AQP4_NOTAL
ID AQP4_NOTAL Reviewed; 326 AA.
AC Q5I4F9;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 25-MAY-2022, entry version 65.
DE RecName: Full=Aquaporin-4;
DE Short=AQP-4;
GN Name=AQP4;
OS Notomys alexis (Spinifex hopping mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Notomys.
OX NCBI_TaxID=184396;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Bartolo R.C., Donald J.A.;
RT "Cloning and expression of aquaporin 4 in the Spinifex hopping mouse,
RT Notomys alexis.";
RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Forms a water-specific channel. Plays an important role in
CC brain water homeostasis and in glymphatic solute transport. Required
CC for a normal rate of water exchange across the blood brain interface.
CC Required for normal levels of cerebrospinal fluid influx into the brain
CC cortex and parenchyma along paravascular spaces that surround
CC penetrating arteries, and for normal drainage of interstitial fluid
CC along paravenous drainage pathways. Thereby, it is required for normal
CC clearance of solutes from the brain interstitial fluid, including
CC soluble beta-amyloid peptides derived from APP. Plays a redundant role
CC in urinary water homeostasis and urinary concentrating ability.
CC {ECO:0000250|UniProtKB:P55088}.
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 -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P55088};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P55087}. Basolateral
CC cell membrane {ECO:0000250|UniProtKB:P55088}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:P55087}. Endosome membrane
CC {ECO:0000250|UniProtKB:P47863}. Cell membrane, sarcolemma
CC {ECO:0000250|UniProtKB:P55088}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P55087}. Cell projection
CC {ECO:0000250|UniProtKB:P55088}. Note=Activation of the vasopressin
CC receptor AVPR1A triggers AQP4 phosphorylation at Ser-183 and promotes
CC its internalization from the cell membrane (By similarity). Detected on
CC brain astrocyte processes and astrocyte endfeet close to capillaries
CC (By similarity). {ECO:0000250|UniProtKB:P47863,
CC ECO:0000250|UniProtKB:P55088}.
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-183 reduces conductance by 50%.
CC Phosphorylation by PKG at Ser-114 in response to glutamate increases
CC conductance by 40% (By similarity). {ECO:0000250}.
CC -!- PTM: Isoform Long: Palmitoylated on its N-terminal region.
CC {ECO:0000250|UniProtKB:P47863}.
CC -!- SIMILARITY: Belongs to the MIP/aquaporin (TC 1.A.8) family.
CC {ECO:0000305}.
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DR EMBL; AY856056; AAW47638.1; -; mRNA.
DR AlphaFoldDB; Q5I4F9; -.
DR SMR; Q5I4F9; -.
DR GO; GO:0097450; C:astrocyte end-foot; ISS:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:GOC.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0042383; C:sarcolemma; ISS:UniProtKB.
DR GO; GO:0015250; F:water channel activity; ISS:UniProtKB.
DR GO; GO:0009992; P:cellular water homeostasis; ISS:UniProtKB.
DR GO; GO:0090660; P:cerebrospinal fluid circulation; ISS:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR GO; GO:0030104; P:water homeostasis; ISS:UniProtKB.
DR GO; GO:0006833; P:water transport; ISS: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 2: Evidence at transcript level;
KW Cell membrane; Cell projection; Endosome; Glycoprotein; Lipoprotein;
KW Membrane; Palmitate; Phosphoprotein; Repeat; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..326
FT /note="Aquaporin-4"
FT /id="PRO_0000257848"
FT TOPO_DOM 1..39
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 40..60
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55087"
FT TOPO_DOM 61..72
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 73..92
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55087"
FT TOPO_DOM 93..96
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 97..104
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:P55087"
FT TOPO_DOM 105..118
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 119..139
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55087"
FT TOPO_DOM 140..158
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 159..179
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55087"
FT TOPO_DOM 180..187
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 188..208
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55087"
FT TOPO_DOM 209..211
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 212..225
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:P55087"
FT TOPO_DOM 226..234
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 235..255
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55087"
FT TOPO_DOM 256..326
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT MOTIF 100..102
FT /note="NPA 1"
FT /evidence="ECO:0000250|UniProtKB:P55087"
FT MOTIF 216..218
FT /note="NPA 2"
FT /evidence="ECO:0000250|UniProtKB:P55087"
FT MOD_RES 114
FT /note="Phosphoserine; by PKG"
FT /evidence="ECO:0000250|UniProtKB:P55088"
FT MOD_RES 183
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:P47863"
FT MOD_RES 279
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P47863"
FT MOD_RES 288
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55088"
FT MOD_RES 292
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P55088"
FT MOD_RES 324
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P47863"
FT LIPID 15
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P47863"
FT LIPID 20
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P47863"
FT CARBOHYD 156
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 209
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 326 AA; 34709 MW; 59E06A74EB8A15B2 CRC64;
MSDGAGAAAR RWGKCGGRSC SRESIMVAFK GVWTQAFWKA VTAEFLAMLI FVLLSVGSTI
NWGGSENPLP VDMVLISLCF GLSIATMVQC FGHISGGHIN PAVTVAMVCT RKISIAKSVF
YITAQCLGAI IGAGILYLVT PPNVVGGLGV TTVHGNLTAG HGLLVELIIT FQLVFTIFAS
CDSKRTDVTG SIALAIGFSV AIGHLFAINY TGASMNPARS FGPAVIMGNW ENHWIYWVGP
IIGAVLAGAL YEYVFCPDVE LKRRLKEAFS KAAQQTKGSY TEVEDNRSQV ETEDLILKPG
VVHVIDIDRG EDKKGKDSAG EVLSSV
