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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

  • glycerol channel activity Source: GO_Central
  • 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
  • cellular water homeostasis Source: GO_Central
  • female pregnancy Source: RGD
  • hyperosmotic salinity response Source: RGD
  • ion transmembrane transport Source: GO_Central
  • 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
  • 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)DescriptionActionsGraphical viewLength
Topological domaini1 – 36CytoplasmicSequence analysisAdd BLAST36
Transmembranei37 – 57HelicalSequence analysisAdd BLAST21
Topological domaini58 – 64ExtracellularSequence analysis7
Transmembranei65 – 85HelicalSequence analysisAdd BLAST21
Topological domaini86 – 115CytoplasmicSequence analysisAdd BLAST30
Transmembranei116 – 136HelicalSequence analysisAdd BLAST21
Topological domaini137 – 155ExtracellularSequence analysisAdd BLAST19
Transmembranei156 – 176HelicalSequence analysisAdd BLAST21
Topological domaini177 – 184CytoplasmicSequence analysis8
Transmembranei185 – 205HelicalSequence analysisAdd BLAST21
Topological domaini206 – 231ExtracellularSequence analysisAdd BLAST26
Transmembranei232 – 252HelicalSequence analysisAdd BLAST21
Topological domaini253 – 323CytoplasmicSequence analysisAdd BLAST71

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)DescriptionActionsGraphical viewLength
Mutagenesisi201H → P: Partial loss of transport activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000639501 – 323Aquaporin-4Add BLAST323

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei111Phosphoserine; by PKG1 Publication1
Glycosylationi153N-linked (GlcNAc...)Sequence analysis1
Modified residuei180Phosphoserine; by PKC1 Publication1
Modified residuei276PhosphoserineCombined sources1
Modified residuei285PhosphoserineCombined sources1 Publication1
Modified residuei289PhosphothreonineBy similarity1
Modified residuei321PhosphoserineCombined sources1

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.
PhosphoSitePlusiP47863.
SwissPalmiP47863.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSRNOG00000016043.
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 interactor.
DIPiDIP-59601N.
STRINGi10116.ENSRNOP00000063720.

Structurei

Secondary structure

1323
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2D57X-ray3.20A23-323[»]
2ZZ9X-ray2.80A23-323[»]
3IYZelectron microscopy10.00A23-323[»]
ProteinModelPortaliP47863.
SMRiP47863.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP47863.

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi97 – 99NPA 13
Motifi213 – 215NPA 23

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.
PhylomeDBiP47863.

Family and domain databases

CDDicd00333. MIP. 1 hit.
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)DescriptionActionsGraphical viewLength
Sequence conflicti201H → P in AAA17730 (PubMed:7509789).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_003235150 – 204Missing in isoform Short. CuratedAdd BLAST55

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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2D57X-ray3.20A23-323[»]
2ZZ9X-ray2.80A23-323[»]
3IYZelectron microscopy10.00A23-323[»]
ProteinModelPortaliP47863.
SMRiP47863.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

PTM databases

iPTMnetiP47863.
PhosphoSitePlusiP47863.
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.
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

BgeeiENSRNOG00000016043.
ExpressionAtlasiP47863. baseline and differential.
GenevisibleiP47863. RN.

Family and domain databases

CDDicd00333. MIP. 1 hit.
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...

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: November 2, 2016
This is version 133 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.