Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Aquaporin-4

Gene

Aqp4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Forms a water-specific channel. Osmoreceptor which regulates body water balance and mediates water flow within the central nervous system. It is expressed predominantly in the ependymal cell lining the aqueductal system and over the space of the brain in contact with the subarachnoid space, as cerebrospinal fluid fills these structures it may facilitate water balance between brain parenchyma and the fluid compartment. In the plasma membranes of the neurons of the paraventricular and supraoptic nuclei, it may mediate rapid changes in cell volume in response to local shifts in extracellular osmolarity.

GO - Molecular functioni

  • porin activity Source: RGD
  • water channel activity Source: RGD

GO - Biological processi

  • carbon dioxide transport Source: UniProtKB
  • cellular response to estradiol stimulus Source: RGD
  • cellular response to glucose stimulus Source: RGD
  • cellular response to interleukin-1 Source: RGD
  • cellular response to interleukin-6 Source: RGD
  • female pregnancy Source: RGD
  • hyperosmotic salinity response Source: RGD
  • negative regulation of cell adhesion molecule production Source: RGD
  • negative regulation of interleukin-1 beta production Source: RGD
  • negative regulation of interleukin-6 production Source: RGD
  • protein homooligomerization Source: RGD
  • regulation of vascular endothelial growth factor production Source: RGD
  • response to glucocorticoid Source: RGD
  • response to radiation Source: RGD
  • transmembrane transport Source: GOC
  • water transport Source: RGD
Complete GO annotation...

Keywords - Biological processi

Transport

Enzyme and pathway databases

ReactomeiR-RNO-432040. Vasopressin regulates renal water homeostasis via Aquaporins.
R-RNO-432047. Passive transport by Aquaporins.

Names & Taxonomyi

Protein namesi
Recommended name:
Aquaporin-4
Short name:
AQP-4
Alternative name(s):
Mercurial-insensitive water channel
Short name:
MIWC
WCH4
Gene namesi
Name:Aqp4
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 18

Organism-specific databases

RGDi2143. Aqp4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3636CytoplasmicSequence analysisAdd
BLAST
Transmembranei37 – 5721HelicalSequence analysisAdd
BLAST
Topological domaini58 – 647ExtracellularSequence analysis
Transmembranei65 – 8521HelicalSequence analysisAdd
BLAST
Topological domaini86 – 11530CytoplasmicSequence analysisAdd
BLAST
Transmembranei116 – 13621HelicalSequence analysisAdd
BLAST
Topological domaini137 – 15519ExtracellularSequence analysisAdd
BLAST
Transmembranei156 – 17621HelicalSequence analysisAdd
BLAST
Topological domaini177 – 1848CytoplasmicSequence analysis
Transmembranei185 – 20521HelicalSequence analysisAdd
BLAST
Topological domaini206 – 23126ExtracellularSequence analysisAdd
BLAST
Transmembranei232 – 25221HelicalSequence analysisAdd
BLAST
Topological domaini253 – 32371CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • basal plasma membrane Source: RGD
  • basolateral plasma membrane Source: RGD
  • cell projection membrane Source: RGD
  • integral component of plasma membrane Source: RGD
  • membrane Source: RGD
  • protein complex Source: RGD
  • sarcolemma Source: RGD
  • T-tubule Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi201 – 2011H → P: Partial loss of transport activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 323323Aquaporin-4PRO_0000063950Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei111 – 1111Phosphoserine; by PKG1 Publication
Glycosylationi153 – 1531N-linked (GlcNAc...)Sequence analysis
Modified residuei180 – 1801Phosphoserine; by PKC1 Publication
Modified residuei276 – 2761PhosphoserineCombined sources
Modified residuei285 – 2851PhosphoserineCombined sources1 Publication
Modified residuei289 – 2891PhosphothreonineBy similarity
Modified residuei321 – 3211PhosphoserineCombined sources

Post-translational modificationi

Phosphorylation by PKC at Ser-180 reduces conductance by 50%. Phosphorylation by PKG at Ser-111 in response to glutamats increases conductance by 40%.3 Publications

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP47863.
PRIDEiP47863.

PTM databases

iPTMnetiP47863.
PhosphoSiteiP47863.
SwissPalmiP47863.

Expressioni

Tissue specificityi

Abundant in mature brain but only weakly detectable in eye, kidney, intestine, and lung.

Gene expression databases

ExpressionAtlasiP47863. baseline and differential.
GenevisibleiP47863. RN.

Interactioni

Subunit structurei

Homotetramer. Part of a complex containing MLC1, TRPV4, HEPACAM and ATP1B1 (By similarity).By similarity

Protein-protein interaction databases

BioGridi247332. 1 interaction.
DIPiDIP-59601N.
STRINGi10116.ENSRNOP00000063720.

Structurei

Secondary structure

1
323
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi33 – 5927
Beta strandi60 – 634
Helixi68 – 9225
Helixi98 – 10710
Helixi112 – 13625
Turni138 – 1403
Helixi141 – 1433
Helixi156 – 17823
Beta strandi179 – 1813
Helixi189 – 20820
Helixi214 – 22411
Turni228 – 2303
Helixi231 – 24919
Turni250 – 2523

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2D57X-ray3.20A23-323[»]
2ZZ9X-ray2.80A23-323[»]
3IYZelectron microscopy10.00A23-323[»]
ProteinModelPortaliP47863.
SMRiP47863. Positions 31-254.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP47863.

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi97 – 993NPA 1
Motifi213 – 2153NPA 2

Domaini

Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA).

Sequence similaritiesi

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0223. Eukaryota.
COG0580. LUCA.
GeneTreeiENSGT00760000119223.
HOGENOMiHOG000288286.
HOVERGENiHBG000312.
InParanoidiP47863.
KOiK09866.
OMAiCRRESIM.
OrthoDBiEOG7N8ZWD.
PhylomeDBiP47863.

Family and domain databases

Gene3Di1.20.1080.10. 1 hit.
InterProiIPR023271. Aquaporin-like.
IPR000425. MIP.
IPR022357. MIP_CS.
[Graphical view]
PANTHERiPTHR19139. PTHR19139. 1 hit.
PfamiPF00230. MIP. 1 hit.
[Graphical view]
PRINTSiPR00783. MINTRINSICP.
SUPFAMiSSF81338. SSF81338. 1 hit.
TIGRFAMsiTIGR00861. MIP. 1 hit.
PROSITEiPS00221. MIP. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Long (identifier: P47863-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSDGAAARRW GKCGPPCSRE SIMVAFKGVW TQAFWKAVTA EFLAMLIFVL
60 70 80 90 100
LSVGSTINWG GSENPLPVDM VLISLCFGLS IATMVQCFGH ISGGHINPAV
110 120 130 140 150
TVAMVCTRKI SIAKSVFYIT AQCLGAIIGA GILYLVTPPS VVGGLGVTTV
160 170 180 190 200
HGNLTAGHGL LVELIITFQL VFTIFASCDS KRTDVTGSVA LAIGFSVAIG
210 220 230 240 250
HLFAINYTGA SMNPARSFGP AVIMGNWENH WIYWVGPIIG AVLAGALYEY
260 270 280 290 300
VFCPDVELKR RLKEAFSKAA QQTKGSYMEV EDNRSQVETE DLILKPGVVH
310 320
VIDIDRGDEK KGKDSSGEVL SSV
Length:323
Mass (Da):34,480
Last modified:February 1, 1996 - v1
Checksum:i6ADD24647713609D
GO
Isoform Short (identifier: P47863-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     150-204: Missing.

Show »
Length:268
Mass (Da):28,768
Checksum:i6ADB26219C2BFE47
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti201 – 2011H → P in AAA17730 (PubMed:7509789).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei150 – 20455Missing in isoform Short. CuratedVSP_003235Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U14007 mRNA. Translation: AAC52152.1.
AF144082 mRNA. Translation: AAD37965.1.
L27588 mRNA. Translation: AAA17730.1.
PIRiI59283.
RefSeqiNP_001257487.1. NM_001270558.2. [P47863-2]
NP_036957.1. NM_012825.4. [P47863-1]
UniGeneiRn.90091.

Genome annotation databases

EnsembliENSRNOT00000068150; ENSRNOP00000063720; ENSRNOG00000016043. [P47863-1]
GeneIDi25293.
KEGGirno:25293.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U14007 mRNA. Translation: AAC52152.1.
AF144082 mRNA. Translation: AAD37965.1.
L27588 mRNA. Translation: AAA17730.1.
PIRiI59283.
RefSeqiNP_001257487.1. NM_001270558.2. [P47863-2]
NP_036957.1. NM_012825.4. [P47863-1]
UniGeneiRn.90091.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2D57X-ray3.20A23-323[»]
2ZZ9X-ray2.80A23-323[»]
3IYZelectron microscopy10.00A23-323[»]
ProteinModelPortaliP47863.
SMRiP47863. Positions 31-254.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247332. 1 interaction.
DIPiDIP-59601N.
STRINGi10116.ENSRNOP00000063720.

PTM databases

iPTMnetiP47863.
PhosphoSiteiP47863.
SwissPalmiP47863.

Proteomic databases

PaxDbiP47863.
PRIDEiP47863.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000068150; ENSRNOP00000063720; ENSRNOG00000016043. [P47863-1]
GeneIDi25293.
KEGGirno:25293.

Organism-specific databases

CTDi361.
RGDi2143. Aqp4.

Phylogenomic databases

eggNOGiKOG0223. Eukaryota.
COG0580. LUCA.
GeneTreeiENSGT00760000119223.
HOGENOMiHOG000288286.
HOVERGENiHBG000312.
InParanoidiP47863.
KOiK09866.
OMAiCRRESIM.
OrthoDBiEOG7N8ZWD.
PhylomeDBiP47863.

Enzyme and pathway databases

ReactomeiR-RNO-432040. Vasopressin regulates renal water homeostasis via Aquaporins.
R-RNO-432047. Passive transport by Aquaporins.

Miscellaneous databases

EvolutionaryTraceiP47863.
PROiP47863.

Gene expression databases

ExpressionAtlasiP47863. baseline and differential.
GenevisibleiP47863. RN.

Family and domain databases

Gene3Di1.20.1080.10. 1 hit.
InterProiIPR023271. Aquaporin-like.
IPR000425. MIP.
IPR022357. MIP_CS.
[Graphical view]
PANTHERiPTHR19139. PTHR19139. 1 hit.
PfamiPF00230. MIP. 1 hit.
[Graphical view]
PRINTSiPR00783. MINTRINSICP.
SUPFAMiSSF81338. SSF81338. 1 hit.
TIGRFAMsiTIGR00861. MIP. 1 hit.
PROSITEiPS00221. MIP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular characterization of an aquaporin cDNA from brain: candidate osmoreceptor and regulator of water balance."
    Jung J.S., Bhat R.V., Preston G.M., Guggino W.B., Baraban J.M., Agre P.
    Proc. Natl. Acad. Sci. U.S.A. 91:13052-13056(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF HIS-201.
    Tissue: Brain.
  2. "Isolation of an aquaporin-4 water channel (AQP4) gene induced following cerebral ischemia from the rat brain using modified subtractive hybridization and differential screening."
    Chen D., Chen J., Jing K., Simon R.P., Graham S.H.
    Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Brain.
  3. "Molecular cloning of a mercurial-insensitive water channel expressed in selected water-transporting tissues."
    Hasegawa H., Ma T., Skach W., Matthay M.A., Verkman A.S.
    J. Biol. Chem. 269:5497-5500(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 23-323.
    Tissue: Lung.
  4. "A method for the comprehensive proteomic analysis of membrane proteins."
    Wu C.C., MacCoss M.J., Howell K.E., Yates J.R. III
    Nat. Biotechnol. 21:532-538(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-285.
  5. "Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites."
    Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.
    Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-321, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  6. "Identification of a molecular target for glutamate regulation of astrocyte water permeability."
    Gunnarson E., Zelenina M., Axehult G., Song Y., Bondar A., Krieger P., Brismar H., Zelenin S., Aperia A.
    Glia 56:587-596(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-111.
  7. "Vasopressin-dependent short-term regulation of aquaporin 4 expressed in Xenopus oocytes."
    Moeller H.B., Fenton R.A., Zeuthen T., Macaulay N.
    Neuroscience 164:1674-1684(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-180.
  8. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-276 AND SER-285, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  9. Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 23-323, SUBUNIT.
  10. "Mechanism of aquaporin-4's fast and highly selective water conduction and proton exclusion."
    Tani K., Mitsuma T., Hiroaki Y., Kamegawa A., Nishikawa K., Tanimura Y., Fujiyoshi Y.
    J. Mol. Biol. 389:694-706(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 23-323, SUBUNIT.

Entry informationi

Entry nameiAQP4_RAT
AccessioniPrimary (citable) accession number: P47863
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: June 8, 2016
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

It is uncertain whether Met-1 or Met-23 is the initiator.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.