UniProtKB - P55088 (AQP4_MOUSE)
Aquaporin-4
Aqp4
Functioni
Forms a water-specific channel (PubMed:8660998, PubMed:9276712, PubMed:18286643).
Plays an important role in brain water homeostasis and in glymphatic solute transport (PubMed:22896675, PubMed:27751903, PubMed:30561329, PubMed:30557661).
Required for a normal rate of water exchange across the blood brain interface (PubMed:30557661).
Required for normal levels of cerebrospinal fluid influx into the brain cortex and parenchyma along paravascular spaces that surround penetrating arteries, and for normal drainage of interstitial fluid along paravenous drainage pathways. Thereby, it is required for normal clearance of solutes from the brain interstitial fluid, including soluble beta-amyloid peptides derived from APP (PubMed:22896675, PubMed:27751903, PubMed:30561329).
Plays a redundant role in urinary water homeostasis and urinary concentrating ability (PubMed:9276712).
7 PublicationsGO - Molecular functioni
- identical protein binding Source: MGI
- water channel activity Source: UniProtKB
GO - Biological processi
- carbon dioxide transport Source: MGI
- cell-cell adhesion Source: MGI
- cellular response to glucose stimulus Source: MGI
- cellular response to interferon-gamma Source: MGI
- cellular water homeostasis Source: UniProtKB
- cerebrospinal fluid circulation Source: UniProtKB
- cerebrospinal fluid secretion Source: CACAO
- negative regulation of cell adhesion molecule production Source: MGI
- negative regulation of interleukin-1 beta production Source: MGI
- negative regulation of interleukin-6 production Source: MGI
- protein homotetramerization Source: UniProtKB
- regulation of vascular endothelial growth factor production Source: MGI
- renal water absorption Source: MGI
- sensory perception of sound Source: MGI
- water homeostasis Source: UniProtKB
- water transport Source: UniProtKB
Keywordsi
Biological process | Transport |
Enzyme and pathway databases
Reactomei | R-MMU-432040, Vasopressin regulates renal water homeostasis via Aquaporins R-MMU-432047, Passive transport by Aquaporins |
Names & Taxonomyi
Protein namesi | Recommended name: Aquaporin-4Short name: AQP-4 Alternative name(s): Mercurial-insensitive water channel1 Publication Short name: MIWC1 Publication WCH4 |
Gene namesi | Name:Aqp4 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:107387, Aqp4 |
VEuPathDBi | HostDB:ENSMUSG00000024411 |
Subcellular locationi
Endosome
- Endosome membrane By similarity
Plasma membrane
- Cell membrane 2 Publications; Multi-pass membrane protein By similarity
- Basolateral cell membrane 4 Publications; Multi-pass membrane protein By similarity
- sarcolemma 1 Publication; Multi-pass membrane protein By similarity
Other locations
- Cell projection 1 Publication
Note: Activation of the vasopressin receptor AVPR1A triggers AQP4 phosphorylation at Ser-180 and promotes its internalization from the cell membrane (By similarity). Detected on brain astrocyte processes and astrocyte endfeet close to capillaries (PubMed:22896675).By similarity1 Publication
Endosome
- endosome membrane Source: UniProtKB-SubCell
Extracellular region or secreted
- extracellular region Source: GOC
Plasma Membrane
- basal plasma membrane Source: MGI
- basolateral plasma membrane Source: UniProtKB
- cell projection membrane Source: MGI
- external side of plasma membrane Source: MGI
- integral component of plasma membrane Source: UniProtKB
- plasma membrane Source: UniProtKB
- sarcolemma Source: UniProtKB
- T-tubule Source: MGI
Other locations
- astrocyte end-foot Source: UniProtKB
- cell-cell junction Source: UniProtKB
- cytoplasm Source: UniProtKB
- integral component of membrane Source: GO_Central
- protein-containing complex Source: MGI
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 36 | CytoplasmicCuratedAdd BLAST | 36 | |
Transmembranei | 37 – 57 | HelicalBy similarityAdd BLAST | 21 | |
Topological domaini | 58 – 69 | ExtracellularCuratedAdd BLAST | 12 | |
Transmembranei | 70 – 89 | HelicalBy similarityAdd BLAST | 20 | |
Topological domaini | 90 – 93 | CytoplasmicCurated | 4 | |
Intramembranei | 94 – 101 | Discontinuously helicalBy similarity | 8 | |
Topological domaini | 102 – 115 | CytoplasmicCuratedAdd BLAST | 14 | |
Transmembranei | 116 – 136 | HelicalBy similarityAdd BLAST | 21 | |
Topological domaini | 137 – 155 | ExtracellularCuratedAdd BLAST | 19 | |
Transmembranei | 156 – 176 | HelicalBy similarityAdd BLAST | 21 | |
Topological domaini | 177 – 184 | CytoplasmicCurated | 8 | |
Transmembranei | 185 – 205 | HelicalBy similarityAdd BLAST | 21 | |
Topological domaini | 206 – 208 | ExtracellularCurated | 3 | |
Intramembranei | 209 – 222 | Discontinuously helicalBy similarityAdd BLAST | 14 | |
Topological domaini | 223 – 231 | ExtracellularCurated | 9 | |
Transmembranei | 232 – 252 | HelicalBy similarityAdd BLAST | 21 | |
Topological domaini | 253 – 323 | CytoplasmicCuratedAdd BLAST | 71 |
Keywords - Cellular componenti
Cell membrane, Cell projection, Endosome, MembranePathology & Biotechi
Disruption phenotypei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 111 | S → A: Loss of phosphorylation by PKG (in vitro). No effect on location at cell membrane. 1 Publication | 1 |
Chemistry databases
ChEMBLi | CHEMBL5965 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000063949 | 1 – 323 | Aquaporin-4Add BLAST | 323 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Lipidationi | 13 | S-palmitoyl cysteineBy similarity | 1 | |
Lipidationi | 17 | S-palmitoyl cysteineBy similarity | 1 | |
Modified residuei | 111 | Phosphoserine; by PKG1 Publication | 1 | |
Glycosylationi | 153 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 180 | Phosphoserine; by PKCBy similarity | 1 | |
Glycosylationi | 206 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 276 | PhosphoserineBy similarity | 1 | |
Modified residuei | 285 | PhosphoserineCombined sources | 1 | |
Modified residuei | 289 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 321 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Glycoprotein, Lipoprotein, Palmitate, PhosphoproteinProteomic databases
MaxQBi | P55088 |
PaxDbi | P55088 |
PeptideAtlasi | P55088 |
PRIDEi | P55088 |
ProteomicsDBi | 273910 [P55088-1] 273911 [P55088-2] 273912 [P55088-3] |
PTM databases
GlyGeni | P55088, 2 sites |
iPTMneti | P55088 |
PhosphoSitePlusi | P55088 |
Expressioni
Tissue specificityi
Gene expression databases
ExpressionAtlasi | P55088, baseline and differential |
Interactioni
Subunit structurei
Homotetramer. The tetramers can form oligomeric arrays in membranes. The size of the oligomers differs between tissues and is smaller in skeletal muscle than in brain. Interaction between AQP4 oligomeric arrays in close-by cells can contribute to cell-cell adhesion (By similarity).
Part of a complex containing MLC1, TRPV4, HEPACAM and ATP1B1 (By similarity).
By similarityBinary interactionsi
P55088
With | #Exp. | IntAct |
---|---|---|
Trpv4 [Q9EPK8] | 2 | EBI-6273066,EBI-7091763 |
GO - Molecular functioni
- identical protein binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 198173, 9 interactors |
DIPi | DIP-59602N |
IntActi | P55088, 2 interactors |
STRINGi | 10090.ENSMUSP00000078088 |
Miscellaneous databases
RNActi | P55088, protein |
Family & Domainsi
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 97 – 99 | NPA 1By similarity | 3 | |
Motifi | 213 – 215 | NPA 2By similarity | 3 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Repeat, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0223, Eukaryota |
GeneTreei | ENSGT00940000156037 |
InParanoidi | P55088 |
OrthoDBi | 1152704at2759 |
PhylomeDBi | P55088 |
TreeFami | TF312940 |
Family and domain databases
CDDi | cd00333, MIP, 1 hit |
Gene3Di | 1.20.1080.10, 1 hit |
InterProi | View protein in InterPro IPR023271, Aquaporin-like IPR034294, Aquaporin_transptr IPR000425, MIP IPR022357, MIP_CS |
PANTHERi | PTHR19139, PTHR19139, 1 hit |
Pfami | View protein in Pfam PF00230, MIP, 1 hit |
PRINTSi | PR00783, MINTRINSICP |
SUPFAMi | SSF81338, SSF81338, 1 hit |
TIGRFAMsi | TIGR00861, MIP, 1 hit |
PROSITEi | View protein in PROSITE PS00221, MIP, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MSDGAAARRW GKCGHSCSRE SIMVAFKGVW TQAFWKAVSA EFLATLIFVL
60 70 80 90 100
LGVGSTINWG GSENPLPVDM VLISLCFGLS IATMVQCFGH ISGGHINPAV
110 120 130 140 150
TVAMVCTRKI SIAKSVFYII AQCLGAIIGA GILYLVTPPS VVGGLGVTTV
160 170 180 190 200
HGNLTAGHGL LVELIITFQL VFTIFASCDS KRTDVTGSIA LAIGFSVAIG
210 220 230 240 250
HLFAINYTGA SMNPARSFGP AVIMGNWANH WIYWVGPIMG AVLAGALYEY
260 270 280 290 300
VFCPDVELKR RLKEAFSKAA QQTKGSYMEV EDNRSQVETE DLILKPGVVH
310 320
VIDIDRGEEK KGKDSSGEVL SSV
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A5F8MQ17 | A0A5F8MQ17_MOUSE | Aquaporin-4 | Aqp4 | 330 | Annotation score: | ||
A0A0R4J0Z3 | A0A0R4J0Z3_MOUSE | Aquaporin-4 | Aqp4 | 323 | Annotation score: | ||
A0A3Q4EI78 | A0A3Q4EI78_MOUSE | Aquaporin-4 | Aqp4 | 83 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 37 | A → S in AAB41571 (PubMed:8660998).Curated | 1 | |
Sequence conflicti | 51 | Missing in AAB41569 (PubMed:8660998).Curated | 1 | |
Sequence conflicti | 51 | Missing in AAB41570 (PubMed:8660998).Curated | 1 | |
Sequence conflicti | 88 | F → L in AAB41569 (PubMed:8660998).Curated | 1 | |
Sequence conflicti | 88 | F → L in AAB41570 (PubMed:8660998).Curated | 1 | |
Sequence conflicti | 174 | I → V in AAB41569 (PubMed:8660998).Curated | 1 | |
Sequence conflicti | 174 | I → V in AAB41570 (PubMed:8660998).Curated | 1 | |
Sequence conflicti | 313 | K → R in AAB41569 (PubMed:8660998).Curated | 1 | |
Sequence conflicti | 313 | K → R in AAB41570 (PubMed:8660998).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural varianti | 4 | G → R1 Publication | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_003233 | 1 – 22 | Missing in isoform 1. 3 PublicationsAdd BLAST | 22 | |
Alternative sequenceiVSP_003234 | 1 – 11 | MSDGAAARRWG → MVHGFGCFVFFFLISLSSLW ASEDSTCNSTLPLCHLATTL DCC in isoform 3. 1 PublicationAdd BLAST | 11 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U48398 mRNA Translation: AAB41569.1 U48397 mRNA Translation: AAB41568.1 U33012 mRNA Translation: AAA84923.1 U48400 Genomic DNA Translation: AAB41571.1 U48399 mRNA Translation: AAB41570.1 U88623 mRNA Translation: AAC53155.1 AF469168 mRNA Translation: AAL73545.1 AF469169 mRNA Translation: AAL73546.1 AF219992 Genomic DNA Translation: AAG44243.2 CT010362 mRNA Translation: CAJ18569.1 BC024526 mRNA Translation: AAH24526.1 |
CCDSi | CCDS29073.1 [P55088-1] CCDS89196.1 [P55088-2] |
RefSeqi | NP_001295570.1, NM_001308641.1 [P55088-2] NP_001295571.1, NM_001308642.1 [P55088-2] NP_001295572.1, NM_001308643.1 [P55088-2] NP_001295573.1, NM_001308644.1 [P55088-2] NP_001295574.1, NM_001308645.1 [P55088-2] NP_001295575.1, NM_001308646.1 [P55088-2] NP_001295576.1, NM_001308647.2 [P55088-2] NP_001304658.1, NM_001317729.1 NP_033830.2, NM_009700.3 |
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U48398 mRNA Translation: AAB41569.1 U48397 mRNA Translation: AAB41568.1 U33012 mRNA Translation: AAA84923.1 U48400 Genomic DNA Translation: AAB41571.1 U48399 mRNA Translation: AAB41570.1 U88623 mRNA Translation: AAC53155.1 AF469168 mRNA Translation: AAL73545.1 AF469169 mRNA Translation: AAL73546.1 AF219992 Genomic DNA Translation: AAG44243.2 CT010362 mRNA Translation: CAJ18569.1 BC024526 mRNA Translation: AAH24526.1 |
CCDSi | CCDS29073.1 [P55088-1] CCDS89196.1 [P55088-2] |
RefSeqi | NP_001295570.1, NM_001308641.1 [P55088-2] NP_001295571.1, NM_001308642.1 [P55088-2] NP_001295572.1, NM_001308643.1 [P55088-2] NP_001295573.1, NM_001308644.1 [P55088-2] NP_001295574.1, NM_001308645.1 [P55088-2] NP_001295575.1, NM_001308646.1 [P55088-2] NP_001295576.1, NM_001308647.2 [P55088-2] NP_001304658.1, NM_001317729.1 NP_033830.2, NM_009700.3 |
3D structure databases
SMRi | P55088 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 198173, 9 interactors |
DIPi | DIP-59602N |
IntActi | P55088, 2 interactors |
STRINGi | 10090.ENSMUSP00000078088 |
Chemistry databases
ChEMBLi | CHEMBL5965 |
PTM databases
GlyGeni | P55088, 2 sites |
iPTMneti | P55088 |
PhosphoSitePlusi | P55088 |
Proteomic databases
MaxQBi | P55088 |
PaxDbi | P55088 |
PeptideAtlasi | P55088 |
PRIDEi | P55088 |
ProteomicsDBi | 273910 [P55088-1] 273911 [P55088-2] 273912 [P55088-3] |
Protocols and materials databases
Antibodypediai | 3103, 580 antibodies from 37 providers |
DNASUi | 11829 |
Genome annotation databases
Organism-specific databases
CTDi | 361 |
MGIi | MGI:107387, Aqp4 |
VEuPathDBi | HostDB:ENSMUSG00000024411 |
Phylogenomic databases
eggNOGi | KOG0223, Eukaryota |
GeneTreei | ENSGT00940000156037 |
InParanoidi | P55088 |
OrthoDBi | 1152704at2759 |
PhylomeDBi | P55088 |
TreeFami | TF312940 |
Enzyme and pathway databases
Reactomei | R-MMU-432040, Vasopressin regulates renal water homeostasis via Aquaporins R-MMU-432047, Passive transport by Aquaporins |
Miscellaneous databases
BioGRID-ORCSi | 11829, 0 hits in 63 CRISPR screens |
ChiTaRSi | Aqp4, mouse |
PROi | PR:P55088 |
RNActi | P55088, protein |
SOURCEi | Search... |
Gene expression databases
ExpressionAtlasi | P55088, baseline and differential |
Family and domain databases
CDDi | cd00333, MIP, 1 hit |
Gene3Di | 1.20.1080.10, 1 hit |
InterProi | View protein in InterPro IPR023271, Aquaporin-like IPR034294, Aquaporin_transptr IPR000425, MIP IPR022357, MIP_CS |
PANTHERi | PTHR19139, PTHR19139, 1 hit |
Pfami | View protein in Pfam PF00230, MIP, 1 hit |
PRINTSi | PR00783, MINTRINSICP |
SUPFAMi | SSF81338, SSF81338, 1 hit |
TIGRFAMsi | TIGR00861, MIP, 1 hit |
PROSITEi | View protein in PROSITE PS00221, MIP, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | AQP4_MOUSE | |
Accessioni | P55088Primary (citable) accession number: P55088 Secondary accession number(s): P97818 Q9EQI3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1996 |
Last sequence update: | May 10, 2004 | |
Last modified: | February 23, 2022 | |
This is version 175 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families