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P55087

- AQP4_HUMAN

UniProt

P55087 - AQP4_HUMAN

Protein

Aquaporin-4

Gene

AQP4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 134 (01 Oct 2014)
      Sequence version 2 (01 Nov 1997)
      Previous versions | rss
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    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

    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

    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

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA24922.

    PTM / Processingi

    Molecule processing

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

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei111 – 1111Phosphoserine; by PKGBy similarity
    Glycosylationi153 – 1531N-linked (GlcNAc...)Sequence Analysis
    Modified residuei180 – 1801Phosphoserine; by PKCBy similarity
    Glycosylationi206 – 2061N-linked (GlcNAc...)Sequence Analysis
    Modified residuei285 – 2851PhosphoserineBy similarity
    Modified residuei321 – 3211PhosphoserineBy 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.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

    1
    323
    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.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP55087.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 3636CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini58 – 647ExtracellularSequence Analysis
    Topological domaini86 – 11530CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini137 – 15519ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini177 – 1848CytoplasmicSequence Analysis
    Topological domaini206 – 23126ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini253 – 32371CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei37 – 5721HelicalSequence AnalysisAdd
    BLAST
    Transmembranei65 – 8521HelicalSequence AnalysisAdd
    BLAST
    Transmembranei116 – 13621HelicalSequence AnalysisAdd
    BLAST
    Transmembranei156 – 17621HelicalSequence AnalysisAdd
    BLAST
    Transmembranei185 – 20521HelicalSequence AnalysisAdd
    BLAST
    Transmembranei232 – 25221HelicalSequence AnalysisAdd
    BLAST

    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.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti246 – 2461G → A in AAC52112. (PubMed:7559426)Curated
    Sequence conflicti287 – 2882VE → AK in AAC52112. (PubMed:7559426)Curated
    Sequence conflicti296 – 2961P → L in AAC52112. (PubMed:7559426)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 2222Missing in isoform 1. CuratedVSP_003232Add
    BLAST

    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...
    MobiDBi 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

    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: October 1, 2014
    This is version 134 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