AQP2_HUMAN
ID AQP2_HUMAN Reviewed; 271 AA.
AC P41181; Q9UD68;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Aquaporin-2;
DE Short=AQP-2;
DE AltName: Full=ADH water channel;
DE AltName: Full=Aquaporin-CD {ECO:0000303|PubMed:7522228};
DE Short=AQP-CD;
DE AltName: Full=Collecting duct water channel protein;
DE AltName: Full=WCH-CD;
DE AltName: Full=Water channel protein for renal collecting duct;
GN Name=AQP2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBCELLULAR LOCATION, VARIANTS
RP ANDI CYS-187 AND PRO-216, AND CHARACTERIZATION OF VARIANTS ANDI CYS-187 AND
RP PRO-216.
RX PubMed=8140421; DOI=10.1126/science.8140421;
RA Deen P.M.T., Verdijk M.A.J., Knoers V.V.A.M., Wieringa B., Monnens L.A.H.,
RA van Os C.H., van Oost B.A.;
RT "Requirement of human renal water channel aquaporin-2 for vasopressin-
RT dependent concentration of urine.";
RL Science 264:92-94(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7522228; DOI=10.1016/s0021-9258(17)31537-5;
RA Uchida S., Sasaki S., Fushimi K., Marumo F.;
RT "Isolation of human aquaporin-CD gene.";
RL J. Biol. Chem. 269:23451-23455(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, VARIANTS ANDI
RP ARG-64; CYS-187 AND PRO-216, AND CHARACTERIZATION OF VARIANT ANDI ARG-64.
RX PubMed=7524315;
RA van Lieburg A.F., Verdijk M.A.J., Knoers V.V.A.M., van Essen A.J.,
RA Proesmans W., Mallmann R., Monnens L.A.H., van Oost B.A., van Os C.H.,
RA Deen P.M.T.;
RT "Patients with autosomal nephrogenic diabetes insipidus homozygous for
RT mutations in the aquaporin 2 water-channel gene.";
RL Am. J. Hum. Genet. 55:648-652(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND GLYCOSYLATION.
RC TISSUE=Kidney;
RX PubMed=7510718; DOI=10.1172/jci117079;
RA Sasaki S., Fushimi K., Saito H., Saito F., Uchida S., Ishibashi K.,
RA Kuwahara M., Ikeuchi T., Inui K., Nakajima K.;
RT "Cloning, characterization, and chromosomal mapping of human aquaporin of
RT collecting duct.";
RL J. Clin. Invest. 93:1250-1256(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Kidney;
RX PubMed=11929850; DOI=10.1093/hmg/11.7.779;
RA Marr N., Bichet D.G., Lonergan M., Arthus M.-F., Jeck N., Seyberth H.W.,
RA Rosenthal W., van Os C.H., Oksche A., Deen P.M.T.;
RT "Heteroligomerization of an aquaporin-2 mutant with wild-type aquaporin-2
RT and their misrouting to late endosomes/lysosomes explains dominant
RT nephrogenic diabetes insipidus.";
RL Hum. Mol. Genet. 11:779-789(2002).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-256, AND MUTAGENESIS OF
RP SER-148; SER-229; SER-231; THR-244 AND SER-256.
RX PubMed=12194985; DOI=10.1074/jbc.m207525200;
RA van Balkom B.W.M., Savelkoul P.J.M., Markovich D., Hofman E., Nielsen S.,
RA van der Sluijs P., Deen P.M.T.;
RT "The role of putative phosphorylation sites in the targeting and shuttling
RT of the aquaporin-2 water channel.";
RL J. Biol. Chem. 277:41473-41479(2002).
RN [8] {ECO:0007744|PDB:4NEF}
RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 3-241, SUBUNIT, SUBCELLULAR
RP LOCATION, TOPOLOGY, AND DOMAIN.
RX PubMed=24733887; DOI=10.1073/pnas.1321406111;
RA Frick A., Eriksson U.K., de Mattia F., Oberg F., Hedfalk K., Neutze R.,
RA de Grip W.J., Deen P.M., Tornroth-Horsefield S.;
RT "X-ray structure of human aquaporin 2 and its implications for nephrogenic
RT diabetes insipidus and trafficking.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:6305-6310(2014).
RN [9]
RP VARIANT ANDI CYS-202.
RX PubMed=8882880; DOI=10.1007/s004390050264;
RA Oksche A., Moeller A., Dickson J., Rosendahl W., Rascher W., Bichet D.G.,
RA Rosenthal W.;
RT "Two novel mutations in the aquaporin-2 and the vasopressin V2 receptor
RT genes in patients with congenital nephrogenic diabetes insipidus.";
RL Hum. Genet. 98:587-589(1996).
RN [10]
RP VARIANTS ANDI VAL-22 AND TRP-181.
RX PubMed=9302264; DOI=10.1093/hmg/6.11.1865;
RA Canfield M.C., Tamarappoo B.K., Moses A.M., Verkman A.S., Holtzman E.J.;
RT "Identification and characterization of aquaporin-2 water channel mutations
RT causing nephrogenic diabetes insipidus with partial vasopressin response.";
RL Hum. Mol. Genet. 6:1865-1871(1997).
RN [11]
RP VARIANTS ANDI SER-68; MET-126 AND THR-147.
RX PubMed=9048343; DOI=10.1681/asn.v82242;
RA Mulders S.M., Knoers N.V., Van Lieburg A.F., Monnens L.A., Leumann E.,
RA Wuhl E., Schober E., Rijss J.P.L., Van Os C.H., Deen P.M.T.;
RT "New mutations in the AQP2 gene in nephrogenic diabetes insipidus resulting
RT in functional but misrouted water channels.";
RL J. Am. Soc. Nephrol. 8:242-248(1997).
RN [12]
RP VARIANTS ANDI MET-168 AND PRO-216.
RX PubMed=9402087; DOI=10.1681/asn.v8121855;
RA Vargas-Poussou R., Forestier L., Dautzenberg M.D., Niaudet P., Dechaux M.,
RA Antignac C.;
RT "Mutations in the vasopressin V2 receptor and aquaporin-2 genes in 12
RT families with congenital nephrogenic diabetes insipidus.";
RL J. Am. Soc. Nephrol. 8:1855-1862(1997).
RN [13]
RP VARIANTS ANDI MET-125; ARG-175; THR-190 AND LEU-262.
RX PubMed=9550615; DOI=10.2169/internalmedicine.37.215;
RA Kuwahara M.;
RT "Aquaporin-2, a vasopressin-sensitive water channel, and nephrogenic
RT diabetes insipidus.";
RL Intern. Med. 37:215-217(1998).
RN [14]
RP VARIANT ANDI LYS-258.
RX PubMed=9649557; DOI=10.1172/jci2605;
RA Mulders S.M., Bichet D.G., Rijss J.P.L., Kamsteeg E.-J., Arthus M.-F.,
RA Lonergan M., Fujiwara M., Morgan K., Leijendekker R., van der Sluijs P.,
RA van Os C.H., Deen P.M.T.;
RT "An aquaporin-2 water channel mutant which causes autosomal dominant
RT nephrogenic diabetes insipidus is retained in the Golgi complex.";
RL J. Clin. Invest. 102:57-66(1998).
RN [15]
RP VARIANTS ANDI MET-125 AND ARG-175.
RX PubMed=9745427; DOI=10.1210/jcem.83.9.5074;
RA Goji K., Kuwahara M., Gu Y., Matsuo M., Marumo F., Sasaki S.;
RT "Novel mutations in aquaporin-2 gene in female siblings with nephrogenic
RT diabetes insipidus: evidence of disrupted water channel function.";
RL J. Clin. Endocrinol. Metab. 83:3205-3209(1998).
RN [16]
RP VARIANTS ANDI PRO-28; VAL-47; MET-71; MET-125; ARG-175 AND ALA-185, AND
RP VARIANT ILE-194.
RX PubMed=12191971; DOI=10.1097/01.asn.0000027355.41663.14;
RA Marr N., Bichet D.G., Hoefs S., Savelkoul P.J.M., Konings I.B.,
RA De Mattia F., Graat M.P., Arthus M.-F., Lonergan M., Fujiwara T.M.,
RA Knoers N.V., Landau D., Balfe W.J., Oksche A., Rosenthal W., Muller D.,
RA Van Os C.H., Deen P.M.;
RT "Cell-biologic and functional analyses of five new Aquaporin-2 missense
RT mutations that cause recessive nephrogenic diabetes insipidus.";
RL J. Am. Soc. Nephrol. 13:2267-2277(2002).
RN [17]
RP VARIANTS ANDI PRO-57 AND VAL-100.
RX PubMed=12050236; DOI=10.1210/jcem.87.6.8617;
RA Lin S.H., Bichet D.G., Sasaki S., Kuwahara M., Arthus M.-F., Lonergan M.,
RA Lin Y.-F.;
RT "Two novel aquaporin-2 mutations responsible for congenital nephrogenic
RT diabetes insipidus in Chinese families.";
RL J. Clin. Endocrinol. Metab. 87:2694-2700(2002).
RN [18]
RP VARIANTS ANDI CYS-187; THR-190 AND LEU-262, CHARACTERIZATION OF VARIANTS
RP ANDI CYS-187; THR-190 AND LEU-262, FUNCTION, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF PRO-262.
RX PubMed=15509592; DOI=10.1093/hmg/ddh339;
RA de Mattia F., Savelkoul P.J.M., Bichet D.G., Kamsteeg E.-J.,
RA Konings I.B.M., Marr N., Arthus M.-F., Lonergan M., van Os C.H.,
RA van der Sluijs P., Robertson G., Deen P.M.T.;
RT "A novel mechanism in recessive nephrogenic diabetes insipidus: wild-type
RT aquaporin-2 rescues the apical membrane expression of intracellularly
RT retained AQP2-P262L.";
RL Hum. Mol. Genet. 13:3045-3056(2004).
RN [19]
RP VARIANT ANDI LEU-254, AND CHARACTERIZATION OF VARIANT ANDI LEU-254.
RX PubMed=16120822; DOI=10.1681/asn.2005010104;
RA de Mattia F., Savelkoul P.J.M., Kamsteeg E.-J., Konings I.B.M.,
RA van der Sluijs P., Mallmann R., Oksche A., Deen P.M.T.;
RT "Lack of arginine vasopressin-induced phosphorylation of aquaporin-2 mutant
RT AQP2-R254L explains dominant nephrogenic diabetes insipidus.";
RL J. Am. Soc. Nephrol. 16:2872-2880(2005).
RN [20]
RP VARIANTS ANDI ASP-70 AND HIS-187.
RX PubMed=16361827; DOI=10.3346/jkms.2005.20.6.1076;
RA Cheong H.I., Cho S.J., Zheng S.H., Cho H.Y., Ha I.S., Choi Y.;
RT "Two novel mutations in the aquaporin 2 gene in a girl with congenital
RT nephrogenic diabetes insipidus.";
RL J. Korean Med. Sci. 20:1076-1078(2005).
RN [21]
RP VARIANTS ANDI ARG-100 AND SER-180.
RX PubMed=16845277; DOI=10.1097/01.gim.0000223554.46981.7a;
RA Carroll P., Al-Mojalli H., Al-Abbad A., Al-Hassoun I., Al-Hamed M.,
RA Al-Amr R., Butt A.I., Meyer B.F.;
RT "Novel mutations underlying nephrogenic diabetes insipidus in Arab
RT families.";
RL Genet. Med. 8:443-447(2006).
RN [22]
RP INVOLVEMENT IN ANDI, VARIANT ANDI GLN-254, AND CHARACTERIZATION OF VARIANT
RP ANDI GLN-254.
RX PubMed=19585583; DOI=10.1002/humu.21082;
RA Savelkoul P.J.M., De Mattia F., Li Y., Kamsteeg E.-J., Konings I.B.M.,
RA van der Sluijs P., Deen P.M.T.;
RT "p.R254Q mutation in the aquaporin-2 water channel causing dominant
RT nephrogenic diabetes insipidus is due to a lack of arginine vasopressin-
RT induced phosphorylation.";
RL Hum. Mutat. 30:E891-E903(2009).
RN [23]
RP MISSORTING MOTIF OF VARIANT ANDI LYS-258.
RX PubMed=19701945; DOI=10.1002/humu.21068;
RA Kamsteeg E.-J., Stoffels M., Tamma G., Konings I.B.M., Deen P.M.T.;
RT "Repulsion between Lys258 and upstream arginines explains the missorting of
RT the AQP2 mutant p.Glu258Lys in nephrogenic diabetes insipidus.";
RL Hum. Mutat. 30:1387-1396(2009).
RN [24]
RP VARIANT ANDI MET-108.
RX PubMed=24944815; DOI=10.3892/br.2014.283;
RA Park Y.J., Baik H.W., Cheong H.I., Kang J.H.;
RT "Congenital nephrogenic diabetes insipidus with a novel mutation in the
RT aquaporin 2 gene.";
RL Biomed. Rep. 2:596-598(2014).
CC -!- FUNCTION: Forms a water-specific channel that provides the plasma
CC membranes of renal collecting duct with high permeability to water,
CC thereby permitting water to move in the direction of an osmotic
CC gradient (PubMed:8140421, PubMed:7524315, PubMed:7510718,
CC PubMed:15509592). Plays an essential role in renal water homeostasis
CC (PubMed:8140421, PubMed:7524315, PubMed:15509592).
CC {ECO:0000269|PubMed:15509592, ECO:0000269|PubMed:7510718,
CC ECO:0000269|PubMed:7524315, ECO:0000269|PubMed:8140421}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:24733887}.
CC -!- INTERACTION:
CC P41181; O14735: CDIPT; NbExp=3; IntAct=EBI-12701138, EBI-358858;
CC P41181; O43889-2: CREB3; NbExp=3; IntAct=EBI-12701138, EBI-625022;
CC P41181; Q96BA8: CREB3L1; NbExp=3; IntAct=EBI-12701138, EBI-6942903;
CC P41181; P52803: EFNA5; NbExp=3; IntAct=EBI-12701138, EBI-1753674;
CC P41181; Q9UKR5: ERG28; NbExp=3; IntAct=EBI-12701138, EBI-711490;
CC P41181; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-12701138, EBI-781551;
CC P41181; Q7Z2K6: ERMP1; NbExp=3; IntAct=EBI-12701138, EBI-10976398;
CC P41181; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-12701138, EBI-18304435;
CC P41181; Q92520: FAM3C; NbExp=3; IntAct=EBI-12701138, EBI-2876774;
CC P41181; Q8TED1: GPX8; NbExp=3; IntAct=EBI-12701138, EBI-11721746;
CC P41181; P24593: IGFBP5; NbExp=3; IntAct=EBI-12701138, EBI-720480;
CC P41181; Q9Y5U4: INSIG2; NbExp=3; IntAct=EBI-12701138, EBI-8503746;
CC P41181; A8MZ59: LEUTX; NbExp=3; IntAct=EBI-12701138, EBI-17490413;
CC P41181; Q8TAF8: LHFPL5; NbExp=3; IntAct=EBI-12701138, EBI-2820517;
CC P41181; Q6IN84: MRM1; NbExp=3; IntAct=EBI-12701138, EBI-5454865;
CC P41181; Q5J8X5: MS4A13; NbExp=3; IntAct=EBI-12701138, EBI-12070086;
CC P41181; P15941-11: MUC1; NbExp=3; IntAct=EBI-12701138, EBI-17263240;
CC P41181; Q8IXM6: NRM; NbExp=3; IntAct=EBI-12701138, EBI-10262547;
CC P41181; Q6UX06: OLFM4; NbExp=3; IntAct=EBI-12701138, EBI-2804156;
CC P41181; Q8NH19: OR10AG1; NbExp=3; IntAct=EBI-12701138, EBI-13339917;
CC P41181; Q96RD7: PANX1; NbExp=3; IntAct=EBI-12701138, EBI-7037612;
CC P41181; Q13113: PDZK1IP1; NbExp=3; IntAct=EBI-12701138, EBI-716063;
CC P41181; Q01453: PMP22; NbExp=3; IntAct=EBI-12701138, EBI-2845982;
CC P41181; P54315: PNLIPRP1; NbExp=3; IntAct=EBI-12701138, EBI-8652812;
CC P41181; Q59EV6: PPGB; NbExp=3; IntAct=EBI-12701138, EBI-14210385;
CC P41181; Q5QGT7: RTP2; NbExp=3; IntAct=EBI-12701138, EBI-10244780;
CC P41181; Q9BXS9-3: SLC26A6; NbExp=3; IntAct=EBI-12701138, EBI-12814225;
CC P41181; Q9BRI3: SLC30A2; NbExp=3; IntAct=EBI-12701138, EBI-8644112;
CC P41181; Q9NVC3: SLC38A7; NbExp=3; IntAct=EBI-12701138, EBI-10314552;
CC P41181; Q5SQN1: SNAP47; NbExp=3; IntAct=EBI-12701138, EBI-10244848;
CC P41181; Q9BVC6: TMEM109; NbExp=3; IntAct=EBI-12701138, EBI-1057733;
CC P41181; A2RU14: TMEM218; NbExp=3; IntAct=EBI-12701138, EBI-10173151;
CC P41181; Q5W0B7: TMEM236; NbExp=3; IntAct=EBI-12701138, EBI-13378608;
CC P41181; Q9H2L4: TMEM60; NbExp=3; IntAct=EBI-12701138, EBI-2852148;
CC P41181; Q8N2M4: TMEM86A; NbExp=3; IntAct=EBI-12701138, EBI-12015604;
CC P41181; Q5BJF2: TMEM97; NbExp=3; IntAct=EBI-12701138, EBI-12111910;
CC P41181; A5PKU2: TUSC5; NbExp=3; IntAct=EBI-12701138, EBI-11988865;
CC P41181; Q96EC8: YIPF6; NbExp=3; IntAct=EBI-12701138, EBI-751210;
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:12194985, ECO:0000269|PubMed:15509592,
CC ECO:0000269|PubMed:7510718}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:12194985, ECO:0000269|PubMed:24733887}. Basolateral
CC cell membrane {ECO:0000250|UniProtKB:P34080}; Multi-pass membrane
CC protein {ECO:0000269|PubMed:24733887}. Cell membrane
CC {ECO:0000269|PubMed:15509592, ECO:0000269|PubMed:24733887,
CC ECO:0000269|PubMed:7524315, ECO:0000269|PubMed:8140421}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:24733887}. Cytoplasmic vesicle
CC membrane {ECO:0000269|PubMed:12194985, ECO:0000269|PubMed:15509592};
CC Multi-pass membrane protein {ECO:0000269|PubMed:12194985,
CC ECO:0000269|PubMed:24733887}. Golgi apparatus, trans-Golgi network
CC membrane {ECO:0000269|PubMed:12194985}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:12194985, ECO:0000269|PubMed:24733887}.
CC Note=Shuttles from vesicles to the apical membrane (PubMed:15509592).
CC Vasopressin-regulated phosphorylation is required for translocation to
CC the apical cell membrane (PubMed:15509592). PLEKHA8/FAPP2 is required
CC to transport AQP2 from the TGN to sites where AQP2 is phosphorylated
CC (By similarity). {ECO:0000250|UniProtKB:P34080,
CC ECO:0000269|PubMed:15509592}.
CC -!- TISSUE SPECIFICITY: Expressed in collecting tubules in kidney medulla
CC (at protein level) (PubMed:7510718). Detected in kidney
CC (PubMed:7510718). {ECO:0000269|PubMed:7510718}.
CC -!- DOMAIN: Aquaporins contain two tandem repeats each containing three
CC membrane-spanning domains and a pore-forming loop with the signature
CC motif Asn-Pro-Ala (NPA). {ECO:0000269|PubMed:24733887}.
CC -!- PTM: Ser-256 phosphorylation is necessary and sufficient for expression
CC at the apical membrane. Endocytosis is not phosphorylation-dependent.
CC {ECO:0000269|PubMed:12194985}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:7510718}.
CC -!- DISEASE: Diabetes insipidus, nephrogenic, autosomal (ANDI)
CC [MIM:125800]: A disorder caused by the inability of the renal
CC collecting ducts to absorb water in response to arginine vasopressin.
CC Characterized by excessive water drinking (polydipsia), excessive urine
CC excretion (polyuria), persistent hypotonic urine, and hypokalemia.
CC Inheritance can be autosomal dominant or recessive.
CC {ECO:0000269|PubMed:12050236, ECO:0000269|PubMed:12191971,
CC ECO:0000269|PubMed:15509592, ECO:0000269|PubMed:16120822,
CC ECO:0000269|PubMed:16361827, ECO:0000269|PubMed:16845277,
CC ECO:0000269|PubMed:19585583, ECO:0000269|PubMed:19701945,
CC ECO:0000269|PubMed:24944815, ECO:0000269|PubMed:7524315,
CC ECO:0000269|PubMed:8140421, ECO:0000269|PubMed:8882880,
CC ECO:0000269|PubMed:9048343, ECO:0000269|PubMed:9302264,
CC ECO:0000269|PubMed:9402087, ECO:0000269|PubMed:9550615,
CC ECO:0000269|PubMed:9649557, ECO:0000269|PubMed:9745427}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the MIP/aquaporin (TC 1.A.8) family.
CC {ECO:0000305}.
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DR EMBL; Z29491; CAA82627.1; -; Genomic_DNA.
DR EMBL; D31846; BAA06632.1; -; Genomic_DNA.
DR EMBL; S73196; AAB31999.1; -; mRNA.
DR EMBL; S73197; AAB31998.1; -; mRNA.
DR EMBL; AF147093; AAD38692.1; -; Genomic_DNA.
DR EMBL; AF147092; AAD38692.1; JOINED; Genomic_DNA.
DR EMBL; BC042496; AAH42496.1; -; mRNA.
DR CCDS; CCDS8792.1; -.
DR PIR; A53442; A53442.
DR PIR; I64818; I64818.
DR RefSeq; NP_000477.1; NM_000486.5.
DR PDB; 4NEF; X-ray; 2.75 A; A/B/C/D=3-241.
DR PDB; 4OJ2; X-ray; 3.05 A; X=1-271.
DR PDB; 6QF5; X-ray; 3.70 A; A/B/C/D=3-242.
DR PDBsum; 4NEF; -.
DR PDBsum; 4OJ2; -.
DR PDBsum; 6QF5; -.
DR AlphaFoldDB; P41181; -.
DR SMR; P41181; -.
DR BioGRID; 106855; 67.
DR IntAct; P41181; 38.
DR STRING; 9606.ENSP00000199280; -.
DR ChEMBL; CHEMBL4523224; -.
DR TCDB; 1.A.8.8.8; the major intrinsic protein (mip) family.
DR GlyGen; P41181; 1 site.
DR iPTMnet; P41181; -.
DR PhosphoSitePlus; P41181; -.
DR BioMuta; AQP2; -.
DR DMDM; 728874; -.
DR jPOST; P41181; -.
DR MassIVE; P41181; -.
DR PaxDb; P41181; -.
DR PeptideAtlas; P41181; -.
DR PRIDE; P41181; -.
DR ProteomicsDB; 55412; -.
DR Antibodypedia; 4081; 631 antibodies from 39 providers.
DR DNASU; 359; -.
DR Ensembl; ENST00000199280.4; ENSP00000199280.3; ENSG00000167580.8.
DR GeneID; 359; -.
DR KEGG; hsa:359; -.
DR MANE-Select; ENST00000199280.4; ENSP00000199280.3; NM_000486.6; NP_000477.1.
DR UCSC; uc001rvn.4; human.
DR CTD; 359; -.
DR DisGeNET; 359; -.
DR GeneCards; AQP2; -.
DR GeneReviews; AQP2; -.
DR HGNC; HGNC:634; AQP2.
DR HPA; ENSG00000167580; Group enriched (kidney, seminal vesicle).
DR MalaCards; AQP2; -.
DR MIM; 107777; gene.
DR MIM; 125800; phenotype.
DR neXtProt; NX_P41181; -.
DR OpenTargets; ENSG00000167580; -.
DR Orphanet; 223; Nephrogenic diabetes insipidus.
DR PharmGKB; PA24920; -.
DR VEuPathDB; HostDB:ENSG00000167580; -.
DR eggNOG; KOG0223; Eukaryota.
DR GeneTree; ENSGT00940000160612; -.
DR InParanoid; P41181; -.
DR OMA; MSSRKLM; -.
DR OrthoDB; 1152704at2759; -.
DR PhylomeDB; P41181; -.
DR TreeFam; TF312940; -.
DR PathwayCommons; P41181; -.
DR Reactome; R-HSA-432040; Vasopressin regulates renal water homeostasis via Aquaporins.
DR Reactome; R-HSA-432047; Passive transport by Aquaporins.
DR SignaLink; P41181; -.
DR SIGNOR; P41181; -.
DR BioGRID-ORCS; 359; 12 hits in 1072 CRISPR screens.
DR GeneWiki; Aquaporin_2; -.
DR GenomeRNAi; 359; -.
DR Pharos; P41181; Tbio.
DR PRO; PR:P41181; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P41181; protein.
DR Bgee; ENSG00000167580; Expressed in renal medulla and 77 other tissues.
DR ExpressionAtlas; P41181; baseline and differential.
DR Genevisible; P41181; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0098576; C:lumenal side of membrane; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; IEA:Ensembl.
DR GO; GO:0030658; C:transport vesicle membrane; TAS:Reactome.
DR GO; GO:0015168; F:glycerol transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015250; F:water channel activity; IMP:UniProtKB.
DR GO; GO:0005372; F:water transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0071280; P:cellular response to copper ion; IDA:UniProtKB.
DR GO; GO:0071288; P:cellular response to mercury ion; IDA:UniProtKB.
DR GO; GO:0042631; P:cellular response to water deprivation; IEA:Ensembl.
DR GO; GO:0015793; P:glycerol transmembrane transport; IDA:UniProtKB.
DR GO; GO:0072205; P:metanephric collecting duct development; IEA:Ensembl.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR GO; GO:0003091; P:renal water homeostasis; IMP:UniProtKB.
DR GO; GO:0003097; P:renal water transport; IEA:Ensembl.
DR GO; GO:0006833; P:water transport; IDA:UniProtKB.
DR CDD; cd00333; MIP; 1.
DR Gene3D; 1.20.1080.10; -; 1.
DR InterPro; IPR023271; Aquaporin-like.
DR InterPro; IPR034294; Aquaporin_transptr.
DR InterPro; IPR000425; MIP.
DR InterPro; IPR022357; MIP_CS.
DR PANTHER; PTHR19139; PTHR19139; 1.
DR Pfam; PF00230; MIP; 1.
DR PRINTS; PR00783; MINTRINSICP.
DR SUPFAM; SSF81338; SSF81338; 1.
DR TIGRFAMs; TIGR00861; MIP; 1.
DR PROSITE; PS00221; MIP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cytoplasmic vesicle; Diabetes insipidus;
KW Disease variant; Glycoprotein; Golgi apparatus; Membrane; Phosphoprotein;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..271
FT /note="Aquaporin-2"
FT /id="PRO_0000063934"
FT TOPO_DOM 1..11
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:24733887"
FT TRANSMEM 12..32
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:24733887"
FT TOPO_DOM 33..40
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:24733887"
FT TRANSMEM 41..59
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:24733887"
FT TOPO_DOM 60..64
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:24733887"
FT INTRAMEM 65..74
FT /note="Discontinuously helical"
FT /evidence="ECO:0000269|PubMed:24733887"
FT TOPO_DOM 75..85
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:24733887"
FT TRANSMEM 86..107
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:24733887"
FT TOPO_DOM 108..127
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:24733887"
FT TRANSMEM 128..148
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:24733887"
FT TOPO_DOM 149..156
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:24733887"
FT TRANSMEM 157..176
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:24733887"
FT TOPO_DOM 177..180
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:24733887"
FT INTRAMEM 181..193
FT /note="Discontinuously helical"
FT /evidence="ECO:0000269|PubMed:24733887"
FT TOPO_DOM 194..201
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:24733887"
FT TRANSMEM 202..222
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:24733887"
FT TOPO_DOM 223..271
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 248..271
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 68..70
FT /note="NPA 1"
FT /evidence="ECO:0000305|PubMed:24733887"
FT MOTIF 184..186
FT /note="NPA 2"
FT /evidence="ECO:0000305|PubMed:24733887"
FT MOD_RES 256
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:12194985"
FT CARBOHYD 123
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 22
FT /note="L -> V (in ANDI; dbSNP:rs104894336)"
FT /evidence="ECO:0000269|PubMed:9302264"
FT /id="VAR_015239"
FT VARIANT 28
FT /note="L -> P (in ANDI)"
FT /evidence="ECO:0000269|PubMed:12191971"
FT /id="VAR_015240"
FT VARIANT 47
FT /note="A -> V (in ANDI; dbSNP:rs995684800)"
FT /evidence="ECO:0000269|PubMed:12191971"
FT /id="VAR_015241"
FT VARIANT 57
FT /note="Q -> P (in ANDI; dbSNP:rs28931580)"
FT /evidence="ECO:0000269|PubMed:12050236"
FT /id="VAR_015256"
FT VARIANT 64
FT /note="G -> R (in ANDI; loss of water channel activity;
FT dbSNP:rs104894326)"
FT /evidence="ECO:0000269|PubMed:7524315"
FT /id="VAR_004401"
FT VARIANT 68
FT /note="N -> S (in ANDI; dbSNP:rs104894331)"
FT /evidence="ECO:0000269|PubMed:9048343"
FT /id="VAR_015242"
FT VARIANT 70
FT /note="A -> D (in ANDI)"
FT /evidence="ECO:0000269|PubMed:16361827"
FT /id="VAR_062585"
FT VARIANT 71
FT /note="V -> M (in ANDI; dbSNP:rs149659001)"
FT /evidence="ECO:0000269|PubMed:12191971"
FT /id="VAR_015243"
FT VARIANT 100
FT /note="G -> R (in ANDI; dbSNP:rs1303076207)"
FT /evidence="ECO:0000269|PubMed:16845277"
FT /id="VAR_062586"
FT VARIANT 100
FT /note="G -> V (in ANDI; dbSNP:rs104894338)"
FT /evidence="ECO:0000269|PubMed:12050236"
FT /id="VAR_015257"
FT VARIANT 108
FT /note="T -> M (in ANDI; dbSNP:rs1468828294)"
FT /evidence="ECO:0000269|PubMed:24944815"
FT /id="VAR_071370"
FT VARIANT 121
FT /note="L -> F (in dbSNP:rs11169226)"
FT /id="VAR_037577"
FT VARIANT 125
FT /note="T -> M (in ANDI; dbSNP:rs104894333)"
FT /evidence="ECO:0000269|PubMed:12191971,
FT ECO:0000269|PubMed:9550615, ECO:0000269|PubMed:9745427"
FT /id="VAR_015244"
FT VARIANT 126
FT /note="T -> M (in ANDI; dbSNP:rs104894330)"
FT /evidence="ECO:0000269|PubMed:9048343"
FT /id="VAR_015245"
FT VARIANT 147
FT /note="A -> T (in ANDI; dbSNP:rs104894334)"
FT /evidence="ECO:0000269|PubMed:9048343"
FT /id="VAR_015246"
FT VARIANT 168
FT /note="V -> M (in ANDI; dbSNP:rs755694590)"
FT /evidence="ECO:0000269|PubMed:9402087"
FT /id="VAR_015247"
FT VARIANT 175
FT /note="G -> R (in ANDI; dbSNP:rs104894335)"
FT /evidence="ECO:0000269|PubMed:12191971,
FT ECO:0000269|PubMed:9550615, ECO:0000269|PubMed:9745427"
FT /id="VAR_015248"
FT VARIANT 180
FT /note="G -> S (in ANDI; dbSNP:rs147039983)"
FT /evidence="ECO:0000269|PubMed:16845277"
FT /id="VAR_062587"
FT VARIANT 181
FT /note="C -> W (in ANDI; dbSNP:rs104894337)"
FT /evidence="ECO:0000269|PubMed:9302264"
FT /id="VAR_015249"
FT VARIANT 185
FT /note="P -> A (in ANDI; dbSNP:rs761713751)"
FT /evidence="ECO:0000269|PubMed:12191971"
FT /id="VAR_015250"
FT VARIANT 187
FT /note="R -> C (in ANDI; loss of water channel activity;
FT mutant protein does not fold properly; dbSNP:rs104894328)"
FT /evidence="ECO:0000269|PubMed:15509592,
FT ECO:0000269|PubMed:7524315, ECO:0000269|PubMed:8140421"
FT /id="VAR_004402"
FT VARIANT 187
FT /note="R -> H (in ANDI; dbSNP:rs193922495)"
FT /evidence="ECO:0000269|PubMed:16361827"
FT /id="VAR_062588"
FT VARIANT 190
FT /note="A -> T (in ANDI; mutant protein does not fold
FT properly and is not functional; dbSNP:rs104894341)"
FT /evidence="ECO:0000269|PubMed:15509592,
FT ECO:0000269|PubMed:9550615"
FT /id="VAR_015251"
FT VARIANT 194
FT /note="V -> I (in dbSNP:rs772051028)"
FT /evidence="ECO:0000269|PubMed:12191971"
FT /id="VAR_015252"
FT VARIANT 202
FT /note="W -> C (in ANDI)"
FT /evidence="ECO:0000269|PubMed:8882880"
FT /id="VAR_015253"
FT VARIANT 216
FT /note="S -> P (in ANDI; loss of water channel activity;
FT dbSNP:rs104894329)"
FT /evidence="ECO:0000269|PubMed:7524315,
FT ECO:0000269|PubMed:8140421, ECO:0000269|PubMed:9402087"
FT /id="VAR_004403"
FT VARIANT 254
FT /note="R -> L (in ANDI; results in the loss of arginine
FT vasopressin-mediated phosphorylation at S-256)"
FT /evidence="ECO:0000269|PubMed:16120822"
FT /id="VAR_062589"
FT VARIANT 254
FT /note="R -> Q (in ANDI; exerts a dominant-negative effect
FT on wild-type-AQP2 in that it interferes with its
FT trafficking to the apical membrane; is a loss of function
FT instead of a gain of function mutation on dominant
FT nephrogenic diabetes insipidus)"
FT /evidence="ECO:0000269|PubMed:19585583"
FT /id="VAR_062590"
FT VARIANT 258
FT /note="E -> K (in ANDI; retained in the Golgi compartment;
FT dbSNP:rs104894332)"
FT /evidence="ECO:0000269|PubMed:19701945,
FT ECO:0000269|PubMed:9649557"
FT /id="VAR_015254"
FT VARIANT 262
FT /note="P -> L (in ANDI; mutant protein folds properly and
FT is functional but is retained in intracellular vesicles;
FT able to assemble into tetramers with wild-type AQP2 that
FT properly localize to the apical membrane;
FT dbSNP:rs104894339)"
FT /evidence="ECO:0000269|PubMed:15509592,
FT ECO:0000269|PubMed:9550615"
FT /id="VAR_015255"
FT MUTAGEN 148
FT /note="S->A: No effect on sorting from the ER to the
FT vesicles, redistribution to apical membrane, or
FT endocytosis."
FT /evidence="ECO:0000269|PubMed:12194985"
FT MUTAGEN 148
FT /note="S->D: Retained in the endoplasmic reticulum."
FT /evidence="ECO:0000269|PubMed:12194985"
FT MUTAGEN 229
FT /note="S->A: No effect on sorting from the ER to the
FT vesicles, redistribution to apical membrane, or
FT endocytosis."
FT /evidence="ECO:0000269|PubMed:12194985"
FT MUTAGEN 229
FT /note="S->D: No effect on sorting from the ER to the
FT vesicles, redistribution to apical membrane, or
FT endocytosis."
FT /evidence="ECO:0000269|PubMed:12194985"
FT MUTAGEN 231
FT /note="S->A: No effect on sorting from the ER to the
FT vesicles, redistribution to apical membrane, or
FT endocytosis."
FT /evidence="ECO:0000269|PubMed:12194985"
FT MUTAGEN 231
FT /note="S->D: No effect on sorting from the ER to the
FT vesicles, redistribution to apical membrane, or
FT endocytosis."
FT /evidence="ECO:0000269|PubMed:12194985"
FT MUTAGEN 244
FT /note="T->A: No effect on sorting from the ER to the
FT vesicles, redistribution to apical membrane, or
FT endocytosis."
FT /evidence="ECO:0000269|PubMed:12194985"
FT MUTAGEN 244
FT /note="T->E: No effect on sorting from the ER to the
FT vesicles, redistribution to apical membrane, or
FT endocytosis."
FT /evidence="ECO:0000269|PubMed:12194985"
FT MUTAGEN 256
FT /note="S->A: Retained in vesicles."
FT /evidence="ECO:0000269|PubMed:12194985"
FT MUTAGEN 256
FT /note="S->D: Expressed in the apical membrane."
FT /evidence="ECO:0000269|PubMed:12194985"
FT MUTAGEN 262
FT /note="P->A: No effect on expression at the apical cell
FT membrane."
FT /evidence="ECO:0000269|PubMed:15509592"
FT CONFLICT 35..38
FT /note="PQAL -> ATAP (in Ref. 4)"
FT /evidence="ECO:0000305"
FT CONFLICT 83
FT /note="V -> F (in Ref. 4)"
FT /evidence="ECO:0000305"
FT HELIX 7..32
FT /evidence="ECO:0007829|PDB:4NEF"
FT STRAND 35..37
FT /evidence="ECO:0007829|PDB:4NEF"
FT HELIX 41..63
FT /evidence="ECO:0007829|PDB:4NEF"
FT HELIX 69..77
FT /evidence="ECO:0007829|PDB:4NEF"
FT HELIX 83..107
FT /evidence="ECO:0007829|PDB:4NEF"
FT HELIX 110..113
FT /evidence="ECO:0007829|PDB:4NEF"
FT HELIX 127..148
FT /evidence="ECO:0007829|PDB:4NEF"
FT HELIX 159..179
FT /evidence="ECO:0007829|PDB:4NEF"
FT HELIX 185..195
FT /evidence="ECO:0007829|PDB:4NEF"
FT TURN 199..202
FT /evidence="ECO:0007829|PDB:4NEF"
FT HELIX 203..221
FT /evidence="ECO:0007829|PDB:4NEF"
FT HELIX 232..237
FT /evidence="ECO:0007829|PDB:4NEF"
SQ SEQUENCE 271 AA; 28837 MW; C2DDE2AF4DDD192A CRC64;
MWELRSIAFS RAVFAEFLAT LLFVFFGLGS ALNWPQALPS VLQIAMAFGL GIGTLVQALG
HISGAHINPA VTVACLVGCH VSVLRAAFYV AAQLLGAVAG AALLHEITPA DIRGDLAVNA
LSNSTTAGQA VTVELFLTLQ LVLCIFASTD ERRGENPGTP ALSIGFSVAL GHLLGIHYTG
CSMNPARSLA PAVVTGKFDD HWVFWIGPLV GAILGSLLYN YVLFPPAKSL SERLAVLKGL
EPDTDWEERE VRRRQSVELH SPQSLPRGTK A
