Aquaporin-3 (AQP3)
The protein contains 292 amino acids for an estimated molecular weight of 31544 Da.
Water channel required to promote glycerol permeability and water transport across cell membranes (PubMed:12239222, PubMed:30420639). Acts as a glycerol transporter in skin and plays an important role in regulating SC (stratum corneum) and epidermal glycerol content. Involved in skin hydration, wound healing, and tumorigenesis. Provides kidney medullary collecting duct with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient. Slightly permeable to urea and may function as a water and urea exit mechanism in antidiuresis in collecting duct cells. It may play an important role in gastrointestinal tract water transport and in glycerol metabolism (By similarity). (updated: May 8, 2019)
Protein identification was indicated in the following studies:
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| dbSNP:rs34942735 |
No binding partner found
Biological Process
Cellular response to hypoxia
Cellular response to oxygen-glucose deprivation
Glycerol transport
Odontogenesis
Positive regulation of immune system process
Regulation of keratinocyte differentiation
Renal water absorption
Renal water homeostasis
Response to calcium ion
Response to retinoic acid
Response to vitamin D
Water transport
The reference OMIM entry for this protein is 600170
Aquaporin 3; aqp3
CLONING
By use of a PCR cloning strategy, Ishibashi et al. (1994) cloned a third member of the major intrinsic protein (MIP) family from rat kidney and designated it aquaporin-3 (AQP3). See also aquaporin-1 (107776). Aquaporin-3 is localized at the basal lateral membranes of collecting duct cells in the kidney. Using a rat AQP3 probe, Ishibashi et al. (1995) screened a human kidney cDNA library and isolated a cDNA coding for human AQP3 protein. The deduced amino acid sequence of AQP3 was 91% identical to rat AQP3. Human AQP3 mRNA was expressed in colon, kidney, liver, pancreas, lung, peripheral leukocytes, spleen, and prostate. Ma et al. (2000) isolated a cDNA encoding mouse Aqp3, which is expressed in kidney, large airways, eye, urinary bladder, skin, and gastrointestinal tract. The 292-amino acid protein is 95% identical to the human sequence.GENE FUNCTION
By functional expression in Xenopus oocytes, Ishibashi et al. (1994) confirmed the water-channel function of AQP3. Moreover, AQP3 facilitated the transport of nonionic small solutes such as urea and glycerol, albeit to a smaller degree. The results suggested that water channels can be functionally heterogeneous and possess water and solute permeation mechanisms. By Western blot analysis and immunofluorescence microscopy of epidermis, Sougrat et al. (2002) showed strong expression of an approximately 33-kD glycosylated AQP3 protein in keratinocyte plasma membranes, 1 layer below the unstained stratum corneum (SC). In the basal layer of the epidermis, AQP3 was expressed intracellularly. AQP1, AQP2 (107777), AQP4 (600308), and AQP5 (600442) were not detected in human skin. Osmotically induced transepidermal water permeability, measured on stripped skin and reconstructed epidermis, was inhibitable by acid pH or mercuric chloride and was mediated by AQP3. Sougrat et al. (2002) concluded that below the water-impermeable SC, viable human epidermis exhibits a high AQP3-mediated water permeability through keratinocyte plasma membranes. They proposed that AQP3 provides a short circuit for water, or water-clamp, between the base of the epidermis and the SC in order to maintain a constant water content and to prevent the formation of a continuous water gradient across the epidermis below the SC.GENE STRUCTURE
Inase et al. (1995) reported the structural organization of the genomic AQP3 gene. It appeared to exist as a single copy and to comprise 6 exons distributed over 7 kb. The initiation site of transcription was identified to be located 64-bp upstream of the first ATG codon by primer extension analysis and ribonuclease protection assay. The 5-prime flanking region contained a TATA box, 2 Sp1 sequences, and some consensus sequences including AP-2 sites.MAPPING
By fluorescence in situ hybridization, Ishibashi et al. (1995) mapped the AQP3 gene to 7q36.2-q36.3. In an erratum, the authors stated that the correct chromosomal assignment of the AQP3 gene is on 9p13. Mulders et al. (1996) mapped the AQP3 gene to 9p21-p12 by fluorescence in situ hybridization; they added a note to their paper stating that after hybridization with another human AQP3 genomic clone and cDNA, Ishibashi et al. (1995) confirmed the localization to 9p.MOLECULAR GENETICS
AQP3 is a water and glycerol channel present on human erythrocytes and in various tissues. By protein and molecular biology analysis, Roudier et al. (2002) showed that 2 unrelated probands who develop ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 600170 was added.
May 11, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).