1.A.8 The Major Intrinsic 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). 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).

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). 

The known aquaporins cluster loosely together 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.

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.

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).

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.

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.

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. Recent genetic evidence has demonstrated a crucial role for specific MIPs in metalloid homeostasis (Bienert et al., 2008).

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.

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).

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).

The MIP superfamily includes three 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). 

13 isoforms of mammalian aquaporins (AQP0 - AQP12),are known, 9 of which is localized in 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).

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.

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

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

or

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



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

 

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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.

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.

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., 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:.

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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.

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.

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.

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.

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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.

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.

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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.

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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.

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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.

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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]

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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.

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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.

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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).

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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.

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Examples:

TC#NameOrganismal TypeExample
Examples:

TC#NameOrganismal TypeExample
1.A.8.1.1

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).

Gram-negative bacteria

GlpF of E. coli

 
Examples:

TC#NameOrganismal TypeExample
1.A.8.10.1Tonoplast intrinsic protein Plants TIP of Arabidopsis thaliana (P26587)
 
1.A.8.10.10Aquaporin TIP2-1 (Delta-tonoplast intrinsic protein) (Delta-TIP) (Tonoplast intrinsic protein 2-1) (AtTIP2;1)PlantsTIP2-1 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)

Plants

SIP2-1 of Oryza sativa subsp. japonica
 
1.A.8.10.13Aquaporin

Plants

AQP of Enterocytozoon bieneusi
 
1.A.8.10.14

Uncharacterized protein of 295 aas and 6 TMSs.

UP of Volvox carteri

 
1.A.8.10.15

Aquaporin-8 (Aqp8) transporter, permeable to water, NH3, formamide and H2O2 (present in the inner membrane of mitochondria and the plasma membrane) (Bienert et al., 2007; Saparov et al., 2007; Soria et al., 2010).

Animals

Aqp8 of Homo sapiens (O94778)

 
1.A.8.10.16

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)

 
1.A.8.10.2Tonoplast intrinsic protein-a (transports water, urea, glycerol and gases (CO2 and NH3) Plants TIPa of Nicotiana tabacum (Q9XG70)
 
1.A.8.10.3Tonoplast intrinsic protein 1.1 (permeable to water and H2O2)PlantsTip1.1 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)
 
1.A.8.10.5

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).

Plants

SIP1;1 of Arabidopsis thaliana (Q9M8W5)

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

Tip1;3 of Arabidopsis thaliana (O82598)

 
1.A.8.10.7

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).

Viridiplantae

Tip5;1 of Arabidopsis thaliana (Q9STX9)

 
1.A.8.10.8

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).

Amoeba

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
 
Examples:

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)
 
1.A.8.11.3

Plasma membrane aquaporin 1 (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). 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.

Plants

PIP1.1 of Arabidopsis thaliana (P61837)

 
1.A.8.11.4

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).

Plants

PIP2;1 of Arabidopsis thaliana (P43286)

 
1.A.8.11.5Probable aquaporin PIP2-6 (Plasma membrane intrinsic protein 2-6) (AtPIP2;6) (Plasma membrane intrinsic protein 2e) (PIP2e)PlantsPIP2-6 of Arabidopsis thaliana
 
1.A.8.11.6

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).

Plants

PIP2-8 of Arabidopsis thaliana

 
1.A.8.11.7

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).

Plants

PIP2;5 of Zea mays

 
Examples:

TC#NameOrganismal TypeExample
1.A.8.12.1

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).

Plants

Nodulin-26 of Glycine max (spP08995)

 
1.A.8.12.10Arsenite export pore, AqpS (Yang et al., 2005)BacteriaAqpS of Sinorhizobium meliloti (CAC45655)
 
1.A.8.12.2

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, also called NIP2;1 (Zhao et al., 2010).

Plants

Lsi1 of Oryza sativa (Q6Z2T3)

 
1.A.8.12.3The boric acid channel protein, NIP5;1 (expressed in the root elongation zone and root hairs in response to boron deficiency) (Takano et al., 2006)PlantsNIP5;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)
 
1.A.8.12.5

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

Plants

Nip2-2 of Oryza sativa (Q67WJ8)

 
1.A.8.12.6

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

Plants

Nip7. 1 of Arabidopsis thaliana (Q8LAI1)

 
1.A.8.12.7Aquaporin NIP1-2 (NOD26-like intrinsic protein 1-2) (AtNIP1;2) (Nodulin-26-like major intrinsic protein 2) (NodLikeMip2) (Protein NLM2)PlantsNIP1-2 of Arabidopsis thaliana
 
1.A.8.12.8Aquaporin NIP1-1 (NOD26-like intrinsic protein 1-1) (AtNIP1;1) (Nodulin-26-like major intrinsic protein 1) (NodLikeMip1) (Protein NLM1)PlantsNIP1-1 of Arabidopsis thaliana
 
1.A.8.12.9Aquaporin NIP6-1 (NOD26-like intrinsic protein 6-1) (AtNIP6;1)PlantsNIP6-1 of Arabidopsis thaliana
 
Examples:

TC#NameOrganismal TypeExample
1.A.8.13.1MIP family homologue Archaea Orf of Archaeoglobus fulgidus, AE000782 (ID# AF1426)
 
1.A.8.13.2

Hg2+-inhibitable aquaporin, AqpM (transports both water and glycerol as well as CO2) (Kozono et al., 2003; Araya-Secchi et al., 2011). 

Archaea

AqpM of Methanothermobacter marburgensis

 
1.A.8.13.3

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

Firmicutes

GlpF5 of Lactobacillus plantarum

 
Examples:

TC#NameOrganismal TypeExample
Examples:

TC#NameOrganismal TypeExample
Examples:

TC#NameOrganismal TypeExample
Examples:

TC#NameOrganismal TypeExample
Examples:

TC#NameOrganismal TypeExample
Examples:

TC#NameOrganismal TypeExample
1.A.8.2.1Glycerol facilitator Gram-positive bacteria and Haemophilus influenzae GlpF of Bacillus subtilis
 
1.A.8.2.2

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

Bacteria

GlpF of Mycoplasma gallisepticum )

 
1.A.8.2.4

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

Firmicutes

GlpF1 of Lactobacillus plantarum

 
1.A.8.2.5

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

Firmicutes

GlpF2 of Lactobacillus plantarum

 
1.A.8.2.6

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

Firmicutes

GlpF3 of Lactobacillus plantarum

 
1.A.8.2.7

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

Firmicutes

GlpF4 of Lactobacillus plantarum

 
1.A.8.2.8

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

Firmicutes

GlpF6 of Lactobacillus plantarum

 
1.A.8.2.9

Glycerol facilitator, GlpF, of 248 aas and 6 TMSs

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

 
Examples:

TC#NameOrganismal TypeExample
1.A.8.3.1

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).

Enteric bacteria

AqpZ of E. coli (P60844)

 
Examples:

TC#NameOrganismal TypeExample
1.A.8.4.1

Aquaporin 11 (Aqp11) transporter (important for the development of kidney proximal tubules (Nozaki et al., 2008)).

Animals

Aqp11 of Homo sapiens (Q8NBQ7)

 
1.A.8.4.2

Aquaporin-12A (AQP-12) of 295 aas and probably 7 TMSs. Expressed in elevated amounts in exocrine glandular cells of the pancreas (Danielsson et al. 2014).

Animals

AQP12A of Homo sapiens

 
1.A.8.4.3

Aquaporin 10, Aqp10 of 259 aas and 6 TMSs

Aqp10 of Haemonchus contortus (Barber pole worm)

 
Examples:

TC#NameOrganismal TypeExample
1.A.8.5.1

FPS1 glycerol efflux facilitator (important for maintaining osmotic balance during mating-induced yeast cell fusion and for tolerating hypoosmotic shock; also transports arsenite and antimonite). FPS1 is a homotetramer (Beese-Sims et al., 2011). Fps1 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. 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).

Yeast

FPS1 protein of Saccharomyces cerevisiae

 
1.A.8.5.2

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

Yeast

Fps1 of Ashbya gossypii (Q75CI7)

 
Examples:

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
 
1.A.8.6.3

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.

Fungi

Aqy1 of Komagataella pastoris (Pichia pastoris)

 
1.A.8.6.4

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

Fungi

AQP1 of Terfezia claveryi

 
Examples:

TC#NameOrganismal TypeExample
1.A.8.7.1

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

Plants

XIP1-1 of Nicotiana tomentosiformis (E3UN01)

 
1.A.8.7.2

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

Plants

XIP1-1 of Solanum tuberosum (E3UMZ6)

 
1.A.8.7.3

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

Plants

XIP1 of Ipomoea nil (E3UMZ5)

 
1.A.8.7.4

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

MIP2 of Chlamydomonas reinhardtii (Chlamydomonas smithii)

 
Examples:

TC#NameOrganismal TypeExample
1.A.8.8.1

Aquaporin 1 (CO2-, O2- and nitrous oxide-permeable and water-selective) (Zwiazek et al. 2017). 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).

Animals

Aquaporin 1 (AQP1) of Homo sapiens

 
1.A.8.8.10

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

Animals

Aquaporin of Blatella germanica (G8YY04)

 
1.A.8.8.11

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).

Animals

Aqp1 of Anopheles gambiae (F2YNF6)

 
1.A.8.8.12

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

Animals

Aqp1 of Eurosta solidaginis (E4W5Y5)

 
1.A.8.8.13

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

Insects

Aqp, DRIP of Drosophila melanogaster (Q9V5Z7)

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

MIP26 of Rana pipiens

 
1.A.8.8.15

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

Insects

Aquaporin-1 of Bemisia tabaci

 
1.A.8.8.16

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)

 
1.A.8.8.17

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)

 
1.A.8.8.18

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

 
1.A.8.8.19

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)

 
1.A.8.8.2

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).

Animals

Major intrinsic protein (MIP or Aqp0) of Bos taurus

 
1.A.8.8.20Channel protein Cyanobacteria Copper homeostasis protein (SmpX) of Synechococcus sp.
 
1.A.8.8.21

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)

 
1.A.8.8.3The BIB aquaporin of D. melanogaster (transports ions by a channel mechanism involving E71 in TMS1) (Yool, 2007). AnimalsBig brain (BIB) of Drosophila melanogaster
 
1.A.8.8.4Aqp6 aquaporin (also transports NO3- and other anions at acidic pH or in the presence of Hg2+) (Ikeda et al., 2002)AnimalsAqp6 of Homo sapiens
 
1.A.8.8.5

Aquaporin-4 (AQP4) (2 splice variants; the shorter assembles into functional, tetrameric square arrays; the longer is palmitoylated on N-terminal cysteyl residues) (Suzuki et al., 2008). Six splice variants have been identified. The longest, Aqp4e, has a novel N-terminal domain and forms a water channel in the plasma membrane. 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).

Animals

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).

Animals

Aqp1 of Polypedilum vanderplanki
(A5A7N9)

 
1.A.8.8.7

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

Animals

Aqp2 of Polypedilum vanderplanki (A5A7P0)

 
1.A.8.8.8

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 2.75Å (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).

Animals

Aqp2 of Homo sapiens (P41181)

 
1.A.8.8.9

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).

Animals

Aquaporin 5 of Homo sapiens (P55064)

 
Examples:

TC#NameOrganismal TypeExample
1.A.8.9.1

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).

Animals

Aquaporin 3 of Rattus norvegicus (P47862)

 
1.A.8.9.10

Aqp9 or Aqp-h9 of 294 aas.  Takes up glycerol and thereby contributes to freeze tolerance (Hirota et al. 2015).

Aqp9 of Hyla japonica

 
1.A.8.9.11

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)

 
1.A.8.9.12

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

Aqp3 of Xenopus laevis

 
1.A.8.9.13Aquaglycerolporin, Aqp (high permeability to ammonium, methylamine, glycerol and water) (Beitz et al., 2004) NH4+/NH3+CH3 transporter (Zeuthen et al., 2006).ProtozoanAqp of Plasmodium falciparum (CAC88373)
 
1.A.8.9.14

Glycerolaquaporin 9, Aqp9 of 295 aas and 6 TMSs.  Transports water, glycerol and arsenic trioxide, As2O3 (Palmgren et al. 2017). Primary APL cells expressed AQP9 significantly (2-3 logs) higher than other acute myeloid leukemias (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).

Aqp9 of Homo sapiens

 
1.A.8.9.15

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

Aqp9 of Echinococcus granulosus (Hydatid tapeworm)

 
1.A.8.9.2

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).  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).

Animals

Aqp9 of Rattus norvegicus (P56627)

 
1.A.8.9.3

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, functions in osmotaxis) (Figarella et al., 2005; Gourbal et al, 2004).

Protozoa

Aqp1 of Leishmania major (Q6Q1Q6)

 
1.A.8.9.4

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

Protozoan

Aqp1 of Trypanosoma brucei (Q6ZXT4)

 
1.A.8.9.5

Aquaporin 10.  Present in keratinocytes and the stratum corneum (Jungersted et al. 2013).

Animals

Aqp10 of Homo sapiens

 
1.A.8.9.6

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). 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).

Animals

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)
 
1.A.8.9.8

Glycerol uptake facilitator of 393 aas

Fungi

Glycerol transporter of Cordyceps militaris (Caterpillar fungus)

 
1.A.8.9.9

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