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1.A.8.8.5
Aquaporin-4 (AQP4) (2 splice variants; the shorter assembles into functional, tetrameric square arrays; the longer is palmitoylated on N-terminal cysteyl residues) (Suzuki et al., 2008). Six splice variants have been identified. The longest, Aqp4e, has a novel N-terminal domain and forms a water channel in the plasma membrane. Various shorter variants don't (Moe et al., 2008). AQP4, like AQP0 (1.A.8.8.2), forms water channels but also forms adhesive junctions (Engel et al., 2008) (causes cytotoxic brain swelling in mice (Yang et al., 2008)) Mice lacking Aqp4 have impaired olfactions (Lu et al., 2008). Aqp4 is down regulated in skeletal muscle in muscular dystrophy (Au et al. 2008). The crystal structure is known to 2.8 Å resolution (Tani et al., 2009). The structure reveals 8 water molecules in each of the four channels, supporting a hydrogen-bond isolation mechanism and explains its fast and selective water conduction and proton exclusion (Tani et al., 2009; Cui and Bastien, 2011). It is an important antigen in Neuromyelitis optica (NMO) patients (Kalluri et al., 2011).  A connection has been made between AQP4-mediated fluid accumulation and post traumatic syringomyelia (Hemley et al. 2013).  AQP4 has increased water permeability at low pH, and His95 is the pH-dependent gate (Kaptan et al. 2015).  Also transports NH3 but not NH4+ (Assentoft et al. 2016). Cerebellar damage following status epilepticus involves down regulation of AQP4 expression (Tang et al. 2017). SUR1-TRPM4 and AQP4 form a complex to increase bulk water influx during astrocyte swelling (Stokum et al. 2017).

Accession Number:P55087
Protein Name:Aqp4
Length:323
Molecular Weight:34830.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:6
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate water, ammonia

Cross database links:

Genevestigator: P55087
eggNOG: prNOG04823
HEGENOM: HBG705794
RefSeq: NP_001641.1    NP_004019.1   
Entrez Gene ID: 361   
Pfam: PF00230   
OMIM: 600308  gene
KEGG: hsa:361   

Gene Ontology

GO:0005737 C:cytoplasm
GO:0009897 C:external side of plasma membrane
GO:0005887 C:integral to plasma membrane
GO:0005372 F:water transmembrane transporter activity
GO:0071346 P:cellular response to interferon-gamma
GO:0007588 P:excretion
GO:0050891 P:multicellular organismal water homeostasis
GO:0007399 P:nervous system development
GO:0055085 P:transmembrane transport

References (4)

[1] “cDNA cloning, gene organization, and chromosomal localization of a human mercurial insensitive water channel. Evidence for distinct transcriptional units.”  Yang B.et.al.   7559426
[2] “A water channel closely related to rat brain aquaporin 4 is expressed in acid- and pepsinogen-secretory cells of human stomach.”  Misaka T.et.al.   8601457
[3] “The human AQP4 gene: definition of the locus encoding two water channel polypeptides in brain.”  Lu M.et.al.   8855281
[4] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
Structure:
3GD8   2d57   2zz9   3iyz     

External Searches:

  • Search: DB with
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  • CDD Search (Conserved Domain Database)
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  • 2° Structure (Network Protein Sequence Analysis)

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MSDRPTARRW GKCGPLCTRE NIMVAFKGVW TQAFWKAVTA EFLAMLIFVL LSLGSTINWG 
61:	GTEKPLPVDM VLISLCFGLS IATMVQCFGH ISGGHINPAV TVAMVCTRKI SIAKSVFYIA 
121:	AQCLGAIIGA GILYLVTPPS VVGGLGVTMV HGNLTAGHGL LVELIITFQL VFTIFASCDS 
181:	KRTDVTGSIA LAIGFSVAIG HLFAINYTGA SMNPARSFGP AVIMGNWENH WIYWVGPIIG 
241:	AVLAGGLYEY VFCPDVEFKR RFKEAFSKAA QQTKGSYMEV EDNRSQVETD DLILKPGVVH 
301:	VIDVDRGEEK KGKDQSGEVL SSV