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1.A.8.8.8
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 2.75Å (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).

Accession Number:P41181
Protein Name:Aqp2
Length:271
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:

Genevestigator: P41181
eggNOG: prNOG11204
HEGENOM: HBG705794
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 P.M.T.et.al.   8140421
[2] “Isolation of human aquaporin-CD gene.”  Uchida S.et.al.   7522228
[3] “Patients with autosomal nephrogenic diabetes insipidus homozygous for mutations in the aquaporin 2 water-channel gene.”  van Lieburg A.F.et.al.   7524315
[4] “Cloning, characterization, and chromosomal mapping of human aquaporin of collecting duct.”  Sasaki S.et.al.   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 N.et.al.   11929850
[6] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[7] “The role of putative phosphorylation sites in the targeting and shuttling of the aquaporin-2 water channel.”  van Balkom B.W.M.et.al.   12194985
[8] “Two novel mutations in the aquaporin-2 and the vasopressin V2 receptor genes in patients with congenital nephrogenic diabetes insipidus.”  Oksche A.et.al.   8882880
[9] “Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopressin response.”  Canfield M.C.et.al.   9302264
[10] “New mutations in the AQP2 gene in nephrogenic diabetes insipidus resulting in functional but misrouted water channels.”  Mulders S.M.et.al.   9048343
[11] “Mutations in the vasopressin V2 receptor and aquaporin-2 genes in 12 families with congenital nephrogenic diabetes insipidus.”  Vargas-Poussou R.et.al.   9402087
[12] “Aquaporin-2, a vasopressin-sensitive water channel, and nephrogenic diabetes insipidus.”  Kuwahara M.et.al.   9550615
[13] “An aquaporin-2 water channel mutant which causes autosomal dominant nephrogenic diabetes insipidus is retained in the Golgi complex.”  Mulders S.M.et.al.   9649557
[14] “Novel mutations in aquaporin-2 gene in female siblings with nephrogenic diabetes insipidus: evidence of disrupted water channel function.”  Goji K.et.al.   9745427
[15] “Cell-biologic and functional analyses of five new Aquaporin-2 missense mutations that cause recessive nephrogenic diabetes insipidus.”  Marr N.et.al.   12191971
[16] “Two novel aquaporin-2 mutations responsible for congenital nephrogenic diabetes insipidus in Chinese families.”  Lin S.H.et.al.   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 F.et.al.   15509592
[18] “Lack of arginine vasopressin-induced phosphorylation of aquaporin-2 mutant AQP2-R254L explains dominant nephrogenic diabetes insipidus.”  de Mattia F.et.al.   16120822
[19] “Two novel mutations in the aquaporin 2 gene in a girl with congenital nephrogenic diabetes insipidus.”  Cheong H.I.et.al.   16361827
[20] “Novel mutations underlying nephrogenic diabetes insipidus in Arab families.”  Carroll P.et.al.   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 P.J.M.et.al.   19585583
[22] “Repulsion between Lys258 and upstream arginines explains the missorting of the AQP2 mutant p.Glu258Lys in nephrogenic diabetes insipidus.”  Kamsteeg E.-J.et.al.   19701945
Structure:
4NEF   4OJ2     

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FASTA formatted sequence
1:	MWELRSIAFS RAVFAEFLAT LLFVFFGLGS ALNWPQALPS VLQIAMAFGL GIGTLVQALG 
61:	HISGAHINPA VTVACLVGCH VSVLRAAFYV AAQLLGAVAG AALLHEITPA DIRGDLAVNA 
121:	LSNSTTAGQA VTVELFLTLQ LVLCIFASTD ERRGENPGTP ALSIGFSVAL GHLLGIHYTG 
181:	CSMNPARSLA PAVVTGKFDD HWVFWIGPLV GAILGSLLYN YVLFPPAKSL SERLAVLKGL 
241:	EPDTDWEERE VRRRQSVELH SPQSLPRGTK A