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Aquaporin 1 (CO2-, O2-, H202- and nitrous oxide-permeable and water-selective) (Zwiazek et al. 2017; Varadaraj and Kumari 2020). Aquaporin-1 tunes pain perception by interacting with Na(v)1.8 Na+ channels in dorsal root ganglion neurons (Zhang and Verkman, 2010). It is upregulated in skeletal muscle in muscular dystrophy (Au et al. 2008). AQP1 has been reported to first insert as a four-helical intermediate, where helices 2 and 4 are not inserted into the membrane. In a second step this intermediate is folded into a six-helical topology. During this process, the orientation of the third helix is inverted, and it can shift out the membrane core (Virkki et al. 2014).  Its synthesis is regluated by Kruppel-like factor 2 (KLF2; Q9Y5W3) which also interacts directly with Aqp1 (Fontijn et al. 2015). A nanoscale ion pump has been derived artificially from Aqp1 (Decker et al. 2017). Mammalian AQP1 channels, activated by cyclic GMP, can carry non-selective monovalent cation currents, selectively blocked by arylsulfonamide compounds AqB007 (IC50 170 muM) and AqB011 (IC50 14 muM). Loop D-domain amino acids activate the channel for ion coductance (Kourghi et al. 2018). Water flux through AQP1s is inhibited by 1 - 10 mμM acetozolaminde (Gao et al. 2006). Aqp1 transports reactive oxygen and nitrogen species (RONS) which may induce oxidative stress in the cell interior. These RONS include both hydrophilic (H2O2 and OH) and hydrophobic (NO2 and NO) RONS (Yusupov et al. 2019).  The position of the Arg-195 side chain shows a number of interactions for loop C (Dingwell et al. 2019). AQP1 play vital roles in cellular homeostasis at rest and during endurance running exercises (Rivera and Fahey 2019). AQP1 and AQP4 activities correlate with the severity of hydrocephalus induced by subarachnoid haemorrhage (Long et al. 2019). AQPs are related to osmoregulation and play a critical role in maturation, cryo-stability and motility activation in boar spermatozoa (Delgado-Bermúdez et al. 2019). In foetal kidney, AQP1 expression appeared in the apical and basolateral parts of cells, lining the proximal convoluted tubules and the descending limb of Henle's loop, then in the tubule pole of Bowman's capsule (Ráduly et al. 2019). Inhibition of aquaporin-1 prevents myocardial remodeling by blocking the transmembrane transport of hydrogen peroxide (Montiel et al. 2020). AQP1 Is up-regulated by hypoxia and leads to increased cell water permeability, motility, and migration in neuroblastoma (Huo et al. 2021). Aqp1 allows the transport of CO2 across membranes (Michenkova et al. 2021). Down-regulation of aquaporin-1 mediates a microglial phenotype switch affecting glioma growth (Hu et al. 2020). AQP1 expression is down-regulated following repeated exposure of UVB via MEK/ERK activation pathways, and this AQP1 reduction leads to changes of physiological functions in dermal fibroblasts (Kim et al. 2020). AQP1 and AQP7 are differentially regulated under hyperosmotic stress conditions, and AQP1 acts as an osmotic stress sensor and response factor (Aggeli et al. 2021). AQP1 plays a role in the pathogenesis of Wilms' tumor (Liu et al. 2023).  Aquaporin-1 plays a role in cell proliferation, apoptosis, and pyroptosis of Wilms' tumor cells (Liu et al. 2024).

Accession Number:P29972
Protein Name:AQP1 or CHIP28
Molecular Weight:28526.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:6
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate hydrogen peroxide, dinitrogen oxide, water, ammonia, dioxygen, carbon dioxide

Cross database links:

DIP: DIP-29607N
RefSeq: NP_932766.1   
Entrez Gene ID: 358   
Pfam: PF00230   
OMIM: 107776  gene
110450  phenotype
KEGG: hsa:358   

Gene Ontology

GO:0016324 C:apical plasma membrane
GO:0009925 C:basal plasma membrane
GO:0031526 C:brush border membrane
GO:0005737 C:cytoplasm
GO:0005887 C:integral to plasma membrane
GO:0031965 C:nuclear membrane
GO:0042383 C:sarcolemma
GO:0051739 F:ammonia transmembrane transporter activity
GO:0035379 F:carbon dioxide transmembrane transporter ac...
GO:0015168 F:glycerol transmembrane transporter activity
GO:0005223 F:intracellular cGMP activated cation channel...
GO:0030184 F:nitric oxide transmembrane transporter acti...
GO:0005267 F:potassium channel activity
GO:0015079 F:potassium ion transmembrane transporter act...
GO:0005515 F:protein binding
GO:0015250 F:water channel activity
GO:0015696 P:ammonium transport
GO:0035378 P:carbon dioxide transmembrane transport
GO:0006884 P:cell volume homeostasis
GO:0071474 P:cellular hyperosmotic response
GO:0071320 P:cellular response to cAMP
GO:0071280 P:cellular response to copper ion
GO:0071549 P:cellular response to dexamethasone stimulus
GO:0070301 P:cellular response to hydrogen peroxide
GO:0071456 P:cellular response to hypoxia
GO:0071260 P:cellular response to mechanical stimulus
GO:0071288 P:cellular response to mercury ion
GO:0071300 P:cellular response to retinoic acid
GO:0071472 P:cellular response to salt stress
GO:0034644 P:cellular response to UV
GO:0033326 P:cerebrospinal fluid secretion
GO:0006182 P:cGMP biosynthetic process
GO:0030950 P:establishment or maintenance of actin cytos...
GO:0015793 P:glycerol transport
GO:0021670 P:lateral ventricle development
GO:0050891 P:multicellular organismal water homeostasis
GO:0043066 P:negative regulation of apoptosis
GO:0030185 P:nitric oxide transport
GO:0042476 P:odontogenesis
GO:0030157 P:pancreatic juice secretion
GO:0045766 P:positive regulation of angiogenesis
GO:0048146 P:positive regulation of fibroblast prolifera...
GO:0046878 P:positive regulation of saliva secretion
GO:0006813 P:potassium ion transport
GO:0003097 P:renal water transport
GO:0042493 P:response to drug
GO:0035377 P:transepithelial water transport

References (19)

[1] “Isolation of the cDNA for erythrocyte integral membrane protein of 28 kilodaltons: member of an ancient channel family.”  Preston   1722319
[2] “The human aquaporin-CHIP gene. Structure, organization, and chromosomal localization.”  Moon   8340403
[3] “Characterization of the 3' UTR sequence encoded by the AQP-1 gene in human retinal pigment epithelium.”  Ruiz   8703970
[4] “The water channel gene in human uterus.”  Li   7517253
[5] “Human protein factory for converting the transcriptome into an in vitro-expressed proteome.”  Goshima   19054851
[6] “The DNA sequence of human chromosome 7.”  Hillier   12853948
[7] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project   15489334
[8] “Erythrocyte Mr 28,000 transmembrane protein exists as a multisubunit oligomer similar to channel proteins.”  Smith   2007592
[9] “Appearance of water channels in Xenopus oocytes expressing red cell CHIP28 protein.”  Preston   1373524
[10] “The mercury-sensitive residue at cysteine 189 in the CHIP28 water channel.”  Preston   7677994
[11] “Membrane topology of aquaporin CHIP. Analysis of functional epitope-scanning mutants by vectorial proteolysis.”  Preston   7507481
[12] “Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.”  Daub   18691976
[13] “The three-dimensional structure of human erythrocyte aquaporin CHIP.”  Walz   7518771
[14] “The three-dimensional structure of aquaporin-1.”  Walz   9177353
[15] “Structural determinants of water permeation through aquaporin-1.”  Murata   11034202
[16] “A refined structure of human aquaporin-1.”  de Groot   11532455
[17] “Visualization of a water-selective pore by electron crystallography in vitreous ice.”  Ren   11171962
[18] “Human red cell aquaporin CHIP. I. Molecular characterization of ABH and Colton blood group antigens.”  Smith   7521882
[19] “Mutations in aquaporin-1 in phenotypically normal humans without functional CHIP water channels.”  Preston   7521540
1FQY   1H6I   1IH5   4CSK   6POJ     

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