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Protein

Aquaporin-4

Gene

Aqp4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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.

Caution

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

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
  • 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

Keywordsi

Biological processTransport

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 18

Organism-specific databases

RGDi2143 Aqp4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

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...) asparagineSequence 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

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi247332, 2 interactors
CORUMiP47863
DIPiDIP-59601N
IntActiP47863, 2 interactors
STRINGi10116.ENSRNOP00000063720

Structurei

Secondary structure

1323
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi32 – 53Combined sources22
Beta strandi60 – 63Combined sources4
Helixi70 – 88Combined sources19
Helixi89 – 91Combined sources3
Helixi98 – 106Combined sources9
Beta strandi108 – 110Combined sources3
Turni112 – 115Combined sources4
Helixi116 – 134Combined sources19
Turni138 – 140Combined sources3
Helixi141 – 143Combined sources3
Helixi156 – 177Combined sources22
Beta strandi180 – 183Combined sources4
Helixi189 – 208Combined sources20
Helixi214 – 224Combined sources11
Turni228 – 231Combined sources4
Helixi232 – 249Combined sources18
Turni250 – 252Combined sources3

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
InterProiView protein in InterPro
IPR023271 Aquaporin-like
IPR034294 Aquaporin_transptr
IPR000425 MIP
IPR022357 MIP_CS
PANTHERiPTHR19139 PTHR19139, 1 hit
PfamiView protein in Pfam
PF00230 MIP, 1 hit
PRINTSiPR00783 MINTRINSICP
SUPFAMiSSF81338 SSF81338, 1 hit
TIGRFAMsiTIGR00861 MIP, 1 hit
PROSITEiView protein in PROSITE
PS00221 MIP, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiAQP4_RAT
AccessioniPrimary (citable) accession number: P47863
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: May 23, 2018
This is version 145 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health