBP)-associated factor, 105kDa KCTD1 18 potassium channel tetramerisation domain containing 1 LOC388472 18 hypothetical gene supported by BC002568 LOC342695 18q12.1 similar to ubiquitin fusion degradation 1-like AQP4 18q11.2.q12.1 aquaporin 4 FLJ30507 18q12.1 hypothetical protein FLJ30507 CHST9 18q11.2 carbohydrate (N-acetylgalactosamine 4-0) sulfotransferase 9 LOC342697 18q12.1 similar to Proliferation-associated protein 2G4 (Cell cycle protein p38-2G4 homolog) (hG4-1) CDH2 18q11.2-q12.2 cadherin 2, type 1, N-cadherin (neuronal) LOC390844 18 similar to Ariadne-2 protein homolog (ARI-2) (Triad1 protein) (HT005)
    RNA
    TRANSCRIPTS type messenger
    text
  • MIWC1 contains TATA, CAAT, AP-1 regulatory elements PMID:7559426
  • five elements of M1 mRNA clustered within the 286-bp region were found to function as a novel astrocyte-specific enhancer PMID:22225570
  • a consensus sequence of Pit-1/Oct/Unc-86 (POU) transcription factors was indispensable to the astrocyte-specific enhancer of M1 mRNA
  • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 splicing 5216 34.8 323 . astrocytes of fetal archicortex and neocortex PMID:16814974 - 18179769
  • also called M1 or variant a
  • longer AQP4M1 isoform interferes with array formation, presumably due to the additional 22 N-terminal AAs
  • two N-terminal cysteines are palmitoylated, suggesting that palmitoylation of the N-terminal cysteines is the reason for the inability of AQP4M1 to form square arrays
  • 4 splicing 5136 32.2 301 . astrocytes of fetal archicortex and neocortex PMID:16814974 - 18179769
  • also called C2, M23 or variant b
  • only the shorter AQP4M23 isoform assembles into square arrays
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   lowly Homo sapiensNM_001650
     vessel     Homo sapiens
    Digestiveintestine   lowly Rattus norvegicus
    Nervousbrainforebraincerebral cortex highly Rattus norvegicus
     brainhindbraincerebellum highly Rattus norvegicus
     brain   highly Rattus norvegicus
     brain   highly Homo sapiensNM_001650
     spinal cord     Homo sapiens
    Respiratorylung   lowly Rattus norvegicus
    Urinarykidneytubulecollecting duct highly Homo sapiensNM_00165
     kidney   lowly Rattus norvegicus
    Visualeye   lowly Rattus norvegicus
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal highly Homo sapiensNM_001650
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell Homo sapiens
    Muscularmyocyte Homo sapiens
    Nervousastrocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • C terminal unique sorting cassette
  • C-terminal signals determine AQP4 basolateral membrane targeting in epithelial MDCK cells
  • two independent basolateral sorting signals
  • mono polymer homomer , polymer
    HOMOLOGY
    interspecies ortholog to Aqp4, Mus musculus
    ortholog to Aqp4, Rattus norvegicus
    ortholog to aqp4, Danio rerio
    ortholog to AQP4, Pan troglodytes
    intraspecies homolog to AQP5
    Homologene
    FAMILY
  • water transport proteins
  • CATEGORY transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane
    text
  • specific membrane domains of astrocytes
  • in the sarcolemma of fast -twitch fibers and astrocyte end- feet
  • associated with the transverse tubules of skeletal myofibers (
  • selectively expressed in endfoot membranes and not in other membranes at the blood–brain interface (PMIDS:
  • basic FUNCTION
  • critical role in inner ear fluid homeostasis
  • ‘‘orthodox’’aquaporin, that transport only water molecules
  • hypothalamic osmoreceptor and regulator of vasopressin secretion, in response to brain edema formation
  • playing a role in accommodating the rapid changes in cell volume and hydrostatic forces that occur during muscular contraction in order to prevent damage to the sarcolemma
  • may be playing a role in a role in olfactory function
  • involved in water homeostasis in the mammalian brain
  • plays a protective role after contusion spinal cord injury by facilitating the clearance of excess water
  • play pivotal roles in cerebral water movement as essential mediators during edema and fluid accumulation
  • not only serves as an influx route for water but also is critical for initiating downstream signaling events that may affect and potentially exacerbate the pathological outcome in clinical conditions associated with brain edema
  • AQP4-mediated cell swelling is inextricably coupled with activation of signaling pathways that may profoundly affect the pathological and pathophysiological outcome in clinical conditions associated with brain edema
  • TRPV4 and AQP4 combined possess the essential features expected of a regulatory volume decrease (RVD) activator
  • major brain water channel AQP4 is implicated in water transport at the blood–brain interface
  • the maintenance of water homeostasis under pathological conditions is mediated by the aquaporin-4 (AQP4) channel in astrocytes
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text water channel
    PATHWAY
    metabolism
    signaling
    a component
  • TRPV4/AQP4 complex in astrocytes, that constitutes a key element in the brain volume homeostasis by acting as an osmosensor that couples osmotic stress to downstream signaling cascades
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • AP2 adaptor complex
  • TRPV4
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in muscle of DMD and BMD (
    constitutional     --low  
    in mesial temporal lobe epilepsy (MTLE) secundary to a disruption of the dystrophin complex, resulting in a perturbed flux of water through astrocytes and K+ homeostasis with propensity for seizures
    constitutional     --over  
    post-partum in pregnancy and in early lung development
    constitutional     --low  
    in sarcoglycanopathies and dysferlinopathies (LGMD2B, LGMD2C, LGMD2D, LGMD2E, LGMD2F)
    Susceptibility
  • to cerebral edema
  • to neuromyelitis optica
  • Variant & Polymorphism other variant reduced normalized water permeability of brain
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurosensorialear 
    aquaporins appear to be important for the development of novel drug therapies for Meniere disease and related disorders
    cancerlung 
    potential role of AQP1 or AQP4 as novel therapeutic targets for the management of lung cancer
    neurologyacquired 
    AQP4 inhibition or downregulation as novel early neuroprotective manoeuvres in spinal cord injury
    ANIMAL & CELL MODELS
  • AQP4 null mice are deaf
  • Aqp4 knockout mice display cochlear dysfunction that is the primary cause of hearing impairment
  • AQP4-dependent spinal cord swelling following compression injury, resulting in remarkably improved outcome in AQP4-null mice
  • AQP4 expression is reduced in Duchenne muscular dystrophy patients, and is reported to correlate with decreased alpha1-syntrophin and altered osmotic permeability
  • AQP4 was significantly reduced despite normal dystrophin and alpha1-syntrophin in dysferlinopathy patients
  • Mice lacking AQP4 (AQP4(-/-) mice) exhibited significantly impaired locomotor function and prolonged bladder dysfunction after spinal cord injury