Reviewed,
UniProtKB/Swiss-Prot P41181 (AQP2_HUMAN)
Last modified
November 24, 2009.
Version 97.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Aquaporin-2 Short name=AQP-2 Alternative name(s): Aquaporin-CD Short name=AQP-CD Water channel protein for renal collecting duct ADH water channel Collecting duct water channel protein WCH-CD | ||
| Gene names |
| ||
| Organism | Homo sapiens (Human) [Complete proteome] | ||
| Taxonomic identifier | 9606 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 271 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Forms a water-specific channel that provides the plasma membranes of renal collecting duct with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient. |
| Subcellular location | Apical cell membrane; Multi-pass membrane protein. Cytoplasmic vesicle membrane; Multi-pass membrane protein. Note: Shuttles from vesicles to the apical membrane. Ref.7 |
| Tissue specificity | Expressed in renal collecting tubules. |
| Domain | Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA). |
| Post-translational modification | Ser-256 phosphorylation is necessary and sufficient for expression at the apical membrane. Endocytosis is not phosphorylation-dependent. |
| Involvement in disease | Defects in AQP2 are the cause of diabetes insipidus nephrogenic autosomal (ANDI) [MIM:125800]; also known as diabetes insipidus nephrogenic type 2. ANDI is caused by the inability of the renal collecting ducts to absorb water in response to arginine vasopressin. It is characterized by excessive water drinking (polydypsia), excessive urine excretion (polyuria), persistent hypotonic urine, and hypokalemia. Inheritance can be autosomal dominant or recessive. Ref.3 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 |
| Sequence similarities | Belongs to the MIP/aquaporin (TC 1.A.8) family. [View classification] |
Ontologies
| Keywords | |
|---|---|
| Biological process | Transport |
| Cellular component | Cell membrane Cytoplasmic vesicle Membrane |
| Coding sequence diversity | Polymorphism |
| Disease | Diabetes insipidus Disease mutation |
| Domain | Repeat Transmembrane |
| PTM | Glycoprotein Phosphoprotein |
| Technical term | Complete proteome |
| Gene Ontology (GO) | |
| Biological process | excretion Traceable author statement. Source: ProtInc transmembrane transportInferred from electronic annotation. Source: InterPro |
| Cellular component | apical plasma membrane Inferred from direct assay. Source: UniProtKB cytoplasmic vesicleInferred from electronic annotation. Source: UniProtKB-KW integral to membraneInferred from electronic annotation. Source: UniProtKB-SubCell |
| Molecular function | water channel activity Traceable author statement. Source: ProtInc |
| Complete GO annotation... | |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 271 | 271 | Aquaporin-2 | PRO_0000063934 | |||||
Regions | |||||||||
| Topological domain | 1 – 16 | 16 | Cytoplasmic Potential | ||||||
| Transmembrane | 17 – 34 | 18 | Potential | ||||||
| Topological domain | 35 – 40 | 6 | Extracellular Potential | ||||||
| Transmembrane | 41 – 59 | 19 | Potential | ||||||
| Topological domain | 60 – 85 | 26 | Cytoplasmic Potential | ||||||
| Transmembrane | 86 – 107 | 22 | Potential | ||||||
| Topological domain | 108 – 127 | 20 | Extracellular Potential | ||||||
| Transmembrane | 128 – 148 | 21 | Potential | ||||||
| Topological domain | 149 – 156 | 8 | Cytoplasmic Potential | ||||||
| Transmembrane | 157 – 176 | 20 | Potential | ||||||
| Topological domain | 177 – 202 | 26 | Extracellular Potential | ||||||
| Transmembrane | 203 – 224 | 22 | Potential | ||||||
| Topological domain | 225 – 271 | 47 | Cytoplasmic Potential | ||||||
| Motif | 68 – 70 | 3 | NPA 1 | ||||||
| Motif | 184 – 186 | 3 | NPA 2 | ||||||
Amino acid modifications | |||||||||
| Modified residue | 256 | 1 | Phosphoserine; by PKA Ref.7 | ||||||
| Modified residue | 261 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 264 | 1 | Phosphoserine By similarity | ||||||
| Glycosylation | 123 | 1 | N-linked (GlcNAc...) Potential | ||||||
Natural variations | |||||||||
| Natural variant | 22 | 1 | L → V in ANDI. Ref.9 | VAR_015239 | |||||
| Natural variant | 28 | 1 | L → P in ANDI. Ref.15 | VAR_015240 | |||||
| Natural variant | 47 | 1 | A → V in ANDI. Ref.15 | VAR_015241 | |||||
| Natural variant | 57 | 1 | Q → P in ANDI. dbSNP rs28931580. Ref.16 | VAR_015256 | |||||
| Natural variant | 64 | 1 | G → R in ANDI. Ref.3 | VAR_004401 | |||||
| Natural variant | 68 | 1 | N → S in ANDI. Ref.10 | VAR_015242 | |||||
| Natural variant | 71 | 1 | V → M in ANDI. Ref.15 | VAR_015243 | |||||
| Natural variant | 100 | 1 | G → V in ANDI. dbSNP rs28929477. | VAR_015257 | |||||
| Natural variant | 121 | 1 | L → F: dbSNP rs11169226. | VAR_037577 | |||||
| Natural variant | 125 | 1 | T → M in ANDI. Ref.12 Ref.14 Ref.15 | VAR_015244 | |||||
| Natural variant | 126 | 1 | T → M in ANDI. Ref.10 | VAR_015245 | |||||
| Natural variant | 147 | 1 | A → T in ANDI. Ref.10 | VAR_015246 | |||||
| Natural variant | 168 | 1 | V → M in ANDI. Ref.11 | VAR_015247 | |||||
| Natural variant | 175 | 1 | G → R in ANDI. Ref.12 Ref.14 Ref.15 | VAR_015248 | |||||
| Natural variant | 181 | 1 | C → W in ANDI. Ref.9 | VAR_015249 | |||||
| Natural variant | 185 | 1 | P → A in ANDI. Ref.15 | VAR_015250 | |||||
| Natural variant | 187 | 1 | R → C in ANDI; mutant protein does not fold properly and is not functional. Ref.3 Ref.17 | VAR_004402 | |||||
| Natural variant | 190 | 1 | A → T in ANDI; mutant protein does not fold properly and is not functional. Ref.12 Ref.17 | VAR_015251 | |||||
| Natural variant | 194 | 1 | V → I | VAR_015252 | |||||
| Natural variant | 202 | 1 | W → C in ANDI. Ref.8 | VAR_015253 | |||||
| Natural variant | 216 | 1 | S → P in ANDI. Ref.3 Ref.11 | VAR_004403 | |||||
| Natural variant | 258 | 1 | E → K in ANDI; retained in the Golgi compartment. Ref.13 | VAR_015254 | |||||
| Natural variant | 262 | 1 | P → L in ANDI; mutant protein folds properly and is functional but is retained in intracellular vesicles and does not localize to the ER; upon coexpression with wild-type AQP2 mutant protein interacts with wild-type AQP2 and the resulting heterotetramer properly localizes to the apical membrane. Ref.12 Ref.17 | VAR_015255 | |||||
Experimental info | |||||||||
| Mutagenesis | 148 | 1 | S → A: No effect on sorting from the ER to the vesicles, redistribution to apical membrane, or endocytosis. Ref.7 | ||||||
| Mutagenesis | 148 | 1 | S → D: Retained in the endoplasmic reticulum. Ref.7 | ||||||
| Mutagenesis | 229 | 1 | S → A: No effect on sorting from the ER to the vesicles, redistribution to apical membrane, or endocytosis. Ref.7 | ||||||
| Mutagenesis | 229 | 1 | S → D: No effect on sorting from the ER to the vesicles, redistribution to apical membrane, or endocytosis. Ref.7 | ||||||
| Mutagenesis | 231 | 1 | S → A: No effect on sorting from the ER to the vesicles, redistribution to apical membrane, or endocytosis. Ref.7 | ||||||
| Mutagenesis | 231 | 1 | S → D: No effect on sorting from the ER to the vesicles, redistribution to apical membrane, or endocytosis. Ref.7 | ||||||
| Mutagenesis | 244 | 1 | T → A: No effect on sorting from the ER to the vesicles, redistribution to apical membrane, or endocytosis. Ref.7 | ||||||
| Mutagenesis | 244 | 1 | T → E: No effect on sorting from the ER to the vesicles, redistribution to apical membrane, or endocytosis. Ref.7 | ||||||
| Mutagenesis | 256 | 1 | S → A: Retained in vesicles. Ref.7 | ||||||
| Mutagenesis | 256 | 1 | S → D: Expressed in the apical membrane. Ref.7 | ||||||
| Sequence conflict | 35 – 38 | 4 | PQAL → ATAP Ref.4 | ||||||
| Sequence conflict | 83 | 1 | V → F Ref.4 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine." Deen P.M.T., Verdijk M.A.J., Knoers V.V.A.M., Wieringa B., Monnens L.A.H., van Os C.H., van Oost B.A. Science 264:92-94(1994) [PubMed: 8140421] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [2] | "Isolation of human aquaporin-CD gene." Uchida S., Sasaki S., Fushimi K., Marumo F. J. Biol. Chem. 269:23451-23455(1994) [PubMed: 7522228] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [3] | "Patients with autosomal nephrogenic diabetes insipidus homozygous for mutations in the aquaporin 2 water-channel gene." van Lieburg A.F., Verdijk M.A.J., Knoers V.V.A.M., van Essen A.J., Proesmans W., Mallmann R., Monnens L.A.H., van Oost B.A., van Os C.H., Deen P.M.T. Am. J. Hum. Genet. 55:648-652(1994) [PubMed: 7524315] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ANDI ARG-64; CYS-187 AND PRO-216. |
| [4] | "Cloning, characterization, and chromosomal mapping of human aquaporin of collecting duct." Sasaki S., Fushimi K., Saito H., Saito F., Uchida S., Ishibashi K., Kuwahara M., Ikeuchi T., Inui K., Nakajima K. J. Clin. Invest. 93:1250-1256(1994) [PubMed: 7510718] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Kidney. |
| [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., Bichet D.G., Lonergan M., Arthus M.-F., Jeck N., Seyberth H.W., Rosenthal W., van Os C.H., Oksche A., Deen P.M.T. Hum. Mol. Genet. 11:779-789(2002) [PubMed: 11929850] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Kidney. |
| [6] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon. |
| [7] | "The role of putative phosphorylation sites in the targeting and shuttling of the aquaporin-2 water channel." van Balkom B.W.M., Savelkoul P.J.M., Markovich D., Hofman E., Nielsen S., van der Sluijs P., Deen P.M.T. J. Biol. Chem. 277:41473-41479(2002) [PubMed: 12194985] [Abstract] Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-256, MUTAGENESIS OF SER-148; SER-229; SER-231; THR-244 AND SER-256. |
| [8] | "Two novel mutations in the aquaporin-2 and the vasopressin V2 receptor genes in patients with congenital nephrogenic diabetes insipidus." Oksche A., Moeller A., Dickson J., Rosendahl W., Rascher W., Bichet D.G., Rosenthal W. Hum. Genet. 98:587-589(1996) [PubMed: 8882880] [Abstract] Cited for: VARIANT ANDI CYS-202. |
| [9] | "Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopressin response." Canfield M.C., Tamarappoo B.K., Moses A.M., Verkman A.S., Holtzman E.J. Hum. Mol. Genet. 6:1865-1871(1997) [PubMed: 9302264] [Abstract] Cited for: VARIANTS ANDI VAL-22 AND TRP-181. |
| [10] | "New mutations in the AQP2 gene in nephrogenic diabetes insipidus resulting in functional but misrouted water channels." Mulders S.M., Knoers N.V., Van Lieburg A.F., Monnens L.A., Leumann E., Wuhl E., Schober E., Rijss J.P.L., Van Os C.H., Deen P.M.T. J. Am. Soc. Nephrol. 8:242-248(1997) [PubMed: 9048343] [Abstract] Cited for: VARIANTS ANDI SER-68; MET-126 AND THR-147. |
| [11] | "Mutations in the vasopressin V2 receptor and aquaporin-2 genes in 12 families with congenital nephrogenic diabetes insipidus." Vargas-Poussou R., Forestier L., Dautzenberg M.D., Niaudet P., Dechaux M., Antignac C. J. Am. Soc. Nephrol. 8:1855-1862(1997) [PubMed: 9402087] [Abstract] Cited for: VARIANTS ANDI MET-168 AND PRO-216. |
| [12] | "Aquaporin-2, a vasopressin-sensitive water channel, and nephrogenic diabetes insipidus." Kuwahara M. Intern. Med. 37:215-217(1998) [PubMed: 9550615] [Abstract] Cited for: VARIANTS ANDI MET-125; ARG-175; THR-190 AND LEU-262. |
| [13] | "An aquaporin-2 water channel mutant which causes autosomal dominant nephrogenic diabetes insipidus is retained in the Golgi complex." Mulders S.M., Bichet D.G., Rijss J.P.L., Kamsteeg E.-J., Arthus M.-F., Lonergan M., Fujiwara M., Morgan K., Leijendekker R., van der Sluijs P., van Os C.H., Deen P.M.T. J. Clin. Invest. 102:57-66(1998) [PubMed: 9649557] [Abstract] Cited for: VARIANT ANDI LYS-258. |
| [14] | "Novel mutations in aquaporin-2 gene in female siblings with nephrogenic diabetes insipidus: evidence of disrupted water channel function." Goji K., Kuwahara M., Gu Y., Matsuo M., Marumo F., Sasaki S. J. Clin. Endocrinol. Metab. 83:3205-3209(1998) [PubMed: 9745427] [Abstract] Cited for: VARIANTS ANDI MET-125 AND ARG-175. |
| [15] | "Cell-biologic and functional analyses of five new Aquaporin-2 missense mutations that cause recessive nephrogenic diabetes insipidus." Marr N., Bichet D.G., Hoefs S., Savelkoul P.J.M., Konings I.B., De Mattia F., Graat M.P., Arthus M.-F., Lonergan M., Fujiwara T.M., Knoers N.V., Landau D., Balfe W.J., Oksche A., Rosenthal W., Muller D., Van Os C.H., Deen P.M. J. Am. Soc. Nephrol. 13:2267-2277(2002) [PubMed: 12191971] [Abstract] Cited for: VARIANTS ANDI PRO-28; VAL-47; MET-71; MET-125; ARG-175 AND ALA-185, VARIANT ILE-194. |
| [16] | "Two novel aquaporin-2 mutations responsible for congenital nephrogenic diabetes insipidus in Chinese families." Lin S.H., Bichet D.G., Sasaki S., Kuwahara M., Arthus M.-F., Lonergan M., Lin Y.-F. J. Clin. Endocrinol. Metab. 87:2694-2700(2002) [PubMed: 12050236] [Abstract] Cited for: VARIANTS ANDI PRO-57 AND VAL-100. |
| [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., Savelkoul P.J.M., Bichet D.G., Kamsteeg E.-J., Konings I.B.M., Marr N., Arthus M.-F., Lonergan M., van Os C.H., van der Sluijs P., Robertson G., Deen P.M.T. Hum. Mol. Genet. 13:3045-3056(2004) [PubMed: 15509592] [Abstract] Cited for: VARIANTS ANDI CYS-187; THR-190 AND LEU-262, CHARACTERIZATION OF VARIANTS ANDI CYS-187; THR-190 AND LEU-262. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| Z29491 Genomic DNA. Translation: CAA82627.1. D31846 Genomic DNA. Translation: BAA06632.1. S73196 mRNA. Translation: AAB31999.1. S73197 mRNA. Translation: AAB31998.1. AF147093, AF147092 Genomic DNA. Translation: AAD38692.1. BC042496 mRNA. Translation: AAH42496.1. | |
| IPI | IPI00012818. |
| PIR | A53442. I64818. |
| RefSeq | NP_000477.1. |
| UniGene | Hs.130730 |
3D structure databases | |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | P41181. |
Protein family/group databases | |
| TCDB | 1.A.8.8.8. major intrinsic protein (MIP) family. |
PTM databases | |
| PhosphoSite | P41181. |
Proteomic databases | |
| PRIDE | P41181. |
Genome annotation databases | |
| Ensembl | ENST00000199280; ENSP00000199280; ENSG00000167580; Homo sapiens. [Genome view] |
| GeneID | 359. |
| KEGG | hsa:359. |
| UCSC | uc001rvn.1. human. |
Organism-specific databases | |
| CTD | 359. |
| GeneCards | GC12P048630. |
| H-InvDB | HIX0010617. |
| HGNC | HGNC:634. AQP2. |
| HPA | CAB009866. |
| MIM | 107777. gene. 125800. phenotype. |
| Orphanet | 223. Diabetes insipidus, nephrogenic. |
| PharmGKB | PA24920. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | P41181. |
| HOVERGEN | P41181. |
| OMA | YVLFPPA |
| OrthoDB | EOG9P2SMS |
Gene expression databases | |
| ArrayExpress | P41181. |
| Bgee | P41181. |
| CleanEx | HS_AQP2. |
| Genevestigator | P41181. |
| GermOnline | ENSG00000167580. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR012269. Aquaporin. IPR000425. MIP. [Graphical view] |
| Gene3D | G3DSA:1.20.1080.10. MIP. 1 hit. |
| PANTHER | PTHR19139. MIP. 1 hit. |
| Pfam | PF00230. MIP. 1 hit. [Graphical view] |
| PRINTS | PR00783. MINTRINSICP. |
| TIGRFAMs | TIGR00861. MIP. 1 hit. |
| PROSITE | PS00221. MIP. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 1501. |
| SOURCE | Search... |
Entry information
| Entry name | AQP2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P41181 Secondary accession number(s): Q9UD68 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 12 Human chromosome 12: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


