UniProt functional annotation for P55087



	UniProt functional annotation for P55087

UniProt code: P55087.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Forms a water-specific channel (PubMed:7559426, PubMed:8601457, PubMed:19383790). Plays an important role in brain water homeostasis and in glymphatic solute transport. 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). {ECO:0000250|UniProtKB:P55088, ECO:0000269|PubMed:19383790, ECO:0000269|PubMed:7559426, ECO:0000269|PubMed:8601457}.

Subunit: Homotetramer (PubMed:19383790). 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). {ECO:0000250|UniProtKB:P47863, ECO:0000269|PubMed:19383790, ECO:0000269|PubMed:22328087}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:7559426, ECO:0000269|PubMed:8601457}; Multi-pass membrane protein {ECO:0000269|PubMed:19383790}. Basolateral cell membrane {ECO:0000250|UniProtKB:P55088}; Multi-pass membrane protein {ECO:0000269|PubMed:19383790}. Endosome membrane {ECO:0000250|UniProtKB:P47863}. Cell membrane, sarcolemma {ECO:0000269|PubMed:29055082}; Multi-pass membrane protein {ECO:0000269|PubMed:19383790}. Cell projection {ECO:0000250|UniProtKB:P47863}. Note=Activation of the vasopressin receptor AVPR1A triggers AQP4 phosphorylation at Ser-180 and promotes its internalization from the cell membrane. Detected on brain astrocyte processes and astrocyte endfeet close to capillaries. {ECO:0000250|UniProtKB:P47863}.

Tissue specificity: Detected in skeletal muscle (PubMed:29055082). 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). {ECO:0000269|PubMed:29055082, ECO:0000269|PubMed:7559426, ECO:0000269|PubMed:8601457}.

Domain: Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA). {ECO:0000269|PubMed:19383790}.

Ptm: Phosphorylation by PKC at Ser-180 reduces conductance by 50%. Phosphorylation by PKG at Ser-111 in response to glutamate increases conductance by 40% (By similarity). {ECO:0000250}.

Ptm: Isoform 2: Palmitoylated on its N-terminal region. Isoform 1: Not palmitoylated. {ECO:0000250|UniProtKB:P47863}.

Similarity: Belongs to the MIP/aquaporin (TC 1.A.8) family. {ECO:0000305}.

Sequence caution: Sequence=AAC52112.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Forms a water-specific channel (PubMed:7559426, PubMed:8601457, PubMed:19383790). Plays an important role in brain water homeostasis and in glymphatic solute transport. 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). {ECO:0000250\|UniProtKB:P55088, ECO:0000269\|PubMed:19383790, ECO:0000269\|PubMed:7559426, ECO:0000269\|PubMed:8601457}.


Subunit:		Homotetramer (PubMed:19383790). 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). {ECO:0000250\|UniProtKB:P47863, ECO:0000269\|PubMed:19383790, ECO:0000269\|PubMed:22328087}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:7559426, ECO:0000269\|PubMed:8601457}; Multi-pass membrane protein {ECO:0000269\|PubMed:19383790}. Basolateral cell membrane {ECO:0000250\|UniProtKB:P55088}; Multi-pass membrane protein {ECO:0000269\|PubMed:19383790}. Endosome membrane {ECO:0000250\|UniProtKB:P47863}. Cell membrane, sarcolemma {ECO:0000269\|PubMed:29055082}; Multi-pass membrane protein {ECO:0000269\|PubMed:19383790}. Cell projection {ECO:0000250\|UniProtKB:P47863}. Note=Activation of the vasopressin receptor AVPR1A triggers AQP4 phosphorylation at Ser-180 and promotes its internalization from the cell membrane. Detected on brain astrocyte processes and astrocyte endfeet close to capillaries. {ECO:0000250\|UniProtKB:P47863}.
Tissue specificity:		Detected in skeletal muscle (PubMed:29055082). 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). {ECO:0000269\|PubMed:29055082, ECO:0000269\|PubMed:7559426, ECO:0000269\|PubMed:8601457}.
Domain:		Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA). {ECO:0000269\|PubMed:19383790}.
Ptm:		Phosphorylation by PKC at Ser-180 reduces conductance by 50%. Phosphorylation by PKG at Ser-111 in response to glutamate increases conductance by 40% (By similarity). {ECO:0000250}.
Ptm:		Isoform 2: Palmitoylated on its N-terminal region. Isoform 1: Not palmitoylated. {ECO:0000250\|UniProtKB:P47863}.
Similarity:		Belongs to the MIP/aquaporin (TC 1.A.8) family. {ECO:0000305}.
Sequence caution:		Sequence=AAC52112.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};