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Protein

Aquaporin-4

Gene

AQP4

Organism
Homo sapiens (Human)
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.

GO - Molecular functioni

GO - Biological processi

  • cellular response to interferon-gamma Source: UniProtKB
  • cellular water homeostasis Source: GO_Central
  • ion transmembrane transport Source: GO_Central
  • multicellular organismal water homeostasis Source: UniProtKB
  • renal water homeostasis Source: Reactome
  • transport Source: ProtInc
  • water transport Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Transport

Enzyme and pathway databases

BioCyciZFISH:ENSG00000171885-MONOMER.
ReactomeiR-HSA-432040. Vasopressin regulates renal water homeostasis via Aquaporins.
R-HSA-432047. Passive transport by Aquaporins.
SIGNORiP55087.

Protein family/group databases

TCDBi1.A.8.8.5. the major intrinsic protein (mip) family.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

HGNCiHGNC:637. 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

  • basolateral plasma membrane Source: GO_Central
  • cytoplasm Source: UniProtKB
  • external side of plasma membrane Source: UniProtKB
  • integral component of plasma membrane Source: GO_Central
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi361.
OpenTargetsiENSG00000171885.
PharmGKBiPA24922.

Chemistry databases

ChEMBLiCHEMBL5964.

Polymorphism and mutation databases

BioMutaiAQP4.
DMDMi2506859.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000639481 – 323Aquaporin-4Add BLAST323

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei111Phosphoserine; by PKGBy similarity1
Glycosylationi153N-linked (GlcNAc...)Sequence analysis1
Modified residuei180Phosphoserine; by PKCBy similarity1
Glycosylationi206N-linked (GlcNAc...)Sequence analysis1
Modified residuei276PhosphoserineBy similarity1
Modified residuei285PhosphoserineBy similarity1
Modified residuei289PhosphothreonineBy similarity1
Modified residuei321PhosphoserineBy similarity1

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% (By similarity).By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP55087.
PeptideAtlasiP55087.
PRIDEiP55087.

PTM databases

iPTMnetiP55087.
PhosphoSitePlusiP55087.
SwissPalmiP55087.

Expressioni

Tissue specificityi

Brain - muscle >> heart, kidney, lung, and trachea.

Gene expression databases

BgeeiENSG00000171885.
CleanExiHS_AQP4.
ExpressionAtlasiP55087. baseline and differential.
GenevisibleiP55087. HS.

Organism-specific databases

HPAiCAB005079.
CAB058689.
HPA014784.

Interactioni

Subunit structurei

Homotetramer. Part of a complex containing MLC1, TRPV4, HEPACAM and ATP1B1.2 Publications

Protein-protein interaction databases

BioGridi106857. 2 interactors.
DIPiDIP-48842N.
STRINGi9606.ENSP00000372654.

Structurei

Secondary structure

1323
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi33 – 55Combined sources23
Turni59 – 63Combined sources5
Helixi70 – 92Combined sources23
Helixi98 – 106Combined sources9
Helixi112 – 136Combined sources25
Helixi139 – 142Combined sources4
Turni143 – 146Combined sources4
Helixi156 – 177Combined sources22
Helixi189 – 208Combined sources20
Helixi214 – 224Combined sources11
Turni228 – 231Combined sources4
Helixi232 – 250Combined sources19

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3GD8X-ray1.80A32-254[»]
ProteinModelPortaliP55087.
SMRiP55087.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP55087.

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.
InParanoidiP55087.
KOiK09866.
OMAiCRRESIM.
OrthoDBiEOG091G166T.
PhylomeDBiP55087.
TreeFamiTF312940.

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 2 (identifier: P55087-1) [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
MSDRPTARRW GKCGPLCTRE NIMVAFKGVW TQAFWKAVTA EFLAMLIFVL
60 70 80 90 100
LSLGSTINWG GTEKPLPVDM VLISLCFGLS IATMVQCFGH ISGGHINPAV
110 120 130 140 150
TVAMVCTRKI SIAKSVFYIA AQCLGAIIGA GILYLVTPPS VVGGLGVTMV
160 170 180 190 200
HGNLTAGHGL LVELIITFQL VFTIFASCDS KRTDVTGSIA LAIGFSVAIG
210 220 230 240 250
HLFAINYTGA SMNPARSFGP AVIMGNWENH WIYWVGPIIG AVLAGGLYEY
260 270 280 290 300
VFCPDVEFKR RFKEAFSKAA QQTKGSYMEV EDNRSQVETD DLILKPGVVH
310 320
VIDVDRGEEK KGKDQSGEVL SSV
Length:323
Mass (Da):34,830
Last modified:November 1, 1997 - v2
Checksum:i1A1600CF0DC11052
GO
Isoform 1 (identifier: P55087-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-22: Missing.

Show »
Length:301
Mass (Da):32,300
Checksum:iC91C3D006C1B75A0
GO

Sequence cautioni

The sequence AAC50284 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAC52112 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti246G → A in AAC52112 (PubMed:7559426).Curated1
Sequence conflicti287 – 288VE → AK in AAC52112 (PubMed:7559426).Curated2
Sequence conflicti296P → L in AAC52112 (PubMed:7559426).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0032321 – 22Missing in isoform 1. CuratedAdd BLAST22

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U34846 mRNA. Translation: AAC52112.1. Different initiation.
U34845 mRNA. Translation: AAC50284.1. Different initiation.
D63412 mRNA. Translation: BAA09715.1.
U63622 mRNA. Translation: AAB26957.1.
U63623 mRNA. Translation: AAB26958.1.
AC018371 Genomic DNA. No translation available.
BC022286 mRNA. Translation: AAH22286.1.
CCDSiCCDS11889.1. [P55087-1]
CCDS58617.1. [P55087-2]
PIRiI39178.
RefSeqiNP_001641.1. NM_001650.5. [P55087-1]
NP_004019.1. NM_004028.4. [P55087-2]
UniGeneiHs.315369.

Genome annotation databases

EnsembliENST00000383168; ENSP00000372654; ENSG00000171885. [P55087-1]
ENST00000440832; ENSP00000393121; ENSG00000171885. [P55087-2]
ENST00000581374; ENSP00000462597; ENSG00000171885. [P55087-2]
GeneIDi361.
KEGGihsa:361.
UCSCiuc002kvz.4. human. [P55087-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U34846 mRNA. Translation: AAC52112.1. Different initiation.
U34845 mRNA. Translation: AAC50284.1. Different initiation.
D63412 mRNA. Translation: BAA09715.1.
U63622 mRNA. Translation: AAB26957.1.
U63623 mRNA. Translation: AAB26958.1.
AC018371 Genomic DNA. No translation available.
BC022286 mRNA. Translation: AAH22286.1.
CCDSiCCDS11889.1. [P55087-1]
CCDS58617.1. [P55087-2]
PIRiI39178.
RefSeqiNP_001641.1. NM_001650.5. [P55087-1]
NP_004019.1. NM_004028.4. [P55087-2]
UniGeneiHs.315369.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3GD8X-ray1.80A32-254[»]
ProteinModelPortaliP55087.
SMRiP55087.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106857. 2 interactors.
DIPiDIP-48842N.
STRINGi9606.ENSP00000372654.

Chemistry databases

ChEMBLiCHEMBL5964.

Protein family/group databases

TCDBi1.A.8.8.5. the major intrinsic protein (mip) family.

PTM databases

iPTMnetiP55087.
PhosphoSitePlusiP55087.
SwissPalmiP55087.

Polymorphism and mutation databases

BioMutaiAQP4.
DMDMi2506859.

Proteomic databases

PaxDbiP55087.
PeptideAtlasiP55087.
PRIDEiP55087.

Protocols and materials databases

DNASUi361.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000383168; ENSP00000372654; ENSG00000171885. [P55087-1]
ENST00000440832; ENSP00000393121; ENSG00000171885. [P55087-2]
ENST00000581374; ENSP00000462597; ENSG00000171885. [P55087-2]
GeneIDi361.
KEGGihsa:361.
UCSCiuc002kvz.4. human. [P55087-1]

Organism-specific databases

CTDi361.
DisGeNETi361.
GeneCardsiAQP4.
HGNCiHGNC:637. AQP4.
HPAiCAB005079.
CAB058689.
HPA014784.
MIMi600308. gene.
neXtProtiNX_P55087.
OpenTargetsiENSG00000171885.
PharmGKBiPA24922.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0223. Eukaryota.
COG0580. LUCA.
GeneTreeiENSGT00760000119223.
HOGENOMiHOG000288286.
HOVERGENiHBG000312.
InParanoidiP55087.
KOiK09866.
OMAiCRRESIM.
OrthoDBiEOG091G166T.
PhylomeDBiP55087.
TreeFamiTF312940.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000171885-MONOMER.
ReactomeiR-HSA-432040. Vasopressin regulates renal water homeostasis via Aquaporins.
R-HSA-432047. Passive transport by Aquaporins.
SIGNORiP55087.

Miscellaneous databases

ChiTaRSiAQP4. human.
EvolutionaryTraceiP55087.
GeneWikiiAquaporin_4.
GenomeRNAii361.
PROiP55087.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000171885.
CleanExiHS_AQP4.
ExpressionAtlasiP55087. baseline and differential.
GenevisibleiP55087. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: P55087
Secondary accession number(s): P78564
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: November 1, 1997
Last modified: November 2, 2016
This is version 152 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.