There are various splicing forms. Canonical form transcript (hg38), including UTRs: chr7:30,911,694 - 30,925,516, size: 13,823bp on forward (+) strand; coding region: chr7:30,911,910 - 30,923,629, size: 11,720bp, according to UCSC. Four exons: exon1 (nt 1 - 600) codes for amino acids (aa) 1-128, exon2 (nt 10373 - 10537) for aa 129-183; exon3 (nt 10871 - 10951) for aa 184-210, and exon4 (nt 11757 - 13823) for aa 211-269 (nextProt).

Aquaporins are a family of hydrophobic transmembrane channel proteins involved in transport of water and small molecules in response to osmotic gradients. They are distributed throughout many tissues, with various known roles of production, secretion, reabsorption and regulation of water, but also of cell migration (angiogenesis), signal transduction, and cell proliferation. There are 14 AQPs in humans (and 5 pseudogenes): MIP (previously called AQP0), AQP1, AQP2, AQP3, AQP4, AQP5, AQP6, AQP7, AQP8, AQP9, AQP10, AQP11, AQP12Aand AQP12B. They are classified into two families: orthodox aquaporins, that transport water only, and aquaglyceroporins (AQP3, AQP7 and AQP9), which also transport glycerol, urea and other small molecules. AQPs form homo-tetramers (Review in Papadopoulos and Saadoun, 2015). The monomeric units of AQPs are ~30 kDa proteins and consist of 6 transmembrane α-helices (M1, M2, M4 to M6 and M8), 2 intramembrane half helices (M3 and M7), and 5 connecting loops (loops A to E) (Review in Verkman et al., 2014). They bear conserved intramembrane Asn-Pro-Ala (NPA) sequence motifs in the intramembrane domains, and six tilted transmembrane helices per monomer, with linkers (loops A to E). The NPA motifs act as hydrogen-bond donors and acceptors that coordinate the transport of water through the pore (Verkman et al., 2014).

Aquaporin-1 canonical form: 269 aa; 28.526kDa; other isoforms; 218, 186, and 154 aa. AQP1 is a transmembrane protein, with a N-term and a C-term cytoplasmic domains: amino acids 2 - 7 (Cytoplasmic), 8 - 36 (Transmembrane), 37 - 48 (Extracellular ("Loop A")), 49 - 66 (Transmembrane), 67 - 70 (Cytoplasmic), 71 - 84 (Intramembrane), 85 - 94 (Cytoplasmic ("Loop B"), 95 - 115 (Transmembrane), 116 - 136 (Extracellular ("Loop C")), 137 - 155 (Transmembrane), 156 - 166 (Cytoplasmic ("Loop D")), 167 - 183 (Transmembrane), 184 - 186 (Extracellular ("Loop E")), 187 - 200 (Intramembrane), 201 - 207 (Extracellular), 208 - 228 (Transmembrane), 229 - 269 (Cytoplasmic) (Figure. 1).

Helical subunits in Loop B and E juxtapose to form a water pore in the monomere. The central pore of the homotetramer (Figure. 2) would be a path for ion and gas (Review in Tomita et al., 2017). Remarkable sites: (Figure. 1)
NPA: aa 76-78, 192-194
N-myristoylation sites (role in membrane targeting): aa 30-35, 40-45, 57-62, 82-87, 104-109, 114-119, 121-126, 132-137, 136-141, 173-178, 190-195, 219-224.
N-glycosylation sites: aa 42-45, 205-208.
Protein kinase C phosphorylation sites: aa 157 - 159, 239-241 (Thr 157 and 239); Casein kinase II phosphorylation site: aa 262 - 265 (Ser 262).
Poly Arg (for preventing proton conduction): aa 159-162.

AQPs are widely expressed. AQP1 is the main water channel in human (especially erythrocytes), but its function in water permeation can be alternatively supported by urea transporters SLC14A1 and SLC14A2 and glucose transporter SLC2A1 (GLUT1). The CO2-transporting function of APQ1 is replaceable by RHAG gas channel. (Hsu 2018). AQP1 is expressed in all tissues, in particular in renal tubules, exocrine pancreas, neuropil (synaptically dense regions of brain), bile ducts, corneal endothelium, bone marrow, myoepithelial cells of breast and endothelial cells (The Human Protein Atlas). AQP1 is present in pleura and microvessels. AQP1 and AQP4 are expressed in the iris and ciliary epithelium and play important roles in regulating aqueous humor (review in Huber et al. 2012).
Choroid plexus epithelium: AQP1 is highly expressed in the apical side of choroid plexus epithelium, where it facilitates cerebrospinal fluid (CSF) secretion and intracranial pressure regulation (Longatti et al., 2006; review in Huber et al. 2012).
Renal proximal tubule and loop of Henle: mice deficient in AQP1 have a reduced ability to concentrate urine and there is also a moderate defective urinary concentrating ability in AQP1 deficient patients (King et al., 2001).
Erythrocyte: CO2 metabolite enters erythrocytes via diffusion and/or gas channels (e.g. AQP1 and RHAG).
AQP1 is a H2O/CO2 channel in the erythrocyte. There are 160,000-200,000 copies of AQP1 on one erythrocyte membrane (Hsu 2018). AQP1 forms complex with SLC4A1 (band 3) and CA2 (carbonic anhydrase II) for intraerythrocytic CO2/HCO3 conversion in relation to desoxy-hemoglobin (Hsu 2018). 60% of CO2 flux in or out of RBCs is via AQP1 gas channel. The rest of CO2 flux is likely through another gas channel, RHAG, and/or direct diffusion (Hsu 2018).

Localized to the plasma membrane.

AQPs mains role is to maintain tissue water balance. AQPs also facilitate cell migration, cell proliferation and cell adhesion. Cell migration: AQPs concentrate at the leading end of migrating cells and facilitate the formation of the lamellipodium (Papadopoulos and Saadoun, 2015). Cell proliferation: AQPs may activates transduction pathways such as the mitogen-activated protein kinase pathways or the Wnt/ β-catenin signaling.
AQP1 may also be involved in down regulation of apoptosis. AQP1 up-regulation induces CTNNB1 (β-catenin) overexpression and serves as co-activator in the nucleus to activate Wnt responsive genes such as MYC, CCND1 (cyclin D1), JUN and FOSL1. AQP1 stabilises the cadherin/ CTNNB1/Lin7/F-actin complex to enhance the migratory and invasive capacity of tumor cells. AQP1 enhances the activity of MMP2 and MMP9 through PTK2 (FAK) and Wnt signalling pathways. Hypoxia induces AQP1 overexpression in tumour cells, in combination with important downstream effectors including CTNNB1, FAK and the Rho family of GTPases known for their role in tumorigenesis. (see review in Tomita et al., 2017).

Polymorphism: AQP1 is responsible for the Colton blood group system, with high incidence of Co(a) allele/antigen (Ala in aa 45), and low incidence of Co(b) allele/antigen (Val in aa 45). Colton-null phenotype Co(a-b-), is an aquaporin-1 deficiency. The patients, under stress, have a defect in urinary concentration capacity (King et al., 2002). AQP1-null mice have a significant decrease in urine osmolarity, but a normal survival.

Increased expression of aquaporins 1 and 4 was found in Creutzfeldt-Jakob disease (Rodrèguez et al. 2006).