Aquaporin-1 (AQP1)

The protein contains 269 amino acids for an estimated molecular weight of 28526 Da.

 

Forms a water-specific channel that provides the plasma membranes of red cells and kidney proximal tubules with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient. (updated: April 1, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. 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.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. 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.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

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.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 100%
Model score: 20

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VariantDescription
Co(A-B-) antigen
Co(A-B+) antigen
dbSNP:rs28362731

Biological Process

Ammonium transmembrane transport GO Logo
Ammonium transport GO Logo
Bicarbonate transport GO Logo
Camera-type eye morphogenesis GO Logo
Carbon dioxide transmembrane transport GO Logo
Carbon dioxide transport GO Logo
Cation transmembrane transport GO Logo
Cell volume homeostasis GO Logo
Cellular homeostasis GO Logo
Cellular hyperosmotic response GO Logo
Cellular response to cAMP GO Logo
Cellular response to copper ion GO Logo
Cellular response to dexamethasone stimulus GO Logo
Cellular response to hydrogen peroxide GO Logo
Cellular response to hypoxia GO Logo
Cellular response to inorganic substance GO Logo
Cellular response to mechanical stimulus GO Logo
Cellular response to mercury ion GO Logo
Cellular response to nitric oxide GO Logo
Cellular response to retinoic acid GO Logo
Cellular response to salt stress GO Logo
Cellular response to stress GO Logo
Cellular response to UV GO Logo
Cellular water homeostasis GO Logo
Cerebrospinal fluid secretion GO Logo
CGMP biosynthetic process GO Logo
CGMP-mediated signaling GO Logo
Corticotropin secretion GO Logo
Establishment or maintenance of actin cytoskeleton polarity GO Logo
Glomerular filtration GO Logo
Glycerol transport GO Logo
Hyperosmotic salinity response GO Logo
Lateral ventricle development GO Logo
Lipid digestion GO Logo
Maintenance of symbiont-containing vacuole by host GO Logo
Metanephric descending thin limb development GO Logo
Metanephric glomerulus vasculature development GO Logo
Metanephric proximal convoluted tubule segment 2 development GO Logo
Metanephric proximal straight tubule development GO Logo
Multicellular organismal water homeostasis GO Logo
Negative regulation of apoptotic process GO Logo
Negative regulation of cysteine-type endopeptidase activity involved in apoptotic process GO Logo
Nitric oxide transport GO Logo
Odontogenesis GO Logo
Pancreatic juice secretion GO Logo
Positive regulation of angiogenesis GO Logo
Positive regulation of epithelial cell migration GO Logo
Positive regulation of fibroblast proliferation GO Logo
Positive regulation of lamellipodium assembly GO Logo
Positive regulation of saliva secretion GO Logo
Potassium ion transmembrane transport GO Logo
Potassium ion transport GO Logo
Renal water absorption GO Logo
Renal water homeostasis GO Logo
Renal water transport GO Logo
Response to drug GO Logo
Response to estrogen GO Logo
Secretory granule organization GO Logo
Sensory perception of pain GO Logo
Small molecule metabolic process GO Logo
Transepithelial water transport GO Logo
Transmembrane transport GO Logo
Water transport GO Logo
Wound healing GO Logo

The reference OMIM entry for this protein is 107776

Aquaporin 1; aqp1
Aquaporin-chip
Aqp-chip
Channel-like integral membrane protein, 28-kd; chip28

CLONING

Aquaporin-CHIP is a 28-kD integral protein purified from the plasma membranes of red cells and renal tubules by Denker et al. (1988). The protein was thought at first to be a breakdown product of the Rh polypeptide but was later shown to be a unique molecule that is abundant in erythrocytes and renal tubules. A subpopulation is N-glycosylated. Preston and Agre (1991) isolated a cDNA for this protein, called CHIP28 (channel forming integral protein of 28 kD), from human fetal liver. Analysis of the deduced amino acid sequence suggested that CHIP28 protein contains 6 bilayer-spanning domains, 2 exofacial potential N-glycosylation sites, and intracellular N and C termini. The sequence showed strong homology with the major intrinsic protein of bovine lens (MIP26; 154050), which is the prototype of an ancient family of membrane channels. These proteins are believed to form channels permeable to water and possibly other small molecules.

GENE STRUCTURE

Moon et al. (1995) showed that the 13-kb Aqp1 gene in the mouse contains 4 exons with intronic boundaries corresponding to other known aquaporin genes.

MAPPING

Moon et al. (1993) isolated the AQP1 structural gene and partially sequenced it. Genomic Southern analysis indicated the existence of a single AQP1 gene, which was localized to 7p14 by in situ hybridization. Sequence comparisons with similar proteins from diverse species suggested a common evolutionary origin. Deen et al. (1994) showed that the gene is on chromosome 7 by Southern blot hybridization to human/rodent hybrid cell lines and regionalized it to 7p15-p14 by in situ hybridization. By interspecific backcross mapping, Moon et al. (1995) showed that the mouse Aqp1 gene is located on chromosome 6 in a region with homology of synteny with human 7p14. Keen et al. (1995) localized the AQP1 gene on chromosome 7 within a YAC contig containing 2 polymorphic markers, D7S632 and D7S526. Since aquaporin is known to be expressed in a diverse range of secretory and absorptive epithelia, including many in the eye, it had been proposed as a possible candidate for disorders involving an imbalance in ocular fluid movement. Keen et al. (1995) raised a question of possible involvement in 2 eye diseases that map to that region, retinitis pigmentosa-9 (180104) and dominant cystoid macular dystrophy (153880).

BIOCHEMICAL FEATURES

Murata et al. (2000) described an atomic model of AQP1 at 3.8-angstrom resolution from electron crystallographic data. Multiple highly conserved amino acid residues stabilize the novel fold of AQP1. The aqueous pathway is lined with conserved hydrophobic residues that permit rapid water transport, whereas the water selectivity is due to a constriction of the pore diameter to about 3 angstroms over a span of 1 residue. The atomic model provided a possible molecular explanation to a longstanding puzzle in physiology--how membranes can be freely permeable to water but impermeable to protons. Sui et al. (2001) reported the structure of the dumbbell-shaped AQP1 water channel at 2.2-angstrom resolution. The channel consists of 3 topologic elements, an extracellular and a cytoplasmic vestibule connected by an extended narrow pore or selectivity filter, averaging 4 angstroms in diameter. Within the selectivity filter, 4 bound waters are localized along 3 hydrophilic nodes, which punctuate an otherwise extremely hydrophobic pore segment, facilitating water transport. The highly conserve ... More on the omim web site

The reference OMIM entry for this protein is 110450

Blood group--colton; co

A number sign (#) is used with this entry because of evidence that the polymorphism is due to variation in the aquaporin-CHIP gene (AQP1; 107776). Co(a) was described by Race and Sanger (1968) as 'well on the way to establishment as a separate system.' Its independence of Lutheran, Kell, Diego and Yt remained to be demonstrated. De la Chapelle et al. (1975) reported the very rare Co(a-b-) phenotype in 2 of 5 cases of monosomy 7 in the bone marrow. Mohr and Eiberg (1977) found a lod score of 2.57 for the linkage of Kidd (JK) and Colton. Each had been tentatively assigned to chromosome 7. Lewis et al. (1984) presented further data that weakened the previously proposed linkage of Colton with Kidd from 'probable' to 'possible.' Combined data gave a peak lod of 0.55 at theta = 0.36. Sherman and Simpson (1985) assigned the Kidd blood group locus, erroneously as it turned out, to 2p, and suggested that the CO locus might be located there also. The observations of de la Chapelle et al. (1975) prompted Zelinski et al. (1990) to revisit chromosome 7 in an attempt to map CO. This was successfully achieved when they demonstrated linkage to the argininosuccinate synthetase pseudogene (ASSP11) which is located on 7p; maximum lod = 5.79 at theta = 0.07 for combined paternal and maternal meiosis. In further linkage studies, Zelinski et al. (1991) provided very strong evidence that the CO locus is on 7p. Smith et al. (1994) described the structure of the aquaporin protein and demonstrated that the Colton blood group antigens result from an ala-val polymorphism at residue 45, located on the first extracellular loop of the aquaporin-1 protein. In red cells from 3 individuals who lacked Colton antigens, i.e., were Co(a-b-), Preston et al. (1994) found mutations in the AQP1 gene that resulted in a nonfunctioning CHIP molecule. Surprisingly, none of the 3 suffered any apparent clinical consequences. King et al. (2001) found that Colton-null individuals who lack aquaporin-1 have, under stress, a demonstrable defect in urinary concentration capacity. King et al. (2002), again studying Colton-null individuals, showed that there is decreased pulmonary vascular permeability in such individuals. Joshi et al. (2001) described a seventh Colton-null individual. Data on gene frequencies of allelic variants were tabulated by Roychoudhury and Nei (1988). ... More on the omim web site

Subscribe to this protein entry history

Oct. 2, 2018: Protein entry updated
Automatic update: OMIM entry 107776 was added.

Oct. 2, 2018: Protein entry updated
Automatic update: OMIM entry 110450 was added.

July 6, 2018: Protein entry updated
Automatic update: OMIM entry 107776 was added.

July 6, 2018: Protein entry updated
Automatic update: OMIM entry 110450 was added.

July 6, 2018: Protein entry updated
Automatic update: OMIM entry 107776 was added.

July 6, 2018: Protein entry updated
Automatic update: OMIM entry 110450 was added.

July 5, 2018: Protein entry updated
Automatic update: OMIM entry 107776 was added.

July 5, 2018: Protein entry updated
Automatic update: OMIM entry 110450 was added.

July 5, 2018: Protein entry updated
Automatic update: OMIM entry 107776 was added.

July 5, 2018: Protein entry updated
Automatic update: OMIM entry 110450 was added.

July 4, 2018: Protein entry updated
Automatic update: OMIM entry 107776 was added.

July 4, 2018: Protein entry updated
Automatic update: OMIM entry 110450 was added.

July 2, 2018: Protein entry updated
Automatic update: OMIM entry 107776 was added.

July 2, 2018: Protein entry updated
Automatic update: OMIM entry 110450 was added.

May 26, 2018: Protein entry updated
Automatic update: OMIM entry 107776 was added.

May 26, 2018: Protein entry updated
Automatic update: OMIM entry 110450 was added.

April 27, 2018: Protein entry updated
Automatic update: OMIM entry 107776 was added.

April 27, 2018: Protein entry updated
Automatic update: OMIM entry 110450 was added.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

Oct. 26, 2017: Protein entry updated
Automatic update: model status changed

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 107776 was added.

March 8, 2016: Additional information
Initial protein addition to the database. This entry was referenced in .

March 8, 2016: Protein entry updated
Automatic update: model status changed