P55087 · AQP4_HUMAN
- ProteinAquaporin-4
- GeneAQP4
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids323 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Plays an important role in brain water homeostasis (PubMed:37143309).
It is involved in glymphatic solute transport and is required for a normal rate of water exchange across the blood brain interface. 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. Plays a redundant role in urinary water homeostasis and urinary concentrating ability (By similarity).
Catalytic activity
- H2O(in) = H2O(out)
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | astrocyte end-foot | |
Cellular Component | basolateral plasma membrane | |
Cellular Component | cytoplasm | |
Cellular Component | endosome membrane | |
Cellular Component | external side of plasma membrane | |
Cellular Component | extracellular region | |
Cellular Component | plasma membrane | |
Cellular Component | sarcolemma | |
Molecular Function | identical protein binding | |
Molecular Function | water channel activity | |
Biological Process | cellular response to type II interferon | |
Biological Process | cerebrospinal fluid circulation | |
Biological Process | intracellular water homeostasis | |
Biological Process | multicellular organismal-level water homeostasis | |
Biological Process | protein homotetramerization | |
Biological Process | renal water homeostasis | |
Biological Process | water transport |
Keywords
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameAquaporin-4
- Short namesAQP-4
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP55087
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Features
Showing features for topological domain, transmembrane, intramembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-36 | Cytoplasmic | ||||
Sequence: MSDRPTARRWGKCGPLCTRENIMVAFKGVWTQAFWK | ||||||
Transmembrane | 37-57 | Helical | ||||
Sequence: AVTAEFLAMLIFVLLSLGSTI | ||||||
Topological domain | 58-69 | Extracellular | ||||
Sequence: NWGGTEKPLPVD | ||||||
Transmembrane | 70-89 | Helical | ||||
Sequence: MVLISLCFGLSIATMVQCFG | ||||||
Topological domain | 90-93 | Cytoplasmic | ||||
Sequence: HISG | ||||||
Intramembrane | 94-101 | Discontinuously helical | ||||
Sequence: GHINPAVT | ||||||
Topological domain | 102-115 | Cytoplasmic | ||||
Sequence: VAMVCTRKISIAKS | ||||||
Transmembrane | 116-136 | Helical | ||||
Sequence: VFYIAAQCLGAIIGAGILYLV | ||||||
Topological domain | 137-155 | Extracellular | ||||
Sequence: TPPSVVGGLGVTMVHGNLT | ||||||
Transmembrane | 156-176 | Helical | ||||
Sequence: AGHGLLVELIITFQLVFTIFA | ||||||
Topological domain | 177-184 | Cytoplasmic | ||||
Sequence: SCDSKRTD | ||||||
Transmembrane | 185-205 | Helical | ||||
Sequence: VTGSIALAIGFSVAIGHLFAI | ||||||
Topological domain | 206-208 | Extracellular | ||||
Sequence: NYT | ||||||
Intramembrane | 209-222 | Discontinuously helical | ||||
Sequence: GASMNPARSFGPAV | ||||||
Topological domain | 223-231 | Extracellular | ||||
Sequence: IMGNWENHW | ||||||
Transmembrane | 232-252 | Helical | ||||
Sequence: IYWVGPIIGAVLAGGLYEYVF | ||||||
Topological domain | 253-323 | Cytoplasmic | ||||
Sequence: CPDVEFKRRFKEAFSKAAQQTKGSYMEVEDNRSQVETDDLILKPGVVHVIDVDRGEEKKGKDQSGEVLSSV |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting (MLC4)
- Note
- DescriptionAn autosomal recessive disorder characterized by macrocephaly apparent in infancy, developmental delay, delayed walking, variable cognitive decline, behavioral abnormalities, and early-onset seizures. Brain imaging shows swelling of the cerebral white matter and subcortical cysts in the anterior temporal region. The severity of neurologic dysfunction and brain abnormalities tends to improve with time, indicating a remitting disease course.
- See alsoMIM:620448
Natural variants in MLC4
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_088778 | 215 | A>T | in MLC4; likely pathogenic; loss of function in cell volume regulation; does not localize to the cell membrane |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_088778 | 215 | in MLC4; likely pathogenic; loss of function in cell volume regulation; does not localize to the cell membrane | |||
Sequence: A → T |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 370 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, lipidation, modified residue, glycosylation, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000063948 | 1-323 | UniProt | Aquaporin-4 | |||
Sequence: MSDRPTARRWGKCGPLCTRENIMVAFKGVWTQAFWKAVTAEFLAMLIFVLLSLGSTINWGGTEKPLPVDMVLISLCFGLSIATMVQCFGHISGGHINPAVTVAMVCTRKISIAKSVFYIAAQCLGAIIGAGILYLVTPPSVVGGLGVTMVHGNLTAGHGLLVELIITFQLVFTIFASCDSKRTDVTGSIALAIGFSVAIGHLFAINYTGASMNPARSFGPAVIMGNWENHWIYWVGPIIGAVLAGGLYEYVFCPDVEFKRRFKEAFSKAAQQTKGSYMEVEDNRSQVETDDLILKPGVVHVIDVDRGEEKKGKDQSGEVLSSV | |||||||
Lipidation | 13 | UniProt | S-palmitoyl cysteine | ||||
Sequence: C | |||||||
Lipidation | 17 | UniProt | S-palmitoyl cysteine | ||||
Sequence: C | |||||||
Modified residue | 111 | UniProt | Phosphoserine; by PKG | ||||
Sequence: S | |||||||
Glycosylation | 153 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Modified residue | 180 | UniProt | Phosphoserine; by PKC | ||||
Sequence: S | |||||||
Glycosylation | 206 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Modified residue | 276 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 276 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 285 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 285 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 289 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 321 | UniProt | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Detected in stomach, along the glandular base region of the fundic gland (at protein level) (PubMed:8601457).
Detected in brain, lung and skeletal muscle, and at much lower levels in heart and ovary (PubMed:7559426, PubMed:8601457).
Gene expression databases
Organism-specific databases
Interaction
Subunit
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 (PubMed:22328087).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P55087 | CREB3 O43889-2 | 3 | EBI-10104898, EBI-625022 | |
BINARY | P55087 | GJA8 P48165 | 3 | EBI-10104898, EBI-17458373 | |
BINARY | P55087 | HPCAL4 Q9UM19 | 3 | EBI-10104898, EBI-744820 | |
BINARY | P55087 | WLS Q5T9L3-1 | 3 | EBI-10104898, EBI-22114623 | |
BINARY | P55087-1 | AQP4 P55087-1 | 2 | EBI-15771758, EBI-15771758 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 97-99 | NPA 1 | ||||
Sequence: NPA | ||||||
Motif | 213-215 | NPA 2 | ||||
Sequence: NPA |
Domain
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
P55087-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name2
- SynonymsAQP4-M1
- Length323
- Mass (Da)34,830
- Last updated1997-11-01 v2
- Checksum1A1600CF0DC11052
P55087-2
- Name1
- SynonymsAQP4-M23
- Differences from canonical
- 1-22: Missing
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
J3KRM4 | J3KRM4_HUMAN | AQP4 | 185 | ||
H0Y3H5 | H0Y3H5_HUMAN | AQP4 | 98 | ||
A0A5F9ZHR4 | A0A5F9ZHR4_HUMAN | AQP4 | 352 | ||
V9PBN7 | V9PBN7_HUMAN | AQP4 | 296 |
Sequence caution
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_003232 | 1-22 | in isoform 1 | |||
Sequence: Missing | ||||||
Sequence conflict | 246 | in Ref. 1; AAC52112 | ||||
Sequence: G → A | ||||||
Sequence conflict | 287-288 | in Ref. 1; AAC52112 | ||||
Sequence: VE → AK | ||||||
Sequence conflict | 296 | in Ref. 1; AAC52112 | ||||
Sequence: P → L |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U34846 EMBL· GenBank· DDBJ | AAC52112.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
U34845 EMBL· GenBank· DDBJ | AAC50284.1 EMBL· GenBank· DDBJ | mRNA | ||
D63412 EMBL· GenBank· DDBJ | BAA09715.1 EMBL· GenBank· DDBJ | mRNA | ||
U63622 EMBL· GenBank· DDBJ | AAB26957.1 EMBL· GenBank· DDBJ | mRNA | ||
U63623 EMBL· GenBank· DDBJ | AAB26958.1 EMBL· GenBank· DDBJ | mRNA | ||
AC018371 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC022286 EMBL· GenBank· DDBJ | AAH22286.1 EMBL· GenBank· DDBJ | mRNA |