AQP4_MOUSE
ID AQP4_MOUSE Reviewed; 323 AA.
AC P55088; P97818; Q4FJP1; Q61131; Q61132; Q8VHE4; Q8VHE5; Q9EQI3;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 2.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Aquaporin-4;
DE Short=AQP-4;
DE AltName: Full=Mercurial-insensitive water channel {ECO:0000303|PubMed:8660998};
DE Short=MIWC {ECO:0000303|PubMed:8660998};
DE AltName: Full=WCH4;
GN Name=Aqp4;
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 [MRNA] (ISOFORMS 1; 2 AND 3), FUNCTION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=8660998; DOI=10.1006/geno.1996.0214;
RA Ma T., Yang B., Verkman A.S.;
RT "Gene structure, cDNA cloning, and expression of a mouse mercurial-
RT insensitive water channel.";
RL Genomics 33:382-388(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Cerebellum;
RX PubMed=9143504; DOI=10.1006/geno.1997.4641;
RA Turtzo L.C., Lee M.D., Lu M., Smith B.L., Copeland N.G., Gilbert D.J.,
RA Jenkins N.A., Agre P.;
RT "Cloning and chromosomal localization of mouse aquaporin 4: exclusion of a
RT candidate mutant phenotype, ataxia.";
RL Genomics 41:267-270(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND VARIANT ARG-4.
RX PubMed=10960499; DOI=10.1203/00006450-200009000-00012;
RA Zelenin S., Gunnarson E., Alikina T., Bondar A., Aperia A.;
RT "Identification of a new form of AQP4 mRNA that is developmentally
RT expressed in mouse brain.";
RL Pediatr. Res. 48:335-339(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Ebert L., Muenstermann E., Schatten R., Henze S., Bohn E., Mollenhauer J.,
RA Wiemann S., Schick M., Korn B.;
RT "Cloning of mouse full open reading frames in Gateway(R) system entry
RT vector (pDONR201).";
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [6]
RP FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=9276712; DOI=10.1172/jci231;
RA Ma T., Yang B., Gillespie A., Carlson E.J., Epstein C.J., Verkman A.S.;
RT "Generation and phenotype of a transgenic knockout mouse lacking the
RT mercurial-insensitive water channel aquaporin-4.";
RL J. Clin. Invest. 100:957-962(1997).
RN [7]
RP DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10915655; DOI=10.1152/ajpgi.2000.279.2.g448;
RA Wang K.S., Komar A.R., Ma T., Filiz F., McLeroy J., Hoda K., Verkman A.S.,
RA Bastidas J.A.;
RT "Gastric acid secretion in aquaporin-4 knockout mice.";
RL Am. J. Physiol. 279:G448-G453(2000).
RN [8]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=11406631; DOI=10.1074/jbc.m104368200;
RA Li J., Verkman A.S.;
RT "Impaired hearing in mice lacking aquaporin-4 water channels.";
RL J. Biol. Chem. 276:31233-31237(2001).
RN [9]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
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 [10]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-111, AND MUTAGENESIS
RP OF SER-111.
RX PubMed=18286643; DOI=10.1002/glia.20627;
RA Gunnarson E., Zelenina M., Axehult G., Song Y., Bondar A., Krieger P.,
RA Brismar H., Zelenin S., Aperia A.;
RT "Identification of a molecular target for glutamate regulation of astrocyte
RT water permeability.";
RL Glia 56:587-596(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-285 AND THR-289, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and 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 [12]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=22896675; DOI=10.1126/scitranslmed.3003748;
RA Iliff J.J., Wang M., Liao Y., Plogg B.A., Peng W., Gundersen G.A.,
RA Benveniste H., Vates G.E., Deane R., Goldman S.A., Nagelhus E.A.,
RA Nedergaard M.;
RT "A paravascular pathway facilitates CSF flow through the brain parenchyma
RT and the clearance of interstitial solutes, including amyloid beta.";
RL Sci. Transl. Med. 4:147RA111-147RA111(2012).
RN [13]
RP FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=27751903; DOI=10.1016/j.mcn.2016.10.004;
RA Vindedal G.F., Thoren A.E., Jensen V., Klungland A., Zhang Y.,
RA Holtzman M.J., Ottersen O.P., Nagelhus E.A.;
RT "Removal of aquaporin-4 from glial and ependymal membranes causes brain
RT water accumulation.";
RL Mol. Cell. Neurosci. 77:47-52(2016).
RN [14]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30561329; DOI=10.7554/elife.40070;
RA Mestre H., Hablitz L.M., Xavier A.L., Feng W., Zou W., Pu T., Monai H.,
RA Murlidharan G., Castellanos Rivera R.M., Simon M.J., Pike M.M., Pla V.,
RA Du T., Kress B.T., Wang X., Plog B.A., Thrane A.S., Lundgaard I., Abe Y.,
RA Yasui M., Thomas J.H., Xiao M., Hirase H., Asokan A., Iliff J.J.,
RA Nedergaard M.;
RT "Aquaporin-4-dependent glymphatic solute transport in the rodent brain.";
RL Elife 7:0-0(2018).
RN [15]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=29055082; DOI=10.1111/jcmm.13401;
RA Rosito S., Nicchia G.P., Palazzo C., Lia A., Buccoliero C., Pisani F.,
RA Svelto M., Trojano M., Frigeri A.;
RT "Supramolecular aggregation of aquaporin-4 is different in muscle and
RT brain: correlation with tissue susceptibility in neuromyelitis optica.";
RL J. Cell. Mol. Med. 22:1236-1246(2018).
RN [16]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30557661; DOI=10.1016/j.neuroimage.2018.12.026;
RA Ohene Y., Harrison I.F., Nahavandi P., Ismail O., Bird E.V., Ottersen O.P.,
RA Nagelhus E.A., Thomas D.L., Lythgoe M.F., Wells J.A.;
RT "Non-invasive MRI of brain clearance pathways using multiple echo time
RT arterial spin labelling: an aquaporin-4 study.";
RL Neuroimage 188:515-523(2019).
CC -!- FUNCTION: Forms a water-specific channel (PubMed:8660998,
CC PubMed:9276712, PubMed:18286643). Plays an important role in brain
CC water homeostasis and in glymphatic solute transport (PubMed:22896675,
CC PubMed:27751903, PubMed:30561329, PubMed:30557661). Required for a
CC normal rate of water exchange across the blood brain interface
CC (PubMed:30557661). Required for normal levels of cerebrospinal fluid
CC influx into the brain cortex and parenchyma along paravascular spaces
CC that surround penetrating arteries, and for normal drainage of
CC interstitial fluid along paravenous drainage pathways. Thereby, it is
CC required for normal clearance of solutes from the brain interstitial
CC fluid, including soluble beta-amyloid peptides derived from APP
CC (PubMed:22896675, PubMed:27751903, PubMed:30561329). Plays a redundant
CC role in urinary water homeostasis and urinary concentrating ability
CC (PubMed:9276712). {ECO:0000269|PubMed:18286643,
CC ECO:0000269|PubMed:22896675, ECO:0000269|PubMed:27751903,
CC ECO:0000269|PubMed:30557661, ECO:0000269|PubMed:30561329,
CC ECO:0000269|PubMed:8660998, ECO:0000269|PubMed:9276712}.
CC -!- SUBUNIT: Homotetramer. The tetramers can form oligomeric arrays in
CC membranes. The size of the oligomers differs between tissues and is
CC smaller in skeletal muscle than in brain. Interaction between AQP4
CC oligomeric arrays in close-by cells can contribute to cell-cell
CC adhesion (By similarity). Part of a complex containing MLC1, TRPV4,
CC HEPACAM and ATP1B1 (By similarity). {ECO:0000250|UniProtKB:P47863,
CC ECO:0000250|UniProtKB:P55087}.
CC -!- INTERACTION:
CC P55088; Q9EPK8: Trpv4; NbExp=2; IntAct=EBI-6273066, EBI-7091763;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18286643,
CC ECO:0000269|PubMed:8660998}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P55087}. Basolateral cell membrane
CC {ECO:0000269|PubMed:10915655, ECO:0000269|PubMed:16641094,
CC ECO:0000269|PubMed:27751903, ECO:0000269|PubMed:9276712}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:P55087}. Endosome membrane
CC {ECO:0000250|UniProtKB:P47863}. Cell membrane, sarcolemma
CC {ECO:0000269|PubMed:29055082}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P55087}. Cell projection
CC {ECO:0000269|PubMed:22896675}. Note=Activation of the vasopressin
CC receptor AVPR1A triggers AQP4 phosphorylation at Ser-180 and promotes
CC its internalization from the cell membrane (By similarity). Detected on
CC brain astrocyte processes and astrocyte endfeet close to capillaries
CC (PubMed:22896675). {ECO:0000250|UniProtKB:P47863,
CC ECO:0000269|PubMed:22896675}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=2; Synonyms=MIWC2, AQP4-M1;
CC IsoId=P55088-1; Sequence=Displayed;
CC Name=1; Synonyms=MIWC1, AQP4-M23;
CC IsoId=P55088-2; Sequence=VSP_003233;
CC Name=3; Synonyms=MIWC3;
CC IsoId=P55088-3; Sequence=VSP_003234;
CC -!- TISSUE SPECIFICITY: Detected in brain cortex, especially around
CC cortical blood vessels, and subjacent to pia, with lower levels in
CC parenchymal membranes (PubMed:27751903). Detected in ependymal and
CC astroglial cells in brain (PubMed:8660998, PubMed:9276712,
CC PubMed:22896675, PubMed:27751903). Detected in supporting Hensen's
CC cells, inner sulcus cells and Claudius cells in the inner ear
CC (PubMed:11406631). Detected in skeletal muscle (PubMed:29055082).
CC Detected in gastric parietal cells (PubMed:10915655). Detected in
CC principal cells in collecting ducts in kidney medulla (at protein
CC level) (PubMed:9276712, PubMed:16641094). Detected in brain, heart and
CC skeletal muscle (PubMed:8660998). {ECO:0000269|PubMed:10915655,
CC ECO:0000269|PubMed:11406631, ECO:0000269|PubMed:16641094,
CC ECO:0000269|PubMed:22896675, ECO:0000269|PubMed:27751903,
CC ECO:0000269|PubMed:29055082, ECO:0000269|PubMed:8660998,
CC ECO:0000269|PubMed:9276712}.
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:P55087}.
CC -!- PTM: Phosphorylation by PKC at Ser-180 reduces conductance by 50% (By
CC similarity). Phosphorylation by PKG at Ser-111 in response to glutamate
CC increases conductance by 40%; this increase is not due to increased
CC presence at the cell membrane (PubMed:18286643).
CC {ECO:0000250|UniProtKB:P47863, ECO:0000269|PubMed:18286643}.
CC -!- PTM: Isoform 2: Palmitoylated on its N-terminal region. Isoform 1: Not
CC palmitoylated. {ECO:0000250|UniProtKB:P47863}.
CC -!- DISRUPTION PHENOTYPE: Mice are born at the expected Mendelian rate and
CC display no obvious phenotype (PubMed:9276712, PubMed:10915655). They
CC have normal urine osmolality under standard conditions, but display
CC reduced urine osmolality after 36 hour water deprivation
CC (PubMed:9276712). Adult mice display incereased brain water content
CC (PubMed:27751903). Mutant mice display a reduced rate of water flux
CC across the blood brain interface (PubMed:30557661). Fluid transport
CC from the brain paravascular space into the surrounding interstitium is
CC abolished. Besides, mice display strongly reduced solute clearance from
CC the brain interstitium (PubMed:22896675). Mice display reduced
CC cerebrospinal fluid influx into the brain, and reduced brain solute
CC transport via the cerebrospinal fluid from the cisterna to the brain
CC parenchyma (PubMed:22896675, PubMed:30561329). The organ of Corti in
CC the inner ear appears morphologically normal, but mice have
CC considerably impaired hearing at an age of 4 to 5 weeks
CC (PubMed:11406631). Mice display unchanged gastric acid secretion
CC (PubMed:10915655). {ECO:0000269|PubMed:10915655,
CC ECO:0000269|PubMed:11406631, ECO:0000269|PubMed:22896675,
CC ECO:0000269|PubMed:27751903, ECO:0000269|PubMed:30557661,
CC ECO:0000269|PubMed:30561329, ECO:0000269|PubMed:9276712}.
CC -!- SIMILARITY: Belongs to the MIP/aquaporin (TC 1.A.8) family.
CC {ECO:0000305}.
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DR EMBL; U48398; AAB41569.1; -; mRNA.
DR EMBL; U48397; AAB41568.1; -; mRNA.
DR EMBL; U33012; AAA84923.1; -; mRNA.
DR EMBL; U48400; AAB41571.1; -; Genomic_DNA.
DR EMBL; U48399; AAB41570.1; -; mRNA.
DR EMBL; U88623; AAC53155.1; -; mRNA.
DR EMBL; AF469168; AAL73545.1; -; mRNA.
DR EMBL; AF469169; AAL73546.1; -; mRNA.
DR EMBL; AF219992; AAG44243.2; -; Genomic_DNA.
DR EMBL; CT010362; CAJ18569.1; -; mRNA.
DR EMBL; BC024526; AAH24526.1; -; mRNA.
DR CCDS; CCDS29073.1; -. [P55088-1]
DR CCDS; CCDS89196.1; -. [P55088-2]
DR RefSeq; NP_001295570.1; NM_001308641.1. [P55088-2]
DR RefSeq; NP_001295571.1; NM_001308642.1. [P55088-2]
DR RefSeq; NP_001295572.1; NM_001308643.1. [P55088-2]
DR RefSeq; NP_001295573.1; NM_001308644.1. [P55088-2]
DR RefSeq; NP_001295574.1; NM_001308645.1. [P55088-2]
DR RefSeq; NP_001295575.1; NM_001308646.1. [P55088-2]
DR RefSeq; NP_001295576.1; NM_001308647.2. [P55088-2]
DR RefSeq; NP_001304658.1; NM_001317729.1.
DR RefSeq; NP_033830.2; NM_009700.3.
DR AlphaFoldDB; P55088; -.
DR SMR; P55088; -.
DR BioGRID; 198173; 9.
DR DIP; DIP-59602N; -.
DR IntAct; P55088; 2.
DR STRING; 10090.ENSMUSP00000078088; -.
DR ChEMBL; CHEMBL5965; -.
DR GlyGen; P55088; 2 sites.
DR iPTMnet; P55088; -.
DR PhosphoSitePlus; P55088; -.
DR MaxQB; P55088; -.
DR PaxDb; P55088; -.
DR PeptideAtlas; P55088; -.
DR PRIDE; P55088; -.
DR ProteomicsDB; 273910; -. [P55088-1]
DR ProteomicsDB; 273911; -. [P55088-2]
DR ProteomicsDB; 273912; -. [P55088-3]
DR Antibodypedia; 3103; 580 antibodies from 37 providers.
DR DNASU; 11829; -.
DR Ensembl; ENSMUST00000234053; ENSMUSP00000157337; ENSMUSG00000024411. [P55088-2]
DR Ensembl; ENSMUST00000234391; ENSMUSP00000157347; ENSMUSG00000024411. [P55088-2]
DR Ensembl; ENSMUST00000234466; ENSMUSP00000157324; ENSMUSG00000024411. [P55088-2]
DR Ensembl; ENSMUST00000234473; ENSMUSP00000157152; ENSMUSG00000024411. [P55088-2]
DR Ensembl; ENSMUST00000234518; ENSMUSP00000157239; ENSMUSG00000024411. [P55088-2]
DR Ensembl; ENSMUST00000234643; ENSMUSP00000157060; ENSMUSG00000024411. [P55088-2]
DR Ensembl; ENSMUST00000235044; ENSMUSP00000157000; ENSMUSG00000024411. [P55088-2]
DR GeneID; 11829; -.
DR KEGG; mmu:11829; -.
DR UCSC; uc008edq.2; mouse. [P55088-1]
DR UCSC; uc008eds.2; mouse. [P55088-3]
DR CTD; 361; -.
DR MGI; MGI:107387; Aqp4.
DR VEuPathDB; HostDB:ENSMUSG00000024411; -.
DR eggNOG; KOG0223; Eukaryota.
DR GeneTree; ENSGT00940000156037; -.
DR InParanoid; P55088; -.
DR OrthoDB; 1152704at2759; -.
DR PhylomeDB; P55088; -.
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; 11829; 2 hits in 70 CRISPR screens.
DR ChiTaRS; Aqp4; mouse.
DR PRO; PR:P55088; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; P55088; protein.
DR Bgee; ENSMUSG00000024411; Expressed in pontine nuclear group and 184 other tissues.
DR ExpressionAtlas; P55088; baseline and differential.
DR GO; GO:0097450; C:astrocyte end-foot; IDA:UniProtKB.
DR GO; GO:0009925; C:basal plasma membrane; ISO:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0031253; C:cell projection membrane; ISO:MGI.
DR GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:MGI.
DR GO; GO:0005576; C:extracellular region; IEA:GOC.
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:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0042383; C:sarcolemma; IDA:UniProtKB.
DR GO; GO:0030315; C:T-tubule; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0015250; F:water channel activity; IDA:UniProtKB.
DR GO; GO:0015670; P:carbon dioxide transport; ISO:MGI.
DR GO; GO:0098609; P:cell-cell adhesion; ISO:MGI.
DR GO; GO:0071333; P:cellular response to glucose stimulus; ISO:MGI.
DR GO; GO:0071346; P:cellular response to interferon-gamma; ISO:MGI.
DR GO; GO:0009992; P:cellular water homeostasis; IDA:UniProtKB.
DR GO; GO:0090660; P:cerebrospinal fluid circulation; IMP:UniProtKB.
DR GO; GO:0033326; P:cerebrospinal fluid secretion; IMP:CACAO.
DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR GO; GO:0060354; P:negative regulation of cell adhesion molecule production; ISO:MGI.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; ISO:MGI.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; ISO:MGI.
DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR GO; GO:0010574; P:regulation of vascular endothelial growth factor production; ISO:MGI.
DR GO; GO:0070295; P:renal water absorption; IMP:MGI.
DR GO; GO:0007605; P:sensory perception of sound; IMP:MGI.
DR GO; GO:0030104; P:water homeostasis; IDA:UniProtKB.
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 Alternative splicing; Cell membrane; Cell projection; Endosome;
KW Glycoprotein; Lipoprotein; Membrane; Palmitate; Phosphoprotein;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..323
FT /note="Aquaporin-4"
FT /id="PRO_0000063949"
FT TOPO_DOM 1..36
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 37..57
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55087"
FT TOPO_DOM 58..69
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 70..89
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55087"
FT TOPO_DOM 90..93
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 94..101
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:P55087"
FT TOPO_DOM 102..115
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 116..136
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55087"
FT TOPO_DOM 137..155
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 156..176
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55087"
FT TOPO_DOM 177..184
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 185..205
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55087"
FT TOPO_DOM 206..208
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 209..222
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:P55087"
FT TOPO_DOM 223..231
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 232..252
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55087"
FT TOPO_DOM 253..323
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT MOTIF 97..99
FT /note="NPA 1"
FT /evidence="ECO:0000250|UniProtKB:P55087"
FT MOTIF 213..215
FT /note="NPA 2"
FT /evidence="ECO:0000250|UniProtKB:P55087"
FT MOD_RES 111
FT /note="Phosphoserine; by PKG"
FT /evidence="ECO:0000269|PubMed:18286643"
FT MOD_RES 180
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:P47863"
FT MOD_RES 276
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P47863"
FT MOD_RES 285
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 289
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 321
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P47863"
FT LIPID 13
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P47863"
FT LIPID 17
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P47863"
FT CARBOHYD 153
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 206
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..22
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:10960499,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:8660998"
FT /id="VSP_003233"
FT VAR_SEQ 1..11
FT /note="MSDGAAARRWG -> MVHGFGCFVFFFLISLSSLWASEDSTCNSTLPLCHLA
FT TTLDCC (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:8660998"
FT /id="VSP_003234"
FT VARIANT 4
FT /note="G -> R"
FT /evidence="ECO:0000269|PubMed:10960499"
FT MUTAGEN 111
FT /note="S->A: Loss of phosphorylation by PKG (in vitro). No
FT effect on location at cell membrane."
FT /evidence="ECO:0000269|PubMed:18286643"
FT CONFLICT 37
FT /note="A -> S (in Ref. 1; AAB41571)"
FT /evidence="ECO:0000305"
FT CONFLICT 51
FT /note="Missing (in Ref. 1; AAB41569/AAB41570)"
FT /evidence="ECO:0000305"
FT CONFLICT 88
FT /note="F -> L (in Ref. 1; AAB41569/AAB41570)"
FT /evidence="ECO:0000305"
FT CONFLICT 174
FT /note="I -> V (in Ref. 1; AAB41569/AAB41570)"
FT /evidence="ECO:0000305"
FT CONFLICT 313
FT /note="K -> R (in Ref. 1; AAB41569/AAB41570)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 323 AA; 34436 MW; 9AC638A3C3F412E2 CRC64;
MSDGAAARRW GKCGHSCSRE SIMVAFKGVW TQAFWKAVSA EFLATLIFVL LGVGSTINWG
GSENPLPVDM VLISLCFGLS IATMVQCFGH ISGGHINPAV TVAMVCTRKI SIAKSVFYII
AQCLGAIIGA GILYLVTPPS VVGGLGVTTV HGNLTAGHGL LVELIITFQL VFTIFASCDS
KRTDVTGSIA LAIGFSVAIG HLFAINYTGA SMNPARSFGP AVIMGNWANH WIYWVGPIMG
AVLAGALYEY VFCPDVELKR RLKEAFSKAA QQTKGSYMEV EDNRSQVETE DLILKPGVVH
VIDIDRGEEK KGKDSSGEVL SSV
