ID AQP8_NOTAL Reviewed; 261 AA.
AC Q5I4F8;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-MAY-2023, entry version 51.
DE RecName: Full=Aquaporin-8 {ECO:0000250|UniProtKB:O94778};
DE Short=AQP-8;
GN Name=AQP8 {ECO:0000250|UniProtKB:O94778};
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 8 in the Spinifex hopping mouse,
RT Notomys alexis.";
RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Channel that allows the facilitated permeation of water and
CC uncharged molecules, such as hydrogen peroxide and the neutral form of
CC ammonia (NH3), through cellular membranes such as plasma membrane,
CC inner mitochondrial membrane and endoplasmic reticulum membrane of
CC several tissues. The transport of ammonia neutral form induces a
CC parallel transport of proton, at alkaline pH when the concentration of
CC ammonia is high. However, it is unclear whether the transport of proton
CC takes place via the aquaporin or via an endogenous pathway. Also, may
CC transport ammonia analogs such as formamide and methylamine, a
CC transport favourited at basic pH due to the increase of unprotonated
CC (neutral) form, which is expected to favor diffusion. Does not
CC transport urea or glycerol. The water transport mechanism is
CC mercury- and copper-sensitive and passive in response to osmotic
CC driving forces (By similarity). At the canicular plasma membrane,
CC mediates the osmotic transport of water toward the bile canaliculus and
CC facilitates the cAMP-induced bile canalicular water secretion, a
CC process involved in bile formation (By similarity). In addition,
CC mediates the hydrogen peroxide release from hepatocyte mitochondria
CC that modulates the SREBF2-mediated cholesterol synthesis and
CC facilitates the mitochondrial ammonia uptake which is metabolized into
CC urea, mainly under glucagon stimulation (By similarity). In B cells,
CC transports the CYBB-generated hydrogen peroxide from the external
CC leaflet of the plasma membrane to the cytosol to promote B cell
CC activation and differentiation for signal amplification (By
CC similarity). In the small intestine and colon system, mediates water
CC transport through mitochondria and apical membrane of epithelial cells
CC (By similarity). May play an important role in the adaptive response of
CC proximal tubule cells to acidosis possibly facilitating mitochondrial
CC ammonia transport (By similarity). {ECO:0000250|UniProtKB:O94778,
CC ECO:0000250|UniProtKB:P56404, ECO:0000250|UniProtKB:P56405}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O(in) = H2O(out); Xref=Rhea:RHEA:29667, ChEBI:CHEBI:15377;
CC Evidence={ECO:0000250|UniProtKB:O94778};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O2(out) = H2O2(in); Xref=Rhea:RHEA:74375, ChEBI:CHEBI:16240;
CC Evidence={ECO:0000250|UniProtKB:O94778};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=formamide(out) = formamide(in); Xref=Rhea:RHEA:74387,
CC ChEBI:CHEBI:16397; Evidence={ECO:0000250|UniProtKB:O94778};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=methylamine(out) = methylamine(in); Xref=Rhea:RHEA:74391,
CC ChEBI:CHEBI:59338; Evidence={ECO:0000250|UniProtKB:O94778};
CC -!- ACTIVITY REGULATION: Reversibly gated by a two-step sulfenylation-
CC persulfidation process in cells undergoing diverse stresses.
CC {ECO:0000250|UniProtKB:O94778}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P56405};
CC Multi-pass membrane protein {ECO:0000255}. Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P56405}; Multi-pass membrane protein
CC {ECO:0000255}. Apical cell membrane {ECO:0000250|UniProtKB:P56405};
CC Multi-pass membrane protein {ECO:0000255}. Basolateral cell membrane
CC {ECO:0000250|UniProtKB:P56405}; Multi-pass membrane protein
CC {ECO:0000255}. Smooth endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P56404}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Localized at the hepatocyte canalicular plasma
CC membrane (By similarity). Localized at the apical membrane of the gall-
CC bladder epithelial cells lining both the neck and corpus regions (By
CC similarity). Localized on the apical membranes of pancreatic acinar
CC cells and mucosal epithelium of the colon and jejunum. Trafficking from
CC intracellular vesicles to the hepatocyte canalicular plasma membrane is
CC induced by glucagon or the second messenger 3',5'-cyclic AMP and the
CC translocation is protein kinase A and microtubule-dependent. Localized
CC at the brush border membranes of epithelial cells from jejunum (By
CC similarity). Localized at the luminal membranes of crypts in ascending
CC colon (By similarity). {ECO:0000250|UniProtKB:P56404,
CC ECO:0000250|UniProtKB:P56405}.
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).
CC -!- PTM: Sulfenylation at Cys-53(C53-SOH) when hydrogen peroxide flows
CC through the AQP8 channel, making it susceptible to hydrogen sulfide
CC produced by CBS. {ECO:0000250|UniProtKB:O94778}.
CC -!- PTM: Persulfidation at Cys-53 is required to gate AQP8 channel; under
CC stress condition, hydrogen peroxide accumulates in the cell leading to
CC CBS activation that produces hydrogen sulfide inducing persulfidation
CC of oxidized Cys-53 (C53-SOH). {ECO:0000250|UniProtKB:O94778}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P56405}.
CC -!- SIMILARITY: Belongs to the MIP/aquaporin (TC 1.A.8) family.
CC {ECO:0000305}.
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DR EMBL; AY856057; AAW47639.1; -; mRNA.
DR AlphaFoldDB; Q5I4F8; -.
DR SMR; Q5I4F8; -.
DR GlyCosmos; Q5I4F8; 1 site, No reported glycans.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0031526; C:brush border membrane; ISS:UniProtKB.
DR GO; GO:0046691; C:intracellular canaliculus; ISS:UniProtKB.
DR GO; GO:0097708; C:intracellular vesicle; ISS:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0031966; C:mitochondrial membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0030868; C:smooth endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008519; F:ammonium transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015264; F:methylammonium channel activity; ISS:UniProtKB.
DR GO; GO:0015265; F:urea channel activity; ISS:UniProtKB.
DR GO; GO:0015250; F:water channel activity; ISS:UniProtKB.
DR GO; GO:0140157; P:ammonium import across plasma membrane; ISS:UniProtKB.
DR GO; GO:0072488; P:ammonium transmembrane transport; ISS:UniProtKB.
DR GO; GO:0030183; P:B cell differentiation; ISS:UniProtKB.
DR GO; GO:1990748; P:cellular detoxification; ISS:UniProtKB.
DR GO; GO:0080170; P:hydrogen peroxide transmembrane transport; ISS:UniProtKB.
DR GO; GO:0072489; P:methylammonium transmembrane transport; ISS:UniProtKB.
DR GO; GO:0015843; P:methylammonium transport; ISS:UniProtKB.
DR GO; GO:0045540; P:regulation of cholesterol biosynthetic process; ISS:UniProtKB.
DR GO; GO:0035377; P:transepithelial water transport; ISS:UniProtKB.
DR GO; GO:0015840; P:urea transport; ISS:UniProtKB.
DR GO; GO:0006833; P:water transport; ISS:UniProtKB.
DR Gene3D; 1.20.1080.10; Glycerol uptake facilitator protein; 1.
DR InterPro; IPR023271; Aquaporin-like.
DR InterPro; IPR023277; Aquaporin_8.
DR InterPro; IPR034294; Aquaporin_transptr.
DR InterPro; IPR000425; MIP.
DR InterPro; IPR022357; MIP_CS.
DR PANTHER; PTHR45665; AQUAPORIN-8; 1.
DR PANTHER; PTHR45665:SF9; AQUAPORIN-8; 1.
DR Pfam; PF00230; MIP; 1.
DR PRINTS; PR02020; AQUAPORIN8.
DR PRINTS; PR00783; MINTRINSICP.
DR SUPFAM; SSF81338; Aquaporin-like; 1.
DR PROSITE; PS00221; MIP; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Endoplasmic reticulum; Glycoprotein; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; Oxidation; Repeat;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..261
FT /note="Aquaporin-8"
FT /id="PRO_0000257849"
FT TOPO_DOM 1..36
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 37..57
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 58..84
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 85..105
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 106..107
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 108..128
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 129..156
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 157..177
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 178..183
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 184..204
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 205..228
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 229..249
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 250..261
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOTIF 92..94
FT /note="NPA 1"
FT MOTIF 210..212
FT /note="NPA 2"
FT MOD_RES 53
FT /note="Cysteine persulfide"
FT /evidence="ECO:0000250|UniProtKB:O94778"
FT MOD_RES 53
FT /note="Cysteine sulfenic acid (-SOH)"
FT /evidence="ECO:0000250|UniProtKB:O94778"
FT CARBOHYD 139
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 261 AA; 27780 MW; 1F6485E71E14BC6B CRC64;
MSGETPMCSI DLSEVKAKET RMAGRFRVSW YEQYIQPCVV ELLGSALFIF IGCLSVIENS
PDTGLLQPAL AHGLALGLII ATLGNISGGH FNPAVSLAVT VIGGLKTMLL IPYWISQIFG
GLIGAALAKV VSPEERFWNA SGAAFAIVQE QEQVTEALGV EIILTILLVL AVCMGAVNEK
TMGPLAPFSI GFSVIVDILA GGGISGACMN PARAFGPAVV AGYWDFHWIY WLGPLLAGLF
VGLLIRLFIG DEKTRLILKS R
//
