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P55087

- AQP4_HUMAN

UniProt

P55087 - AQP4_HUMAN

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Protein
Aquaporin-4
Gene
AQP4
Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. porin activity Source: Ensembl
  2. water channel activity Source: Reactome
  3. water transmembrane transporter activity Source: ProtInc
Complete GO annotation...

GO - Biological processi

  1. carbon dioxide transport Source: Ensembl
  2. cellular response to estradiol stimulus Source: Ensembl
  3. cellular response to interferon-gamma Source: UniProtKB
  4. excretion Source: ProtInc
  5. female pregnancy Source: Ensembl
  6. hyperosmotic salinity response Source: Ensembl
  7. multicellular organismal water homeostasis Source: UniProtKB
  8. nervous system development Source: ProtInc
  9. protein homooligomerization Source: Ensembl
  10. renal water absorption Source: Ensembl
  11. response to glucocorticoid Source: Ensembl
  12. response to radiation Source: Ensembl
  13. sensory perception of sound Source: Ensembl
  14. transmembrane transport Source: Reactome
  15. transport Source: ProtInc
  16. water transport Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Transport

Enzyme and pathway databases

ReactomeiREACT_23826. Passive transport by Aquaporins.
REACT_24023. Regulation of water balance by renal Aquaporins.

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
ProteomesiUP000005640: Chromosome 18

Organism-specific databases

HGNCiHGNC:637. AQP4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3636Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei37 – 5721Helical; Reviewed prediction
Add
BLAST
Topological domaini58 – 647Extracellular Reviewed prediction
Transmembranei65 – 8521Helical; Reviewed prediction
Add
BLAST
Topological domaini86 – 11530Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei116 – 13621Helical; Reviewed prediction
Add
BLAST
Topological domaini137 – 15519Extracellular Reviewed prediction
Add
BLAST
Transmembranei156 – 17621Helical; Reviewed prediction
Add
BLAST
Topological domaini177 – 1848Cytoplasmic Reviewed prediction
Transmembranei185 – 20521Helical; Reviewed prediction
Add
BLAST
Topological domaini206 – 23126Extracellular Reviewed prediction
Add
BLAST
Transmembranei232 – 25221Helical; Reviewed prediction
Add
BLAST
Topological domaini253 – 32371Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. T-tubule Source: Ensembl
  2. basolateral plasma membrane Source: Ensembl
  3. cell-cell junction Source: Ensembl
  4. cytoplasm Source: UniProtKB
  5. external side of plasma membrane Source: UniProtKB
  6. integral component of plasma membrane Source: ProtInc
  7. plasma membrane Source: UniProtKB
  8. protein complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA24922.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 323323Aquaporin-4
PRO_0000063948Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei111 – 1111Phosphoserine; by PKG By similarity
Glycosylationi153 – 1531N-linked (GlcNAc...) Reviewed prediction
Modified residuei180 – 1801Phosphoserine; by PKC By similarity
Glycosylationi206 – 2061N-linked (GlcNAc...) Reviewed prediction
Modified residuei285 – 2851Phosphoserine By similarity
Modified residuei321 – 3211Phosphoserine By similarity

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.

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP55087.
PRIDEiP55087.

PTM databases

PhosphoSiteiP55087.

Expressioni

Tissue specificityi

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

Gene expression databases

ArrayExpressiP55087.
BgeeiP55087.
CleanExiHS_AQP4.
GenevestigatoriP55087.

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 interactions.
DIPiDIP-48842N.
STRINGi9606.ENSP00000372654.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi33 – 5523
Turni59 – 635
Helixi70 – 9223
Helixi98 – 1069
Helixi112 – 13625
Helixi139 – 1424
Turni143 – 1464
Helixi156 – 17722
Helixi189 – 20820
Helixi214 – 22411
Turni228 – 2314
Helixi232 – 25019

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3GD8X-ray1.80A32-254[»]
ProteinModelPortaliP55087.
SMRiP55087. Positions 32-254.

Miscellaneous databases

EvolutionaryTraceiP55087.

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

eggNOGiCOG0580.
HOGENOMiHOG000288286.
HOVERGENiHBG000312.
InParanoidiP55087.
KOiK09866.
OMAiNWENHWV.
OrthoDBiEOG7N8ZWD.
PhylomeDBiP55087.
TreeFamiTF312940.

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. Align

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

MSDRPTARRW GKCGPLCTRE NIMVAFKGVW TQAFWKAVTA EFLAMLIFVL    50
LSLGSTINWG GTEKPLPVDM VLISLCFGLS IATMVQCFGH ISGGHINPAV 100
TVAMVCTRKI SIAKSVFYIA AQCLGAIIGA GILYLVTPPS VVGGLGVTMV 150
HGNLTAGHGL LVELIITFQL VFTIFASCDS KRTDVTGSIA LAIGFSVAIG 200
HLFAINYTGA SMNPARSFGP AVIMGNWENH WIYWVGPIIG AVLAGGLYEY 250
VFCPDVEFKR RFKEAFSKAA QQTKGSYMEV EDNRSQVETD DLILKPGVVH 300
VIDVDRGEEK KGKDQSGEVL SSV 323
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 AAC50284.1 differs from that shown. Reason: Erroneous initiation.
The sequence AAC52112.1 differs from that shown. Reason: Erroneous initiation.

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 2222Missing in isoform 1.
VSP_003232Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti246 – 2461G → A in AAC52112. 1 Publication
Sequence conflicti287 – 2882VE → AK in AAC52112. 1 Publication
Sequence conflicti296 – 2961P → L in AAC52112. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_001650.4. [P55087-1]
NP_004019.1. NM_004028.3. [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.3. human. [P55087-1]

Polymorphism databases

DMDMi2506859.

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:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS11889.1. [P55087-1 ]
CCDS58617.1. [P55087-2 ]
PIRi I39178.
RefSeqi NP_001641.1. NM_001650.4. [P55087-1 ]
NP_004019.1. NM_004028.3. [P55087-2 ]
UniGenei Hs.315369.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
3GD8 X-ray 1.80 A 32-254 [» ]
ProteinModelPortali P55087.
SMRi P55087. Positions 32-254.
ModBasei Search...

Protein-protein interaction databases

BioGridi 106857. 2 interactions.
DIPi DIP-48842N.
STRINGi 9606.ENSP00000372654.

Chemistry

ChEMBLi CHEMBL5964.

Protein family/group databases

TCDBi 1.A.8.8.5. the major intrinsic protein (mip) family.

PTM databases

PhosphoSitei P55087.

Polymorphism databases

DMDMi 2506859.

Proteomic databases

PaxDbi P55087.
PRIDEi P55087.

Protocols and materials databases

DNASUi 361.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000383168 ; ENSP00000372654 ; ENSG00000171885 . [P55087-1 ]
ENST00000440832 ; ENSP00000393121 ; ENSG00000171885 . [P55087-2 ]
ENST00000581374 ; ENSP00000462597 ; ENSG00000171885 . [P55087-2 ]
GeneIDi 361.
KEGGi hsa:361.
UCSCi uc002kvz.3. human. [P55087-1 ]

Organism-specific databases

CTDi 361.
GeneCardsi GC18M024432.
HGNCi HGNC:637. AQP4.
HPAi CAB005079.
CAB058689.
HPA014784.
MIMi 600308. gene.
neXtProti NX_P55087.
PharmGKBi PA24922.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0580.
HOGENOMi HOG000288286.
HOVERGENi HBG000312.
InParanoidi P55087.
KOi K09866.
OMAi NWENHWV.
OrthoDBi EOG7N8ZWD.
PhylomeDBi P55087.
TreeFami TF312940.

Enzyme and pathway databases

Reactomei REACT_23826. Passive transport by Aquaporins.
REACT_24023. Regulation of water balance by renal Aquaporins.

Miscellaneous databases

EvolutionaryTracei P55087.
GeneWikii Aquaporin_4.
GenomeRNAii 361.
NextBioi 1509.
PROi P55087.
SOURCEi Search...

Gene expression databases

ArrayExpressi P55087.
Bgeei P55087.
CleanExi HS_AQP4.
Genevestigatori P55087.

Family and domain databases

Gene3Di 1.20.1080.10. 1 hit.
InterProi IPR023271. Aquaporin-like.
IPR000425. MIP.
IPR022357. MIP_CS.
[Graphical view ]
PANTHERi PTHR19139. PTHR19139. 1 hit.
Pfami PF00230. MIP. 1 hit.
[Graphical view ]
PRINTSi PR00783. MINTRINSICP.
SUPFAMi SSF81338. SSF81338. 1 hit.
TIGRFAMsi TIGR00861. MIP. 1 hit.
PROSITEi PS00221. MIP. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.

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: September 3, 2014
This is version 133 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

External Data

Dasty 3

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