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FLASH GENE

Symbol

AQP4

contributors: mct/shn - updated : 05-01-2013

HGNC name	aquaporin 4
HGNC id	637

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

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

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001650 5 splicing 5216 NP_001641 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 NM_004028 4 splicing 5136 NP_004019 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)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       lowly Homo sapiens NM_001650   vessel         Homo sapiens Digestive intestine       lowly Rattus norvegicus Nervous brain       highly Rattus norvegicus   brain       highly Homo sapiens NM_001650   brain forebrain cerebral cortex   highly Rattus norvegicus   brain hindbrain cerebellum   highly Rattus norvegicus Respiratory lung       lowly Rattus norvegicus Urinary kidney tubule collecting duct   highly Homo sapiens NM_00165   kidney       lowly Rattus norvegicus Visual eye       lowly Rattus norvegicus

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal   highly Homo sapiens NM_001650

cells

System Cell Pubmed Species Stage Rna symbol Cardiovascular endothelial cell Homo sapiens Muscular myocyte Homo sapiens Nervous astrocyte 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
	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

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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

Variant & Polymorphism other	variant reduced normalized water permeability of brain

Candidate gene
Marker
Therapy target	AQP4 inhibition or downregulation as novel early neuroprotective manoeuvres in spinal cord injury
	System Type Disorder Pubmed neurosensorial ear   aquaporins appear to be important for the development of novel drug therapies for Meniere disease and related disorders

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