TCDB is operated by the Saier Lab Bioinformatics Group
« See all members of the family

Vasopressin-sensitive aquaporin-2 (Aqp2) in the apical membrane of the renal collecting duct (Fenton et al., 2008).  Controls cell volume and thereby influences cell proliferation (Di Giusto et al. 2012).  It  plays a key role in concentrating urine. Water reabsorption is regulated by AQP2 trafficking between intracellular storage vesicles and the apical membrane. This process is tightly controlled by the pituitary hormone arginine vasopressin, and defective trafficking results in nephrogenic diabetes insipidus (NDI).  The crystal structure of Aqp2 has been solved to 2.75 Å (Frick et al. 2014).  In terrestrial vertebrates, AQP2 function is generally regulated by arginine-vasopressin to accomplish key functions in osmoregulation such as the maintenance of body water homeostasis by a cyclic AMP-independent mechanism (Olesen and Fenton 2017; Martos-Sitcha et al. 2015). AQP2 is expressed in the anterior vaginal wall and fibroblasts, and regulates the expression level of collagen I/III i, suggesting that AQP2 is associated with the pathogenesis of stress urinary incontinence through collagen metabolism during ECM remodeling (Zhang et al. 2017). As in humans, the chicken ortholog, Aqp2, is found only in the kidney (Ramírez-Lorca et al. 2006).  AQP2 is critical in regulating urine concentrating ability. The expression and function of AQP2 are regulated by a series of transcriptional factors and post-transcriptional phosphorylation, ubiquitination, and glycosylation (He and Yang 2019). Mutation or functional deficiency of AQP2 leads to severe nephrogenic diabetes insipidus, and inhibition of various aquaporins leads to many water-related diseases such as, edema, cardiac arrest, and stroke. Maroli et al. 2019 reported on the molecular mechanisms of mycotoxin (citrinin, ochratoxin-A, and T-2 mycotoxin) inhibition of AQP2 and arginine vasopressin receptor 2 (AVPR2). Aquaporin-2 mutations cause Nephrogenic diabetes insipidus (Li et al. 2021). Meniere's disease is affected by dexamethasone which is a direct modulator of AQP2. The molecular mechanisms involved in dexamethasone binding to and its regulatory action upon AQP2 function have been described (Mom et al. 2022). Interaction of cortisol with aquaporin-2 modulates its water permeability (Mom et al. 2023).

Accession Number:P41181
Protein Name:Aqp2
Molecular Weight:28837.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:6
Location1 / Topology2 / Orientation3: Apical cell membrane1 / Multi-pass membrane protein2
Substrate water

Cross database links:

RefSeq: NP_000477.1   
Entrez Gene ID: 359   
Pfam: PF00230   
OMIM: 107777  gene
125800  phenotype
KEGG: hsa:359   

Gene Ontology

GO:0016324 C:apical plasma membrane
GO:0030659 C:cytoplasmic vesicle membrane
GO:0016021 C:integral to membrane
GO:0015168 F:glycerol transmembrane transporter activity
GO:0015250 F:water channel activity
GO:0071280 P:cellular response to copper ion
GO:0071288 P:cellular response to mercury ion
GO:0007588 P:excretion
GO:0015793 P:glycerol transport
GO:0055085 P:transmembrane transport

References (22)

[1] “Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine.”  Deen   8140421
[2] “Isolation of human aquaporin-CD gene.”  Uchida   7522228
[3] “Patients with autosomal nephrogenic diabetes insipidus homozygous for mutations in the aquaporin 2 water-channel gene.”  van Lieburg   7524315
[4] “Cloning, characterization, and chromosomal mapping of human aquaporin of collecting duct.”  Sasaki   7510718
[5] “Heteroligomerization of an aquaporin-2 mutant with wild-type aquaporin-2 and their misrouting to late endosomes/lysosomes explains dominant nephrogenic diabetes insipidus.”  Marr   11929850
[6] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project   15489334
[7] “The role of putative phosphorylation sites in the targeting and shuttling of the aquaporin-2 water channel.”  van Balkom   12194985
[8] “Two novel mutations in the aquaporin-2 and the vasopressin V2 receptor genes in patients with congenital nephrogenic diabetes insipidus.”  Oksche   8882880
[9] “Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopressin response.”  Canfield   9302264
[10] “New mutations in the AQP2 gene in nephrogenic diabetes insipidus resulting in functional but misrouted water channels.”  Mulders   9048343
[11] “Mutations in the vasopressin V2 receptor and aquaporin-2 genes in 12 families with congenital nephrogenic diabetes insipidus.”  Vargas-Poussou   9402087
[12] “Aquaporin-2, a vasopressin-sensitive water channel, and nephrogenic diabetes insipidus.”  Kuwahara   9550615
[13] “An aquaporin-2 water channel mutant which causes autosomal dominant nephrogenic diabetes insipidus is retained in the Golgi complex.”  Mulders   9649557
[14] “Novel mutations in aquaporin-2 gene in female siblings with nephrogenic diabetes insipidus: evidence of disrupted water channel function.”  Goji   9745427
[15] “Cell-biologic and functional analyses of five new Aquaporin-2 missense mutations that cause recessive nephrogenic diabetes insipidus.”  Marr   12191971
[16] “Two novel aquaporin-2 mutations responsible for congenital nephrogenic diabetes insipidus in Chinese families.”  Lin   12050236
[17] “A novel mechanism in recessive nephrogenic diabetes insipidus: wild-type aquaporin-2 rescues the apical membrane expression of intracellularly retained AQP2-P262L.”  de Mattia   15509592
[18] “Lack of arginine vasopressin-induced phosphorylation of aquaporin-2 mutant AQP2-R254L explains dominant nephrogenic diabetes insipidus.”  de Mattia   16120822
[19] “Two novel mutations in the aquaporin 2 gene in a girl with congenital nephrogenic diabetes insipidus.”  Cheong   16361827
[20] “Novel mutations underlying nephrogenic diabetes insipidus in Arab families.”  Carroll   16845277
[21] “p.R254Q mutation in the aquaporin-2 water channel causing dominant nephrogenic diabetes insipidus is due to a lack of arginine vasopressin-induced phosphorylation.”  Savelkoul   19585583
[22] “Repulsion between Lys258 and upstream arginines explains the missorting of the AQP2 mutant p.Glu258Lys in nephrogenic diabetes insipidus.”  Kamsteeg   19701945
4NEF   4OJ2   6QF5     

External Searches:


Predict TMSs (Predict number of transmembrane segments)
Window Size: Angle:  
FASTA formatted sequence