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:

Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
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.
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.
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.
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.

No sequence conservation computed yet.

Protein sequence (FASTA)

Protein coevolution profile (FreeContact)

Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.

Topcons

Total structural coverage: 100%

Model score: 100

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Variant	Description
	Co(A-B-) antigen
	Co(A-B+) antigen
	dbSNP:rs28362731

Biological Process

Ammonium transmembrane transport

Ammonium transport

Bicarbonate transport

Camera-type eye morphogenesis

Carbon dioxide transmembrane transport

Carbon dioxide transport

Cation transmembrane transport

Cell volume homeostasis

Cellular homeostasis

Cellular hyperosmotic response

Cellular response to cAMP

Cellular response to copper ion

Cellular response to dexamethasone stimulus

Cellular response to hydrogen peroxide

Cellular response to hypoxia

Cellular response to inorganic substance

Cellular response to mechanical stimulus

Cellular response to mercury ion

Cellular response to nitric oxide

Cellular response to retinoic acid

Cellular response to salt stress

Cellular response to stress

Cellular response to UV

Cellular water homeostasis

Cerebrospinal fluid secretion

CGMP biosynthetic process

CGMP-mediated signaling

Corticotropin secretion

Defense response to Gram-negative bacterium

Establishment or maintenance of actin cytoskeleton polarity

Glomerular filtration

Glycerol transport

Hyperosmotic response

Hyperosmotic salinity response

Lateral ventricle development

Lipid digestion

Maintenance of symbiont-containing vacuole by host

Metanephric descending thin limb development

Metanephric glomerulus vasculature development

Metanephric proximal convoluted tubule segment 2 development

Metanephric proximal straight tubule development

Multicellular organismal water homeostasis

Negative regulation of apoptotic process

Negative regulation of cysteine-type endopeptidase activity involved in apoptotic process

Nitric oxide transport

Odontogenesis

Pancreatic juice secretion

Positive regulation of angiogenesis

Positive regulation of epithelial cell migration

Positive regulation of fibroblast proliferation

Positive regulation of lamellipodium assembly

Positive regulation of saliva secretion

Potassium ion transmembrane transport

Potassium ion transport

Renal water absorption

Renal water homeostasis

Renal water transport

Response to drug

Response to estrogen

Secretory granule organization

Sensory perception of pain

Small molecule metabolic process

Transepithelial water transport

Transmembrane transport

Water transport

Wound healing

Cellular Component

Apical part of cell

Apical plasma membrane

Axon

Axon terminus

Basal plasma membrane

Basolateral plasma membrane

Brush border

Brush border membrane

Cytoplasm

Extracellular exosome

Integral component of membrane

Integral component of plasma membrane

Nuclear membrane

Nucleus

Obsolete cell

Plasma membrane

Sarcolemma

Symbiont-containing vacuole

Molecular Function

Ammonium transmembrane transporter activity

Carbon dioxide transmembrane transporter activity

Ephrin receptor binding

Glycerol channel activity

Glycerol transmembrane transporter activity

Identical protein binding

Intracellular cGMP-activated cation channel activity

Nitric oxide transmembrane transporter activity

Potassium channel activity

Potassium ion transmembrane transporter activity

Transmembrane transporter activity

Water channel activity

Water transmembrane transporter activity

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

July 1, 2021: Protein entry updated
Automatic update: OMIM entry 107776 was added.

July 1, 2021: Protein entry updated
Automatic update: OMIM entry 110450 was added.

April 11, 2021: Protein entry updated
Automatic update: OMIM entry 107776 was added.

April 11, 2021: Protein entry updated
Automatic update: OMIM entry 110450 was added.

Feb. 16, 2021: Protein entry updated
Automatic update: OMIM entry 107776 was added.

Feb. 16, 2021: Protein entry updated
Automatic update: OMIM entry 110450 was added.

Oct. 21, 2020: Protein entry updated
Automatic update: OMIM entry 107776 was added.

Oct. 21, 2020: Protein entry updated
Automatic update: OMIM entry 110450 was added.

Aug. 24, 2020: Protein entry updated
Automatic update: OMIM entry 110450 was added.

Aug. 24, 2020: Protein entry updated
Automatic update: OMIM entry 107776 was added.

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 107776 was added.

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 110450 was added.

April 25, 2020: Protein entry updated
Automatic update: OMIM entry 107776 was added.

April 25, 2020: Protein entry updated
Automatic update: OMIM entry 110450 was added.

March 4, 2020: Protein entry updated
Automatic update: OMIM entry 107776 was added.

March 4, 2020: Protein entry updated
Automatic update: OMIM entry 110450 was added.

Dec. 3, 2019: Protein entry updated
Automatic update: OMIM entry 107776 was added.

Dec. 3, 2019: Protein entry updated
Automatic update: OMIM entry 110450 was added.

Oct. 28, 2019: Protein entry updated
Automatic update: OMIM entry 107776 was added.

Oct. 28, 2019: Protein entry updated
Automatic update: OMIM entry 110450 was added.

May 12, 2019: Protein entry updated
Automatic update: OMIM entry 107776 was added.

May 12, 2019: Protein entry updated
Automatic update: OMIM entry 110450 was added.

May 12, 2019: Protein entry updated
Automatic update: model status changed

Nov. 16, 2018: Protein entry updated
Automatic update: model status changed

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

Aquaporin-1 (AQP1)