AQP2_MOUSE
ID AQP2_MOUSE Reviewed; 271 AA.
AC P56402; Q8VCG5; Q9R232;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 19-SEP-2002, sequence version 2.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Aquaporin-2;
DE Short=AQP-2;
DE AltName: Full=ADH water channel;
DE AltName: Full=Aquaporin-CD;
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; Synonyms=cph {ECO:0000303|PubMed:16641094};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], INDUCTION, TISSUE SPECIFICITY,
RP FUNCTION, SUBCELLULAR LOCATION, GLYCOSYLATION, AND MUTAGENESIS OF THR-126.
RC STRAIN=C57BL/6J; TISSUE=Kidney;
RX PubMed=10191086; DOI=10.1006/geno.1999.5759;
RA Yang B., Ma T., Xu Z., Verkman A.S.;
RT "cDNA and genomic cloning of mouse aquaporin-2: functional analysis of an
RT orthologous mutant causing nephrogenic diabetes insipidus.";
RL Genomics 57:79-83(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RC STRAIN=129/SvJ;
RX PubMed=12426236; DOI=10.1152/ajprenal.0224.2001;
RA Zharkikh L., Zhu X., Stricklett P.K., Kohan D.E., Chipman G., Breton S.,
RA Brown D., Nelson R.D.;
RT "Renal principal cell-specific expression of green fluorescent protein in
RT transgenic mice.";
RL Am. J. Physiol. 283:F1351-F1364(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [4]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16735444; DOI=10.1242/jcs.02971;
RA Gooch J.L., Guler R.L., Barnes J.L., Toro J.J.;
RT "Loss of calcineurin Aalpha results in altered trafficking of AQP2 and in
RT nephrogenic diabetes insipidus.";
RL J. Cell Sci. 119:2468-2476(2006).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-256, DISEASE,
RP VARIANT CPH LEU-256, TISSUE SPECIFICITY, AND GLYCOSYLATION.
RX PubMed=16641094; DOI=10.1073/pnas.0602087103;
RA McDill B.W., Li S.Z., Kovach P.A., Ding L., Chen F.;
RT "Congenital progressive hydronephrosis (cph) is caused by an S256L mutation
RT in aquaporin-2 that affects its phosphorylation and apical membrane
RT accumulation.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:6952-6957(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-256 AND SER-261, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=31605441; DOI=10.1111/febs.15088;
RA Kumaran G.K., Hanukoglu I.;
RT "Identification and classification of epithelial cells in nephron segments
RT by actin cytoskeleton patterns.";
RL FEBS J. 287:1176-1194(2020).
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:10191086). Plays an essential role in renal water
CC homeostasis (PubMed:16641094). {ECO:0000269|PubMed:10191086,
CC ECO:0000269|PubMed:16641094}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P41181}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:16641094, ECO:0000269|PubMed:16735444}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:P41181}. Basolateral cell
CC membrane {ECO:0000250|UniProtKB:P34080}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P41181}. Cell membrane
CC {ECO:0000269|PubMed:10191086}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P41181}. Cytoplasmic vesicle membrane
CC {ECO:0000269|PubMed:10191086}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P41181}. Golgi apparatus, trans-Golgi network
CC membrane {ECO:0000250|UniProtKB:P41181}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P41181}. Note=Shuttles from vesicles to the
CC apical membrane. Vasopressin-regulated phosphorylation is required for
CC translocation to the apical cell membrane (PubMed:16735444).
CC PLEKHA8/FAPP2 is required to transport AQP2 from the TGN to sites where
CC AQP2 is phosphorylated. {ECO:0000250|UniProtKB:P41181,
CC ECO:0000269|PubMed:16735444}.
CC -!- TISSUE SPECIFICITY: Detected in principal cells in the collecting duct
CC in kidney medulla and cortex (at protein level) (PubMed:10191086,
CC PubMed:16735444, PubMed:16641094, PubMed:31605441). Expressed in a
CC radial pattern from the cortex through the outer medulla into the inner
CC medulla (PubMed:12426236). Higher levels in the inner medulla
CC (PubMed:12426236). {ECO:0000269|PubMed:10191086,
CC ECO:0000269|PubMed:12426236, ECO:0000269|PubMed:16641094,
CC ECO:0000269|PubMed:16735444, ECO:0000269|PubMed:31605441}.
CC -!- INDUCTION: Increased levels on water deprivation.
CC {ECO:0000269|PubMed:10191086}.
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:0000250|UniProtKB:P41181}.
CC -!- PTM: Ser-256 phosphorylation is necessary and sufficient for expression
CC at the apical membrane (PubMed:16641094). Endocytosis is not
CC phosphorylation-dependent (By similarity).
CC {ECO:0000250|UniProtKB:P41181, ECO:0000269|PubMed:16641094}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:16641094}.
CC -!- DISEASE: Note=Defects in Aqp2 are a cause of congenital progressive
CC hydronephrosis (cph). Homozygous mice appear grossly normal at birth,
CC but grow slowly, and 90% die between 2 and 4 weeks after birth. They
CC display symptoms reminiscent of diabetes insipidus, with excessive
CC water drinking (polydipsia), excessive urine excretion (polyuria), and
CC persistent hypotonic urine. When older than 14 days, they nearly always
CC display severe bilateral hydronephrosis resulting from impaired
CC downward urine transport, in spite of the absence of physical blockage
CC of the urinary tract. Surviving adults have a shortened lifespan and
CC die at the latest at an age of 10 months. They display reduced
CC fertility or are infertile. {ECO:0000269|PubMed:16641094}.
CC -!- SIMILARITY: Belongs to the MIP/aquaporin (TC 1.A.8) family.
CC {ECO:0000305}.
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DR EMBL; AF020519; AAB71414.1; -; mRNA.
DR EMBL; AF105336; AAD21017.1; -; Genomic_DNA.
DR EMBL; AY055468; AAL15462.1; -; Genomic_DNA.
DR EMBL; BC019966; AAH19966.1; -; mRNA.
DR CCDS; CCDS27822.1; -.
DR RefSeq; NP_033829.3; NM_009699.3.
DR AlphaFoldDB; P56402; -.
DR SMR; P56402; -.
DR BioGRID; 198171; 3.
DR DIP; DIP-58509N; -.
DR IntAct; P56402; 2.
DR STRING; 10090.ENSMUSP00000023752; -.
DR GlyGen; P56402; 1 site.
DR iPTMnet; P56402; -.
DR PhosphoSitePlus; P56402; -.
DR jPOST; P56402; -.
DR PaxDb; P56402; -.
DR PRIDE; P56402; -.
DR ProteomicsDB; 283249; -.
DR Antibodypedia; 4081; 631 antibodies from 39 providers.
DR DNASU; 11827; -.
DR Ensembl; ENSMUST00000023752; ENSMUSP00000023752; ENSMUSG00000023013.
DR GeneID; 11827; -.
DR KEGG; mmu:11827; -.
DR UCSC; uc007xps.2; mouse.
DR CTD; 359; -.
DR MGI; MGI:1096865; Aqp2.
DR VEuPathDB; HostDB:ENSMUSG00000023013; -.
DR eggNOG; KOG0223; Eukaryota.
DR GeneTree; ENSGT00940000160612; -.
DR HOGENOM; CLU_020019_3_3_1; -.
DR InParanoid; P56402; -.
DR OMA; MSSRKLM; -.
DR OrthoDB; 1152704at2759; -.
DR PhylomeDB; P56402; -.
DR TreeFam; TF312940; -.
DR Reactome; R-MMU-432040; Vasopressin regulates renal water homeostasis via Aquaporins.
DR Reactome; R-MMU-432047; Passive transport by Aquaporins.
DR BioGRID-ORCS; 11827; 4 hits in 72 CRISPR screens.
DR ChiTaRS; Aqp2; mouse.
DR PRO; PR:P56402; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; P56402; protein.
DR Bgee; ENSMUSG00000023013; Expressed in right kidney and 22 other tissues.
DR ExpressionAtlas; P56402; baseline and differential.
DR Genevisible; P56402; MM.
DR GO; GO:0016324; C:apical plasma membrane; IDA:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0030136; C:clathrin-coated vesicle; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:MGI.
DR GO; GO:0005769; C:early endosome; ISO:MGI.
DR GO; GO:0070382; C:exocytic vesicle; ISO:MGI.
DR GO; GO:0070062; C:extracellular exosome; ISO:MGI.
DR GO; GO:0031303; C:integral component of endosome membrane; IC:MGI.
DR GO; GO:0016021; C:integral component of membrane; ISM:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0098576; C:lumenal side of membrane; IDA:MGI.
DR GO; GO:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0055037; C:recycling endosome; IDA:MGI.
DR GO; GO:0055038; C:recycling endosome membrane; IC:MGI.
DR GO; GO:0005791; C:rough endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005802; C:trans-Golgi network; ISO:MGI.
DR GO; GO:0030133; C:transport vesicle; ISO:MGI.
DR GO; GO:0003779; F:actin binding; ISO:MGI.
DR GO; GO:0015168; F:glycerol transmembrane transporter activity; ISO:MGI.
DR GO; GO:0030165; F:PDZ domain binding; ISO:MGI.
DR GO; GO:0015250; F:water channel activity; IDA:MGI.
DR GO; GO:0005372; F:water transmembrane transporter activity; ISO:MGI.
DR GO; GO:0030042; P:actin filament depolymerization; ISO:MGI.
DR GO; GO:0006915; P:apoptotic process; ISO:MGI.
DR GO; GO:0006884; P:cell volume homeostasis; ISO:MGI.
DR GO; GO:0071280; P:cellular response to copper ion; ISO:MGI.
DR GO; GO:0071288; P:cellular response to mercury ion; ISO:MGI.
DR GO; GO:0042631; P:cellular response to water deprivation; IDA:MGI.
DR GO; GO:0015793; P:glycerol transmembrane transport; ISO:MGI.
DR GO; GO:0072205; P:metanephric collecting duct development; IEP:UniProtKB.
DR GO; GO:0051928; P:positive regulation of calcium ion transport; ISO:MGI.
DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR GO; GO:0003091; P:renal water homeostasis; IDA:MGI.
DR GO; GO:0003097; P:renal water transport; IMP:MGI.
DR GO; GO:0006833; P:water transport; IDA:MGI.
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 Cell membrane; Cytoplasmic vesicle; Glycoprotein; Golgi apparatus;
KW Membrane; Phosphoprotein; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..271
FT /note="Aquaporin-2"
FT /id="PRO_0000063936"
FT TOPO_DOM 1..11
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 12..32
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P41181"
FT TOPO_DOM 33..40
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 41..59
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P41181"
FT TOPO_DOM 60..64
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 65..74
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:P41181"
FT TOPO_DOM 75..85
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 86..107
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P41181"
FT TOPO_DOM 108..127
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 128..148
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P41181"
FT TOPO_DOM 149..156
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 157..176
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P41181"
FT TOPO_DOM 177..180
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 181..193
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:P41181"
FT TOPO_DOM 194..201
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 202..222
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P41181"
FT TOPO_DOM 223..271
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 251..271
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 68..70
FT /note="NPA 1"
FT /evidence="ECO:0000250|UniProtKB:P41181"
FT MOTIF 184..186
FT /note="NPA 2"
FT /evidence="ECO:0000250|UniProtKB:P41181"
FT MOD_RES 256
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16641094,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 261
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 124
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 256
FT /note="S -> L (in cph; loss of a phosphorylation site and
FT loss of trafficking to the apical cell membrane; causes
FT aberrant location at the basolateral cell membrane)"
FT /evidence="ECO:0000269|PubMed:16641094"
FT MUTAGEN 126
FT /note="T->M: Does not cause loss of water channel activity,
FT but impairs trafficking from cytoplasmic vesicles to the
FT cell membrane."
FT /evidence="ECO:0000269|PubMed:10191086"
FT CONFLICT 9..10
FT /note="FS -> YC (in Ref. 1; AAB71414)"
FT /evidence="ECO:0000305"
FT CONFLICT 213
FT /note="V -> I (in Ref. 1; AAB71414 and 3; AAH19966)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 271 AA; 28965 MW; 41601C37BFD11CBA CRC64;
MWELRSIAFS RAVLAEFLAT LLFVFFGLGS ALQWASSPPS VLQIAVAFGL GIGTLVQALG
HVSGAHINPA VTVACLVGCH VSFLRAAFYV AAQLLGAVAG AAILHEITPV EIRGDLAVNA
LHNNATAGQA VTVELFLTMQ LVLCIFASTD ERRSDNLGSP ALSIGFSVTL GHLLGIYFTG
CSMNPARSLA PAVVTGKFDD HWVFWIGPLV GAVIGSLLYN YLLFPSTKSL QERLAVLKGL
EPDTDWEERE VRRRQSVELH SPQSLPRGSK A
