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P55087 (AQP4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Aquaporin-4

Short name=AQP-4
Alternative name(s):
Mercurial-insensitive water channel
Short name=MIWC
WCH4
Gene names
Name:AQP4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length323 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Forms a water-specific channel. Osmoreceptor which regulates body water balance and mediates water flow within the central nervous system.

Subunit structure

Homotetramer. Part of a complex containing MLC1, TRPV4, HEPACAM and ATP1B1. Ref.6 Ref.7

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

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

Domain

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

Post-translational modification

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.

Sequence similarities

Belongs to the MIP/aquaporin (TC 1.A.8) family. [View classification]

Sequence caution

The sequence AAC50284.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAC52112.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processTransport
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
   DomainRepeat
Transmembrane
Transmembrane helix
   PTMGlycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcarbon dioxide transport

Inferred from electronic annotation. Source: Ensembl

cellular response to estradiol stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to interferon-gamma

Inferred from direct assay PubMed 17645239. Source: UniProtKB

excretion

Traceable author statement PubMed 7528931. Source: ProtInc

female pregnancy

Inferred from electronic annotation. Source: Ensembl

hyperosmotic salinity response

Inferred from electronic annotation. Source: Ensembl

multicellular organismal water homeostasis

Inferred from expression pattern PubMed 16814974PubMed 17645239. Source: UniProtKB

nervous system development

Traceable author statement PubMed 7528931. Source: ProtInc

protein homooligomerization

Inferred from electronic annotation. Source: Ensembl

renal water absorption

Inferred from electronic annotation. Source: Ensembl

response to glucocorticoid

Inferred from electronic annotation. Source: Ensembl

response to radiation

Inferred from electronic annotation. Source: Ensembl

sensory perception of sound

Inferred from electronic annotation. Source: Ensembl

transmembrane transport

Traceable author statement. Source: Reactome

transport

Traceable author statement Ref.1. Source: ProtInc

water transport

Traceable author statement. Source: Reactome

   Cellular_componentT-tubule

Inferred from electronic annotation. Source: Ensembl

basolateral plasma membrane

Inferred from electronic annotation. Source: Ensembl

cell-cell junction

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay PubMed 18392839. Source: UniProtKB

external side of plasma membrane

Inferred from direct assay PubMed 17645239. Source: UniProtKB

integral component of plasma membrane

Traceable author statement PubMed 7528931. Source: ProtInc

plasma membrane

Inferred from direct assay PubMed 16814974. Source: UniProtKB

protein complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionporin activity

Inferred from electronic annotation. Source: Ensembl

water channel activity

Inferred from experiment. Source: Reactome

water transmembrane transporter activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 2 (identifier: P55087-1)

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.
Isoform 1 (identifier: P55087-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 323323Aquaporin-4
PRO_0000063948

Regions

Topological domain1 – 3636Cytoplasmic Potential
Transmembrane37 – 5721Helical; Potential
Topological domain58 – 647Extracellular Potential
Transmembrane65 – 8521Helical; Potential
Topological domain86 – 11530Cytoplasmic Potential
Transmembrane116 – 13621Helical; Potential
Topological domain137 – 15519Extracellular Potential
Transmembrane156 – 17621Helical; Potential
Topological domain177 – 1848Cytoplasmic Potential
Transmembrane185 – 20521Helical; Potential
Topological domain206 – 23126Extracellular Potential
Transmembrane232 – 25221Helical; Potential
Topological domain253 – 32371Cytoplasmic Potential
Motif97 – 993NPA 1
Motif213 – 2153NPA 2

Amino acid modifications

Modified residue1111Phosphoserine; by PKG By similarity
Modified residue1801Phosphoserine; by PKC By similarity
Modified residue2851Phosphoserine By similarity
Modified residue3211Phosphoserine By similarity
Glycosylation1531N-linked (GlcNAc...) Potential
Glycosylation2061N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 2222Missing in isoform 1.
VSP_003232

Experimental info

Sequence conflict2461G → A in AAC52112. Ref.1
Sequence conflict287 – 2882VE → AK in AAC52112. Ref.1
Sequence conflict2961P → L in AAC52112. Ref.1

Secondary structure

....................... 323
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 2 [UniParc].

Last modified November 1, 1997. Version 2.
Checksum: 1A1600CF0DC11052

FASTA32334,830
        10         20         30         40         50         60 
MSDRPTARRW GKCGPLCTRE NIMVAFKGVW TQAFWKAVTA EFLAMLIFVL LSLGSTINWG 

        70         80         90        100        110        120 
GTEKPLPVDM VLISLCFGLS IATMVQCFGH ISGGHINPAV TVAMVCTRKI SIAKSVFYIA 

       130        140        150        160        170        180 
AQCLGAIIGA GILYLVTPPS VVGGLGVTMV HGNLTAGHGL LVELIITFQL VFTIFASCDS 

       190        200        210        220        230        240 
KRTDVTGSIA LAIGFSVAIG HLFAINYTGA SMNPARSFGP AVIMGNWENH WIYWVGPIIG 

       250        260        270        280        290        300 
AVLAGGLYEY VFCPDVEFKR RFKEAFSKAA QQTKGSYMEV EDNRSQVETD DLILKPGVVH 

       310        320 
VIDVDRGEEK KGKDQSGEVL SSV 

« Hide

Isoform 1 [UniParc].

Checksum: C91C3D006C1B75A0
Show »

FASTA30132,300

References

« Hide 'large scale' references
[1]"cDNA cloning, gene organization, and chromosomal localization of a human mercurial insensitive water channel. Evidence for distinct transcriptional units."
Yang B., Ma T., Verkman A.S.
J. Biol. Chem. 270:22907-22913(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal brain.
[2]"A water channel closely related to rat brain aquaporin 4 is expressed in acid- and pepsinogen-secretory cells of human stomach."
Misaka T., Abe K., Iwabuchi K., Kusakabe Y., Ichinose M., Miki K., Emori Y., Arai S.
FEBS Lett. 381:208-212(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"The human AQP4 gene: definition of the locus encoding two water channel polypeptides in brain."
Lu M., Lee M.D., Smith B.L., Jung J.S., Agre P., Verdijk M.A.J., Merkx G., Rijss J.P.L., Deen P.M.T.
Proc. Natl. Acad. Sci. U.S.A. 93:10908-10912(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"DNA sequence and analysis of human chromosome 18."
Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J. expand/collapse author list , Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.
Nature 437:551-555(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung.
[6]"Megalencephalic leukoencephalopathy with subcortical cysts protein 1 functionally cooperates with the TRPV4 cation channel to activate the response of astrocytes to osmotic stress: dysregulation by pathological mutations."
Lanciotti A., Brignone M.S., Molinari P., Visentin S., De Nuccio C., Macchia G., Aiello C., Bertini E., Aloisi F., Petrucci T.C., Ambrosini E.
Hum. Mol. Genet. 21:2166-2180(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[7]"Crystal structure of human aquaporin 4 at 1.8 A and its mechanism of conductance."
Ho J.D., Yeh R., Sandstrom A., Chorny I., Harries W.E., Robbins R.A., Miercke L.J., Stroud R.M.
Proc. Natl. Acad. Sci. U.S.A. 106:7437-7442(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 32-254, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRI39178.
RefSeqNP_001641.1. NM_001650.4.
NP_004019.1. NM_004028.3.
UniGeneHs.315369.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3GD8X-ray1.80A32-254[»]
ProteinModelPortalP55087.
SMRP55087. Positions 32-254.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106857. 2 interactions.
DIPDIP-48842N.
STRING9606.ENSP00000372654.

Chemistry

ChEMBLCHEMBL5964.

Protein family/group databases

TCDB1.A.8.8.5. the major intrinsic protein (mip) family.

PTM databases

PhosphoSiteP55087.

Polymorphism databases

DMDM2506859.

Proteomic databases

PaxDbP55087.
PRIDEP55087.

Protocols and materials databases

DNASU361.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000383168; ENSP00000372654; ENSG00000171885. [P55087-1]
ENST00000440832; ENSP00000393121; ENSG00000171885. [P55087-2]
ENST00000581374; ENSP00000462597; ENSG00000171885. [P55087-2]
GeneID361.
KEGGhsa:361.
UCSCuc002kvz.3. human. [P55087-1]

Organism-specific databases

CTD361.
GeneCardsGC18M024432.
HGNCHGNC:637. AQP4.
HPACAB005079.
CAB058689.
HPA014784.
MIM600308. gene.
neXtProtNX_P55087.
PharmGKBPA24922.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0580.
HOGENOMHOG000288286.
HOVERGENHBG000312.
InParanoidP55087.
KOK09866.
OMACRRENIM.
OrthoDBEOG7N8ZWD.
PhylomeDBP55087.
TreeFamTF312940.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressP55087.
BgeeP55087.
CleanExHS_AQP4.
GenevestigatorP55087.

Family and domain databases

Gene3D1.20.1080.10. 1 hit.
InterProIPR023271. Aquaporin-like.
IPR000425. MIP.
IPR022357. MIP_CS.
[Graphical view]
PANTHERPTHR19139. PTHR19139. 1 hit.
PfamPF00230. MIP. 1 hit.
[Graphical view]
PRINTSPR00783. MINTRINSICP.
SUPFAMSSF81338. SSF81338. 1 hit.
TIGRFAMsTIGR00861. MIP. 1 hit.
PROSITEPS00221. MIP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP55087.
GeneWikiAquaporin_4.
GenomeRNAi361.
NextBio1509.
PROP55087.
SOURCESearch...

Entry information

Entry nameAQP4_HUMAN
AccessionPrimary (citable) accession number: P55087
Secondary accession number(s): P78564
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: November 1, 1997
Last modified: April 16, 2014
This is version 130 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM