1.A.8 The Major Intrinsic Aquaporin Protein, (MIP) Family

The Major Intrinsic Protein (MIP) of the human lens of the eye (Aqp0), after which the MIP family was named, represents about 60% of the protein in the lens cell. In the native form, it is an aquaporin, but during lens development, it becomes proteolytically truncated. The channel, which normally houses 6-9 water molecules, becomes constricted so only three remain, and these are trapped in a closed conformation (Gonen et al., 2004a,b). These truncated tetramers form intercellular adhesive junctions (head to head), yielding a crystalline array that mediates lens formation with cells tightly packed as required to form a clear lens (Gonen and Walz, 2006). Aquaporin ion conductance properties are defined by the membrane environment, the protein structure, and the cell physiology (Henderson et al. 2022). Aqps in some organisms have been the subject of studies such as ticks. Gene expression of AQPs in different tick tissues and stages showed the highest expression levels in salivary glands and gut of adult female Haemaphysalis qinghaiensis. (Niu et al. 2022). AQPs are differentially expressed in various cardiovascular tissues of humans and participate in water transmembrane transport, cell migration, metabolism, and inflammatory responses (Shangzu et al. 2022). AQP1, AQP2, AQP4, AQP5, and AQP8 are primarily water selective, whereas AQP3, AQP7, AQP9, and AQP10 (called 'aqua-glyceroporins') also transport glycerol and other small solutes. AQPs play roles in cancer cell growth, migration, invasion, and angiogenesis (Moon et al. 2022). In the bivalve, the invasive freshwater mussel Dreissena rostriformis, midbody-localized aquaporin mediates intercellular lumen expansion during early cleavage (Zieger et al. 2022). Aqp-mediated water distributions' in astrocytes under normal and pathological conditions have been reviewed (Zhou et al. 2022). Several methods have been developed for the measurement of water permeability, both in living cells and in tissues (Solenov et al. 2023). The importance of aquaporins in fetal developmenthas been reviewed (Martínez and Damiano 2023). The biological functions of AQPs are regulated by posttranslational modifications, e.g., phosphorylation, ubiquitination, glycosylation, subcellular distribution, degradation and protein interactions (Xiong et al. 2023). dbAQP-SNP is a database of missense single-nucleotide polymorphisms in human aquaporins (Dande and Sankararamakrishnan 2023). Raza et al. 2023 unveiled the complete genomic atlas of aquaporins across the genus Oryza. The genome-wide identification and gene expression analysis of sweet cherry aquaporins (Prunus avium L.) under abiotic stresses have been reported (Salvatierra et al. 2023). The genome-wide identification of Aqp family members related to spermatogenesis in turbot (Scophthalmus maximus) has been achieved (Wang et al. 2023).  Plasma membrane aquaporins of the PIP1 and PIP2 subfamilies facilitate hydrogen peroxide diffusion into plant roots (Israel et al. 2022). Roles of AQPs in epilepsy and seizure onset in humans have been discussed and reviewed (Bonosi et al. 2023).

Lipids crystallize with the protein (Gonen et al., 2005). Ion channel activity has been shown for Aquaporins 0, 1, and 6, Drosophila Big Brain and plant Nodulin-26 (Yool and Campbell, 2012).  Roles of aquaporins in human cancer have been reviewed (Pareek et al. 2013) as have their folding pathways (Klein et al. 2015). AQPs may act as transmembrane osmosensors in red cells, secretory granules and microorganisms (Hill and Shachar-Hill 2015).  MIP superfamly proteins and variations of their selectivity filters have been reviewed (Verma et al. 2015). Their evolution has been discussed (Ishibashi et al. 2017). AQPs have a variety of functions and are related to inner ear diseases such as Meniere's disease, sensorineural hearing loss, and presbycusis (Dong et al. 2019). AQPs are also important for male reproductive health (Carrageta et al. 2019).  The evolution of the aquaporin superfamily has been discussed (Ishibashi et al. 2020). The cellular functions of aquaporins are regulated mainly by posttranslational modifications, e.g., phosphorylation, ubiquitination, glycosylation, subcellular distribution, degradation, and protein interactions (Li et al. 2020). Aquaporins play roles in inflammation (Mariajoseph-Antony et al. 2020) and in various aspects of health and disease (Magouliotis et al. 2020). They play major roles in secretion of saliva by salivary glands, and their disruption can cause a variety of diseases (D'Agostino et al. 2020). Aquaporins in mamalian lungs have been reviewed (Yadav et al. 2020). Lineage-level divergence of copepod glycerol transporters and the emergence of isoform-specific trafficking regulation has been documented (Catalán-García et al. 2021). Aquaporins play key roles in fluid homeostasis, glandular secretions, signal transduction and sensation, barrier function, immunity and inflammation, cell migration, and angiogenesis (Wagner et al. 2022). Aquaporins are gated, opening and closing to control water permeation (Ozu et al. 2022). They play roles in breast cancer progression and treatment (Charlestin et al. 2022). The function of aquaporins in gastrointestinal fluid absorption and secretion have been discussed (Calamita and Delporte 2023).

The MIP family is large and diverse, possessing thousands of members that form transmembrane channels. These channel proteins function in water, small carbohydrate (e.g., glycerol), urea, NH3, CO2, H2O2 and ion transport by energy-independent mechanisms. For example, the glycerol channel, FPS1p of Saccharomyces cerevisiae mediates uptake of arsenite and antimonite (Wysocki et al., 2001). Ion permeability appears to occur through a pathway different than that used for water/glycerol transport and may involve a channel at the 4 subunit interface rather than the channels through the subunits (Saparov et al., 2001). MIP family members are found ubiquitously in bacteria, archaea and eukaryotes. Phylogenetic clustering of the proteins is largely according to phylum of the organisms of origin, but one or more clusters are observed for each phylogenetic kingdom (plants, animals, yeast, bacteria and archaea) (Park and Saier, 1996). MIPs are classified into five subfamilies in higher plants, including plasma membrane (PIPs), tonoplast (TIPs), NOD26-like (NIPs), small basic (SIPs) and unclassified X (XIPs) intrinsic proteins.  One of the plant clusters includes only tonoplast (TIP) proteins, while another includes plasma membrane (PIP) proteins (de Paula Santos Martins et al. 2015). Aquaporins in Nicotiana tabacum have been tabulated, and their relationships to other Solanaceae species have been described (De Rosa et al. 2020). A genome analysis of Betula pendula (silver birch) identified 33 putative genes encoding full-length AQP sequences (BpeAQPs). They are grouped into five subfamilies, representing ten plasma membrane intrinsic proteins (PIPs), eight tonoplast intrinsic proteins (TIPs), eight NOD26-like intrinsic proteins (NIPs), four X intrinsic proteins (XIPs), and three small basic intrinsic proteins (SIPs) (Venisse et al. 2021). Fungal X-intrinsic protein aquaporins from Trichoderma atroviride have been studied (Amira et al. 2021). In the parasidic helminthes, AQPs play  roles in promoting the transport of water, osmoregulation, uptake of nutrients, release of toxic metabolic products and transport of antiparasitic drugs (Wang and Ye 2020). Their involvement in diseases pathogenesis has been reviewed (Ala et al. 2021). In humans, AQP3, AQP7, AQP9, and AQP10, play critical roles in cancer. Overexpression or knockdown of AQGPs can promote or inhibit cancer cell proliferation, migration, invasion, apoptosis, epithelial-mesenchymal transition and metastasis, and the expression levels of AQGPs are closely linked to the prognosis of cancer patients. The expression patterns of AQPs in different cancers as well as the relationship between the expression patterns and prognosis have been reviewed (Wang et al. 2022). The role of AQP5 in the biology of lung adenocarcinoma as well as its prognostic value have been reviewed (Jaskiewicz et al. 2023).

The known aquaporins cluster loosely together on a pylogenetic tree as do the known glycerol facilitators. MIP family proteins are believed to form aqueous pores that selectively allow passive transport of their solute(s) across the membrane with minimal apparent recognition. Aquaporins selectively transport water (but not glycerol) while glycerol facilitators selectively transport glycerol but not water. Some aquaporins can transport NH3 and CO2. Glycerol facilitators function as solute nonspecific channels, and may transport glycerol, dihydroxyacetone, propanediol, urea and other small neutral molecules in physiologically important processes. Some members of the family, including the yeast Fps1 protein (TC #1.A.8.5.1) and tobacco NtTIPa (TC #1.A.8.10.2) may transport both water and small solutes. A constriction within the pore, the aromatic/arginine (ar/R) selectivity filter, is thought to control solute permeability: narrow channels conduct water, whilst wider channels permit passage of solutes. Substrate discrimination depends on a complex interplay between the solute, pore size, and polarity (Kitchen et al. 2019). Brain fluid can be secreted against an osmotic gradient, suggesting that conventional osmotic water flow via aquaporins may not fully describe transmembrane fluid transport in the brain (MacAulay 2021). Aquaporins are essential to maintain motility and membrane lipid architecture during mammalian sperm capacitation (Delgado-Bermúdez et al. 2021). The effects of Aloe-Emodin on the expression of brain aquaporins and secretion of neurotrophic factors has been reported (Liu et al. 2023). AQPs are expressed in various parts of the body, and the unique roles they play in tumorigenesis, and the novel therapeutic approaches that could be adopted to treat carcinoma have been reviewed (Bhattacharjee et al. 2024).

Calamita et al. 2018 review the expression, regulation and physiological roles of AQPs in adipose tissue, liver and endocrine pancreas that are involved in energy metabolism. The review also summarizes the involvement of AQPs in metabolic disorders, such as obesity, diabetes and liver diseases. Challenges and recent advances related to pharmacological modulation of AQPs expression and function to control and treat metabolic diseases are discussed (Calamita et al. 2018). Jain et al. 2018 have shown that an intra-helical salt-bridge in the Loop E half-helix can influence the transport properties of AQP1 and GlpF channels.  AQPs are homotetramers with two conserved asparagine-proline-alanine (NPA) motifs embedding in the plasma membrane. The cellular functions of aquaporins are regulated mainly by posttranslational modifications, e.g., phosphorylation, ubiquitination, glycosylation, subcellular distribution, degradation, and protein interactions. Aquaporins, in particular, AQP2, play important roles in some disease conditions such as water loss and gain (Li et al. 2020). The expression of AQP-1, -3, -4, -5, -8 and -9 were documented in the digestive system, where these six AQP isoforms serve essential roles including mediating the transmembrane water transport and regulating the secretion of gastrointestinal (GI) fluids, consequently facilitating the digestion and absorption of GI contents (Liao et al. 2021). The expression levels of AQPs are controlled by various factors, and AQPs can stimulate various signaling pathways; however, aberrant expression of AQPs in the GI tracts are associated with the initiation and development of numerous diseases (Liao et al. 2021). Altered iris aquaporin expression and aqueous humor osmolality in glaucoma have been compared (Huang et al. 2021).

Zardoya and Villalba (2001) have conducted phylogenetic analyses of the MIP family, analyzing 153 homologues. They divided the proteins into six major 'paralogous' groups: (1) GLPs, or glycerol-transporting channel proteins, which include mammalian AQP3, AQP7, and AQP9, several nematode paralogues, a yeast paralogue, and Escherichia coli GLP; (2) AQPs, or aquaporins, which include metazoan AQP0, AQP1, AQP2, AQP4, AQP5, and AQP6; (3) PIPs, or plasma membrane intrinsic proteins of plants, which include PIP1 and PIP2; (4) TIPs, or tonoplast intrinsic proteins of plants, which include αTIP, γTIP, and δTIP; (5) NODs, or nodulins of plants; and (6) AQP8s, or metazoan aquaporin 8 proteins. Of these groups, AQPs, PIPs, and TIPs cluster together as noted above. Wild and domesticated olive species have 52 and 79 genes encoding full-length AQP sequences, respectively (Faize et al. 2020). They fall into five established subfamilies: PIP, TIP, NIP, SIP, and XIP and their substrate specificities and cellular localizations were predicted (Faize et al. 2020). AQPs' selectivities are not exclusively shaped by pore-lining residues but are also determined by the relative arrangement of transmembrane helices (Gössweiner-Mohr et al. 2022). Aquaporins in astrocytes have been reviewed (Zhou et al. 2022). The diverse range of substrates conducted by aquaporin family members, particularly those of human origin, have been reviewed (Sachdeva et al. 2022), and current knowledge of the AQP interactomes and the molecular basis and functional significance of these protein-protein interactions in health and diseases have also been reviewed (Törnroth-Horsefield et al. 2022). Aquaporins in the digestive system have similarly been reviewed (Ye et al. 2023). Their functions and mechanisms have also been reviewed (Calamita 2023).

In agreement with their divergent sequences, human AQP1-9 have very different physiological functions. They are involved in (1) nephrogenic diabetes insipidus, (2) brain water balance and hearing and (3) salivary secretion (Li and Verkman, 2001).  Bacterial homologues also have diverse functions.  Two proteins in E. coli function as water and glycerol transporters, respectively.  Lactobacillus plantarum has 6 homologues, some of which transport water, glycerol and dihydroxyacetone, and some which transporter these compounds as well as D,L-lactic acid (Bienert et al. 2013).  The pH sensitivities of Aqp0 channels in lenses of tetraploid and diploid teleosts have been reported (Chauvigné et al. 2015).  In the heart, AQPs are implicated in proper cardiac water homeostasis and energy balance as well as heart failure and arsenic cardiotoxicity (Verkerk et al. 2019). Because of their glycerol permeability, aquaglyceroporins are involved in energy homeostasis. Calamita and Delporte 2021 provided an overview of the functional implication and control of aquaglyceroporins in tissues involved in energy metabolism, i.e. liver, adipose tissue and the endocrine pancreas. The expression, role and (dys)regulation of aquaglyceroporins in disorders affecting energy metabolism is also addressed. Aquaporins (AQPs) are involved in autoimmune diseases including neuromyelitis optica, Sjogren's syndrome and rheumatoid arthritis. Both autoantibodies against AQPs and altered expression and/or trafficking of AQPs in various tissue cell types as well as inflammatory cells play key roles in pathogenesis of autoimmune diseases. Detection of autoantibodies against AQP4 in the central nervous system has paved the way for a deeper understanding in disease pathophysiology (Delporte and Soyfoo 2022).

Several reports of MIP family proteins transporting ions may or may not be physiologically significant. For example, the influx of arsenite and antimonite via the Fps1 protein into yeast cells is well documented (Wysocki et al., 2001). Similarly, these compounds are taken up via aquaporins in Leishmania (Gourbal et al., 2004). Moreover, AQP6 of renal epithelia have been reported to transport anions at low pH (Yasui et al., 1999). Demonstration of the involvement of the cyanobacterial channel protein (TC #1.A.8.4.1) in copper homeostasis suggests that it may transport Cu2+. Finally, Yang et al. (2005) showed that arsenite exists the Mesorhizobium meliloti cell by downhill movement through AqpS (1.A.8.15.1). The physiological functions of many MIP family proteins are unknown. Differential expression of aquaporin genes and the influence of environmental hypertonicity on their expression in juveniles of air-breathing stinging catfish (Heteropneustes fossilis) has been examined (Chutia et al. 2022). The results show that AQPs play crucial roles in maintaining the water and ionic balances under anisotonic conditions, even at the early developmental stages of stinging catfish.  In humans, AQP1 is present in myoepithelial cells and in endothelial cells of small blood vessels; AQP3 shows basolateral plasmamembrane localization in glandular endpieces, and AQP5 is localized at the apical cytomembrane in serous and mucous glandular cells and at the lateral membrane in serous cells (Stoeckelhuber et al. 2023).

MIP family channels consist of homotetramers (e.g., GlpF of E. coli; TC #1.A.8.1.1, AqpZ of E. coli; TC #1.A.8.3.1, and MIP or Aqp0 of Bos taurus; TC #1.A.8.8.1). Each subunit spans the membrane six times as putative α-helices and arose from a 3-spanner-encoding genetic element by a tandem, intragenic duplication event. The two halves of the proteins are therefore of opposite orientation in the membrane. However, a well-conserved region between TMSs 2 and 3 and TMSs 5 and 6 dip into the membrane, each loop forming a half TMS. A voltage-related gating mechanism involving the conserved arginine of the channel's main constriction was captured for human aquaporins through molecular dynamics studies. Mom et al. 2020 showed that this voltage-gating is probably conserved among members of this family and that the underlying mechanism may explain part of plant AQPs diversity when contextualized to high ionic concentrations provoked by drought.

Several MIPs within all domains of life have been shown to facilitate the diffusion of reduced and non-charged species of the metalloids silicon, boron, arsenic and antimony (Bienert et al., 2008). Metalloids encompass a group of biologically important elements ranging from the essential to the highly toxic. Consequently, all organisms require efficient membrane transport systems to control the exchange of metalloids with the environment. Genetic evidence has demonstrated a crucial role for specific MIPs in metalloid homeostasis (Bienert et al., 2008). Permeation through each monomer of a tetrameric Aqp is consistent with closed and open states, introducing the term 'gating mechanism' into the field (Ozu et al. 2022).

The crystal structure of the glycerol facilitator of E. coli was solved at 2.2 Å resolution (Fu et al., 2000). Glycerol molecules line up in single file within the amphipathic channel. In the narrow selectivity filter of the channel, the glycerol alkyl backbone is wedged against a hydrophobic corner, and successive hydroxyl groups form hydrogen bonds with a pair of acceptor and donor atoms. The two conserved D-P-A motifs in the loops between TMSs 2 and 3 and TMSs 5 and 6 form the interface between the two duplicated halves of each subunit. Thus each half of the protein forms 3.5 TMSs surrounding the channel. The structure explains why GlpF is selectively permeable to straight chain carbohydrates, and why water and ions are excluded. Aquaporin-1 (AQP1) and the bacterial glycerol facilitator, GlpF can transport O2, CO2, NH3, glycerol, urea, and water to varying degrees. For small solutes permeating through AQP1, a remarkable anticorrelation between permeability and solute hydrophobicity was observed whereas the opposite trend was observed for permeation through the membrane (Hub and Groot, 2008). AQP1 is thus a selective filter for small polar solutes, whereas GlpF is highly permeable to small solutes and less permeable to larger solutes. 

Aquaporin-1 (Aqp1) from the human red blood cell has been solved by x-ray crystallography to 3.8 Å resolution (Murata et al., 2000). The aqueous pathway is lined with conserved hydrophobic residues that permit rapid water transport. Water selectivity is due to a constriction of the inner pore diameter to about 3 Å over the span of a single residue, superficially similar to that in the glycerol facilitator of E. coli. The role of aquaporins in corneal healing post chemical injury has been described (Bhend et al. 2023).

AqpZ, a homotetramer (tAqpZ) of four water-conducting channels that facilitate rapid water movements across the plasma membrane of E. coli, has been solved to 3.2 Å resolution. All channel-lining residues in the four monomeric channels are found orientated in nearly identical positions with one marked exception at the narrowest channel constriction, where the side chain of a conserved Arg-189 adopts two distinct conformational orientations. In one of the four monomers, the guanidino group of Arg-189 points toward the periplasmic vestibule, opening up the constriction to accommodate the binding of a water molecule through a tridentate H-bond. In the other three monomers, the Arg-189 guanidino group bends over to form an H-bond with carbonyl oxygen of Thr-183 occluding the channel. Therefore, the tAqpZ structure reveals two distinct Arg-189 conformations associated with water permeation through the channel constrictions. Alternating between the two Arg-189 conformations disrupts continuous flow of water, thus regulating the open probability of the water pore. Further, the difference in Arg-189 displacements is correlated with a strong electron density found between the first transmembrane helices of two open channels, suggesting that the observed Arg-189 conformations are stabilized by asymmetrical subunit interactions in tAqpZ (Jiang et al., 2006). 

Plants exhibits high diversity in aquaporin isoforms and broadly classified into five different subfamilies on the basis of phylogenetic distribution and subcellular occurrence: plasma membrane intrinsic proteins (PIPs), tonoplast intrinsic proteins (TIPs), nodulin 26-like proteins (NIPs), small basic intrinsic proteins (SIPs) and uncharacterized intrinsic proteins (XIPs) (Singh et al. 2020). The gating mechanism of aquaporin channels is regulated by post-translational modifications such as phosphorylation, methylation, acetylation, glycosylation, and deamination. Aquaporin expression and transport functions are also modulated by the various phytohormone-mediated signalling in plants. Combined physiology and transcriptome analyses revealed the role of aquaporins in regulating hydraulic conductance in roots and leaves. Aquaporin activities during solute transport, plant development, abiotic stress response, and plant-microbe symbiosis have been reviewed (Singh et al. 2020). Plant aquaporin gating is reversed by phosphorylation on intracellular loop D as estimated using evidence from molecular dynamics simulations (Mom et al. 2023).


The 3-D structures of the open and closed forms of plant aquaporins, PIP1 and PIP2, have been solved (Törnroth-Horsefield et al., 2006). In the closed conformation, loop D caps the channel from the cytoplasm and thereby occludes the pore. In the open conformation, loop D is displaced up to 16 Å, and this movement opens a hydrophobic gate blocking the channel entrance from the cytoplasm. These results reveal a molecular gating mechanism which appears conserved throughout all plant plasma membrane aquaporins. In plants it regulates water intake/export in response to water availability and cytoplasmic pH during anoxia (Törnroth-Horsefield et al., 2006).

43 AQP genes were identified in the forage crop Medicago sativa. The MsAQP proteins clustered into four subfamilies based on sequence similarity and phylogenetic relationship, including 17 TIPs, 14 NIPs, 9 PIPs and 3 SIPs (Luo et al. 2022). Analyses on cis-acting elements in the promoter regions of MsAQP genes revealed the presence of multiple and diverse stress-responsive and hormone-responsive cis-acting elements. By analyzing the gene expression data of M. truncatula, ten representative MtAQP genes were responsive to NaCl or drought stress. By analyzing the sequence similarity and phylogenetic relationship, the corresponding ten salt- or drought-responsive AQP genes in M. sativa, including three MsTIPs, three MsPIPs and four MsNIPs. The qPCRs showed that the relative expression levels of these ten MsAQP genes responded differently to NaCl or drought treatment in M. sativa. Most MsAQP genes were preferentially expressed in roots or leaves (Luo et al. 2022).

The MIP superfamily includes three functional subfamilies: aquaporins, aquaglyceroporins and S-aquaporins. (1) The aquaporins (AQPs) are water selective. (2) The aquaglyceroporins are permeable to water, but also to other small uncharged molecules. (3) The third subfamily, with little conserved amino acid sequences around the NPA boxes, include 'superaquaporins' (S-aquaporins).The phylogeny of insect MIP family channels has been published (Finn et al. 2015). The arylsulfonamide AqB011 which selectively blocks the central ion pore of mammalian AQP1 has been shown to impair migration of HT29 colon cancer cells. Traditional herbal medicines are sources of selective AQP1 inhibitors that also slow cancer cell migration (Kourghi et al. 2018).

13 isoforms of mammalian aquaporins (AQP0 - AQP12),are known, nine of which localize to different parts of the renal tubular epithelium.  Additional transport functions of renal AQPs (AQP3, AQP6, AQP7 and AQP8) are known. Aquaglyceroporins are most probably key elements in the renal regulation of nitrogen balance and maintenance of the correct pH of body fluids (Michalek 2016). In human sperm, AQP3 and AQP11 are expressed mainly in the tail, AQP7 in the head and AQP8 in the midpiece (Pellavio and Laforenza 2021). AQPs are important for the normal functioning of sperm to ensure normal fertility. AQP3, AQP7 and AQP11 are involved in sperm volume regulation, a key role for fertility because osmoadaptation protects the sperm against swelling and tail bending that could affect sperm motility. AQP8 has a fundamental role in regulating the elimination of hydrogen peroxide, the most abundant reactive oxygen species (ROS), and therefore plays a role in the response to oxidative stress (Pellavio and Laforenza 2021). 

Otitis media (OM) refers to inflammatory diseases of the middle ear (ME), regardless of cause or pathological mechanism. The expression of aquaporins (AQPs) in the ME and Eustachian tube (ET) is relevant. Eleven types of AQPs, AQP1 to AQP11, have been found to be expressed in mammalian ME and ET (Jung et al. 2017). The distribution and levels of expression of AQPs depend on the presence or absence of inflammation. Fluid accumulation in the ME and ET is a common mechanism for all types of OM, causing edema in the tissue and inducing inflammation involving various AQPs. The expression patterns of several AQPs, especially AQP1, 4 and 5, may have immunological functions in OM.

Some classes of AQPs conduct ions, glycerol, urea, CO2 , nitric oxide, and other small solutes. Ion channel activity has been demonstrated for mammalian AQPs 0, 1, 6, Drosophila big brain (BIB), soybean nodulin 26, and rockcress AtPIP2;1 (Kourghi et al. 2017). Classification of AQPs into three categories (orthodox AQPs, aquaglyceroporins and superaquaporins) is based on their sequence similarities and substrate selectivities. In the male reproductive tract of mammals, most AQPs (except AQP6 and AQP12) are found in different organs (including testis, efferent ducts and epididymis). AQP1 and AQP9 are the most abundant AQPs in the efferent ducts and epididymis and play a crucial role for the secretion/reabsorption dynamics of luminal fluid during sperm transport and maturation. AQP3, AQP7, AQP8 and AQP11 are the most abundant AQPs in sperm and are involved in the regulation of their volumes, which is required for the differentiation of spermatids into spermatozoa during spermatogenesis, as well as in sperm transit along environments of different osmolality (male and female reproductive tracts). Mounting evidence indicates that AQP3, AQP7 and AQP11 are involved in cryotolerance as well as the sperm response to variations of osmolality and to freeze-thawing procedures (Yeste et al. 2017).

In mammals, aquaporins are subdivided into classical aquaporins that are permeable to water; aquaglyceroporins that are permeable to water, glycerol and urea; peroxiporins that facilitate the diffusion of H2O2 through cell membranes; and so called unorthodox aquaporins. Aquaporins ensure important physiological functions in both exocrine and endocrine pancreas and are involved in pancreatic fluid and insulin secretion. Modification of aquaporin expression and/or subcellular localization may be involved in the pathogenesis of pancreatic insufficiencies, diabetes and pancreatic cancer (Arsenijevic et al. 2019).

Mechanisms that drive the development of multiple inflammatory diseases that occur in the nose and contribute to the process of olfactory recognition of compounds entering the nasal cavity involve the action of water channels such as AQPs. Jung et al. 2020 reviewed the relationship between AQPs and rhinologic conditions, focusing on the current state of knowledge and mechanisms that link AQPs and rhinologic conditions. Key conclusions include the following: (1) Various AQPs are expressed in both nasal mucosa and olfactory mucosa; (2) the expression of AQPs in these tissues is different in inflammatory diseases such as AR or CRS, as compared with that in normal tissues; (3) the expression of AQPs in CRS differs depending on the presence or absence of nasal polyps; and (4) the expression of AQPs in tissues associated with olfaction is different from that in the respiratory epithelium.

Water homeostasis plays a crucial role in different reproductive processes, e.g., oocyte transport, hormonal secretion, completion of successful fertilization, blastocyst formation, pregnancy, and birth (Kordowitzki et al. 2020). Further, aquaporins are involved in the process of spermatogenesis, and they have been reported to be involved in the storage of spermatozoa. Aquaporins are relevant for seveeral physiological functions in the female reproductive system, and they are relevant to different pathologies in the female reproductive system. Four Impatiens walleriana aquaporins: IwPIP1;4, IwPIP2;2, IwPIP2;7 and IwTIP4;1, have been characteerized (Đurić et al. 2021). Drought stress  affected the aquaporin expression in I. walleriana leaves, which was up- or downregulated depending on stress intensity. Expression of IwPIP2;7 was the most affected of these four aquaporins. At 15% and 5% soil moisture and recovery from 15% and 5% soil moisture, IwPIP2;7 expression significantly decreased and increased, respectively. Aquaporins IwPIP1;4 and IwTIP4;1 had lower expression than IwPIP2;7, with moderate expression changes in response to drought and recovery, while IwPIP2;2 expression was of significance only in recovered plants (Đurić et al. 2021).

Humans contain 13 AQPs (AQP0-AQP12) which are divided into three sub-classes namely orthodox aquaporin (AQP0, 1, 2, 4, 5, 6, and 8), aquaglyceroporin (AQP3, 7, 9, and 10) and super or unorthodox aquaporin (AQP11 and 12) based on their pore selectivity. They are involved in a wide variety of non-infectious diseases including cancer, renal dysfunction, neurological disorders, epilepsy, skin diseases, metabolic syndrome, and even cardiac diseases. AQPs can be regulated by microbial and parasitic infections that suggest their involvement in microbial pathogenesis, inflammation-associated responses and AQP-mediated cell water homeostasis. In a review, Azad et al. 2021 examine the involvement of AQPs in infectious and non-infectious diseases and potential AQPs-target modulators. AQP structures, tissue-specific distributions and physiological relevance, functional diversity and regulation were considered. Human AQPs play roles in edema, glaucoma, nephrogenic diabetes insipidus, oxidative stress, sepsis, cancer, and metabolic dysfunctions (da Silva et al. 2022). The 13 AQPs draw cell lineage-specific expression patterns related to cell native functions. Compelling evidence indicates that AQPs have potential as biomarkers and targets for therapeutic intervention. AQP9 is most expressed in the liver, influencing general metabolic and redox balance due to its aquaglyceroporin and peroxiporin activities. AQP9 levels in other tissues are altered in several human diseases, such as liver injury, inflammation, cancer, infertility, and immune disorders (da Silva et al. 2022). Aqp activities are sensitive to mercury ions (Hg2+). While most aquaporins are inhibited by Hg2+, several are activated. Xie et al. 2022 investigated AqpZ of E. coli (TC# 1.A.8.3.1) inhibition and human AQP6 (TC# 1.A.8.8.4) activation. Based on the structure of the Hg-AqpZ complex, they found that pore closure was caused by mercury-induced conformational changes of the key residue R189 in the selectivity filter region, while pore opening was caused by conformational changes of residues H181 and R196 in the selectivity filter region in AQP6. Both conformational changes were caused by the disruption of the H-bond network of R189/R196 by mercury (Xie et al. 2022). 

As small ectotherms, insects need to cope with the challenges of winter cold by regulating their water content. Aquaporins (AQPs) are key players to enhance cold resistance by mediating essential homeostatic processes in many animals but remain poorly characterized in insects. Agriphila aeneociliella is a winter wheat pest in China, and its early-stage larvae have strong tolerance to low temperature stress. Six AQP genes were identified, which belong to five AQP subfamilies (RPIP, Eglp, AQP12L, PRIP, DRIP) (Zhao et al. 2023). All of them contained six hydrophobic TMSs and two relatively conservative Asparagine-Proline-Alanine motifs. The three-dimensional homology modeling showed that the six TMSs folded into an hourglass-like shape, and the imperceptible replacement of four ar/R residues in the contraction region had critical effects on changing the pore size of the channels. Moreover, the transcript levels of AaAQPs 1, 3, and 6 increased significantly with the treatment time below 0 degrees C. Combined with the results of pore radius variations, it was suggested that AaAQP1 and AaAQP3 are the key anti-hypothermia proteins in A. aeneociliella by regulating rapid cell dehydration and allowing the influx of extracellular cold resistance molecules, thus avoiding death in winter.

The generalized transport reaction for channel proteins of the MIP family is:

Reversible H2O (out) → H2O (in) (e.g., aquaporins)


Reversible solute (out) → solute (in) (e.g., glycerol or H2O2 facilitators).

This family belongs to the Major Intrinsic Protein (MIP) Superfamily.



Bienert, G.P., M.D. Schüssler, and T.P. Jahn. (2008). Metalloids: essential, beneficial or toxic? Major intrinsic proteins sort it out. Trends Biochem. Sci. 33: 20-26.

Aggeli, I.K., A. Kapogiannatou, F. Paraskevopoulou, and C. Gaitanaki. (2021). Differential response of cardiac aquaporins to hyperosmotic stress; salutary role of AQP1 against the induced apoptosis. Eur Rev Med Pharmacol Sci 25: 313-325.

Ahmadpour, D., E. Maciaszczyk-Dziubinska, R. Babazadeh, S. Dahal, M. Migocka, M. Andersson, R. Wysocki, M.J. Tamás, and S. Hohmann. (2016). The MAP kinase Slt2 modulates arsenite transport through the aquaglyceroporin Fps1. FEBS Lett. [Epub: Ahead of Print]

Ahmed, J., A. Ismail, L. Ding, A.J. Yool, and F. Chaumont. (2023). A new method to measure aquaporin-facilitated membrane diffusion of hydrogen peroxide and cations in plant suspension cells. Plant Cell Environ. [Epub: Ahead of Print]

Ahmed, S. and Y. Kim. (2019). An aquaporin mediates cell shape change required for cellular immunity in the beet armyworm, Spodoptera exigua. Sci Rep 9: 4988.

Ala, M., R. Mohammad Jafari, A. Hajiabbasi, and A.R. Dehpour. (2021). Aquaporins and diseases pathogenesis: From trivial to undeniable involvements, a disease-based point of view. J Cell Physiol 236: 6115-6135.

Amanzougaghene, N., S. Tajeri, S. Yalaoui, A. Lorthiois, V. Soulard, A. Gego, A. Rametti, V. Risco-Castillo, A. Moreno, M. Tefit, G.J. van Gemert, R.W. Sauerwein, J.C. Vaillant, P. Ravassard, J.L. Pérignon, P. Froissard, D. Mazier, and J.F. Franetich. (2021). The Host Protein Aquaporin-9 is Required for Efficient Sporozoite Entry into Human Hepatocytes. Front Cell Infect Microbiol 11: 704662.

Amezcua-Romero JC., Pantoja O. and Vera-Estrella R. (2010). Ser123 is essential for the water channel activity of McPIP2;1 from Mesembryanthemum crystallinum. J Biol Chem. 285(22):16739-47.

Amira, M.B., M. Faize, M. Karlsson, M. Dubey, M. Frąc, J. Panek, B. Fumanal, A. Gousset-Dupont, J.L. Julien, H. Chaar, D. Auguin, R. Mom, P. Label, and J.S. Venisse. (2021). Fungal -Intrinsic Protein Aquaporin from : Structural and Functional Considerations. Biomolecules 11:.

Araya-Secchi, R., J.A. Garate, D.S. Holmes, and T. Perez-Acle. (2011). Molecular dynamics study of the archaeal aquaporin AqpM. BMC Genomics 12Suppl4: S8.

Arsenijevic, T., J. Perret, J.L. Van Laethem, and C. Delporte. (2019). Aquaporins Involvement in Pancreas Physiology and in Pancreatic Diseases. Int J Mol Sci 20:.

Assentoft, M., S. Kaptan, H.P. Schneider, J.W. Deitmer, B.L. de Groot, and N. MacAulay. (2016). Aquaporin 4 as a NH3 Channel. J. Biol. Chem. [Epub: Ahead of Print]

Au, C.G., T.L. Butler, J.R. Egan, S.T. Cooper, H.P. Lo, A.G. Compton, K.N. North, and D.S. Winlaw. (2008). Changes in skeletal muscle expression of AQP1 and AQP4 in dystrophinopathy and dysferlinopathy patients. Acta Neuropathol 116: 235-246.

Ayadi, M., D. Cavez, N. Miled, F. Chaumont, and K. Masmoudi. (2011). Identification and characterization of two plasma membrane aquaporins in durum wheat (Triticum turgidum L. subsp. durum) and their role in abiotic stress tolerance. Plant Physiol. Biochem 49: 1029-1039.

Azad, A.K., T. Raihan, J. Ahmed, A. Hakim, T.H. Emon, and P.A. Chowdhury. (2021). Human Aquaporins: Functional Diversity and Potential Roles in Infectious and Non-infectious Diseases. Front Genet 12: 654865.

Balasaheb Karle, S., K. Kumar, S. Srivastava, and P. Suprasanna. (2020). Cloning, in silico characterization and expression analysis of TIP subfamily from rice (Oryza sativa L.). Gene 761: 145043.

Beese-Sims, S.E., J. Lee, and D.E. Levin. (2011). Yeast Fps1 glycerol facilitator functions as a homotetramer. Yeast 28: 815-819.

Beitz, E., S. Pavlovic-Djuranovic, M. Yasui, P. Agre, and J.E. Schultz. (2004). Molecular dissection of water and glycerol permeability of the aquaglyceroporin from Plasmodium falciparum by mutational analysis. Proc. Natl. Acad. Sci. USA 101: 1153-1158.

Bellati, J., K. Alleva, G. Soto, V. Vitali, C. Jozefkowicz, and G. Amodeo. (2010). Intracellular pH sensing is altered by plasma membrane PIP aquaporin co-expression. Plant Mol. Biol. 74: 105-118.

Ben Amira, M., R. Mom, D. Lopez, H. Chaar, A. Khouaja, V. Pujade-Renaud, B. Fumanal, A. Gousset-Dupont, G. Bronner, P. Label, J.L. Julien, M.A. Triki, D. Auguin, and J.S. Venisse. (2018). MIP diversity from Trichoderma: Structural considerations and transcriptional modulation during mycoparasitic association with Fusarium solani olive trees. PLoS One 13: e0193760.

Berland, S., T.L. Toft-Bertelsen, I. Aukrust, J. Byska, M. Vaudel, L.A. Bindoff, N. MacAulay, and G. Houge. (2018). A de novo Ser111Thr variant in aquaporin-4 in a patient with intellectual disability, transient signs of brain ischemia, transient cardiac hypertrophy, and progressive gait disturbance. Cold Spring Harb Mol Case Stud 4:.

Berliner, J.A., M.A. Lam, E. Najafi, S.J. Hemley, L.E. Bilston, and M.A. Stoodley. (2023). Aquaporin-4 expression and modulation in a rat model of post-traumatic syringomyelia. Sci Rep 13: 9662.

Berny, M.C., D. Gilis, M. Rooman, and F. Chaumont. (2016). Single mutations in the transmembrane domains of maize plasma membrane aquaporins affect the activity of the monomers within a heterotetramer. Mol Plant. [Epub: Ahead of Print]

Berthaud A., Manzi J., Perez J. and Mangenot S. (2012). Modeling detergent organization around aquaporin-0 using small-angle X-ray scattering. J Am Chem Soc. 134(24):10080-8.

Berthaud, A., F. Quemeneur, M. Deforet, P. Bassereau, F. Brochard-Wyart, and S. Mangenot. (2015). Spreading of porous vesicles subjected to osmotic shocks: the role of aquaporins. Soft Matter. [Epub: Ahead of Print]

Bertl, A., and R. Kaldenhoff. (2007). Function of a separate NH3-pore in Aquaporin TIP2;2 from wheat. FEBS Lett. 581: 5413-5417.

Bhattacharjee, A., A. Jana, S. Bhattacharjee, S. Mitra, S. De, B.S. Alghamdi, M.Z. Alam, A.B. Mahmoud, Z. Al Shareef, W.M. Abdel-Rahman, C. Woon-Khiong, A. Alexiou, M. Papadakis, and G.M. Ashraf. (2024). The role of Aquaporins in tumorigenesis: implications for therapeutic development. Cell Commun Signal 22: 106.

Bhend, M.E., D. Kempuraj, N.R. Sinha, S. Gupta, and R.R. Mohan. (2023). Role of aquaporins in corneal healing post chemical injury. Exp Eye Res 228: 109390. [Epub: Ahead of Print]

Bienert, G.P., A.L. Moller, K.A. Kristiansen, A. Schulz, I.M. Moller, J.K. Schjoerring, and T.P. Jahn. (2007). Specific aquaporins facilitate the diffusion of hydrogen peroxide across membranes. J. Biol. Chem. 282: 1183-1192.

Bienert, G.P., B. Desguin, F. Chaumont, and P. Hols. (2013). Channel-mediated lactic acid transport: a novel function for aquaglyceroporins in bacteria. Biochem. J. 454: 559-570.

Bienert, M.D., T.A. Diehn, N. Richet, F. Chaumont, and G.P. Bienert. (2018). Heterotetramerization of Plant PIP1 and PIP2 Aquaporins Is an Evolutionary Ancient Feature to Guide PIP1 Plasma Membrane Localization and Function. Front Plant Sci 9: 382.

Bonilla-Correal, S., F. Noto, E. Garcia-Bonavila, J.E. Rodríguez-Gil, M. Yeste, and J. Miro. (2017). First evidence for the presence of aquaporins in stallion sperm. Reprod Domest Anim 52Suppl4: 61-64.

Bonosi, L., U.E. Benigno, S. Musso, K. Giardina, R.M. Gerardi, L. Brunasso, R. Costanzo, F. Paolini, F. Buscemi, C. Avallone, V. Gulino, D.G. Iacopino, and R. Maugeri. (2023). The Role of Aquaporins in Epileptogenesis-A Systematic Review. Int J Mol Sci 24:.

Bui, L.C., C. Tomkiewicz, S. Pierre, A. Chevallier, R. Barouki, and X. Coumoul. (2016). Regulation of Aquaporin 3 Expression by the AhR Pathway Is Critical to Cell Migration. Toxicol Sci 149: 158-166.

Buzhynskyy, N., J.F. Girmens, W. Faigle, S. Scheuring. (2007). Human cataract lens membrane at subnanometer resolution. J. Mol. Biol. 374: 162-169.

Byrt, C.S., M. Zhao, M. Kourghi, J. Bose, S.W. Henderson, J. Qiu, M. Gilliham, C. Schultz, M. Schwarz, S.A. Ramesh, A. Yool, and S. Tyerman. (2017). Non-selective cation channel activity of aquaporin AtPIP2;1 regulated by Ca and pH. Plant Cell Environ 40: 802-815.

Calamita, G. (2023). Advances in Aquaporins. Cells 12:.

Calamita, G. and C. Delporte. (2021). Involvement of aquaglyceroporins in energy metabolism in health and disease. Biochimie 188: 20-34.

Calamita, G. and C. Delporte. (2023). Insights into the Function of Aquaporins in Gastrointestinal Fluid Absorption and Secretion in Health and Disease. Cells 12:.

Calamita, G., B. Kempf, M. Bonhivers, W.R. Bishai, E. Bremer, and P. Agre. (1998). Regulation of the Escherichia coli water channel gene aqpZ. Proc. Natl. Acad. Sci. USA 95: 3627-3631.

Calamita, G., J. Perret, and C. Delporte. (2018). Aquaglyceroporins: Drug Targets for Metabolic Diseases? Front Physiol 9: 851.

Calamita. G. (2000). The Escherichia coli aquaporin-Z water channel. Mol. Microbiol. 37: 254-262.

Cao, Y., H. Wei, S. Jiang, T. Lu, P. Nie, C. Yang, N. Liu, I. Lee, X. Meng, W. Wang, and Z. Yuan. (2023). Effect of AQP4 and its palmitoylation on the permeability of exogenous reactive oxygen species: Insights from computational study. Int J Biol Macromol 127568. [Epub: Ahead of Print]

Carbrey, J.M., D.A. Gorelick-Feldman, D. Kozono, J. Praetorius, S. Nielsen, and P. Agre. (2003). Aquaglyceroporin AQP9: solute permeation and metabolic control of expression in liver. Proc. Natl. Acad. Sci. USA 100: 2945-2950.

Carbrey, J.M., M. Bonhivers, J.D. Boeke, and P. Agre. (2001). Aquaporins in Saccharomyces: characterization of a second functional water channel protein. Proc. Natl. Acad. Sci. USA 98: 1000-1005.

Carrageta, D.F., R.L. Bernardino, G. Soveral, G. Calamita, M.G. Alves, and P.F. Oliveira. (2019). Aquaporins and male (in)fertility: Expression and role throughout the male reproductive tract. Arch Biochem Biophys 108222. [Epub: Ahead of Print]

Catalán-García, M., F. Chauvigné, J.A. Stavang, F. Nilsen, J. Cerdà, and R.N. Finn. (2021). Lineage-level divergence of copepod glycerol transporters and the emergence of isoform-specific trafficking regulation. Commun Biol 4: 643.

Charlestin, V., D. Fulkerson, C.E. Arias Matus, Z.T. Walker, K. Carthy, and L.E. Littlepage. (2022). Aquaporins: New players in breast cancer progression and treatment response. Front Oncol 12: 988119.

Chau, D., K. Ng, T.S. Chan, Y.Y. Cheng, B. Fong, S. Tam, Y.L. Kwong, and E. Tse. (2015). Azacytidine sensitizes acute myeloid leukemia cells to arsenic trioxide by up-regulating the arsenic transporter aquaglyceroporin 9. J Hematol Oncol 8: 46.

Chau, S., A. Fujii, Y. Wang, A. Vandebroek, W. Goda, M. Yasui, and Y. Abe. (2021). Di-lysine motif-like sequences formed by deleting the C-terminal domain of aquaporin-4 prevent its trafficking to the plasma membrane. Genes Cells. [Epub: Ahead of Print]

Chauvigne F., Zapater C., Stavang JA., Taranger GL., Cerda J. and Finn RN. (2015). The pH sensitivity of Aqp0 channels in tetraploid and diploid teleosts. FASEB J. 29(5):2172-84.

Cheng, C., J. Gao, X. Sun, and R.T. Mathias. (2021). Eph-ephrin Signaling Affects Eye Lens Fiber Cell Intracellular Voltage and Membrane Conductance. Front Physiol 12: 772276.

Chevalier, A.S. and F. Chaumont. (2015). The LxxxA motif in the third transmembrane helix of the maize aquaporin ZmPIP2;5 acts as an ER export signal. Plant Signal Behav 10: e990845.

Chiba, Y., N. Mitani, N. Yamaji, and J.F. Ma. (2009). HvLsi1 is a silicon influx transporter in barley. Plant J. 57: 810-818.

Choi, W.G., and D.M. Roberts. (2007). Arabidopsis NIP2;1, a major intrinsic protein transporter of lactic acid induced by anoxic stress. J. Biol. Chem. 282: 24209-24218.

Chrispeels, M.J. and C. Maurel. (1994). Aquaporins: the molecular basis of facilitated water movement through living plant cells? Plant Physiol. 105: 9-13.

Chutia, P., N. Saha, M. Das, and L.M. Goswami. (2022). Differential expression of aquaporin genes and the influence of environmental hypertonicity on their expression in juveniles of air-breathing stinging catfish (Heteropneustes fossilis). Comp Biochem Physiol A Mol Integr Physiol 274: 111314.

Cui, Y. and D.A. Bastien. (2011). Water transport in human aquaporin-4: Molecular dynamics (MD) simulations. Biochem. Biophys. Res. Commun. 412: 654-659.

D''Agostino, C., D. Parisis, C. Chivasso, M. Hajiabbas, M.S. Soyfoo, and C. Delporte. (2023). Aquaporin-5 Dynamic Regulation. Int J Mol Sci 24:.

D''Agostino, C., O.A. Elkashty, C. Chivasso, J. Perret, S.D. Tran, and C. Delporte. (2020). Insight into Salivary Gland Aquaporins. Cells 9:.

da Silva, I.V., S. Garra, G. Calamita, and G. Soveral. (2022). The Multifaceted Role of Aquaporin-9 in Health and Its Potential as a Clinical Biomarker. Biomolecules 12:.

Dai, Y.H., B.R. Liu, H.J. Chiang, and H.J. Lee. (2011). Gene transport and expression by arginine-rich cell-penetrating peptides in Paramecium. Gene 489: 89-97.

Dande, R. and R. Sankararamakrishnan. (2023). dbAQP-SNP: a database of missense single-nucleotide polymorphisms in human aquaporins. Database (Oxford) 2023:.

Danielli, M., J. Marrone, A.M. Capiglioni, and R.A. Marinelli. (2019). Mitochondrial aquaporin-8 is involved in SREBP-controlled hepatocyte cholesterol biosynthesis. Free Radic Biol Med 131: 370-375.

Daniels, M.J., F. Chaumont, T.E. Mirkov, and M.J. Chrispeels. (1996). Characterization of a new vacuolar membrane aquaporin sensitive to mercury at a unique site. Plant Cell 8: 587-599.

Danielsson, A., F. Pontén, L. Fagerberg, B.M. Hallström, J.M. Schwenk, M. Uhlén, O. Korsgren, and C. Lindskog. (2014). The human pancreas proteome defined by transcriptomics and antibody-based profiling. PLoS One 9: e115421.

de Paula Santos Martins, C., A.M. Pedrosa, D. Du, L.P. Gonçalves, Q. Yu, F.G. Gmitter, Jr, and M.G. Costa. (2015). Genome-Wide Characterization and Expression Analysis of Major Intrinsic Proteins during Abiotic and Biotic Stresses in Sweet Orange (Citrus sinensis L. Osb.). PLoS One 10: e0138786.

De Rosa, A., A. Watson-Lazowski, J.R. Evans, and M. Groszmann. (2020). Genome-wide identification and characterisation of Aquaporins in Nicotiana tabacum and their relationships with other Solanaceae species. BMC Plant Biol 20: 266.

Dean, R.M., R.L. Rivers, M.L. Zeide, and D.M. Roberts. (1999). Purification and functional reconstitution of soybean nodulin 26. An aquaporin with water and glycerol transport properties. Biochemistry 38: 347-353.

Debbarma, S., Ashutosh, S. Saini, and S.B. Gowda. (2020). Seasonal effect in expression of AQP1, AQP3 and AQP5 in skin of Murrah buffaloes. J Therm Biol 93: 102727.

Decker, K., M. Page, and A. Aksimentiev. (2017). Nanoscale Ion Pump Derived from a Biological Water Channel. J Phys Chem B 121: 7899-7906.

Deen, P.M.T. and C.H. van Os. (1998). Epithelial aquaporins. Curr. Opin. Cell Biol. 10: 435-442.

Del Puerto, A., J. Pose-Utrilla, A. Simón-García, C. López-Menéndez, A.J. Jiménez, E. Porlan, L.S.M. Pajuelo, G. Cano-García, B. Martí-Prado, &.#.1.9.3.;. Sebastián-Serrano, M.P. Sánchez-Carralero, F. Cesca, G. Schiavo, I. Ferrer, I. Fariñas, M.R. Campanero, and T. Iglesias. (2021). Kidins220 deficiency causes ventriculomegaly via SNX27-retromer-dependent AQP4 degradation. Mol Psychiatry. [Epub: Ahead of Print]

Delgado-Bermúdez, A., M. Llavanera, S. Recuero, Y. Mateo-Otero, S. Bonet, I. Barranco, B. Fernandez-Fuertes, and M. Yeste. (2019). Effect of AQP Inhibition on Boar Sperm Cryotolerance Depends on the Intrinsic Freezability of the Ejaculate. Int J Mol Sci 20:.

Delgado-Bermúdez, A., S. Recuero, M. Llavanera, Y. Mateo-Otero, A. Sandu, I. Barranco, J. Ribas-Maynou, and M. Yeste. (2021). Aquaporins Are Essential to Maintain Motility and Membrane Lipid Architecture During Mammalian Sperm Capacitation. Front Cell Dev Biol 9: 656438.

Delporte, C. and M. Soyfoo. (2022). Aquaporins: Unexpected actors in autoimmune diseases. Autoimmun Rev 21: 103131.

Di Giusto, G., P. Flamenco, V. Rivarola, J. Fernández, L. Melamud, P. Ford, and C. Capurro. (2012). Aquaporin 2-increased renal cell proliferation is associated with cell volume regulation. J. Cell. Biochem. 113: 3721-3729.

Diehn, T.A., M.D. Bienert, B. Pommerrenig, Z. Liu, C. Spitzer, N. Bernhardt, J. Fuge, A. Bieber, N. Richet, F. Chaumont, and G.P. Bienert. (2019). Boron demanding tissues of Brassica napus express specific sets of functional Nodulin26-like Intrinsic Proteins and BOR1 transporters. Plant J. [Epub: Ahead of Print]

Dingwell, D., L.S. Brown, and V. Ladizhansky. (2019). Structure of the Functionally Important Extracellular Loop C of Human Aquaporin 1 Obtained by Solid-State NMR Under Nearly Physiological Conditions. J Phys Chem B. [Epub: Ahead of Print]

Docampo, R., V. Jimenez, S. King-Keller, Z.H. Li, and S.N. Moreno. (2011). The role of acidocalcisomes in the stress response of Trypanosoma cruzi. Adv Parasitol 75: 307-324.

Dong, S.H., S.S. Kim, S.H. Kim, and S.G. Yeo. (2019). Expression of aquaporins in inner ear disease. Laryngoscope. [Epub: Ahead of Print]

Dynowski, M., G. Schaaf, D. Loque, O. Moran, and U. Ludewig. (2008). Plant plasma membrane water channels conduct the signalling molecule H2O2. Biochem. J. 414: 53-61.

Engel, A., Y. Fujiyoshi, and P. Agre. (2000). The importance of aquaporin water channel protein structures. EMBO J. 19: 800-806.

Engel, A., Y. Fujiyoshi, T. Gonen, and T. Walz. (2008). Junction-forming aquaporins. Curr. Opin. Struct. Biol. 18: 229-235.

Eslami, G., M. Ghavami, A.R. Moradi, H. Nadri, and S. Ahmadian. (2020). Molecular Characterization of Aquaglyceroporine: A Novel Mutation in from (MRHO/IR/75/ER). Iran J Parasitol 14: 465-471.

Faize, M., B. Fumanal, F. Luque, J.A. Ramírez-Tejero, Z. Zou, X. Qiao, L. Faize, A. Gousset-Dupont, P. Roeckel-Drevet, P. Label, and J.S. Venisse. (2020). Genome Wild Analysis and Molecular Understanding of the Aquaporin Diversity in Olive Trees ( L.). Int J Mol Sci 21:.

Fan, S., E. Amombo, Y. Yin, G. Wang, S. Avoga, N. Wu, and Y. Li. (2023). Root system architecture and genomic plasticity to salinity provide insights into salt-tolerant traits in tall fescue. Ecotoxicol Environ Saf 262: 115315. [Epub: Ahead of Print]

Fenton, R.A., H.B. Moeller, J.D. Hoffert, M.J. Yu, S. Nielsen, and M.A. Knepper. (2008). Acute regulation of aquaporin-2 phosphorylation at Ser-264 by vasopressin. Proc. Natl. Acad. Sci. U. S. A. 105: 3134-3139.

Figarella, K., M. Rawer, N.L. Uzcategui, B.K. Kubata, K. Lauber, F. Madeo, S. Wesselborg, and M. Duszenko. (2005). Prostaglandin D2 induces programmed cell death in Trypanosoma brucei bloodstream form. Cell Death Differ. 12: 335-346.

Figarella, K., N.L. Uzcategui, Y. Zhou, A. LeFurgey, M. Ouellette, H. Bhattacharjee, and R. Mukhopadhyay. (2007). Biochemical characterization of Leishmania major aquaglyceroporin LmAQP1: possible role in volume regulation and osmotaxis. Mol. Microbiol. 65: 1006-1017.

Figueiredo, B.C., N.R. De Assis, S.B. De Morais, V.P. Martins, N.D. Ricci, R.M. Bicalho, C.d.a.S. Pinheiro, and S.C. Oliveira. (2014). Immunological characterization of a chimeric form of Schistosoma mansoni aquaporin in the murine model. Parasitology 141: 1277-1288.

Finn, R.N., F. Chauvigné, J.A. Stavang, X. Belles, and J. Cerdà. (2015). Insect glycerol transporters evolved by functional co-option and gene replacement. Nat Commun 6: 7814.

Florio, M., A. Engfors, P. Gena, J. Larsson, A. Massaro, S. Timpka, M.K. Reimer, P. Kjellbom, E. Beitz, U. Johanson, M. Rützler, and G. Calamita. (2022). Characterization of the Aquaporin-9 Inhibitor RG100204 In Vitro and in Mice. Cells 11:.

Fontijn, R.D., O.L. Volger, T.C. van der Pouw-Kraan, A. Doddaballapur, T. Leyen, J.M. Baggen, R.A. Boon, and A.J. Horrevoets. (2015). Expression of Nitric Oxide-Transporting Aquaporin-1 Is Controlled by KLF2 and Marks Non-Activated Endothelium In Vivo. PLoS One 10: e0145777.

Frick, A., U.K. Eriksson, F. de Mattia, F. Oberg, K. Hedfalk, R. Neutze, W.J. de Grip, P.M. Deen, and S. Törnroth-Horsefield. (2014). X-ray structure of human aquaporin 2 and its implications for nephrogenic diabetes insipidus and trafficking. Proc. Natl. Acad. Sci. USA 111: 6305-6310.

Froger, A., J.-P. Rolland, P. Bron, V. Lagrée, F. Le Cahérec, S. Deschamps, J.-F. Hubert, I. Pellerin, D. Thomas, and C. Delamarche. (2001). Functional characterization of a microbial aquaglyceroporin. Microbiology 147: 1129-1135.

Fu, D., A. Libson, L.J.W. Miercke, C. Weitzman, P. Nollert, J. Krucinski, and R.M. Stroud. (2000). Structure of a glycerol-conducting channel and the basis for its selectivity. Science 290: 481-486.

Gao, J., X. Wang, Y. Chang, J. Zhang, Q. Song, H. Yu, and X. Li. (2006). Acetazolamide inhibits osmotic water permeability by interaction with aquaporin-1. Anal Biochem 350: 165-170.

Geadkaew, A., J. von Bülow, E. Beitz, S. Tesana, S. Vichasri Grams, and R. Grams. (2015). Bi-functionality of Opisthorchis viverrini aquaporins. Biochimie 108: 149-159.

Geijer C., Ahmadpour D., Palmgren M., Filipsson C., Klein DM., Tamas MJ., Hohmann S. and Lindkvist-Petersson K. (2012). Yeast aquaglyceroporins use the transmembrane core to restrict glycerol transport. J Biol Chem. 287(28):23562-70.

Geistlinger, K., J.D.R. Schmidt, and E. Beitz. (2022). Lactic Acid Permeability of Aquaporin-9 Enables Cytoplasmic Lactate Accumulation via an Ion Trap. Life (Basel) 12:.

Geng, X., J. McDermott, J. Lundgren, L. Liu, K.J. Tsai, J. Shen, and Z. Liu. (2017). Role of AQP9 in transport of monomethyselenic acid and selenite. Biometals 30: 747-755.

Gerbeau, P., J. Güçlü, P. Ripoche, and C. Maurel. (1999). Aquaporin Nt-TIPa can account for the high permeability of tobacco cell vacuolar membrane to small neutral solutes. Plant J. 18: 577-587.

Ghosh, K., C.D. Cappiello, S.M. McBride, J.L. Occi, A. Cali, P.M. Takvorian, T.V. McDonald, and L.M. Weiss. (2006). Functional characterization of a putative aquaporin from Encephalitozoon cuniculi, a microsporidia pathogenic to humans. Int J Parasitol 36: 57-62.

Gonen, T. and T. Walz. (2006). The structure of aquaporins. Q. Rev. Biophys. 39: 361-396.

Gonen, T., P. Sliz, J. Kistler, Y. Cheng, and T. Walz. (2004b). Aquaporin-0 membrane junctions reveal the structure of a closed water pore. Nature 429: 193-197.

Gonen, T., Y. Cheng, J. Kistler, and T. Walz. (2004a). Aquaporin-0 membrane junctions form upon proteolytic cleavage. J. Mol. Biol. 342: 1337-1345.

Gonen, T., Y. Cheng, P. Sliz, Y. Hiroaki, Y. Fujiyoshi, S.C. Harrison, and T. Walz. (2005). Lipid-protein interactions in double-layered two-dimensional AQP0 crystals. Nature 438: 633-638. Erratum in: Nature (2006) 441: 248.

Gössweiner-Mohr, N., C. Siligan, K. Pluhackova, L. Umlandt, S. Koefler, N. Trajkovska, and A. Horner. (2022). The Hidden Intricacies of Aquaporins: Remarkable Details in a Common Structural Scaffold. Small 18: e2202056.

Gotfryd, K., A.F. Mósca, J.W. Missel, S.F. Truelsen, K. Wang, M. Spulber, S. Krabbe, C. Hélix-Nielsen, U. Laforenza, G. Soveral, P.A. Pedersen, and P. Gourdon. (2018). Human adipose glycerol flux is regulated by a pH gate in AQP10. Nat Commun 9: 4749.

Gourbal, B., N. Sonuc, H. Bhattacharjee, D. Legare, S. Sundar, M. Ouellette, B.P. Rosen, and R. Mukhopadhyay. (2004). Drug uptake and modulation of drug resistance in Leishmania by an aquaglyceroporin. J. Biol. Chem. 279: 31010-31017.

Guibourdenche, J., F. Bonnet-Serrano, L. Younes Chaouch, V. Sapin, V. Tsatsaris, D. Combarel, C. Laguillier, and G. Grange. (2021). Amniotic Aaquaporins (AQP) in Normal and Pathological Pregnancies: Interest in Polyhydramnios. Reprod Sci. [Epub: Ahead of Print]

Guo, H., M. Wei, Y. Liu, Y. Zhu, W. Xu, L. Meng, N. Wang, C. Shao, S. Lu, F. Gao, Z. Cui, Z. Wei, F. Zhao, and S. Chen. (2017). Molecular cloning and expression analysis of the aqp1aa gene in half-smooth tongue sole (Cynoglossus semilaevis). PLoS One 12: e0175033.

Hagströmer, C.J., J. Hyld Steffen, S. Kreida, T. Al-Jubair, A. Frick, P. Gourdon, and S. Törnroth-Horsefield. (2023). Structural and functional analysis of aquaporin-2 mutants involved in nephrogenic diabetes insipidus. Sci Rep 13: 14674.

Hara-Chikuma, M., and A.S. Verkman. (2008). Prevention of skin tumorigenesis and impairment of epidermal cell proliferation by targeted aquaporin-3 gene disruption. Mol. Cell. Biol. 28: 326-332.

He, J. and B. Yang. (2019). Aquaporins in Renal Diseases. Int J Mol Sci 20:.

Hedfalk, K., R.M. Bill, J.G. Mullins, S. Karlgren, C. Filipsson, J. Bergstrom, M.J. Tamás, J. Rydström, and S. Hohmann. (2004). A regulatory domain in the C-terminal extension of the yeast glycerol channel Fps1p. J. Biol. Chem. 279: 14954-14960.

Heller, K.B., E.C. Lin, and T.H. Wilson. (1980). Substrate specificity and transport properties of the glycerol facilitator of Escherichia coli. J. Bacteriol. 144: 274-278.

Hemley SJ., Bilston LE., Cheng S., Chan JN. and Stoodley MA. (2013). Aquaporin-4 expression in post-traumatic syringomyelia. J Neurotrauma. 30(16):1457-67.

Henderson, S.W., S. Nourmohammadi, S.A. Ramesh, and A.J. Yool. (2022). Aquaporin ion conductance properties defined by membrane environment, protein structure, and cell physiology. Biophys Rev 14: 181-198.

Hermo, L., D. Krzeczunowicz, and R. Ruz. (2019). Cell specificity of aquaporins 0, 3, and 10 expressed in the testis, efferent ducts, and epididymis of adult rats. J Androl 25: 494-505.

Herraiz, A., F. Chauvigné, J. Cerdà, X. Bellés, and M.D. Piulachs. (2011). Identification and functional characterization of an ovarian aquaporin from the cockroach Blattella germanica L. (Dictyoptera, Blattellidae). J Exp Biol 214: 3630-3638.

Hesler, R.A., J.J. Huang, M.D. Starr, V.M. Treboschi, A.G. Bernanke, A.B. Nixon, S.J. McCall, R.R. White, and G.C. Blobe. (2016). TGF-β-Induced Stromal CYR61 Promotes Resistance to Gemcitabine in Pancreatic Ductal Adenocarcinoma Through Down-Regulation of the Nucleoside Transporters hENT1 and hCNT3. Carcinogenesis. [Epub: Ahead of Print]

Heymann, J.B. and A. Engel. (2000). Structural clues in the sequences of the aquaporins. J. Mol. Biol. 295: 1039-1053.

Hill AE. and Shachar-Hill Y. (2015). Are Aquaporins the Missing Transmembrane Osmosensors? J Membr Biol. 248(4):753-65.

Hirota, A., Y. Takiya, J. Sakamoto, N. Shiojiri, M. Suzuki, S. Tanaka, and R. Okada. (2015). Molecular Cloning of cDNA Encoding an Aquaglyceroporin, AQP-h9, in the Japanese Tree Frog, Hyla japonica: Possible Roles of AQP-h9 in Freeze Tolerance. Zoolog Sci 32: 296-306.

Horsefield, R., K. Nordén, M. Fellert, A. Backmark, S. Törnroth-Horsefield, A.C. Terwisscha van Scheltinga, J. Kvassman, P. Kjellbom, U. Johanson, and R. Neutze. (2008). High-resolution x-ray structure of human aquaporin 5. Proc. Natl. Acad. Sci. USA 105: 13327-13332.

Hu, F., Y. Huang, M. Semtner, K. Zhao, Z. Tan, O. Dzaye, H. Kettenmann, K. Shu, and T. Lei. (2020). Down-regulation of Aquaporin-1 mediates a microglial phenotype switch affecting glioma growth. Exp Cell Res 396: 112323.

Huang, O.S., L.F. Seet, H.W. Ho, S.W. Chu, A. Narayanaswamy, S.A. Perera, R. Husain, T. Aung, and T.T. Wong. (2021). Altered Iris Aquaporin Expression and Aqueous Humor Osmolality in Glaucoma. Invest Ophthalmol Vis Sci 62: 34.

Hub, J.S. and B.L. de Groot. (2008). Mechanism of selectivity in aquaporins and aquaglyceroporins. Proc. Natl. Acad. Sci. USA 105: 1198-1203.

Huo, Z., M. Lomora, U. Kym, C. Palivan, S.G. Holland-Cunz, and S.J. Gros. (2021). AQP1 Is Up-Regulated by Hypoxia and Leads to Increased Cell Water Permeability, Motility, and Migration in Neuroblastoma. Front Cell Dev Biol 9: 605272.

Hwang, J.H., S.R. Ellingson, and D.M. Roberts. (2010). Ammonia permeability of the soybean nodulin 26 channel. FEBS Lett. 584: 4339-4343.

Iena, F.M. and J. Lebeck. (2018). Implications of Aquaglyceroporin 7 in Energy Metabolism. Int J Mol Sci 19:.

Ikarashi, N., C. Nagoya, R. Kon, S. Kitaoka, S. Kajiwara, M. Saito, A. Kawabata, W. Ochiai, and K. Sugiyama. (2019). Changes in the Expression of Aquaporin-3 in the Gastrointestinal Tract Affect Drug Absorption. Int J Mol Sci 20:.

Ikeda, M., E. Beitz, D. Kozono, W.B. Guggino, P. Agre, and M. Yasui. (2002). Characterization of aquaporin-6 as a nitrate channel in mammalian cells. Requirement of pore-lining residue threonine. J. Biol. Chem. 277: 39873-39879.

Ikezoe, K., T. Oga, T. Honda, M. Hara-Chikuma, X. Ma, T. Tsuruyama, K. Uno, J. Fuchikami, K. Tanizawa, T. Handa, Y. Taguchi, A.S. Verkman, S. Narumiya, M. Mishima, and K. Chin. (2016). Aquaporin-3 potentiates allergic airway inflammation in ovalbumin-induced murine asthma. Sci Rep 6: 25781.

Isayenkov, S.V. and F.J. Maathuis. (2008). The Arabidopsis thaliana aquaglyceroporin AtNIP7;1 is a pathway for arsenite uptake. FEBS Lett. 582: 1625-1628.

Ishibashi, K. (2006). Aquaporin subfamily with unusual NPA boxes. Biochim. Biophys. Acta. 1758: 989-993.

Ishibashi, K., Y. Morishita, and Y. Tanaka. (2017). The Evolutionary Aspects of Aquaporin Family. Adv Exp Med Biol 969: 35-50.

Ishibashi, K., Y. Tanaka, and Y. Morishita. (2020). Perspectives on the evolution of aquaporin superfamily. Vitam Horm 112: 1-27.

Ishida Y., Nagae T. and Azuma M. (2012). A water-specific aquaporin is expressed in the olfactory organs of the blowfly, Phormia regina. J Chem Ecol. 38(8):1057-61.

Ishida, H., H.J. Vogel, A.C. Conner, P. Kitchen, R.M. Bill, and J.A. MacDonald. (2021). Simultaneous binding of the N- and C-terminal cytoplasmic domains of aquaporin 4 to calmodulin. Biochim. Biophys. Acta. Biomembr 1864: 183837. [Epub: Ahead of Print]

Ishida, M., M. Hori, Y. Ooba, M. Kinoshita, T. Matsutani, M. Naito, T. Hagimoto, K. Miyazaki, S. Ueda, K. Miura, and T. Tominaga. (2021). A Functional Aqp1 Gene Product Localizes on The Contractile Vacuole Complex in Paramecium multimicronucleatum. J Eukaryot Microbiol 68: e12843.

Ishikawa, F., S. Suga, T. Uemura, M.H. Sato, and M. Maeshima. (2005). Novel type aquaporin SIPs are mainly localized to the ER membrane and show cell-specific expression in Arabidopsis thaliana. FEBS Lett. 579: 5814-5820.

Israel, D., S.H. Lee, T.M. Robson, and J.J. Zwiazek. (2022). Plasma membrane aquaporins of the PIP1 and PIP2 subfamilies facilitate hydrogen peroxide diffusion into plant roots. BMC Plant Biol 22: 566.

Jain, A., R.K. Verma, and R. Sankararamakrishnan. (2018). Presence of Intra-helical Salt-Bridge in Loop E Half-Helix Can Influence the Transport Properties of AQP1 and GlpF Channels: Molecular Dynamics Simulations of In Silico Mutants. J. Membr. Biol. [Epub: Ahead of Print]

Jaskiewicz, L., A. Romaszko-Wojtowicz, A. Doboszynska, and A. Skowronska. (2023). The Role of Aquaporin 5 (AQP5) in Lung Adenocarcinoma: A Review Article. Cells 12:.

Jelen S., Gena P., Lebeck J., Rojek A., Praetorius J., Frokiaer J., Fenton RA., Nielsen S., Calamita G. and Rutzler M. (2012). Aquaporin-9 and urea transporter-A gene deletions affect urea transmembrane passage in murine hepatocytes. Am J Physiol Gastrointest Liver Physiol. 303(11):G1279-87.

Jia, Y., S. Xu, G. Han, B. Wang, Z. Wang, C. Lan, P. Zhao, M. Gao, Y. Zhang, W. Jiang, B. Qiu, R. Liu, Y.C. Hsu, Y. Sun, C. Liu, Y. Liu, and R. Bai. (2022). Transmembrane water-efflux rate measured by magnetic resonance imaging as a biomarker of the expression of aquaporin-4 in gliomas. Nat Biomed Eng. [Epub: Ahead of Print]

Jiang, J., B.V. Daniels, and D. Fu. (2006). Crystal structure of AqpZ tetramer reveals two distinct Arg-189 conformations associated with water permeation through the narrowest constriction of the water-conducting channel. J. Biol. Chem. 281: 454-460.

Jung, H.J., J.Y. Park, H.S. Jeon, and T.H. Kwon. (2011). Aquaporin-5: a marker protein for proliferation and migration of human breast cancer cells. PLoS One 6: e28492.

Jung, S.Y., D.C. Park, S.S. Kim, and S.G. Yeo. (2020). Expression, Distribution and Role of Aquaporins in Various Rhinologic Conditions. Int J Mol Sci 21:.

Jung, S.Y., S.S. Kim, Y.I. Kim, S.H. Kim, and S.G. Yeo. (2017). A Review: Expression of Aquaporins in Otitis Media. Int J Mol Sci 18:.

Jungersted JM., Bomholt J., Bajraktari N., Hansen JS., Klaerke DA., Pedersen PA., Hedfalk K., Nielsen KH., Agner T. and Helix-Nielsen C. (2013). In vivo studies of aquaporins 3 and 10 in human stratum corneum. Arch Dermatol Res. 305(8):699-704.

Kalluri, S.R., V. Rothhammer, O. Staszewski, R. Srivastava, F. Petermann, M. Prinz, B. Hemmer, and T. Korn. (2011). Functional characterization of aquaporin-4 specific T cells: towards a model for neuromyelitis optica. PLoS One 6: e16083.

Kannan, A., L.F. Mariajoseph-Antony, A. Panneerselvam, C. Loganathan, D. Kiduva Jothiraman, K. Anbarasu, and C. Prahalathan. (2022). Aquaporin 9 regulates Leydig cell steroidogenesis in diabetes. Syst Biol Reprod Med 68: 213-226.

Kaptan S., Assentoft M., Schneider HP., Fenton RA., Deitmer JW., MacAulay N. and de Groot BL. (2015). H95 Is a pH-Dependent Gate in Aquaporin 4. Structure. 23(12):2309-18.

Karlgren, S., C. Filipsson, J.G. Mullins, R.M. Bill, M.J. Tamás, and S. Hohmann. (2004). Identification of residues controlling transport through the yeast aquaglyceroporin Fps1 using a genetic screen. Eur J Biochem 271: 771-779.

Kemény, K.K. and E. Ducza. (2022). Physiological Cooperation between Aquaporin 5 and TRPV4. Int J Mol Sci 23:.

Kikawada, T., A. Saito, Y. Kanamori, M. Fujita, K. Snigórska, M. Watanabe, and T. Okuda. (2008). Dehydration-inducible changes in expression of two aquaporins in the sleeping chironomid, Polypedilum vanderplanki. Biochim. Biophys. Acta. 1778: 514-520.

Kim, W.O., S.A. Kim, Y.A. Jung, S.I. Suh, and Y.W. Ryoo. (2020). Ultraviolet B Downregulated Aquaporin 1 Expression via the MEK/ERK pathway in the Dermal Fibroblasts. Ann Dermatol 32: 213-222.

Kirscht, A., S. Survery, P. Kjellbom, and U. Johanson. (2016). Increased Permeability of the Aquaporin SoPIP2;1 by Mercury and Mutations in Loop A. Front Plant Sci 7: 1249.

Kirscht, A., S.S. Kaptan, G.P. Bienert, F. Chaumont, P. Nissen, B.L. de Groot, P. Kjellbom, P. Gourdon, and U. Johanson. (2016). Crystal Structure of an Ammonia-Permeable Aquaporin. PLoS Biol 14: e1002411.

Kitahara, T., M. Fukushima, Y. Uno, Y. Mishiro, and T. Kubo. (2003). Up-regulation of cochlear aquaporin-3 mRNA expression after intra-endolymphatic sac application of dexamethasone. Neurol Res 25: 865-870.

Kitchen, P., M.M. Salman, S.U. Pickel, J. Jennings, S. Törnroth-Horsefield, M.T. Conner, R.M. Bill, and A.C. Conner. (2019). Water channel pore size determines exclusion properties but not solute selectivity. Sci Rep 9: 20369.

Klein, N., J. Neumann, J.D. O''Neil, and D. Schneider. (2015). Folding and stability of the aquaglyceroporin GlpF: Implications for human aqua(glycero)porin diseases. Biochim. Biophys. Acta. 1848: 622-633.

Klein, N., M. Trefz, and D. Schneider. (2019). Covalently Linking Oligomerization-Impaired GlpF Protomers Does Not Completely Re-establish Wild-Type Channel Activity. Int J Mol Sci 20:.

Kluge, C., M. Pöhnl, and R.A. Böckmann. (2022). Spontaneous local membrane curvature induced by transmembrane proteins. Biophys. J. 121: 671-683.

Kordowitzki, P., W. Kranc, R. Bryl, B. Kempisty, A. Skowronska, and M.T. Skowronski. (2020). The Relevance of Aquaporins for the Physiology, Pathology, and Aging of the Female Reproductive System in Mammals. Cells 9:.

Kosinska Eriksson, U., G. Fischer, R. Friemann, G. Enkavi, E. Tajkhorshid, and R. Neutze. (2013). Subangstrom resolution X-ray structure details aquaporin-water interactions. Science 340: 1346-1349.

Koun, S., J.D. Kim, M. Rhee, M.J. Kim, and T.L. Huh. (2016). Spatiotemporal expression pattern of the zebrafish aquaporin 8 family during early developmental stages. Gene Expr Patterns 21: 1-6.

Kourghi, M., J.V. Pei, M.L. De Ieso, S. Nourmohammadi, P.H. Chow, and A.J. Yool. (2018). Fundamental structural and functional properties of Aquaporin ion channels found across the kingdoms of life. Clin Exp Pharmacol Physiol 45: 401-409.

Kourghi, M., M.L. De Ieso, S. Nourmohammadi, J.V. Pei, and A.J. Yool. (2018). Identification of Loop D Domain Amino Acids in the Human Aquaporin-1 Channel Involved in Activation of the Ionic Conductance and Inhibition by AqB011. Front Chem 6: 142.

Kozono, D., X. Ding, I. Iwasaki, X. Meng, Y. Kamagata, P. Agre, and Y. Kitagawa. (2003). Functional expression and characterization of an archaeal aquaporin. AqpM from Methanothermobacter marburgensis. J. Biol. Chem. 278: 10649-10656.

Krüger, C., A. Jörns, J. Kaynert, M. Waldeck-Weiermair, T. Michel, M. Elsner, and S. Lenzen. (2021). The importance of aquaporin-8 for cytokine-mediated toxicity in rat insulin-producing cells. Free Radic Biol Med 174: 135-143.

Kubota, M., T. Hasegawa, T. Nakakura, H. Tanii, M. Suzuki, and S. Tanaka. (2006). Molecular and cellular characterization of a new aquaporin, AQP-x5, specifically expressed in the small granular glands of Xenopus skin. J Exp Biol 209: 3199-3208.

Laothanachareon, T., E. Asin-Garcia, R.J.M. Volkers, J.A. Tamayo-Ramos, V.A.P. Martins Dos Santos, and P.J. Schaap. (2023). Identification of Aquaporins Involved in Hydrogen Peroxide Signaling. J Fungi (Basel) 9:.

Lebeck, J. (2014). Metabolic impact of the glycerol channels AQP7 and AQP9 in adipose tissue and liver. J Mol Endocrinol 52: R165-178.

Lebeck, J., M.U. Cheema, M.T. Skowronski, S. Nielsen, and J. Praetorius. (2015). Hepatic AQP9 expression in male rats is reduced in response to PPARα agonist treatment. Am. J. Physiol. Gastrointest Liver Physiol 308: G198-205.

Lee, J.K., D. Kozono, J. Remis, Y. Kitagawa, P. Agre, and R.M. Stroud. (2005). Structural basis for conductance by the archaeal aquaporin AqpM at 1.68 Å. Proc. Natl. Acad. Sci. USA 102: 18932-18937.

Leung, J., A. Pang, W.H. Yuen, Y.L. Kwong, and E.W. Tse. (2007). Relationship of expression of aquaglyceroporin 9 with arsenic uptake and sensitivity in leukemia cells. Blood 109: 740-746.

Levy, M. (2024). Immune-Mediated Myelopathies. Continuum (Minneap Minn) 30: 180-198.

Li, H., S. Lee, and B.K. Jap. (1997). Molecular design of aquaporin-1 water channel as revealed by electrocrystallography. Nature Struc. Biol. 4: 263-265.

Li, J. and A.S. Verkman. (2001). Impaired hearing in mice lacking aquaporin-4 water channels. J. Biol. Chem. 276: 31233-31237.

Li, Q., B. Lu, J. Yang, C. Li, Y. Li, H. Chen, N. Li, L. Duan, F. Gu, J. Zhang, and W. Xia. (2021). Molecular Characterization of an Aquaporin-2 Mutation Causing Nephrogenic Diabetes Insipidus. Front Endocrinol (Lausanne) 12: 665145.

Li, R.Y., Y. Ago, W.J. Liu, N. Mitani, J. Feldmann, S.P. McGrath, J.F. Ma, and F.J. Zhao. (2009). The rice aquaporin Lsi1 mediates uptake of methylated arsenic species. Plant Physiol. 150: 2071-2080.

Li, S., C. Li, and W. Wang. (2020). Molecular aspects of aquaporins. Vitam Horm 113: 129-181.

Li, T., W.G. Choi, I.S. Wallace, J. Baudry, and D.M. Roberts. (2011). Arabidopsis thaliana NIP7;1: an anther-specific boric acid transporter of the aquaporin superfamily regulated by an unusual tyrosine in helix 2 of the transport pore. Biochemistry 50: 6633-6641.

Li, W., X.J. Qiang, X.R. Han, L.L. Jiang, S.H. Zhang, J. Han, R. He, and X.G. Cheng. (2018). Ectopic Expression of a Thellungiella salsuginea Aquaporin Gene, TsPIP1;1, Increased the Salt Tolerance of Rice. Int J Mol Sci 19:.

Li, Z., B. Li, L. Zhang, L. Chen, G. Sun, Q. Zhang, J. Wang, X. Zhi, L. Wang, Z. Xu, and H. Xu. (2016). The proliferation impairment induced by AQP3 deficiency is the result of glycerol uptake and metabolism inhibition in gastric cancer cells. Tumour Biol 37: 9169-9179.

Li, Z.H., V.E. Alvarez, J.G. De Gaudenzi, C. Sant''Anna, A.C. Frasch, J.J. Cazzulo, and R. Docampo. (2011). Hyperosmotic stress induces aquaporin-dependent cell shrinkage, polyphosphate synthesis, amino acid accumulation, and global gene expression changes in Trypanosoma cruzi. J. Biol. Chem. 286: 43959-43971.

Liao, S., L. Gan, L. Lv, and Z. Mei. (2021). The regulatory roles of aquaporins in the digestive system. Genes Dis 8: 250-258.

Lind, U., M. Järvå, M. Alm Rosenblad, P. Pingitore, E. Karlsson, A.L. Wrange, E. Kamdal, K. Sundell, C. André, P.R. Jonsson, J. Havenhand, L.A. Eriksson, K. Hedfalk, and A. Blomberg. (2017). Analysis of aquaporins from the euryhaline barnacle Balanus improvisus reveals differential expression in response to changes in salinity. PLoS One 12: e0181192.

Liu, H., C. Jin, N. Xia, and Q. Dong. (2024). Overexpression of aquaporin-1 plays a vital role in proliferation, apoptosis, and pyroptosis of Wilms'' tumor cells. J Cancer Res Clin Oncol 150: 85.

Liu, H., C. Jin, X. Yang, N. Xia, C. Guo, and Q. Dong. (2023). Identification of key genes and validation of key gene aquaporin 1 on Wilms'' tumor metastasis. PeerJ 11: e16025.

Liu, J., Y. Jin, Q. Wei, Y. Hu, L. Liu, Y. Feng, Y. Jin, and Y. Jiang. (2023). The relationship between aquaporins and skin diseases. Eur J Dermatol 33: 350-359.

Liu, K., D. Kozono, Y. Kato, P. Agre, A. Hazama, and M. Yasui. (2005). Conversion of aquaporin 6 from an anion channel to a water-selective channel by a single amino acid substitution. Proc. Natl. Acad. Sci. USA 102: 2192-2197.

Liu, K., H. Tsujimoto, S.J. Cha, P. Agre, and J.L. Rasgon. (2011). Aquaporin water channel AgAQP1 in the malaria vector mosquito Anopheles gambiae during blood feeding and humidity adaptation. Proc. Natl. Acad. Sci. USA 108: 6062-6066.

Liu, L.H., U. Ludewig, B. Gassert, W.B. Frommer, and N. von Wirén. (2003). Urea transport by nitrogen-regulated tonoplast intrinsic proteins in Arabidopsis. Plant Physiol. 133: 1220-1228.

Liu, Y., J. Peng, Q. Leng, Y. Tian, X. Wu, and R. Tan. (2023). Effects of Aloe-Emodin on the Expression of Brain Aquaporins and Secretion of Neurotrophic Factors in a Rat Model of Post-Stroke Depression. Int J Mol Sci 24:.

Long, C.Y., G.Q. Huang, Q. Du, L.Q. Zhou, and J.H. Zhou. (2019). The dynamic expression of aquaporins 1 and 4 in rats with hydrocephalus induced by subarachnoid haemorrhage. Folia Neuropathol 57: 182-195.

Loqué, D., U. Ludewig, L. Yuan, and N. von Wirén. (2005). Tonoplast intrinsic proteins AtTIP2;1 and AtTIP2;3 facilitate NH3 transport into the vacuole. Plant Physiology 137: 671-680.

Lu, D.C., H. Zhang, Z. Zador, and A.S. Verkman. (2008). Impaired olfaction in mice lacking aquaporin-4 water channels. FASEB J. 22: 3216-3223.

Lu, M.X., D.D. Pan, J. Xu, Y. Liu, G.R. Wang, and Y.Z. Du. (2018). Identification and Functional Analysis of the First Aquaporin from Striped Stem Borer,. Front Physiol 9: 57.

Lu, M.X., F.J. He, J. Xu, Y. Liu, G.R. Wang, and Y.Z. Du. (2021). Identification and physiological function of CsPrip, a new aquaporin in Chilo suppressalis. Int J Biol Macromol 184: 721-730. [Epub: Ahead of Print]

Luo, Y., L. Ma, W. Du, S. Yan, Z. Wang, and Y. Pang. (2022). Identification and Characterization of Salt- and Drought-Responsive Family Genes in L. Int J Mol Sci 23:.

Ma, J.F., K. Tamai, N. Yamaji, N. Mitani, S. Konishi, M. Katsuhara, M. Ishiguro, Y. Murata, and M. Yano. (2007b). A silicon transporter in rice. Nature 440: 688-691.

Ma, J.F., N. Yamaji, K. Tamai, and N. Mitani. (2007a). Genotypic difference in silicon uptake and expression of silicon transporter genes in rice. Plant Physiol. 145: 919-924.

MacAulay, N. (2021). Molecular mechanisms of brain water transport. Nat Rev Neurosci 22: 326-344.

Magouliotis, D.E., V.S. Tasiopoulou, A.A. Svokos, and K.A. Svokos. (2020). Aquaporins in health and disease. Adv Clin Chem 98: 149-171.

Mahdieh, M., A. Mostajeran, T. Horie, and M. Katsuhara. (2008). Drought stress alters water relations and expression of PIP-type aquaporin genes in Nicotiana tabacum plants. Plant Cell Physiol. 49: 801-813.

Mallo, R.C. and Ashby, M.T. (2006). AqpZ-mediated water permeability in Escherichia coli measured by stopped-flow spectroscopy. J. Bacteriol. 188:820-822.

Marchbank, T. and R.J. Playford. (2018). Trefoil factor family peptides enhance cell migration by increasing cellular osmotic permeability and aquaporin 3 levels. FASEB J. 32: 1017-1024.

Mariajoseph-Antony, L.F., A. Kannan, A. Panneerselvam, C. Loganathan, E.M. Shankar, K. Anbarasu, and C. Prahalathan. (2020). Role of Aquaporins in Inflammation-a Scientific Curation. Inflammation. [Epub: Ahead of Print]

Maroli, N., A. Jayakrishnan, R. Ramalingam Manoharan, P. Kolandaivel, and K. Krishna. (2019). Combined Inhibitory Effects of Citrinin, Ochratoxin-A, and T-2 Toxin on Aquaporin-2. J Phys Chem B. [Epub: Ahead of Print]

Marracino, P., M. Bernardi, M. Liberti, F. Del Signore, E. Trapani, J.A. Gárate, C.J. Burnham, F. Apollonio, and N.J. English. (2018). Transprotein-Electropore Characterization: A Molecular Dynamics Investigation on Human AQP4. ACS Omega 3: 15361-15369.

Martínez, N. and A.E. Damiano. (2023). Aquaporins in Fetal Development. Adv Exp Med Biol 1398: 251-266.

Martos-Sitcha, J.A., M.A. Campinho, J.M. Mancera, G. Martínez-Rodríguez, and J. Fuentes. (2015). Vasotocin and isotocin regulate aquaporin 1 function in the sea bream. J Exp Biol 218: 684-693.

Mashini, A.G., C.A. Oakley, A.R. Grossman, V.M. Weis, and S.K. Davy. (2022). Immunolocalization of Metabolite Transporter Proteins in a Model Cnidarian-Dinoflagellate Symbiosis. Appl. Environ. Microbiol. 88: e0041222.

Mathew, L.G., E.M. Campbell, A.J. Yool, and J.A. Fabrick. (2011). Identification and characterization of functional aquaporin water channel protein from alimentary tract of whitefly, Bemisia tabaci. Insect Biochem Mol Biol 41: 178-190.

Matsui, H., B. Hopkinson, K. Nakajima, and Y. Matsuda. (2018). Plasma-membrane-type aquaporins from marine diatoms function as CO2/NH3 channels and provide photoprotection. Plant Physiol. [Epub: Ahead of Print]

McDermott JR., Jiang X., Beene LC., Rosen BP. and Liu Z. (2010). Pentavalent methylated arsenicals are substrates of human AQP9. Biometals. 23(1):119-27.

Meenakshi, M., A. Kannan, M. Jothimani, T. Selvi, M. Karthikeyan, C. Prahalathan, and K. Srinivasan. (2023). Evaluation of dual potentiality of 2,4,5-trisubstituted oxazole derivatives as aquaporin-4 inhibitors and anti-inflammatory agents in lung cells. RSC Adv 13: 26111-26120.

Méndez-Giménez, L., S. Ezquerro, I.V. da Silva, G. Soveral, G. Frühbeck, and A. Rodríguez. (2018). Pancreatic Aquaporin-7: A Novel Target for Anti-diabetic Drugs? Front Chem 6: 99.

Meng, Y.-L., Z. Liu, and B.P. Rosen. (2004). As(III) and Sb(III) uptake by GlpF and efflux by ArsB in Escherichia coli. J. Biol. Chem. 279: 18334-18341.

Meselhy, A.G., K. Mosa, S. Chhikara, K. Kumar, C. Musante, J.C. White, and O.P. Dhankher. (2024). Plasma membrane intrinsic protein OsPIP2;6 is involved in root-to-shoot arsenic translocation in rice (Oryza sativa L.). Plant Cell Rep 43: 64.

Michalek, K. (2016). Aquaglyceroporins in the kidney: present state of knowledge and prospects. J. Physiol. Pharmacol 67: 185-193.

Michenkova, M., S. Taki, M.C. Blosser, H.J. Hwang, T. Kowatz, F.J. Moss, R. Occhipinti, X. Qin, S. Sen, E. Shinn, D. Wang, B.S. Zeise, P. Zhao, N. Malmstadt, A. Vahedi-Faridi, E. Tajkhorshid, and W.F. Boron. (2021). Carbon dioxide transport across membranes. Interface Focus 11: 20200090.

Mirabella, N., A. Pelagalli, G. Liguori, M.A. Rashedul, and C. Squillacioti. (2021). Differential abundances of AQP3 and AQP5 in reproductive tissues from dogs with and without cryptorchidism. Anim Reprod Sci 228: 106735. [Epub: Ahead of Print]

Misyura, L., E. Grieco Guardian, A.C. Durant, and A. Donini. (2020). A comparison of aquaporin expression in mosquito larvae (Aedes aegypti) that develop in hypo-osmotic freshwater and iso-osmotic brackish water. PLoS One 15: e0234892.

Mitani N., N. Yamaji, J.F. Ma. (2008). Characterization of substrate specificity of a rice silicon transporter, Lsi1. Pflugers Arch : .

Mitani-Ueno, N., N. Yamaji, F.J. Zhao, and J.F. Ma. (2011). The aromatic/arginine selectivity filter of NIP aquaporins plays a critical role in substrate selectivity for silicon, boron, and arsenic. J Exp Bot 62: 4391-4398.

Moe, S.E., J.G. Sorbo, R. Sogaard, T. Zeuthen, O. Petter Ottersen, and T. Holen. (2008). New isoforms of rat Aquaporin-4. Genomics 91: 367-377.

Molodenskiy, D.S., H.D.T. Mertens, and D.I. Svergun. (2020). An automated data processing and analysis pipeline for transmembrane proteins in detergent solutions. Sci Rep 10: 8081.

Mom, R., B. Muries, P. Benoit, J. Robert-Paganin, S. Réty, J.S. Venisse, A. Padua, P. Label, and D. Auguin. (2020). Voltage-gating of aquaporins, a putative conserved safety mechanism during ionic stresses. FEBS Lett. [Epub: Ahead of Print]

Mom, R., J. Robert-Paganin, T. Mom, C. Chabbert, S. Réty, and D. Auguin. (2022). A Perspective for Ménière''s Disease: In Silico Investigations of Dexamethasone as a Direct Modulator of AQP2. Biomolecules 12:.

Mom, R., S. Réty, and D. Auguin. (2023). Cortisol Interaction with Aquaporin-2 Modulates Its Water Permeability: Perspectives for Non-Genomic Effects of Corticosteroids. Int J Mol Sci 24:.

Mom, R., S. Réty, V. Mocquet, and D. Auguin. (2023). Plant Aquaporin Gating Is Reversed by Phosphorylation on Intracellular Loop D-Evidence from Molecular Dynamics Simulations. Int J Mol Sci 24:.

Montalvetti, A., P. Rohloff, and R. Docampo. (2004). A functional aquaporin co-localizes with the vacuolar proton pyrophosphatase to acidocalcisomes and the contractile vacuole complex of Trypanosoma cruzi. J. Biol. Chem. 279: 38673-38682.

Montiel, V., R. Bella, L.Y.M. Michel, H. Esfahani, D. De Mulder, E.L. Robinson, J.P. Deglasse, M. Tiburcy, P.H. Chow, J.C. Jonas, P. Gilon, B. Steinhorn, T. Michel, C. Beauloye, L. Bertrand, C. Farah, F. Dei Zotti, H. Debaix, C. Bouzin, D. Brusa, S. Horman, J.L. Vanoverschelde, O. Bergmann, D. Gilis, M. Rooman, A. Ghigo, S. Geninatti-Crich, A. Yool, W.H. Zimmermann, H.L. Roderick, O. Devuyst, and J.L. Balligand. (2020). Inhibition of aquaporin-1 prevents myocardial remodeling by blocking the transmembrane transport of hydrogen peroxide. Sci Transl Med 12:.

Moon, C.S., D. Moon, and S.K. Kang. (2022). Aquaporins in Cancer Biology. Front Oncol 12: 782829.

Mukhopadhyay R., Bhattacharjee H. and Rosen BP. (2014). Aquaglyceroporins: generalized metalloid channels. Biochim Biophys Acta. 1840(5):1583-91.

Murata, K., K. Mitsuoka, T. Hirai, T. Walz, P. Agre, J.B. Heymann, A. Engel, and Y. Fujiyoshi. (2000). Structural determinants of water permeation through aquaporin-1. Science 407: 599-605.

Najafabadi, H.S., N. Torabi, and M. Chamankhah. (2008). Designing multiple degenerate primers via consecutive pairwise alignments. BMC Bioinformatics 9: 55.

Nakazawa, Y., M. Oka, A. Mitsuishi, M. Bando, and M. Takehana. (2011). Quantitative analysis of ascorbic acid permeability of aquaporin 0 in the lens. Biochem. Biophys. Res. Commun. 415: 125-130.

Navarro-Ródenas, A., J.M. Ruíz-Lozano, R. Kaldenhoff, and A. Morte. (2012). The aquaporin TcAQP1 of the desert truffle Terfezia claveryi is a membrane pore for water and CO(2) transport. Mol. Plant Microbe Interact. 25: 259-266.

Nemeth-Cahalan, K.L., K. Kalman, A. Froger, and J. E. Hall. (2007). Zinc Modulation of Water Permeability Reveals that Aquaporin 0 Functions as a Cooperative Tetramer. J. Gen. Physiol. 130(5):457-464.

Nicosia, M., J. Lee, A. Beavers, D. Kish, G.W. Farr, P.R. McGuirk, M.F. Pelletier, J.D. Lathia, R.L. Fairchild, and A. Valujskikh. (2023). Water channel aquaporin 4 is required for T cell receptor mediated lymphocyte activation. J Leukoc Biol. [Epub: Ahead of Print]

Niemietz, C.M. and S.D. Tyerman. (2000). Channel-mediated permeation of ammonia gas through the peribacteroid membrane of soybean nodules. FEBS Lett. 465: 110-114.

Nishihara, E., E. Yokota, A. Tazaki, H. Orii, M. Katsuhara, K. Kataoka, H. Igarashi, Y. Moriyama, T. Shimmen, and S. Sonobe. (2008). Presence of aquaporin and V-ATPase on the contractile vacuole of Amoeba proteus. Biol Cell 100: 179-188.

Niu, Q., R. Hao, Y. Pan, Z. Liu, J. Yang, G. Guan, J. Luo, and H. Yin. (2022). Molecular Characterization and Gene Expression Analysis of Aquaporin in. Front Physiol 13: 811628.

Nozaki, K., D. Ishii, and K. Ishibashi. (2008). Intracellular aquaporins: clues for intracellular water transport? Pflugers Arch 456(4): 701-707.

Ohene, Y., W.J. Harris, E. Powell, N.W. Wycech, K.F. Smethers, S. Lasič, K. South, G. Coutts, A. Sharp, C.B. Lawrence, H. Boutin, G.J.M. Parker, L.M. Parkes, and B.R. Dickie. (2023). Filter exchange imaging with crusher gradient modelling detects increased blood-brain barrier water permeability in response to mild lung infection. Fluids Barriers CNS 20: 25.

Olesen, E.T. and R.A. Fenton. (2017). Aquaporin-2 membrane targeting: still a conundrum. Am. J. Physiol. Renal Physiol ajprenal.00010.2017. [Epub: Ahead of Print]

Oliveira, R., F. Lages, M. Silva-Graça, and C. Lucas. (2003). Fps1p channel is the mediator of the major part of glycerol passive diffusion in Saccharomyces cerevisiae: artefacts and re-definitions. Biochim. Biophys. Acta. 1613: 57-71.

Ozu, M., J.J. Alvear-Arias, M. Fernandez, A. Caviglia, A. Peña-Pichicoi, C. Carrillo, E. Carmona, A. Otero-Gonzalez, J.A. Garate, G. Amodeo, and C. Gonzalez. (2022). Aquaporin Gating: A New Twist to Unravel Permeation through Water Channels. Int J Mol Sci 23:.

Paccetti-Alves, I., M.S.P. Batista, C. Pimpão, B.L. Victor, and G. Soveral. (2023). Unraveling the Aquaporin-3 Inhibitory Effect of Rottlerin by Experimental and Computational Approaches. Int J Mol Sci 24:.

Palmgren, M., M. Hernebring, S. Eriksson, K. Elbing, C. Geijer, S. Lasič, P. Dahl, J.S. Hansen, D. Topgaard, and K. Lindkvist-Petersson. (2017). Quantification of the Intracellular Life Time of Water Molecules to Measure Transport Rates of Human Aquaglyceroporins. J. Membr. Biol. [Epub: Ahead of Print]

Pan, Q.L., F.X. Lin, N. Liu, and R.C. Chen. (2022). The role of aquaporin 4 (AQP4) in spinal cord injury. Biomed Pharmacother 145: 112384.

Pareek G., Krishnamoorthy V. and D'Silva P. (2013). Molecular insights revealing interaction of Tim23 and channel subunits of presequence translocase. Mol Cell Biol. 33(23):4641-59.

Park, J.H. and M.H. Saier, Jr. (1996). Phylogenetic characterization of the MIP family of transmembrane channel proteins. J. Membr. Biol. 153: 171-180.

Pellavio, G. and U. Laforenza. (2021). Human sperm functioning is related to the aquaporin-mediated water and hydrogen peroxide transport regulation. Biochimie. [Epub: Ahead of Print]

Petersen, L.M. and E. Beitz. (2020). The Ionophores CCCP and Gramicidin but Not Nigericin Inhibit Aquaglyceroporins at Neutral pH. Cells 9:.

Petrova, R.S., N. Francis, K.L. Schey, and P.J. Donaldson. (2024). Verification of the gene and protein expression of the aquaglyceroporin AQP3 in the mammalian lens. Exp Eye Res 240: 109828.

Petrova, R.S., N. Nair, N. Bavana, Y. Chen, K.L. Schey, and P.J. Donaldson. (2023). Modulation of Membrane Trafficking of AQP5 in the Lens in Response to Changes in Zonular Tension Is Mediated by the Mechanosensitive Channel TRPV1. Int J Mol Sci 24:.

Philip, B.N., A.J. Kiss, and R.E. Lee, Jr. (2011). The protective role of aquaporins in the freeze-tolerant insect Eurosta solidaginis: functional characterization and tissue abundance of EsAQP1. J Exp Biol 214: 848-857.

Pietrement, C., N. Da Silva, C. Silberstein, M. James, M. Marsolais, A. Van Hoek, D. Brown, N. Pastor-Soler, N. Ameen, R. Laprade, V. Ramesh, and S. Breton. (2008). Role of NHERF1, Cystic Fibrosis transmembrane conductance regulator, and cAMP in the regulation of aquaporin 9. J. Biol. Chem. 283: 2986-2996.

Pillitteri, L.J., N.L. Bogenschutz, and K.U. Torii. (2008). The bHLH protein, MUTE, controls differentiation of stomata and the hydathode pore in arabidopsis. Plant Cell Physiol. 49: 934-943.

Ping, Z., F. Zhou, X. Lin, and H. Su. (2018). Coupled Mutations-Enabled Glycerol Transportation in an Aquaporin Z Mutant. ACS Omega 3: 4113-4122.

Pinilla, C.M.B., P. Stincone, and A. Brandelli. (2021). Proteomic analysis reveals differential responses of Listeria monocytogenes to free and nanoencapsulated nisin. Int J Food Microbiol 346: 109170. [Epub: Ahead of Print]

Pluhackova, K., V. Schittny, P.C. Bürkner, C. Siligan, and A. Horner. (2022). Multiple pore lining residues modulate water permeability of GlpF. Protein. Sci. 31: e4431.

Pust, A., D. Kylies, C. Hube-Magg, M. Kluth, S. Minner, C. Koop, T. Grob, M. Graefen, G. Salomon, M.C. Tsourlakis, J. Izbicki, C. Wittmer, H. Huland, R. Simon, W. Wilczak, G. Sauter, S. Steurer, T. Krech, T. Schlomm, and N. Melling. (2015). Aquaporin 5 expression is frequent in prostate cancer and shows a dichotomous correlation with tumor phenotype and PSA recurrence. Hum Pathol. [Epub: Ahead of Print]

Ráduly, G., Z. Pap, L. Dénes, A. Szántó, T.C. Sipos, and Z. Pávai. (2019). The immunoexpression of aquaporin 1, PAX2, PAX8, connexin 36, connexin 43 in human fetal kidney. Rom J Morphol Embryol 60: 437-444.

Ramírez-Lorca, R., A.M. Muñoz-Cabello, J.J. Toledo-Aral, A.A. Ilundáin, and M. Echevarría. (2006). Aquaporins in chicken: localization of ck-AQP5 along the small and large intestine. Comp Biochem Physiol A Mol Integr Physiol 143: 269-277.

Raza, Q., M.A.R. Rashid, M. Waqas, Z. Ali, I.A. Rana, S.H. Khan, I.A. Khan, and R.M. Atif. (2023). Genomic diversity of aquaporins across genus Oryza provides a rich genetic resource for development of climate resilient rice cultivars. BMC Plant Biol 23: 172.

Reizer, J., A. Reizer, and M.H. Saier, Jr. (1993). The MIP family of integral membrane channel proteins: sequence comparisons, evolutionary relationships, reconstructed pathway of evolution and proposed functional differentiation of the two repeated halves of the proteins. Crit. Rev. Biochem. Mol. Biol. 28: 235-257.

Ribeiro, J.C., R.L. Bernardino, A. Gonçalves, A. Barros, G. Calamita, M.G. Alves, and P.F. Oliveira. (2023). Aquaporin-7-Mediated Glycerol Permeability Is Linked to Human Sperm Motility in Asthenozoospermia and during Sperm Capacitation. Cells 12:.

Rivera, M.A. and T.D. Fahey. (2019). Association Between aquaporin-1 and Endurance Performance: A Systematic Review. Sports Med Open 5: 40.

Rohloff, P., A. Montalvetti, and R. Docampo. (2004). Acidocalcisomes and the contractile vacuole complex are involved in osmoregulation in Trypanosoma cruzi. J. Biol. Chem. 279: 52270-52281.

Roudier, N., P. Ripoche, P. Gane, P.Y. Le Pennec, G. Daniels, J.P. Cartron, and P. Bailly. (2002). AQP3 deficiency in humans and the molecular basis of a novel blood group system, GIL. J. Biol. Chem. 277: 45854-45859.

Rump, K., B. Koos, D. Ziehe, P. Thon, T. Rahmel, L. Palmowski, B. Marko, A. Wolf, A. Witowski, Z. Bazzi, M. Bazzi, J. Orlowski, M. Adamzik, L. Bergmann, and M. Unterberg. (2024). Methazolamide Reduces the AQP5 mRNA Expression and Immune Cell Migration-A New Potential Drug in Sepsis Therapy? Int J Mol Sci 25:.

Sabir, F., S. Gomes, M.C. Loureiro-Dias, G. Soveral, and C. Prista. (2020). Molecular and Functional Characterization of Grapevine NIPs through Heterologous Expression in Null. Int J Mol Sci 21:.

Sachdeva, R., P. Priyadarshini, and S. Gupta. (2022). Aquaporins Display a Diversity in their Substrates. J. Membr. Biol. [Epub: Ahead of Print]

Saitoh, Y., N. Mitani-Ueno, K. Saito, K. Matsuki, S. Huang, L. Yang, N. Yamaji, H. Ishikita, J.R. Shen, J.F. Ma, and M. Suga. (2021). Structural basis for high selectivity of a rice silicon channel Lsi1. Nat Commun 12: 6236.

Salvatierra, A., P. Mateluna, G. Toro, S. Solís, and P. Pimentel. (2023). Genome-Wide Identification and Gene Expression Analysis of Sweet Cherry Aquaporins ( L.) under Abiotic Stresses. Genes (Basel) 14:.

Santos, C.R., M.D. Estêvão, J. Fuentes, J.C. Cardoso, M. Fabra, A.L. Passos, F.J. Detmers, P.M. Deen, J. Cerdà, and D.M. Power. (2004). Isolation of a novel aquaglyceroporin from a marine teleost (Sparus auratus): function and tissue distribution. J Exp Biol 207: 1217-1227.

Saparov, S.M., D. Kozono, U. Rothe, P. Agre, and P. Pohl. (2001). Water and ion permeation of aquaporin-1 in planar lipid bilayers. Major differences in structural determinants and stoichiometry. J. Biol. Chem. 276: 31515-31520.

Saparov, S.M., K. Liu, P. Agre, and P. Pohl. (2007). Fast and selective ammonia transport by aquaporin-8. J. Biol. Chem. 282: 5296-5301.

Savage, D.F., P.F. Egea, Y. Robles-Colmenares, J.D. O''Connell, 3rd, and R.M. Stroud. (2003). Architecture and selectivity in aquaporins: 2.5 a X-ray structure of aquaporin Z. PLoS Biol 1: E72.

Schlosser, P., N. Scherer, F. Grundner-Culemann, S. Monteiro-Martins, S. Haug, I. Steinbrenner, B. Uluvar, M. Wuttke, Y. Cheng, A.B. Ekici, G. Gyimesi, E.D. Karoly, F. Kotsis, J. Mielke, M.F. Gomez, B. Yu, M.E. Grams, J. Coresh, E. Boerwinkle, M. Köttgen, F. Kronenberg, H. Meiselbach, R.P. Mohney, S. Akilesh, , M. Schmidts, M.A. Hediger, U.T. Schultheiss, K.U. Eckardt, P.J. Oefner, P. Sekula, Y. Li, and A. Köttgen. (2023). Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine. Nat. Genet. [Epub: Ahead of Print]

Schmidt, R.S., J.P. Macêdo, M.E. Steinmann, A.G. Salgado, P. Bütikofer, E. Sigel, D. Rentsch, and P. Mäser. (2018). Transporters of Trypanosoma brucei-phylogeny, physiology, pharmacology. FEBS J. 285: 1012-1023.

Shangzu, Z., X. Dingxiong, M. ChengJun, C. Yan, L. Yangyang, L. Zhiwei, Z. Ting, M. Zhiming, Z. Yiming, Z. Liying, and L. Yongqi. (2022). Aquaporins: Important players in the cardiovascular pathophysiology. Pharmacol Res 183: 106363. [Epub: Ahead of Print]

Sharma, Y., V. Thakral, G. Raturi, K. Dutta Dubey, H. Sonah, A. Pareek, T. Raj Sharma, and R. Deshmukh. (2023). Structural assessment of OsNIP2;1 highlighted critical residues defining solute specificity and functionality of NIP class aquaporins. J Adv Res. [Epub: Ahead of Print]

Shashkova, S., M. Andersson, S. Hohmann, and M.C. Leake. (2021). Correlating single-molecule characteristics of the yeast aquaglyceroporin Fps1 with environmental perturbations directly in living cells. Methods 193: 46-53.

Shibata, Y., I. Katayama, T. Nakakura, Y. Ogushi, R. Okada, S. Tanaka, and M. Suzuki. (2015). Molecular and cellular characterization of urinary bladder-type aquaporin in Xenopus laevis. Gen Comp Endocrinol 222: 11-19.

Shukla, V.K. and M.J. Chrispeels. (1998). Aquaporins: their role and regulation in cellular water movement. NATO-ASI Series (subseries H). Cellular integration of signaling pathways in plant development, pp.11-22. Springer-Verlag.

Sidoux-Walter, F., N. Pettersson, and S. Hohmann. (2004). The Saccharomyces cerevisiae aquaporin Aqy1 is involved in sporulation. Proc. Natl. Acad. Sci. USA 101: 17422-17427.

Silverglate, B., X. Gao, H.P. Lee, P. Maliha, and G.T. Grossberg. (2023). The aquaporin-4 water channel and updates on its potential as a drug target for Alzheimer''s disease. Expert Opin Ther Targets 1-8. [Epub: Ahead of Print]

Singh, R.K., R. Deshmukh, M. Muthamilarasan, R. Rani, and M. Prasad. (2020). Versatile roles of aquaporin in physiological processes and stress tolerance in plants. Plant Physiol. Biochem 149: 178-189. [Epub: Ahead of Print]

Solenov, E.I., G.S. Baturina, L.E. Katkova, B. Yang, and S.G. Zarogiannis. (2023). Methods to Measure Water Permeability. Adv Exp Med Biol 1398: 343-361.

Soria LR., Fanelli E., Altamura N., Svelto M., Marinelli RA. and Calamita G. (2010). Aquaporin-8-facilitated mitochondrial ammonia transport. Biochem Biophys Res Commun. 393(2):217-21.

Soto, G., K. Alleva, M.A. Mazzella, G. Amodeo, and J.P. Muschietti. (2008). AtTIP1;3 and AtTIP5;1, the only highly expressed Arabidopsis pollen-specific aquaporins, transport water and urea. FEBS Lett. 582: 4077-4082.

Soto, G., R. Fox, N. Ayub, K. Alleva, F. Guaimas, E.J. Erijman, A. Mazzella, G. Amodeo, and J. Muschietti. (2010). TIP5;1 is an aquaporin specifically targeted to pollen mitochondria and is probably involved in nitrogen remobilization in Arabidopsis thaliana. Plant J. 64: 1038-1047.

Stavang, J.A., F. Chauvigné, H. Kongshaug, J. Cerdà, F. Nilsen, and R.N. Finn. (2015). Phylogenomic and functional analyses of salmon lice aquaporins uncover the molecular diversity of the superfamily in Arthropoda. BMC Genomics 16: 618.

Stoeckelhuber, M., F.D. Grill, K.D. Wolff, M.R. Kesting, C.T. Wolff, A.M. Fichter, D.J. Loeffelbein, C. Schmitz, and L.M. Ritschl. (2023). Infantile human labial glands: Distribution of aquaporins and claudins in the context of paracellular and transcellular pathways. Tissue Cell 82: 102052. [Epub: Ahead of Print]

Stogsdill, B., J. Frisbie, C.M. Krane, and D.L. Goldstein. (2017). Expression of the aquaglyceroporin HC-9 in a freeze-tolerant amphibian that accumulates glycerol seasonally. Physiol Rep 5:.

Stokum, J.A., B. Shim, S. Negoita, N. Tsymbalyuk, O. Tsymbalyuk, S. Ivanova, K. Keledjian, J. Bryan, M.P. Blaustein, R.M. Jha, K.T. Kahle, V. Gerzanich, and J.M. Simard. (2023). Cation flux through SUR1-TRPM4 and NCX1 in astrocyte endfeet induces water influx through AQP4 and brain swelling after ischemic stroke. Sci Signal 16: eadd6364.

Stokum, J.A., M.S. Kwon, S.K. Woo, O. Tsymbalyuk, R. Vennekens, V. Gerzanich, and J.M. Simard. (2017). SUR1-TRPM4 and AQP4 form a heteromultimeric complex that amplifies ion/water osmotic coupling and drives astrocyte swelling. Glia. [Epub: Ahead of Print]

Sudhakaran, S., V. Thakral, G. Padalkar, N. Rajora, P. Dhiman, G. Raturi, Y. Sharma, D.K. Tripathi, R. Deshmukh, T.R. Sharma, and H. Sonah. (2021). Significance of solute specificity, expression, and gating mechanism of tonoplast intrinsic protein during development and stress response in plants. Physiol Plant. [Epub: Ahead of Print]

Sugiura, K., N. Aste, M. Fujii, K. Shimada, and N. Saito. (2008). Effect of hyperosmotic stimulation on aquaporins gene expression in chick kidney. Comp Biochem Physiol A Mol Integr Physiol 151: 173-179.

Suzuki, H., K. Nishikawa, Y. Hiroaki, and Y. Fujiyoshi. (2008). Formation of aquaporin-4 arrays is inhibited by palmitoylation of N-terminal cysteine residues. Biochim. Biophys. Acta. 1778(4): 1181-1189.

Törnroth-Horsefield, S., Y. Wang, K. Hedfalk, U. Johanson, M. Karlsson, E. Tajkhorshid, R. Neutze, and P. Kjellbom. (2006). Structural mechanism of plant aquaporin gating. Nature 439: 688-694.

Takahashi, G., S. Hasegawa, Y. Fukutomi, C. Harada, M. Furugori, Y. Seki, Y. Kikkawa, and K. Wada. (2017). A novel missense mutation of Mip causes semi-dominant cataracts in the Nat mouse. Exp Anim 66: 271-282.

Takano, J., M. Wada, U. Ludewig, G. Schaaf, N. von Wirén, and T. Fujiwara. (2006). The Arabidopsis major intrinsic protein NIP5;1 is essential for efficient boron uptake and plant development under boron limitation. The Plant Cell 18: 1498-1509.

Tang, H., C. Shao, and J. He. (2017). Down-regulated expression of aquaporin-4 in the cerebellum after status epilepticus. Cogn Neurodyn 11: 183-188.

Tani, K., T. Mitsuma, Y. Hiroaki, A. Kamegawa, K. Nishikawa, Y. Tanimura, and Y. Fujiyoshi. (2009). Mechanism of aquaporin-4's fast and highly selective water conduction and proton exclusion. J. Mol. Biol. 389: 694-706.

Thormann, M., N. Traube, N. Yehia, R. Koestler, G. Galabova, N. MacAulay, and T.L. Toft-Bertelsen. (2024). Toward New AQP4 Inhibitors: ORI-TRN-002. Int J Mol Sci 25:.

Tong, H., X. Wang, Y. Dong, Q. Hu, Z. Zhao, Y. Zhu, L. Dong, F. Bai, and X. Dong. (2019). A s aquaporin acts as peroxiporin for efflux of cellular hydrogen peroxide and alleviation of oxidative stress. J. Biol. Chem. 294: 4583-4595.

Törnroth-Horsefield, S., C. Chivasso, H. Strandberg, C. D'Agostino, C.V.T. O'Neale, K.L. Schey, and C. Delporte. (2022). Insight into the Mammalian Aquaporin Interactome. Int J Mol Sci 23:.

Tsujimoto, H., J.M. Sakamoto, and J.L. Rasgon. (2017). Functional characterization of Aquaporin-like genes in the human bed bug Cimex lectularius. Sci Rep 7: 3214.

Tunes, L.G., D.B. Ascher, D.E.V. Pires, and R.L. Monte-Neto. (2021). The mutation G133D on Leishmania guyanensis AQP1 is highly destabilizing as revealed by molecular modeling and hypo-osmotic shock assay. Biochim. Biophys. Acta. Biomembr 1863: 183682.

Uehlein, N., B. Otto, D.T. Hanson, M. Fischer, N. McDowell, and R. Kaldenhoff. (2008). Function of Nicotiana tabacum Aquaporins as Chloroplast Gas Pores Challenges the Concept of Membrane CO2 Permeability. Plant Cell 20: 648-657.

Uehlein, N., C. Lovisolo, F. Siefritz, and R. Kaldenhoff. (2003). The tobacco aquaporin NtAQP1 is a membrane CO2 pore with physiological functions. Nature (in press).

Uzcategui, N.L., A. Szallies, S. Pavlovic-Djuranovic, M. Palmada, K. Figarella, C. Boehmer, F. Lang, E. Beitz, and M. Duszenko. (2004). Cloning, heterologous expression, and characterization of three aquaglyceroporins from Trypanosoma brucei. J. Biol. Chem. 279: 42669-42676.

Vajpai, M., M. Mukherjee, and R. Sankararamakrishnan. (2018). Cooperativity in Plant Plasma Membrane Intrinsic Proteins (PIPs): Mechanism of Increased Water Transport in Maize PIP1 Channels in Hetero-tetramers. Sci Rep 8: 12055.

van den Berg, B., C. Pedebos, J.R. Bolla, C.V. Robinson, A. Baslé, and S. Khalid. (2021). Structural Basis for Silicic Acid Uptake by Higher Plants. J. Mol. Biol. 433: 167226. [Epub: Ahead of Print]

Varadaraj, K. and S.S. Kumari. (2020). Lens aquaporins function as peroxiporins to facilitate membrane transport of hydrogen peroxide. Biochem. Biophys. Res. Commun. 524: 1025-1029.

Varadaraj, K., S.S. Kumari, R. Patil, M.B. Wax, and R.T. Mathias. (2008). Functional characterization of a human aquaporin 0 mutation that leads to a congenital dominant lens cataract. Exp Eye Res 87: 9-21.

Venisse, J.S., E. Õunapuu-Pikas, M. Dupont, A. Gousset-Dupont, M. Saadaoui, M. Faize, S. Chen, S. Chen, G. Petel, B. Fumanal, P. Roeckel-Drevet, A. Sellin, and P. Label. (2021). Genome-Wide Identification, Structure Characterization, and Expression Pattern Profiling of the Aquaporin Gene Family in. Int J Mol Sci 22:.

Verdoucq, L., A. Grondin, and C. Maurel. (2008). Structure-function analysis of plant aquaporin AtPIP2;1 gating by divalent cations and protons. Biochem. J. 415: 409-416.

Verkerk, A.O., E.M. Lodder, and R. Wilders. (2019). Aquaporin Channels in the Heart-Physiology and Pathophysiology. Int J Mol Sci 20:.

Verma, R.K., A.B. Gupta, and R. Sankararamakrishnan. (2015). Major intrinsic protein superfamily: channels with unique structural features and diverse selectivity filters. Methods Enzymol 557: 485-520.

Viadiu, H., T. Gonen, and T. Walz. (2007). Projection map of aquaporin-9 at 7 Å resolution. J. Mol. Biol. 367: 80-88.

Vireak, C., A.N. Seo, M.H. Han, T.I. Park, Y.J. Kim, and J.Y. Jeong. (2019). Aquaporin 5 expression correlates with tumor multiplicity and vascular invasion in hepatocellular carcinoma. Int J Clin Exp Pathol 12: 516-527.

Virkki MT., Agrawal N., Edsbacker E., Cristobal S., Elofsson A. and Kauko A. (2014). Folding of Aquaporin 1: multiple evidence that helix 3 can shift out of the membrane core. Protein Sci. 23(7):981-92.

Von Bülow, J. and E. Beitz. (2015). Number and regulation of protozoan aquaporins reflect environmental complexity. Biol Bull 229: 38-46.

von Bülow, J., A. Golldack, T. Albers, and E. Beitz. (2015). The amoeboidal Dictyostelium aquaporin AqpB is gated via Tyr216 and aqpB gene deletion affects random cell motility. Biol Cell 107: 78-88.

Vorob''ev, V.N., T.A. Sibgatullin, K.A. Sterkhova, E.A. Alexandrov, Y.V. Gogolev, O.A. Timofeeva, V.Y. Gorshkov, and V.V. Chevela. (2019). Ytterbium increases transmembrane water transport in Zea mays roots via aquaporin modulation. Biometals 32: 901-908.

Wagner, K., L. Unger, M.M. Salman, P. Kitchen, R.M. Bill, and A.J. Yool. (2022). Signaling Mechanisms and Pharmacological Modulators Governing Diverse Aquaporin Functions in Human Health and Disease. Int J Mol Sci 23:.

Wan, Q., Y. Li, J. Cheng, Y. Wang, J. Ge, T. Liu, L. Ma, Y. Li, J. Liu, C. Zhou, H. Li, X. Sun, X. Chen, Q.X. Li, and X. Yu. (2024). Two aquaporins PIP1;1 and PIP2;1 mediate the uptake of neonicotinoid pesticides in plants. Plant Commun 100830. [Epub: Ahead of Print]

Wang, F. and B. Ye. (2016). Bioinformatics analysis and construction of phylogenetic tree of aquaporins from Echinococcus granulosus. Parasitol Res 115: 3499-3511.

Wang, F. and B. Ye. (2020). [Advances in research on aquaporins in medical helminthes]. Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi 32: 542-547.

Wang, G., H. Zhang, Z. Zhou, W. Jin, X. Zhang, Z. Ma, and X. Wang. (2023). AQP3-mediated activation of the AMPK/SIRT1 signaling pathway curtails gallstone formation in mice by inhibiting inflammatory injury of gallbladder mucosal epithelial cells. Mol Med 29: 116.

Wang, H., L. Zhang, Y. Tao, Z. Wang, D. Shen, and H. Dong. (2019). Transmembrane Helices 2 and 3 Determine the Localization of Plasma Membrane Intrinsic Proteins in Eukaryotic Cells. Front Plant Sci 10: 1671.

Wang, J., L. Yang, S. Chai, Y. Ren, M. Guan, F. Ma, and J. Liu. (2022). An aquaporin gene MdPIP1;2 from Malus domestica confers salt tolerance in transgenic Arabidopsis. J Plant Physiol. 273: 153711.

Wang, L., Q. Li, Q. Lei, C. Feng, Y. Gao, X. Zheng, Y. Zhao, Z. Wang, and J. Kong. (2015). MzPIP2;1: An Aquaporin Involved in Radial Water Movement in Both Water Uptake and Transportation, Altered the Drought and Salt Tolerance of Transgenic Arabidopsis. PLoS One 10: e0142446.

Wang, R., X. Wang, J. Zhao, J. Jin, W. Fan, X. Zhu, Q. Chen, B. Zhang, L. Lan, K. Qu, L. Zhu, and J. Wang. (2022). Clinical value and molecular mechanism of AQGPs in different tumors. Med Oncol 39: 174.

Wang, X., N. Zhao, T. Wang, J. Huang, Q. Liu, and J. Li. (2023). Genome-Wide Identification of Family Related to Spermatogenesis in Turbot (). Int J Mol Sci 24:.

Wang, Y., E. Xiao, G. Wu, Q. Bai, F. Xu, X. Ji, C. Li, L. Li, and J. Liu. (2021). The roles of selectivity filters in determining aluminum transport by AtNIP1;2. Plant Signal Behav 1991686. [Epub: Ahead of Print]

Wang, Z. and K.L. Schey. (2018). Proteomic Analysis of S-Palmitoylated Proteins in Ocular Lens Reveals Palmitoylation of AQP5 and MP20. Invest Ophthalmol Vis Sci 59: 5648-5658.

Wang, Z., Y. Wang, Y. He, N. Zhang, W. Chang, and Y. Niu. (2020). Aquaporin-1 facilitates proliferation and invasion of gastric cancer cells via GRB7-mediated ERK and Ras activation. Anim Cells Syst (Seoul) 24: 253-259.

Watanabe, S., C.S. Moniaga, S. Nielsen, and M. Hara-Chikuma. (2016). Aquaporin-9 facilitates membrane transport of hydrogen peroxide in mammalian cells. Biochem. Biophys. Res. Commun. 471: 191-197.

Watanabe, T., K. Sato, T. Kono, Y. Yamagishi, F. Kumazawa, M. Miyamoto, M. Takano, and H. Tsuda. (2020). Aquaporin 3 Expression in Endometrioid Carcinoma of the Uterine Body Correlated With Early Stage and Lower Grade. Pathol Oncol Res. [Epub: Ahead of Print]

Wysocki, R., C.C. Chéry, D. Wawrzycka, M. Van Hulle, R. Cornelis, J.M. Thevelein, and M.J. Tamás. (2001). The glycerol channel Fps1p mediates the uptake of arsenite and antimonite in Saccharomyces cerevisiae. Mol. Microbiol. 40: 1391-1401.

Xiang, M., X. Qian, L. Han, H. Wang, J. Wang, W. Liu, Y. Gu, S. Yao, J. Yang, Y. Zhang, Y. Peng, and Z. Zhang. (2023). Aquaporin-8 ameliorates hepatic steatosis through farnesoid X receptor in obese mice. iScience 26: 106561.

Xie, H., S. Ma, Y. Zhao, H. Zhou, Q. Tong, Y. Chen, Z. Zhang, K. Yu, Q. Lin, L. Kai, M. Liu, and J. Yang. (2022). Molecular Mechanisms of Mercury-Sensitive Aquaporins. J. Am. Chem. Soc. 144: 22229-22241.

Xing, R., J. Cheng, J. Yu, S. Li, H. Ma, and Y. Zhao. (2023). Trifluoperazine reduces apoptosis and inflammatory responses in traumatic brain injury by preventing the accumulation of Aquaporin4 on the surface of brain cells. Int J Med Sci 20: 797-809.

Xiong, M., C. Li, W. Wang, and B. Yang. (2023). Protein Structure and Modification of Aquaporins. Adv Exp Med Biol 1398: 15-38.

Xu, C., X. Yi, L. Tang, H. Wang, S. Chu, and J. Yu. (2023). Differential regulation of autophagy on urine-concentrating capability through modulating the renal AQP2 expression and renin-angiotensin system in mice. Am. J. Physiol. Renal Physiol 325: F503-F518.

Yaba, A., B. Sozen, B. Suzen, and N. Demir. (2017). Expression of aquaporin-7 and aquaporin-9 in tanycyte cells and choroid plexus during mouse estrus cycle. Morphologie 101: 39-46.

Yadav, E., N. Yadav, A. Hus, and J.S. Yadav. (2020). Aquaporins in lung health and disease: Emerging roles, regulation, and clinical implications. Respir Med 174: 106193.

Yang, B., Z. Zador, and A.S. Verkman. (2008). Glial cell aquaporin-4 overexpression in transgenic mice accelerates cytotoxic brain swelling. J. Biol. Chem. 283: 15280-15286.

Yang, G., G. Zhang, Q. Wu, and J. Zhao. (2011). A novel mutation in the MIP gene is associated with autosomal dominant congenital nuclear cataract in a Chinese family. Mol Vis 17: 1320-1323.

Yang, H.-C., J. Cheng, T.M. Finan, B.P. Rosen, and H. Bhattacharjee. (2005). Novel pathway for arsenic detoxification in the legume symbiont Sinorhizobium meliloti. J. Bacteriol. 187: 6991-6997.

Yang, X., X. Dai, H. Jin, G. Lin, Z. Wang, Y. Song, W. Zhang, C. Man, and Y. Jiang. (2021). Physicochemical and transcriptomic responses of Lactobacillus brevis JLD715 to sodium selenite. J Sci Food Agric. [Epub: Ahead of Print]

Yang, Y., Y. Cui, W. Wang, L. Zhang, L. Bufford, S. Sasaki, Z. Fan, and H. Nishimura. (2004). Molecular and functional characterization of a vasotocin-sensitive aquaporin water channel in quail kidney. Am. J. Physiol. Regul Integr Comp Physiol 287: R915-924.

Yanochko, G.M. and A.J. Yool. (2004). Block by extracellular divalent cations of Drosophila big brain channels expressed in Xenopus oocytes. Biophys. J. 86: 1470-1478.

Yasui, M., A. Hazama, T.-H. Kwon, S. Nielsen, W.B. Guggino, and P. Agre. (1999). Rapid gating and anion permeability of an intracellular aquaporin. Nature 402: 184-187.

Ye, Y., J. Ran, B. Yang, and Z. Mei. (2023). Aquaporins in Digestive System. Adv Exp Med Biol 1398: 145-154.

Yeste, M., R. Morató, J.E. Rodríguez-Gil, S. Bonet, and N. Prieto-Martínez. (2017). Aquaporins in the male reproductive tract and sperm: Functional implications and cryobiology. Reprod Domest Anim 52Suppl4: 12-27.

Yi, X., X. Sun, R. Tian, K. Li, M. Ni, J. Ying, L. Xu, L. Liu, and Y. Wang. (2022). Genome-Wide Characterization of the Aquaporin Gene Family in Radish and Functional Analysis of Involved in Salt Stress. Front Plant Sci 13: 860742.

Yilmaz, O., F. Chauvigné, A. Ferré, F. Nilsen, P.G. Fjelldal, J. Cerdà, and R.N. Finn. (2020). Unravelling the Complex Duplication History of Deuterostome Glycerol Transporters. Cells 9:.

Yoo, Y.J., H.K. Lee, W. Han, D.H. Kim, M. Lee, J. Jeon, D.W. Lee, J. Lee, Y. Lee, J. Lee, J.S. Kim, Y. Cho, J.K. Han, and I. Hwang. (2016). Interactions between transmembrane helices within monomers of the aquaporin AtPIP2;1 play a crucial role in tetramer formation. Mol Plant. [Epub: Ahead of Print]

Yool, A.J. (2007). Dominant-negative suppression of big brain ion channel activity by mutation of a conserved glutamate in the first transmembrane domain. Gene Expr. 13: 329-337.

Yool, A.J. and E.M. Campbell. (2012). Structure, function and translational relevance of aquaporin dual water and ion channels. Mol Aspects Med 33: 553-561.

Yu, X.S., X. Yin, E.M. Lafer, and J.X. Jiang. (2005). Developmental regulation of the direct interaction between the intracellular loop of connexin 45.6 and the C terminus of major intrinsic protein (aquaporin-0). J. Biol. Chem. 280: 22081-22090.

Yusupov, M., J. Razzokov, R.M. Cordeiro, and A. Bogaerts. (2019). Transport of Reactive Oxygen and Nitrogen Species across Aquaporin: A Molecular Level Picture. Oxid Med Cell Longev 2019: 2930504.

Zardoya, R. and S. Villalba. (2001). A phylogenetic framework for the aquaporin family in eukaryotes. J. Mol. Evol. 52: 391-404.

Zeuthen T., B. Wu, S. Pavlovic-Djuranovic, L.M. Holm, N.L. Uzcategui, M. Duszenko, J.F. Kun, J.E. Schultz, E. Beitz. (2006). Ammonia permeability of the aquaglyceroporins from Plasmodium falciparum, Toxoplasma gondii and Trypansoma brucei. Mol. Microbiol. 61: 1598-1608.

Zhang, H. and A.S. Verkman. (2010). Aquaporin-1 tunes pain perception by interaction with Na(v)1.8 Na+ channels in dorsal root ganglion neurons. J. Biol. Chem. 285: 5896-5906.

Zhang, H., Z. Yang, G. Cheng, T. Luo, K. Zeng, W. Jiao, Y. Zhou, G. Huang, J. Zhang, and J. Xu. (2023). Sugarcane mosaic virus employs 6K2 protein to impair ScPIP2; 4 transport of H2O2 to facilitate virus infection. Plant Physiol. [Epub: Ahead of Print]

Zhang, W., A. Khan, J. Vitale, A. Neuner, K. Rink, C. Lüchtenborg, B. Brügger, T.H. Söllner, and E. Schiebel. (2021). A short perinuclear amphipathic α-helix in Apq12 promotes nuclear pore complex biogenesis. Open Biol 11: 210250.

Zhang, X., X. Ma, Y. Li, W. Yan, Q. Zheng, L. Li, Y. Yan, X. Liu, and J. Zheng. (2020). Dexamethasone Upregulates the Expression of Aquaporin4 by Increasing SUMOylation in A549 Cells. Inflammation 43: 1925-1935.

Zhang, Z., P. Xu, Z. Xie, F. Shen, N. Chen, L. Yu, and R. He. (2017). Downregulation of AQP2 in the anterior vaginal wall is associated with the pathogenesis of female stress urinary incontinence. Mol Med Rep 16: 3503-3509.

Zhao, C., Z. Liu, Y. Liu, and Y. Zhan. (2023). Identification and characterization of cold-responsive aquaporins from the larvae of a crambid pest (Eversmann) (Lepidoptera: Crambidae). PeerJ 11: e16403.

Zhao, R., X. Liang, M. Zhao, S.L. Liu, Y. Huang, S. Idell, X. Li, and H.L. Ji. (2014). Correlation of apical fluid-regulating channel proteins with lung function in human COPD lungs. PLoS One 9: e109725.

Zhao, X.Q., N. Mitani, N. Yamaji, R.F. Shen, and J.F. Ma. (2010). Involvement of silicon influx transporter OsNIP2;1 in selenite uptake in rice. Plant Physiol. 153: 1871-1877.

Zheng, J., R. Lin, L. Pu, Z. Wang, Q. Mei, M. Zhang, and S. Jian. (2021). Ectopic Expression of , a Plasma Membrane Intrinsic Protein Gene from the Halophyte , Enhances Drought and Salt-Alkali Stress Tolerance in Arabidopsis. Int J Mol Sci 22:.

Zheng, X., C. Li, K. Yu, S. Shi, H. Chen, Y. Qian, and Z. Mei. (2020). Aquaporin-9, Mediated by IGF2, Suppresses Liver Cancer Stem Cell Properties via Augmenting ROS/β-Catenin/FOXO3a Signaling. Mol Cancer Res 18: 992-1003.

Zhong, L., Y. Xia, T. He, S. Wenjie, A. Jinxia, Y. Lijun, and G. Hui. (2022). Polymeric photothermal nanoplatform with the inhibition of aquaporin 3 for anti-metastasis therapy of breast cancer. Acta Biomater. [Epub: Ahead of Print]

Zhou, Y., L. Li, J. Qian, H. Jia, and Y. Cui. (2018). Identification of three aquaporin subgroups from Blomia tropicalis by transcriptomics. Int J Mol Med. [Epub: Ahead of Print]

Zhou, Z., J. Zhan, Q. Cai, F. Xu, R. Chai, K. Lam, Z. Luan, G. Zhou, S. Tsang, M. Kipp, W. Han, R. Zhang, and A.C.H. Yu. (2022). The Water Transport System in Astrocytes-Aquaporins. Cells 11:.

Zhu, X., S. Wang, Y. Du, Z. Liang, H. Yao, X. Chen, and Z. Wu. (2023). A novel aquaporin Aagp contributes to HO efflux and virulence. Virulence 14: 2249789.

Zieger, E., T. Schwaha, K. Burger, I. Bergheim, A. Wanninger, and A.D. Calcino. (2022). Midbody-Localized Aquaporin Mediates Intercellular Lumen Expansion During Early Cleavage of an Invasive Freshwater Bivalve. Front Cell Dev Biol 10: 894434.

Zwiazek, J.J., H. Xu, X. Tan, A. Navarro-Ródenas, and A. Morte. (2017). Significance of oxygen transport through aquaporins. Sci Rep 7: 40411.

Đurić, M.J., A.R. Subotić, L.T. Prokić, M.M. Trifunović-Momčilov, A.D. Cingel, M.B. Dragićević, A.D. Simonović, and S.M. Milošević. (2021). Molecular Characterization and Expression of Four Aquaporin Genes in During Drought Stress and Recovery. Plants (Basel) 10:.


TC#NameOrganismal TypeExample

TC#NameOrganismal TypeExample

Glycerol facilitator, GlpF. Transports various polyols with decreasing rates as size increases (Heller et al. 1980); also transports arsenite (As(III) and antimonite (Sb(III)) (Meng et al., 2004). Oligomerization may play a role in determining the rates of transport (Klein et al. 2019). AQP water permeability through GlpF can be regulated by lipid bilayer asymmetry and the transmembrane potential. The conserved Arg in the selectivity filter and positions and dynamics of multiple other pore lining residues modulate water passage through GlpF (Pluhackova et al. 2022).

Gram-negative bacteria

GlpF of E. coli


Aqp1 of 270 aas and 6 TMSs. Induced by NH3 but not CO2, but transports both gases. Aqp1 is found in the plasma membrae as well as the ER/chloroplast. Aqp1 may be involved in photoprotection. It may facilitate the efflux of NH3, preventing the uncoupling effect of high intracellular ammonia concentrations (Matsui et al. 2018).

Aqp1 of Phaeodactylum tricornutum, a marine photoautotrophic diatoms


TC#NameOrganismal TypeExample

Tonoplast intrinsic protein, TIPA or Tip3.1, of 268 aas and 6 TMSs.  Phylogenetic distribution, structure, transport dynamics, gating mechanism, sub-cellular localization, tissue-specific expression, and co-expression of TIPs have been reviewed to define their versatile role in plants (Sudhakaran et al. 2021). Based on the phylogenetic distribution, TIPs are classified into five distinct groups with aromatic-arginine (Ar/R) selectivity filters, typical pore-morphology, and tissue-specific gene expression patterns. The tissue-specific expression of TIPs is conserved among diverse plant species, especially for TIP3s, which are expressed exclusively in seeds. The solute specificities of TIPs plays a role in physiological processes like stomatal movement and vacuolar sequestration as well as in alleviating environmental stress. TIPs also play a role in growth and developmental processes like radicle protrusion, anther dehiscence, seed germination, cell elongation, and expansion. The gating mechanism of TIPs regulates the solute flow in response to external signals, which helps to maintain the physiological functions of the cell (Sudhakaran et al. 2021).


TIP of Arabidopsis thaliana (P26587)


Aquaporin TIP2-1 (Delta-tonoplast intrinsic protein) (Delta-TIP) (Tonoplast intrinsic protein 2-1) (AtTIP2;1) (Daniels et al. 1996). Transports water and ammonia, and can be activated by mercury (Kirscht et al. 2016). The 3-d structure is known to 1.2Å resolution (Kirscht et al. 2016). It may participate in vacuolar compartmentation and detoxification of ammonium.


TIP2-1 of Arabidopsis thaliana

1.A.8.10.11Probable aquaporin TIP-type alpha (Alpha TIP) (Tonoplast intrinsic protein alpha)PlantsTIPA_PHAVU of Phaseolus vulgaris
1.A.8.10.12Aquaporin SIP2-1 (OsSIP2;1) (Small basic intrinsic protein 2-1)


SIP2-1 of Oryza sativa subsp. japonica


AQP of Enterocytozoon bieneusi

Uncharacterized protein of 295 aas and 6 TMSs.

UP of Volvox carteri


The Aquaporin-8 (Aqp8) transporter is permeable to water, NH3, formamide and H2O2, and it is present in the inner membrane of mitochondria and the plasma membrane (Bienert et al., 2007; Saparov et al., 2007; Soria et al., 2010). Cholesterol, via sterol regulatory element-binding protein (SREBP) transcription factors, activates or represses genes involved in its hepatic biosynthetic pathway, and also modulates the expression of hepatocyte mitochondrial aquaporin-8 (mtAQP8), a channel that can function as peroxiporin by facilitating the transmembrane diffusion of H2O2. The peroxiporin, mtAQP8, plays a role in the SREBP-controlled hepatocyte cholesterogenesis (Danielli et al. 2019). Aquaporin-8 is important for cytokine-mediated toxicity in rat insulin-producing cells (Krüger et al. 2021). Aquaporin-8 ameliorates hepatic steatosis through the farnesoid X receptor in obese mice (Xiang et al. 2023).


Aqp8 of Homo sapiens (O94778)


Aqp8a.1 of 260 aas and 6 TMSs.  The spaciotemporal pattern of induction of three aquaporins during embyonic development in Zebrafish has been determined, and all three, Aqp8a.1, Aqp8a.2 and Aqp8b, show distictive patterns (Koun et al. 2016).

Aqp8a.1 of Danio rerio (Zebrafish) (Brachydanio rerio)


Aquaporin of 250 aas and 6 TMSs.  It is a water channel required to facilitate the transport of water across membranes; it is involved in osmotolerance (Ghosh et al. 2006).

Aquaporin of Encephalitozoon cuniculi (Microsporidian parasite)

1.A.8.10.2Tonoplast intrinsic protein-a (transports water, urea, glycerol and gases (CO2 and NH3) Plants TIPa of Nicotiana tabacum (Q9XG70)

Tonoplast intrinsic protein 1.1 of 251 aas and probably 6 TMSs. TIPs control water trade among cytosolic and vacuolar compartments and can also transport glycerol, ammonia, urea, hydrogen peroxide, metals/metalloids, and several amino acids (Liu et al. 2003). Additionally, TIPs, which can be responsive to nitrogen availability and salt sensitivity, are engaged with different abiotic stress responses and developmental processes like leaf expansion, root elongation and seed germination (Fan et al. 2023).  TIPs of rice have also been studied (Balasaheb Karle et al. 2020).


Tip1.1 of Arabidopsis thaliana (P25818)

1.A.8.10.4Vacuolar (tonoplast) NH3 channel, TIP2;3 (Loque et al., 2005). [Tip2;2 of wheat is also an NH3/H2O channel (Bertl and Kaldenhoff, 2007)]. PlantsTIP2;3 of Arabidopsis thaliana (Q9FGL2)

Endoplasmic reticulum Small and Basic Intrinsic Protein; (SIP1;1) water channel (present in all plant tissues except seeds) (Ishikawa et al., 2005) May play a role in gas and water exchange between the plant and its environment via stromata (turgor-driven epidermal valves) and the hydathode pore (Pillitteri et al., 2008).


SIP1;1 of Arabidopsis thaliana (Q9M8W5)

1.A.8.10.6The pollen-specific water/urea aquaporin, Tip1;3 (Soto et al. 2008)

Tip1;3 of Arabidopsis thaliana (O82598)


The pollen-specific water/urea aquaporin. Tip5;1 (Soto et al. 2008) An aquaporin specifically targeted to pollen mitochondria; probably involved in nitrogen remobilization (Soto et al., 2010).


Tip5;1 of Arabidopsis thaliana (Q9STX9)


Aquaporin-B, AqpB of 294 aas and 6 TMSs.  Tyr216 in loop D is a key residue in gating, possibly involving phosphorylation. Mutation of Tyr216 to aspartate or glutamate initiated water permeability. The truncated, permanently open AqpB yielded cells with reduced capability to cope with hypotonic stress (von Bülow et al. 2015).


AqpB of Dictyostelium discoideum

1.A.8.10.9Aquaporin TIP1-2 (Gamma-tonoplast intrinsic protein 2) (Gamma-TIP2) (Salt stress-induced tonoplast intrinsic protein) (Tonoplast intrinsic protein 1-2) (AtTIP1;2)PlantsTIP1-2 of Arabidopsis thaliana

TC#NameOrganismal TypeExample
1.A.8.11.1Tonoplast intrinsic protein (ωTIP) PlantsωTIP of Pisum sativum (spP25794)
1.A.8.11.2The plasma membrane aquaporin, NtAQP1 (H2O and CO2 permeable; important for photosynthesis, stomatal opening and leaf growth) (Uehlein et al., 2003; Uehlein et al., 2008)PlantsNtAQP1 of Nicotiana tabacum (CAA04750)

Plasma membrane aquaporin 1, PIP1, PIP1;2, PIP1b, of 286 aas and 6 TMSs (Törnroth-Horsefield et al., 2006).  Transports H2O, H2O2 (Dynowski et al., 2008), O2 and CO2 (Zwiazek et al. 2017).  Forms active heterotetramers with PIP2;1 (1.A.8.11.4); down regulated under drought stress (Najafabadi et al., 2008); plays a role in salt tolerance (Li et al. 2018). Gated by H+, Ca2+, Mn2+ and Cd2+ (Verdoucq et al., 2008). The wheat orthologue has been described (Ayadi et al., 2011). 96% identical to PIP1;3. In Selaginella moellendorffii (Sm; spikemoss), SmPIP1;1 is retained in the ER while SmPIP2;1 is found in the plasma membrane but, upon co-expression, both isoforms are found in the plasma membrane as a heterotetramer, leading to a synergistic effect on water membrane permeability (Bienert et al. 2018). In some speices, PIP1 is inactive (e.g., in maize), but formation of a hetrotetramer with PIP2 allows transport (Vajpai et al. 2018). Transmembrane helices 2 and 3 determine the localization of plasma membrane PIPs (Wang et al. 2019). PIP1;2 from Malus domestica confers salt tolerance in transgenic Arabidopsis (Wang et al. 2022).  The Pip1.1 and Pip1.2 of Brassica rapa mediate the uptake of neonicotinoid pesticides (Wan et al. 2024).



PIP1.1 of Arabidopsis thaliana (P61837)


Plasma membrane intrinsic protein 2a (forms active heterotetramers with PIP1;1 (TC# 1.A.8.11.3); down regulated under drought stress (Najafabadi et al., 2008). Transports H2O2 (Dynowski et al., 2008). The Mesembryanthemum crystallinum PIP2;1 orthologue is an aquaporin impermeable to urea and glycerol. It is positively regulated by PKA- and PKC- mediated phosphorylation (Amezcua-Romero et al., 2010). PIP1;1 and PIP2;2 (Q9ATM8) co-expression modulates the membrane water permeability in the halophyte Beta vulgaris storage root through a pH regulatory response, enhancing membrane versatility to adjust its water transfer capacity (Bellati et al., 2010). The wheat orthologue has been described (Ayadi et al., 2011).  Inter-TMS interactions occurring both within and between monomers play crucial roles in tetramer formation, and assembly of tetramers is critical for their trafficking from the ER to the plasma membrane as well as water permeability (Yoo et al. 2016).  This protein as well as 1.A.8.11.6 is possibly orthologous to spinach PIP1;2 for which the crystal structure is available (PDP# 4JC6) (Berny et al. 2016).  Plays a role in drought and salt tolerance (Wang et al. 2015). PIP-type aqauporins may also transport CO2, boric acid, glycerol, arsenic and Na+ (Byrt et al. 2017). TMS2 and TMS3 are necessary and sufficient in AtPIP2 for its PM localization (Wang et al. 2019).


PIP2;1 of Arabidopsis thaliana (P43286)


Probable aquaporin PIP2-6 (Plasma membrane intrinsic protein 2-6) (AtPIP2;6) (Plasma membrane intrinsic protein 2e) (PIP2e). In the radish (Raphaus sativus), there are 61 genes encoding aquaporins, and RsPIP2-6 is induced with high NaCl, and is involved in the salt stress response (Yi et al. 2022).  The plasma membrane intrinsic protein OsPIP2;6 is involved in root-to-shoot arsenic translocation in rice (Oryza sativa L.) (Meselhy et al. 2024).


PIP2-6 of Arabidopsis thaliana


Aquaporin PIP2-8 (Plasma membrane intrinsic protein 2-8) (AtPIP2;8) (Plasma membrane intrinsic protein 3b) (PIP3b).  This protein as well as 1.A.8.11.4 are possibly orthologous to spinach PIP1;2 for which the crystal structure is available (PDP# 4JC6) (Berny et al. 2016).


PIP2-8 of Arabidopsis thaliana


Aquaporin PIP2;5 (PIP2-5) of 285 aas.  Transports water and hydrogen peroxide (H2O2) (Bienert et al. 2014; ).  PIP1;2 doesn't transport H2O2.  TMS3 contains an LxxA motif that targets the protein to the plasma membrane from the ER.  While PIP2s are in the plasma mebrane, PIP1s are retained in the ER; this motif only partly explains the difference (Chevalier and Chaumont 2015).  PIP1;2 AND PIP2;5 form homo- and heterotetramers (Berny et al. 2016). PIP2;6 is 85% identical, and Ytterbium, Yb3+, increases water flow in corn roots by activiating PIP2;6, PIP2;2 and TIP2;2 (Vorob'ev et al. 2019).  Incubation with abscisic acid and the elicitor flg22 peptide induced the intracellular H2O2 accumulation in cells expressing ZmPIP2;5 (Ahmed et al. 2023).  Sugarcane mosaic virus employs the 6K2 protein to impair ScPIP2; 4 transport of H2O2 to facilitate virus infection (Zhang et al. 2023).


PIP2;5 of Zea mays


Aqp2 of 297 aas and 6 TMSs. Induced by both NH3 and CO2, and transports both gases. Aqp2 is found in the plasma membrane and may be involved in photoprotection. It may facilitate the efflux of NH3, preventing the uncoupling effect of high intracellular ammonia concentrations (Matsui et al. 2018).

Aqp2 of Phaeodactylum tricornutum, a marine photoautotrophic diatoms


Water channel, Aqp2-3 or Aqp2;3 or PIP2C of 285 aas and 6 TMSs. Ectopic expression of CrPIP2;3, a plasma membrane intrinsic protein gene from the halophyte, Canavalia rosea, enhanced drought and salt-alkali stress tolerance in Arabidopsis (Zheng et al. 2021). The Arabidopsis ortholog is presented here.

PIP2C of Arabidopsis thaliana


TC#NameOrganismal TypeExample

Nodulin-26 aquaporin and glycerol facilitator, NIP (de Paula Santos Martins et al. 2015). Transports NH3 5-fold better than water in Hg2+-sensitive fashion (Hwang et al., 2010).


Nodulin-26 of Glycine max (spP08995)

1.A.8.12.10Arsenite export pore, AqpS (Yang et al., 2005)BacteriaAqpS of Sinorhizobium meliloti (CAC45655)

Uncharacterized MIP family protein of 274 aas and 6 TMSs.

UP of Entamoeba histolytica


Uncharacterized MIP family protein of 314 aas and 8 putative TMSs. The extra 2 non-homologous TMSs appear to be N-terminal.

UP of Entamoeba histolytica


Rice NIP2.1 (NIP2-1; NIP2;1) of 295 aas and 6 or 7 TMSs. It transports metaloids such as arsenous acid (arsenic) and silisic acid (silicon).  The 3-D structure has been determined (Sharma et al. 2023). This protein is most similar to TC# 1.A.8.12.2 within TCDB.

NIP2.1 of Zea mays


The silicon (silicic acid) (undissociated form) transporter, Lsi1 (Ma et al., 2007a, b; Mitani et al., 2008). The barley orthologue Lsi1 (also called NIP2-1) is also a silicon (silicic acid) uptake channel (Chiba et al., 2009). Rice Lsi1 also transports arsenite and pentavalent mono and dimethyl arsenite (Li et al., 2009). In addition to silicon (Si), selenite (Se) uptake is mediated by Lsi1 (Zhao et al., 2010).  Physicochemical and transcriptomic responses of Lactobacillus brevis JLD715 to sodium selenite have been reported (Yang et al. 2021). Many of the world's most important food crops such as rice, barley and maize accumulate silicon (Si) to high levels, resulting in better plant growth and crop yields (van den Berg et al. 2021). The first step in Si accumulation is the uptake of silicic acid by the roots, a process mediated by the NIP subfamily of aquaporins, also named metalloid porins. van den Berg et al. 2021 presented the X-ray crystal structure of the archetypal NIP family member from Oryza sativa (OsNIP2;1). The OsNIP2;1 channel is closed in the crystal structure by the cytoplasmic loop D, which is known to regulate channel opening in classical plant aquaporins. The structure reveals a novel, five-residue extracellular selectivity filter with a large diameter. Unbiased molecular dynamics simulations show a rapid opening of the channel to visualise how silicic acid interacts with the selectivity filter prior to transmembrane diffusion. These results may enable detailed structure-function studies of metalloid porins, including the basis of their substrate selectivity (van den Berg et al. 2021). Silicon (Si), the most abundant mineral element in the earth's crust, is taken up by plant roots in the form of silicic acid through Low silicon rice 1 (Lsi1). Lsi1 belongs to the Nodulin 26-like intrinsic protein subfamily and shows high selectivity for silicic acid. The crystal structure of rice Lsi1 at a resolution of 1.8 Å reveals transmembrane helical orientations different from other aquaporins, characterized by a unique, widely opened, and hydrophilic selectivity filter composed of five residues. Structural, functional, and theoretical investigations provided a solid basis for the Si uptake mechanism in plants (Saitoh et al. 2021).



Lsi1 of Oryza sativa (Q6Z2T3)


The boric acid channel protein, NIP5;1 (expressed in the root elongation zone and root hairs in response to boron deficiency) (Takano et al., 2006).  Borate is an essential nutrient in plants.     The ortholog in Brassica napus ( XP_013652160.1) is 301 aas in length with 6 TMSs and is 90% identical to the A. thaliana protein.  Synthesis of the B. napus protein is induced in roots and shoots by a borate deficiency (Diehn et al. 2019). NIP2, 3, 4, 6 and 7 can also transport boric acid (Diehn et al. 2019). the grape ortholog can transport the same molecules (Sabir et al. 2020).


NIP5;1 of Arabidopsis thaliana (NP_192776)

1.A.8.12.4The root-expressed MIP transporter of lactic acid, NIP2;1 (Nod26-like MIP-4; NLM4) (induced by water logging and anoxic stress; shows minimal water and glycerol transport). It may play a role in adaptation to lactic fermentaion under anaerobic stress (Choi and Roberts, 2007). Lactic acid transport is induced by anoxic stress (Choi and Roberts, 2007).Plants NIP2;1 of Arabidopsis thaliana (Q8W037)

The silicon (silicic acid) transporter, Nip2-2 (Nip2;2) (Mitani et al., 2008). Also transports arsenite (Li et al., 2009).


Nip2-2 of Oryza sativa (Q67WJ8)


Nip7;1 arsenite and borate channel (Isayenkov and Maathuis, 2008; Li et al., 2011)


Nip7. 1 of Arabidopsis thaliana (Q8LAI1)


Aquaporin NIP1-2 (NOD26-like intrinsic protein 1-2) (AtNIP1;2) (Nodulin-26-like major intrinsic protein 2) (NodLikeMip2) (Protein NLM2). Selectivity filters play roles in determining aluminum transport by AtNIP1;2 (Wang et al. 2021).


NIP1-2 of Arabidopsis thaliana


Aquaporin NIP1-1 (NOD26-like intrinsic protein 1-1) (AtNIP1;1) (Nodulin-26-like major intrinsic protein 1) (NodLikeMip1) (Protein NLM1).  NIP-like aquaporins transport water, but also arsenic, boric acid, sliicon, glycerol, urea, lactic acid and ammonia (Mitani-Ueno et al. 2011; Hwang et al. 2010). The grape ortholog appears to transport the same molecules including water and glycerol, but also arsenate, borate, selenate and cadmium (Sabir et al. 2020).


NIP1-1 of Arabidopsis thaliana


Aquaporin NIP6-1 (NOD26-like intrinsic protein 6-1) (AtNIP6;1).  The grape ortholog is impermeable to water, but permeable to glycerol (Sabir et al. 2020).


NIP6-1 of Arabidopsis thaliana


TC#NameOrganismal TypeExample
1.A.8.13.1MIP family homologue Archaea Orf of Archaeoglobus fulgidus, AE000782 (ID# AF1426)

Hg2+-inhibitable aquaporin, AqpM (transports both water and glycerol as well as CO2) (Kozono et al., 2003; Araya-Secchi et al., 2011). Its 3-d structure has been determined to 1.7 Å. In AqpM, isoleucine replaces a key histidine residue found in the lumen of water channels, which becomes a glycine residue in aquaglyceroporins. As a result of this and other side-chain substituents in the walls of the channel, the channel is intermediate in size and exhibits differentially tuned electrostatics when compared with the other subfamilies (Lee et al. 2005).


AqpM of Methanothermobacter marburgensis


Putative aquaporin, GlpF5, of  216 aas; probably transports water, glycerol and dihydroxyacetone (Bienert et al. 2013).


GlpF5 of Lactobacillus plantarum


Aquaporin, Aqp, of 222 aas and 6 TMSs.  It functions in hydrogen peroxide (H2O2) export from the cell, relieving oxidative stress (Tong et al. 2019). It is an H2O2-inducible bacterial "peroxiporin".

Aqp of Streptococcus oligofermentans or Streptococcus cristatus


Aquaporin, Aqp9, of 231 aas and 6 TMSs.  This protein co-localizes with the vacuolar proton pyrophosphatase to acidocalcisomes and the contractile vacuole complex (Montalvetti et al. 2004) which are involved in osmoregulation (Rohloff et al. 2004). Acidocalcisomes function as storage sites for cations and phosphorus, participate in PPi and poly P metabolism as well as volume regulation and are essential for virulence. A signalling pathway involving cyclic AMP generation is important for fusion of acidocalcisomes to the contractile vacuole complex, transference of aquaporin and volume regulation (Docampo et al. 2011). Hyperosmotic stress induces aquaporin-dependent cell shrinkage, polyphosphate synthesis, amino acid accumulation, and global gene expression changes in Trypanosoma cruzi (Li et al. 2011). Plasmodium spp. express a single AQP, Toxoplasma gondii two, while Trypanosoma cruzi and Leishamnia spp. encode up to five AQPs. Their AQPs are thought to import metabolic precursors and simultaneously to dispose of waste and to help parasites survive osmotic stress (Von Bülow and Beitz 2015).

Aqp9 of Trypanosoma cruzi


Aquaporin of 214 aas and 6 TMSs in a 2 + 1 + 2 + 1 TMS arrangement.

Aqp of Bacteroidia bacterium (subsurface metagenome)


TC#NameOrganismal TypeExample

Putative aquaporin, Aqp2, with a large 300 residue amino terminal hydrophilic domain. The protein is of 603 aas and 7 TMSs in a 1 + 3 + 3 TMS arrangement.

Aqp2 of Plasmodium falciparum


Erythrocyte membrane-associated antigen, putative, of 541 aas and 4 - 7 TMSs.

EMA of Plasmodium yoelii yoelii


Erythrocyte membrane-associated antigen, putative, of 651 aas and 7 TMSs in a 1 + 3 + 3 TMS arrangement.

Aqp, putative, of Plasmodium yoelii yoelii


TC#NameOrganismal TypeExample

TC#NameOrganismal TypeExample

TC#NameOrganismal TypeExample

TC#NameOrganismal TypeExample

TC#NameOrganismal TypeExample
1.A.8.2.1Glycerol facilitator Gram-positive bacteria and Haemophilus influenzae GlpF of Bacillus subtilis

Aquaglyceroporin of 270 aas and 6 TMSs.

Aquaporin of Paramecium bursaria chlorella virus MT325


Lmo1539 of 272 aas and 7 possible TMSs. Lmo1539 is related to activation of the LiaR-mediated stress defense mechanism and is induced by treatment with nisin (TC# 1.C.20.1.1) (Pinilla et al. 2021).

Lmo1539 of Listeria monocytogenes


Aquaglyceroporin, AagP, of 298 aas and 6 TMSs.  This protein transports water, glycerol and H2O2. It catalyzes H2O2 efflux during glycerol uptake and contributes to virulence in mice (Zhu et al. 2023). 

AagP of Streptococcus suis


Mixed function glycerol facilitator/aquaporin, GlpF (Froger et al. 2001).

Gram-positive Firmicutes

GlpF of Lactococcus lactis

1.A.8.2.3Probable glycerol uptake facilitator protein


GlpF of Mycoplasma gallisepticum )


GlpF1; transports water, dihydroxyacetone and glycerol as well as D,L-lactic acid (Bienert et al. 2013).


GlpF1 of Lactobacillus plantarum


GlpF2.  Transporter of water, dihydroxyacetone and glycerol (Bienert et al. 2013).


GlpF2 of Lactobacillus plantarum


GlpF3.  Transports water, dihydroxyacetone and glycerol (Bienert et al. 2013).


GlpF3 of Lactobacillus plantarum


GlpF4.  Transports water, dihydroxyacetone and glycerol as well as D,L-lactic acid (Bienert et al. 2013).


GlpF4 of Lactobacillus plantarum


Putative aquaporin, GlpF6.  Probably transports water, glycerol and dihydroxyacetone (Bienert et al. 2013).


GlpF6 of Lactobacillus plantarum


Glycerol facilitator, GlpF, of 248 aas and 6 TMSs

GlpF of Blattabacterium sp. subsp. Blattella germanica (strain Bge) (Blattella germanica symbiotic bacterium)


TC#NameOrganismal TypeExample

Aquaporin Z water channel (aqpZ gene expression is under sigma S control; induced at the onset of stationary phase) (Mallo and Ashby, 2006).  The high resolution 3-d structure is available (PDB 1RC2) revealing two re-entrant coil-helix domains from the selectivity filter (Savage et al. 2003).  Coupled mutations enabled glycerol transport (Ping et al. 2018).

Enteric bacteria

AqpZ of E. coli (P60844)


TC#NameOrganismal TypeExample

Intracellular endoplasmic reticulum (ER)-localized Aquaporin 11 (Aqp11, AqpX1) water channel (important for the development of kidney proximal tubules; disruption produces neonatally fatal polycystic kidneys (Ishibashi 2006). Has a positively charged C-terminal amino acid cluster similar to the di-lysine motif (-KKXX) for ER retention (Nozaki et al., 2008)). In the horse, AQP3 and AQP11 are involved in the resilience of stallion sperm to withstand cryopreservation (Bonilla-Correal et al. 2017).


Aqp11 of Homo sapiens (Q8NBQ7)


Aquaporin-12A (AQP-12) of 295 aas and probably 7 TMSs with an extra N-terminal TMS. It bears a C-terminal KKXX-like ER retention sequence and is found intracelllularly (Ishibashi 2006).  It is expressed in elevated amounts in exocrine glandular cells of the pancreas (Danielsson et al. 2014) but is also present in the nuclear envelope. A short perinuclear amphipathic α-helix in Apq12 promotes nuclear pore complex biogenesis (Zhang et al. 2021).


AQP12A of Homo sapiens


Aquaporin 10, Aqp10 of 259 aas and 6 TMSs

Aqp10 of Haemonchus contortus (Barber pole worm)


Aquaporin of 263 aas and 7 TMSs (Stavang et al. 2015).

Aquaporin of the salmon leach, Lepeophtheirus salmonis


Aquaporin of 256 aas with 6 TMSs in a 3 (N-terminus) + 3 TMS (C-terminus) arrangement (Zhou et al. 2018).

Aqp of Blomia tropicalis (mite)


Aquaporin of 261 aas and 6 TMSs. Aquaporins may not play major roles in adapting to longterm survival in brackish water or they be regulated by non-transcriptional mechanisms like post-translational modifications (Misyura et al. 2020).

Aqp of Aedes aegypti (Yellowfever mosquito) (Culex aegypti)


TC#NameOrganismal TypeExample

FPS1 glycerol efflux facilitator. It is important for maintaining osmotic balance during mating-induced yeast cell fusion and for tolerating hypoosmotic shock; it also transports arsenite and antimonite). FPS1 is a homotetramer (Beese-Sims et al., 2011). It is important for osmo-adaptation by regulating intracellular glycerol levels during changes in external osmolarity. Upon high osmolarity conditions, yeast accumulate glycerol by increased production of the osmolyte and by restricting glycerol efflux through Fps1. The extended cytosolic termini of Fps1 contain short domains that are important for regulating glycerol flux through the channel (Hedfalk et al. 2004). The transmembrane core of the protein plays an equally important role (Geijer et al., 2012).  The MAP kinase, Slt2, physically interacts with Fps1, and this interaction, dependent on phosphorylation of S537, regulates arsenite uptake (Ahmadpour et al. 2016). The N-terminal regulatory domain and the B-loop may interact in channel control (Karlgren et al. 2004). Fps1 resides in multi tetrameric clusters, and hyperosmotic and oxidative stress conditions cause Fps1 reorganization, and rapid exposure to hydrogen peroxide causes Fps1 degradation (Shashkova et al. 2021). Activation of the CWI pathway through high hydrostatic pressure, enhances glycerol efflux via Fps1 in Saccharomyces cerevisiae (see family 9.B.454 in TCDB).


FPS1 protein of Saccharomyces cerevisiae


Fps1 hyperactive orthologue of the S. cerevisiae Fps1 (1.A.8.5.1) (Geijer et al., 2012).


Fps1 of Ashbya gossypii (Q75CI7)


TC#NameOrganismal TypeExample
1.A.8.6.1Aqy1, aquaporin (mediates H2O efflux during sporulation) (spore maturation) (Sidoux-Walter et al., 2004)YeastAqy1 of Saccharomyces cerevisiae
1.A.8.6.2Aquaporin-2 Aqy2 (plays a role in reducing surface hydrophobicity promoting cell dispersion during starvation and reproduction)YeastAqy2 of Saccharomyces chevalieri

Aquaporin, Aqy1 (PIP2-7 7).  The subangstron (0.88Å) structure is available (Kosinska Eriksson et al. 2013).  the H-bond donor interactions of the NPA motif''s asparagine residues to passing water molecules are revealed. A polarized water-water H-bond configuration is observed within the channel.  Four selectivity filter water positions are too closely spaced to be simultaneously occupied. Strongly correlated movements break the connectivity of selectivity filter water molecules to other water molecules within the channel, thereby preventing proton transport via a Grotthuss mechanism.


Aqy1 of Komagataella pastoris (Pichia pastoris)


Water and CO2 permeable aquaporin, AQP1, of an edible mycorhizal fungus (desert truffles) (Navarro-Ródenas et al. 2012).


AQP1 of Terfezia claveryi


TC#NameOrganismal TypeExample

Tobacco X-intrinsic protein (XIP1-1-β). Transports glycerol, urea and boric acid, but not water (Bienert et al., 2011).


XIP1-1 of Nicotiana tomentosiformis (E3UN01)


Potato X intrinsic protein, XIP1.  Transports glycerol, urea and boric acid, but not water (Bienert et al., 2011).


XIP1-1 of Solanum tuberosum (E3UMZ6)


Morning glory XIP-1-1-α. Transports glycerol, urea and boric acid, but not water (Bienert et al., 2011).


XIP1 of Ipomoea nil (E3UMZ5)


Aquaporin F (AqpF) of 321 aas and 6 TMSs.  It transports water and glycerol, but additionally transporters hydrogen peroxide (H2O2) for signaling purposes (Laothanachareon et al. 2023). It may be the only aquaporin capable of H2O2 transport and signalling.

AqpF of Aspergillus niger


TC#NameOrganismal TypeExample

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).


Aquaporin 1 (AQP1) of Homo sapiens


Water and urea transporting aquaporin (cockroach) (Herraiz et al., 2011).


Aquaporin of Blatella germanica (G8YY04)


Water channel, Aqp1; inhibited by HgCl2 and tetraethylammonium. Plays a role in water homeostasis during blood feeding and humidity adaptation of A. gambiae, a major mosquito vector of human malaria in Africa (Liu et al., 2011).


Aqp1 of Anopheles gambiae (F2YNF6)


Aquaporin, Aqp1 in the gall fly. Transports water but not glycerol or urea. Promotes freeze-tolerance (Philip et al., 2011).


Aqp1 of Eurosta solidaginis (E4W5Y5)


The Drosophila melanogaster integral protein, DRIP (Ishida et al., 2012).


Aqp, DRIP of Drosophila melanogaster (Q9V5Z7)

1.A.8.8.14Lens fiber major intrinsic protein (MIP26) (MP26)Amphibians

MIP26 of Rana pipiens


Mercury-sensitive whitefly aquaporin-1 of the specialized filter chamber of the alimentary tract (Mathew et al. 2011).


Aquaporin-1 of Bemisia tabaci


Aquaporin-1 or Aquaporin1, Aqp1, of 258 aas and 6 TMSs. Three Aqp1 isoforms are differentially  regluated by the function of the vasotocin (AVTR) and isotocin (ITR) receptors (Martos-Sitcha et al. 2015). Aqp1aa, one of two isoforms in teleosts, may play a role in spermatogenesis in Cynoglossus semilaevis (Guo et al. 2017).

Aqp1 of Sparus aurata (Gilthead sea bream)


Aquaporin-3, Aqp-3 of 271 aas.  Transports water, glycerol, hydrogen peroxide and urea (Geadkaew et al. 2015).  AQP3 induces the production of chemokines such as CCL24 and CCL22 through regulating the amount of cellular H2O2 in M2 polarized alveolar macrophages, implying a role of AQP3 in asthma (Ikezoe et al. 2016).

Aqp3 of Opisthorchis viverrini (liver fluke)


Aqp-x2 water channel in the luminal epithelium of urinary bladder cells and lungs.  Responsive to Vasotocin (AVT) (Shibata et al. 2015).

Aqp-x2 of Xenopus laevis


Contractile vacuole aquaporin of 295 aas and 6 TMSs, Aqp.  Shown to transport water, accounting for the high water permeability of the contractile vacuole (Nishihara et al. 2008).

Aqp of Amoeba proteus (Amoeba) (Chaos diffluens)


The lens fiber MIP aquaporin (Aqp0) of B. taurus (forms membrane junctions in vivo and double layered crystals in vitro that resemble the in vivo junctions). The water pore is closed in the in vitro structure (Gonen et al., 2004b). It interacts directly with the intracellular loop of connexin 45.6 via its C-terminal extension (Yu et al., 2005). Forms human cataract lens membranes (Buzhynskyy et al., 2007; Yang et al., 2011).  A mutation that causes congenital dominant lens cataracts has been identified (Varadaraj et al. 2008). AqpO catalyzes Zn2+-modulated water permeability as a cooperative tetramer (Nemeth-Cahalan et al., 2007). It transports ascorbic acid (Nakazawa et al., 2011). The Detergent organization around solubilized aquaporin-0 using Small Angle X-ray Scattering has been reported (Berthaud et al., 2012).  Aquaporin 0 (AQP0) in the eye lens is truncated by proteolytic cleavage during lens maturation. This truncated AQP0 is no longer a water channel (Berthaud et al. 2015).  A mutation that causes congenital dominant lens cataracts has been identified (Varadaraj et al. 2008). Cataractogenesis in MIP mutants are probably caused by defects in MIP gene expression in mice (Takahashi et al. 2017). This may be caused by the ability of Aqp0 (as well as Aqp1 and Aqp5) to transport hydrogen peroxide (H2O2) which can cause cataracts (Varadaraj and Kumari 2020).  An automated data processing and analysis pipeline for transmembrane proteins including Aqp0 in detergent solutions has been presented (Molodenskiy et al. 2020). EphA2 is required for normal Cx50 localization to the cell membrane, and conductance of lens fiber cells requires normal Eph-ephrin signaling and water channel (Aqp0) localization (Cheng et al. 2021). The local curvature of cellular membranes acts as a driving force for the targeting of membrane-associated proteins to specific membrane domains, as well as a sorting mechanism for transmembrane proteins, as demonstrated for Aqp0; AQP0 causes small negative curvature (Kluge et al. 2022).


Major intrinsic protein (MIP or Aqp0) of Bos taurus

1.A.8.8.20Channel protein Cyanobacteria Copper homeostasis protein (SmpX) of Synechococcus sp.

Aquaporin x5 of 273 aas and 6 TMSs, Aqp-x5. The sequence reveals a mercurial-sensitive cysteine and a putative phosphorylation motif site for protein kinase A at Ser-257 (Kubota et al. 2006). A swelling assay using Xenopus oocytes revealed that AQP-x5 facilitated water permeability. Expression of AQP-x5 mRNA was restricted to the skin, brain, lungs and testes. Immunofluorescence and immunoelectron microscopical studies using an anti-peptide antibody (ST-156) against the C-terminal region of the AQP-x5 protein revealed the presence of immunopositive cells in the skin, with the label predominately localized in the apical plasma membrane of the secretory cells of the small granular glands. These glands are unique both in being close to the epidermal layer of the skin and in containing mitochondria-rich cells with vacuolar H+-ATPase dispersed among its secretory cells. Results from immunohistochemical experiments on the mucous or seromucous glands of several other anurans verified this result (Kubota et al. 2006).

Aqp-x5 of Xenopus laevis (African clawed frog)


Aqp-1A of 258 aas and 6 TMSs, DRIP1. Transports water but not glycerol or urea. Functions in water homeostasis in many tissues and stages of development (Lu et al. 2018). An aquaporin in the beet armyworm, Spodoptera exigua, (79% identical to the one in Chilo suppressalis, mediates cell shape change required for cellular immunity (Ahmed and Kim 2019).

Aqp-1A of Chilo suppressalis (Asiatic rice borer moth)


Aqp-2A of 269 aas and 6 TMSs, PRIP2. It transports water and urea but not glycerol or trehalose. It functions in water homeostasis in many tissues and stages of development (Lu et al. 2018). Its production in various tissues and stages of growth have been examined (Lu et al. 2021).

Aqp-2A of Chilo suppressalis (Asiatic rice borer moth)


Big brain-like protein of 309 aas and 6 probable TMSs, BibL1 (Lind et al. 2017).

BibL1 of the euryhaline bay barnacle, Balanus improvisus (Darwin, 1854) (Amphibalanus improvisus)


Aquaporin 1, AQP1, of 261 aas and 6 TMSs, which selectively transports water (Lind et al. 2017).

AQP1 of the euryhaline bay barnacle Balanus improvisus (Darwin, 1854) (Amphibalanus improvisus)


Aquaporin (Aqp) of 458 aas, 6 N-terminal TMSs and a 200 aa hydrophilic C-terminal domain.

Aqp of Blomia tropicalis (mite)


Aquaglyceroporin, Glp1, of 269 aas and 6 TMSs. Transports glycerol and water (Tsujimoto et al. 2017).

Glp1 of Cimex lectularius (Bed bug) (Acanthia lectularia)


Aquaporin-2, Aqp2, of 275 aas and 6 TMSs.It is subject to hyperosmotic stimulation in Chick Kidney (Sugiura et al. 2008). It is highly similar to the quail (Coturnix coturnix) ortholog which has been studied and shown to be a mercury-inhibited, vasotocin-sensitive water channel in the kidney (Yang et al. 2004).

Aqp2 of Gallus gallus


Aquaporin/glycerol transporter of 294 aas and 6 TMSs.  Tandem duplication (TD) was the major mechanism of gene expansion in echinoderms and hemichordates, which, together with whole genome duplications (WGD) in the chordate lineage, continued to shape the genomic repertoires in craniates. Molecular phylogenies indicated that Aqp3-like and Aqp13-like channels were the probable stem subfamilies in craniates, with WGD generating Aqp9 and Aqp10 in gnathostomes but Aqp7 arising through TD in Osteichthyes (Yilmaz et al. 2020).

Aqp of Saccoglossus kowalevskii (Acorn worm)


The Big Brain, BIB aquaporin of 696 aas and 6 TMSs, transports ions by a channel mechanism involving E71 in TMS1) (Yool, 2007).  BIB expressed in Xenopus oocytes is a monovalent cation channel modulated by tyrosine kinase signaling. BIB conductance shows voltage- and dose-dependent block by extracellular divalent cations Ca2+ and Ba2+ but not by Mg2+ in wild-type channels (Yanochko and Yool 2004). Site-directed mutagenesis of negatively charged glutamate (Glu274) and aspartate (Asp253) residues had no effect on divalent cation block, but mutation of Glu71 in the first TMS altered channel properties (Yanochko and Yool 2004).


Big brain (BIB) of Drosophila melanogaster


Aquaporin-A, AqpA of 249 aas and 6 TMSs. Aquaporins may not play major roles in adapting to longterm survival in brackish water or they be regulated by non-transcriptional mechanisms like post-translational modifications (Misyura et al. 2020).

AqpA of Aedes aegypti (Yellowfever mosquito) (Culex aegypti)


Aqp1 of 250 aas and 6 TMSs. Aqp1 localizes on the contractile vacuole complex in Paramecium multimicronucleatum (Ishida et al. 2021).

Aqp1 of Paramecium multimicronucleatum


Major intrinsic protein superfamily, aquaporin-like protein. MIP2, of 247 aas and 6 TMSs.

MIP2 of Chlamydomonas reinhardtii (Chlamydomonas smithii)


Aqp6 aquaporin (also transports NO3- and other anions at acidic pH or in the presence of Hg2+) (Ikeda et al., 2002). AQP6 flicker rapidly between closed and open states. Two well conserved glycine residues: Gly-57 in TMS 2 and Gly-173 in TMS 5 reside at the contact point where the two helices cross. Mammalian orthologs of AQP6 have an asparagine residue (Asn-60) at the position corresponding to Gly-57 in Aqp6. Liu et al. 2005 showed that a single residue substitution (N60G in rat AQP6) eliminates anion permeability but increases water permeability.


Aqp6 of Homo sapiens


Aquaporin-4 (AQP4) is the major water channel in the central nervous system and plays an important role in the brain's water balance, including edema formation and clearance. There are 6 splice variants; the shorter ones assemble into functional, tetrameric square arrays; the longer is palmitoylated on N-terminal cysteyl residues) (Suzuki et al., 2008). The longest, Aqp4e, has a novel N-terminal domain and forms a water channel in the plasma membrane although various shorter variants don't (Moe et al., 2008). AQP4, like AQP0 (1.A.8.8.2), forms water channels but also forms adhesive junctions (Engel et al., 2008) (causes cytotoxic brain swelling in mice (Yang et al., 2008)) Mice lacking Aqp4 have impaired olfactions (Lu et al., 2008). Aqp4 is down regulated in skeletal muscle in muscular dystrophy (Au et al. 2008). The crystal structure is known to 2.8 Å resolution (Tani et al., 2009). The structure reveals 8 water molecules in each of the four channels, supporting a hydrogen-bond isolation mechanism and explains its fast and selective water conduction and proton exclusion (Tani et al., 2009; Cui and Bastien, 2011). It is an important antigen in Neuromyelitis optica (NMO) patients (Kalluri et al., 2011).  A connection has been made between AQP4-mediated fluid accumulation and post traumatic syringomyelia (Hemley et al. 2013).  AQP4 has increased water permeability at low pH, and His95 is the pH-dependent gate (Kaptan et al. 2015).  Also transports NH3 but not NH4+ (Assentoft et al. 2016). Cerebellar damage following status epilepticus involves down regulation of AQP4 expression (Tang et al. 2017). SUR1-TRPM4 and AQP4 form a complex to increase bulk water influx during astrocyte swelling (Stokum et al. 2017). A mutation, S111T, causes intellectual disability, hearing loss, and progressive gait dysfunction (Berland et al. 2018). As in humans, the chicken ortholog, Aqp4, is found in brain > kidney > stomach (Ramírez-Lorca et al. 2006). A Molecular Dynamics Investigation on Human AQP4 has been published (Marracino et al. 2018). AQP1 and AQP4 activities correlate with the severity of hydrocephalus induced by subarachnoid haemorrhage (Long et al. 2019). Di-lysine motif-like sequences formed by deleting the C-terminal domain of aquaporin-4 prevent its trafficking to the plasma membrane (Chau et al. 2021). Kidins220 deficiency causes ventriculomegaly via SNX27-retromer-dependent AQP4 degradation (Del Puerto et al. 2021). AQP4 expression is upregulated in cells exposed to dexamethasone, and SUMOylation [Small ubiquitin-like modifiers (SUMOs)] may participate in this regulation (Zhang et al. 2020). Simultaneous calmodulin binding to the N- and C-terminal cytoplasmic domains of aquaporin 4 has been demonstrated (Ishida et al. 2021). Aqp-4 plays a role in secondary pathological processes (spinal cord edema, glial scar formation, and inflammatory response) after spinal cord injury, SCI. Loss of AQP-4 is associated with reduced spinal edema and improved prognosis after SCI in mice, and downregulation of AQP-4 reduces glial scar formation and the inflammatory response after SCI (Pan et al. 2022). AQP4 contributes to the migration and proliferation of gliomas, and to their resistance to therapy. In glioma cell cultures, in both subcutaneous and orthotopic gliomas in rats, and in glioma tumours in patients, that transmembrane water-efflux rate is a sensitive biomarker of AQP4 expression (Jia et al. 2022). Aquaporin 4 is required for T cell receptor-mediated lymphocyte activation (Nicosia et al. 2023). Peripheral lung infections influence the blood brain barrier (BBB) water exchange, which appears to be mediated by endothelial dysfunction and is associated with an increase in perivascular AQP4 (Ohene et al. 2023). Trifluoperazine reduces apoptosis and inflammatory responses in traumatic brain injury by preventing the accumulation of Aquaporin4 on the surface of brain cells (Xing et al. 2023). Cation flux through SUR1-TRPM4 and NCX1 in astrocyte endfeet induces water influx through AQP4 and brain swelling after ischemic stroke (Stokum et al. 2023). Aquaporin-4 expression and modulation may be important in a rat model of post-traumatic syringomyelia (Berliner et al. 2023).  The Aqp4 water channel may be a drug target for Alzheimer's Disease (Silverglate et al. 2023). A series of 2,4,5-trisubstituted oxazoles 3a-j were synthesized by a Lewis acid mediated reaction of aroylmethylidene malonates with nitriles. In silico studies conducted using the protein data bank (PDB) structure 3gd8 for AQP4 revealed that compound 3a would serve as a suitable candidate to inhibit AQP4 in human lung cells (NCI-H460). In vitro studies demonstrated that compound 3a could effectively inhibit AQP4 and inflammatory cytokines in lung cells, and hence it may be considered as a viable drug candidate for the treatment of various lung diseases (Meenakshi et al. 2023).   The effect of AQP4 and its palmitoylation on the permeability of exogenous reactive oxygen species has been considered (Cao et al. 2023). ORI-TRN-002 exhibits superior solubility and overcomes free fraction limitations compared to other reported AQP4 inhibitors, suggesting its potential as a promising anti-edema therapy for treating cerebral edema (Thormann et al. 2024).  New biomarkers, such as aquaporin 4 have led to the identification of antigen-specific immune-mediated myelopathies and approved therapies to prevent disease progression (Levy 2024).


AQP4 of Homo sapiens (P55087)

1.A.8.8.6Aqp1 water channel of the sleeping chironomid (functions in water removal during anhydrobiosis, Kikawada et al., 2008).


Aqp1 of Polypedilum vanderplanki


Aqp2 water channel of the sleeping chironomid (functions in water homeostasis during anhydrobiosis (Kikawada et al., 2008).


Aqp2 of Polypedilum vanderplanki (A5A7P0)


Vasopressin-sensitive aquaporin-2 (Aqp2) in the apical membrane of the renal collecting duct (Fenton et al., 2008).  Controls cell volume and thereby influences cell proliferation (Di Giusto et al. 2012).  It  plays a key role in concentrating urine. Water reabsorption is regulated by AQP2 trafficking between intracellular storage vesicles and the apical membrane. This process is tightly controlled by the pituitary hormone arginine vasopressin, and defective trafficking results in nephrogenic diabetes insipidus (NDI).  The crystal structure of Aqp2 has been solved to 2.75 Å (Frick et al. 2014).  In terrestrial vertebrates, AQP2 function is generally regulated by arginine-vasopressin to accomplish key functions in osmoregulation such as the maintenance of body water homeostasis by a cyclic AMP-independent mechanism (Olesen and Fenton 2017; Martos-Sitcha et al. 2015). AQP2 is expressed in the anterior vaginal wall and fibroblasts, and regulates the expression level of collagen I/III i, suggesting that AQP2 is associated with the pathogenesis of stress urinary incontinence through collagen metabolism during ECM remodeling (Zhang et al. 2017). As in humans, the chicken ortholog, Aqp2, is found only in the kidney (Ramírez-Lorca et al. 2006).  AQP2 is critical in regulating urine concentrating ability. The expression and function of AQP2 are regulated by a series of transcriptional factors and post-transcriptional phosphorylation, ubiquitination, and glycosylation (He and Yang 2019). Mutation or functional deficiency of AQP2 leads to severe nephrogenic diabetes insipidus, and inhibition of various aquaporins leads to many water-related diseases such as, edema, cardiac arrest, and stroke. Maroli et al. 2019 reported on the molecular mechanisms of mycotoxin (citrinin, ochratoxin-A, and T-2 mycotoxin) inhibition of AQP2 and arginine vasopressin receptor 2 (AVPR2). Aquaporin-2 mutations cause Nephrogenic diabetes insipidus (Li et al. 2021). Meniere's disease is affected by dexamethasone which is a direct modulator of AQP2. The molecular mechanisms involved in dexamethasone binding to and its regulatory action upon AQP2 function have been described (Mom et al. 2022). Interaction of cortisol with aquaporin-2 modulates its water permeability (Mom et al. 2023). In the kidney collecting duct, arginine vasopressin-dependent trafficking of AQP2 fine-tunes reabsorption of water from pre-urine, allowing precise regulation of the final urine volume. Point mutations in the gene for AQP2 disturbs this process and leads to nephrogenic diabetes insipidus (NDI), wherein patients void large volumes of hypo-osmotic urine. In recessive NDI, mutants of AQP2 are retained in the endoplasmic reticulum due to misfolding. The structures allow interpretation of these results (Hagströmer et al. 2023). Differential regulation of autophagy on urine-concentrating capability occurs through modulating renal AQP2 expression (Xu et al. 2023).


Aqp2 of Homo sapiens (P41181)


Aquaporin 5 (x-ray structure at 2.0 Å resolution (PDB# 3D9S) is available) (Horsefield et al., 2008). Aqp5 is a marker for proliferation and migration of human breast cancer cells (Jung et al., 2011). Plays a role in chronic obstructive pulmonary diseases (COPD) (Zhao et al. 2014).  Its expression is regulated by androgens (Pust et al. 2015). As in humans, the chicken ortholog, Aqp5, is found in the intestine, the jejunum, ileum and colon (Ramírez-Lorca et al. 2006). Proteomic analyses of the ocular lens revealed palmitoylation (Wang and Schey 2018). Aquaporin 5 expression correlates with tumor multiplicity and vascular invasion in hepatocellular carcinoma (Vireak et al. 2019). The ability of Aqp5 (as well as Aqp0 and Aqp1) to transport hydrogen peroxide (H2O2) may cause cataracts in the eye (Varadaraj and Kumari 2020). AQP3 and AQP5 play important but different roles in spermatogenesis and sperm maturation in dogs (Mirabella et al. 2021). The up-regulation of AQP1, AQP3 and AQP5 in skin during summer season indicates roles in thermoregulation (Debbarma et al. 2020). Aqp5 interacts with TRPV4 (see 1.A.4.2.5 for the rat ortholog) (Kemény and Ducza 2022). AQP5 facilitates osmotically driven water flux across biological membranes as well as the movement of hydrogen peroxide and CO2. Various mechanisms dynamically regulate AQP5 expression, trafficking, and function. Besides fulfilling its primary water permeability function, AQP5 regulates downstream effectors (D'Agostino et al. 2023). Modulation of membrane trafficking of AQP5 in the lens in response to changes in zonular tension is mediated by TRPV1 (Petrova et al. 2023).Methazolamide reduces AQP5 mRNA expression and immune cell migration, and may be a drug for sepsis therapy (Rump et al. 2024). 


Aquaporin 5 of Homo sapiens (P55064)


TC#NameOrganismal TypeExample

Aquaporin 3. 95% identical to the human orthologue. Poorly permeable to water, but more permeable to glycerol and arsenic trioxide (Palmgren et al. 2017).  It is expressed in the plasma membrane of basal epidermal cells in the skin; loss of function prevents skin tumorigenesis and epidermal cell proliferation (Hara-Chikuma and Verkman, 2008).  The human orthologue also transports both water and glycerol and is the predominant AQP in skin (Jungersted et al. 2013). It's function is necessary for normal proliferation of colon cancer cells due to glycerol uptake (Li et al. 2016). Aqp3 is implicated in cancer progression to the metastatic state as its function promotes cell migration and cell shape plasticity.  Its synthesis is regulated by the AhR (aryl hydrocarbon (pollutant) receptor or dioxin receptor), a transcription factor triggered by environmental pollutants (Bui et al. 2016). Trefoil factor (TFF) peptides increase cell water permeability and induce prodcution of Aqp3 (Marchbank and Playford 2018). Although AQP3 and other similar transmembrane proteins do not themselves transport drugs, changes in their expression levels can cause changes in cell membrane fluidity, thus affecting drug absorption rates (Ikarashi et al. 2019).  AQP3 levels are elevated in human endometrioid carcinoma (Watanabe et al. 2020). AQP3 and AQP5 play important roles in spermatogenesis and sperm maturation in dogs (Mirabella et al. 2021). AQP-1, 3 and 8 levels in amniotic fluid were measured in patients suffering from polyhydramnios. They were compared to the levels observed in control subjects, and their relationship with maternal factors and neonatal issues was analyzed. AQP-1, 3, 8 levels physiologically fluctuated, AQP-1 levels were the lowest and AQP-3 the highest, with a decrease at the end of pregnancy (Guibourdenche et al. 2021). The human ortholog, Aqp3 (Q92482) is 95% identical. It transports water, glycerol and urea, and is the blood group antigen, GIL (Roudier et al. 2002). Intra-endolymphatic sac steroids have regulatory effects on inner ear AQP-3 expression via the vestibular aqueduct and modulate the homeostasis of endolymphatic fluids (Kitahara et al. 2003).



Aquaporin 3 of Rattus norvegicus (P47862)


Aqp9 or Aqp-h9 of 294 aas.  Takes up glycerol as well as water, and thereby contributes to freeze tolerance (Hirota et al. 2015). An almost identical orthologue, HC-9 in Dryophytes chrysoscelis (gray treefrog), similarly facilitates glycerol permeability. Both the transcriptional and translational levels of HC-9 change in response to thermal challenges, with a unique increase in liver during freezing and thawing (Stogsdill et al. 2017).

Aqp9 of Hyla japonica


Aqp1 of 304 aas and 6 TMSs; the most abundant transmembrane protein in the tegument of Schistosoma mansoni. This protein is expressed in all developmental stages and seems to be essential in parasite survival since it plays a crucial role in osmoregulation, nutrient transport and drug uptake (Figueiredo et al. 2014).

Aqp1 of Schistosoma mansoni (Blood fluke)


Basolateral Aqp3 of 292 aas and 6 TMSs in the frog urinary bladder (Shibata et al. 2015).

Aqp3 of Xenopus laevis


Aquaglycerolporin, Aqp (high permeability to ammonium, methylamine, glycerol and water) (Beitz et al., 2004) NH4+/NH3+CH3/glycerol/water transporter (Zeuthen et al., 2006).


Aqp of Plasmodium falciparum (CAC88373)


Glycerolaquaporin 9, Aqp9 of 295 aas and 6 TMSs.  Transports water, glycerol and arsenic trioxide, As2O3 (Palmgren et al. 2017) as well as urea and lactic acid (but not lactate) (Geistlinger et al. 2022). Primary APL cells express AQP9 significantly (2-3 logs) higher than other acute myeloid leukemia cells (AMLs), explaining their exquisite As2O3 sensitivity (Leung et al. 2007). AQP-7 and AQP-9-mediated glycerol transport in tanycyte cells may be under hormonal control to use glycerol as an energy source during the mouse estrus cycle (Yaba et al. 2017). It transports multiple neutral and ionic arsenic species including arsenic trioxide, monomethylarsenous acid (MAs(III)) and dimethylarsenic acid (DMA(V)). It also transports clinically relevant selenium species including monomethylselenic acid (MSeA), especially at acidic pH. FCCP, valinomycin and nigericin do not significantly inhibit MSeA uptake, but AQP9 also transport ionic selenite and lactate, with low efficiency compared with MSeA uptake. Selenite and lactate uptake is pH dependent and inhibited by FCCP and nigericin but not valinomycin. The selenite and lactate uptake via AQP9 can be inhibited by different lactate analogs. AQP9 transport of MSeA, selenite and lactate is inhibited by an AQP9 inhibitor, phloretin, and the AQP9 substrate, arsenite (As(III)) (Geng et al. 2017). The host aquaporin-9 is required for efficient Plasmodium falciparum sporozoite entry into human hepatocytes (Amanzougaghene et al. 2021). RG100204 is a direct blocker of the AQP9 channel (Florio et al. 2022).

Aqp9 of Homo sapiens


Aquaporin 9, Aqp9, small solute channel 1 of 296 aas and 6 TMSs (Wang and Ye 2016). 

Aqp9 of Echinococcus granulosus (Hydatid tapeworm)


Water/glycerol aquaglyceroporin 2, AQP2, of 294 aas and 6 TMSs (Lind et al. 2017).

AQP2 of the euryhaline bay barnacle, Balanus improvisus (Darwin, 1854) (Amphibalanus improvisus)


Glycerol-aquaporin of 332 aas and 6 TMSs (Stavang et al. 2015).

Aqp of the salmon leach, Lepeophtheirus salmonis


Aquaporin of 341 aas and 7 TMSs (Ben Amira et al. 2018).

Aqp of Hypocrea atroviridis (Trichoderma atroviride)


AQP2 (AQP9) of 312 aas and 6 TMSs; transports water, glycerol and urea as well as the drugs, melarsoprol and pentamidine (Schmidt et al. 2018). CCCP and gramicidin but not nigericin inhibit Trypanosoma brucei Aquaglyceroporins Aqp2 and Aqp3 at neutral pH (Petersen and Beitz 2020).

AQP2 of Trypanosoma brucei


Aquaporin-9 (Aqp9) (permeable to glycerol, urea, polyols, carbamides, purines, pyrmidines, nucleosides, monocarboxylates, pentavalent methylated arsenicals and the arsenic chemotherapeutic drug, trisenox (McDermott et al., 2009).  It is poorly permeable to water and not permeable to β-hydroxybutyrate (Carbrey et al., 2003). (Regulated by CFTR and NHERF1 in response to cyclic AMP (Pietrement et al., 2008)) The 7 Å projection structure and a homology model revealed that pore-lining residues and the hydrophobic edge of the tripathic pore of GlpF (1.A.8.1.1) provide the basis for broad substrate specificity (Viadiu et al., 2007).  It is important for urea transport in mouse hepatocytes (Jelen et al. 2012).  Activation of the PPARα transcription factor results in reduction in the abundance of AQP9 in periportal hepatocytes, but its activation in the fed state directs glycerol into glycerolipid synthesis rather than into de novo synthesis of glucose (Lebeck et al. 2015).  Azacytidine up-regulates AQP9 and enhances arsenic trioxide (As2O3)-mediated cytotoxicity in acute myeloid leukemia (AML) (Chau et al. 2015).  Human Aqp9 transports hydrogen peroxide (HOOH) (Watanabe et al. 2016) and plays a role in certain types of cancer (Zheng et al. 2020). Human aquaporin 9 regulates Leydig cell steroidogenesis in diabetes (Kannan et al. 2022).


Aqp9 of Rattus norvegicus (P56627)


Aquaporin of 274 aas and 6 TMSs. See Zhou et al. 2018 for its identification.

Aqp of Blomia tropicalis (mite)


Aquaporin 3, Aqp3, of 304 aas and 6 TMSs. CCCP and gramicidin but not nigericin inhibit Trypanosoma brucei Aquaglyceroporins Aqp2 and Aqp3 at neutral pH (Petersen and Beitz 2020).

Aqp3 of Trypanosoma brucei


Aquaporin-3-like protein, Aqp10b, of 374 aas and 6 TMSs (Santos et al. 2004).

Aqp10b of Sparus aurata (gilthead seabream)


Aqp3 of 294 aas and 6 TMSs (Mashini et al. 2022).

Aqp3 of Exaiptasia diaphana


Aqp3 of 292 aas and 6 TMSs. It is a water channel required to promote glycerol permeability and water transport across cell membranes (Roudier et al. 2002, Gotfryd et al. 2018). It acts as a glycerol transporter in skin and plays an important role in regulating the stratum corneum and epidermal glycerol content. It is involved in skin hydration, wound healing, and tumorigenesis, and it provides the kidney medullary collecting duct with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient. It is slightly permeable to urea and H2O2, 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. Breast cancer cell invasion and metastasis are related to AQP3, which is the transmembrane transport channel for H2O2 molecules (Zhong et al. 2022). AQP3 plays a key role in cancer and metastasis. RoT inhibits human AQP3 activity with an IC50 in the micromolar range (22.8 ± 5.8 µM for water and 6.7 ± 3.0 µM for glycerol permeability inhibition). RoT blocks AQP3-glycerol permeation by establishing strong and stable interactions at the extracellular region of AQP3 pores (Paccetti-Alves et al. 2023). AQP3-mediated activation of the AMPK/SIRT1 signaling pathway curtails gallstone formation in mice by inhibiting inflammatory injury of gallbladder mucosal epithelial cells (Wang et al. 2023).  The main subtype expressed in the epidermis and dermis is AQP3. AQPs exert certain physiological functions in the skin, such as the maintenance of normal shape, the regulation of body temperature, moisturization and hydration, anti-aging, damage repair and antigen presentation. The abnormal expression of AQPs in skin cells can lead to a variety of skin diseases (Liu et al. 2023).  AQP3 promotes the invasion and metastasis in cervical cancer by regulating NOX4-derived H2O2 activation of the Syk/PI3K/Akt signaling axis. Aquaglyceroporin AQP3 is expressed in the mammalian lens (Petrova et al. 2024).

Aqp3 of Homo sapiens


Major aquaglyceroporin, LmAQP1: transports water, glycerol, methylglyoxal, trivalent metalloids such as arsenite and antimonite, dihydroxyacetone and sugar alcohols. Also takes up the activated form or the drug, pentostam.  It localizes to the flagellum of the Leishmania promastigotes and is used to regulate volume in response to hypoosmotic stress; it functions in osmotaxis (Figarella et al., 2005; Gourbal et al, 2004).  The first line treatment for cutaneous leishmaniasis is pentavalent antimony such as sodium stibogluconate (pentostam) and meglumine antimonite (glucantime), and both compounds are transported by LmAQP1 (Eslami et al. 2020). The mutation G133D in the Leishmania guyanensis AQP1 is highly destabilizing (Tunes et al. 2021).


Aqp1 of Leishmania major (Q6Q1Q6)


Aquaporin 1 (permeable to water, glycerol, dihydroxyacetone and urea) (Uzcategui et al., 2004)


Aqp1 of Trypanosoma brucei (Q6ZXT4)


Aquaporin 10 of 301 aas and 6 TMSs. Cell- and tissue-specific expression of AQP-0, AQP-3, and AQP-10 in the testis, efferent ducts, and epididymis has been demonstrated (Hermo et al. 2019). It is also present in keratinocytes and the stratum corneum (Jungersted et al. 2013).


Aqp10 of Homo sapiens


Glycerol/water/urea/arsenic trioxide-transporting channel protein, aqaporin 7 or Aqp7, but water is a poor substrate (Palmgren et al. 2017).  Present in adipose tissue where it allows glycerol efflux.  Defects result in increased accumulation of triglycerides, obesity and adult onset (type 2) diabetes (Lebeck 2014). It may be a drug target for anti-type 2 diabetes (Méndez-Giménez et al. 2018). AQP-7- and AQP-9-mediated glycerol transport in tanycyte cells may be under hormonal control to use glycerol as an energy source during the mouse estrus cycle (Yaba et al. 2017).  It may also influence whole body energy metabolism (Iena and Lebeck 2018) including in the kidney (Schlosser et al. 2023). Aquaporin-7-mediated glycerol permeability is linked to human sperm motility in asthenozoospermia and during sperm capacitation (Ribeiro et al. 2023).


Aqp7 of Homo sapiens

1.A.8.9.7Glycerol facilitator, Yf1054c (70.5 kDa protein) (Oliveira et al., 2003)Yeast Yf1054c of Saccharomyces cerevisiae (P43549)

Glycerol uptake facilitator of 393 aas


Glycerol transporter of Cordyceps militaris (Caterpillar fungus)


Aquaporin/glycerol facilitator of 294 aas and 6 TMSs.  May play a role in freeze tolerance (Hirota et al. 2015).

Aqp-9 of Xenopus tropicalis