AQP4_DIPME
ID AQP4_DIPME Reviewed; 324 AA.
AC Q923J4; Q923J5;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 25-MAY-2022, entry version 82.
DE RecName: Full=Aquaporin-4;
DE Short=AQP-4;
GN Name=AQP4;
OS Dipodomys merriami (Merriam's kangaroo rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Castorimorpha; Heteromyidae;
OC Dipodomyinae; Dipodomys.
OX NCBI_TaxID=94247;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Fang P.K., Huang Y., Walsberg G.E., Brown D., van Hoek A.N.;
RT "Molecular cloning and characterization of Merriam's kangaroo rat aquaporin
RT 4.";
RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP TISSUE SPECIFICITY.
RX PubMed=11292621; DOI=10.1152/ajprenal.2001.280.5.f794;
RA Huang Y., Tracy R., Walsberg G.E., Makkinje A., Fang P., Brown D.,
RA Van Hoek A.N.;
RT "Absence of aquaporin-4 water channels from kidneys of the desert rodent
RT Dipodomys merriami merriami.";
RL Am. J. Physiol. 280:F794-F802(2001).
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-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 (By similarity). {ECO:0000250|UniProtKB:P47863,
CC ECO:0000250|UniProtKB:P55088}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=2;
CC IsoId=Q923J4-1; Sequence=Displayed;
CC Name=1;
CC IsoId=Q923J4-2; Sequence=VSP_010210;
CC -!- TISSUE SPECIFICITY: Not expressed in kidney, Detectable in gastric
CC parietal and brain astroglial cells. The absence of AQP4 in kidney may
CC be critical for the extreme urinary concentration that occurs in this
CC species (up to 5,000 mosmol/kg H(2)O). {ECO:0000269|PubMed:11292621}.
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%.
CC Phosphorylation by PKG at Ser-111 in response to glutamate increases
CC conductance by 40% (By similarity). {ECO:0000250}.
CC -!- PTM: Isoform 2: Palmitoylated on its N-terminal region. Isoform 1: Not
CC palmitoylated. {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; AY032857; AAK66823.1; -; mRNA.
DR EMBL; AY032858; AAK66824.1; -; mRNA.
DR AlphaFoldDB; Q923J4; -.
DR SMR; Q923J4; -.
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 Alternative splicing; Cell membrane; Cell projection; Endosome;
KW Glycoprotein; Lipoprotein; Membrane; Palmitate; Phosphoprotein; Repeat;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..324
FT /note="Aquaporin-4"
FT /id="PRO_0000063947"
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..324
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 305..324
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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:0000250|UniProtKB:P55088"
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:0000250|UniProtKB:P55088"
FT MOD_RES 289
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P55088"
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:0000305"
FT /id="VSP_010210"
SQ SEQUENCE 324 AA; 34940 MW; EAE9CE3B17952CDD CRC64;
MSDRPAARPW GKCGSLCRRE EIMVAFKGVW TQAFWKAVTA EFLAMLIFVL LSLGSTINWG
GKENPLPVDM VLISLCFGLS IATMVQCFGH ISGGHINPAV TVAMVCTRKI SIAKSVFYIA
AQCLGAIIGA GILYLVTPPS VVGGLGVTTV HGNLTAGHGL LVELIITFQL VFTIFASCDS
KRTDVTGSIA LAIGFSVAIG HLFAINYTGA SMNPARSFGP AVIMGNWENH WIYWVGPIIG
AVLAGGLYEY VFCPDVELKR RFKEAFSKAA QQTKGSYMEV EDNRSQVETE DLILKPGLVH
VIDIDRGDEK KGKDPSGEIA QTQH
