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9.B.9 The Galectin (Galectin) or Putative Urate Transporter (UAT) Family
Several reports have p;rovided evidence for a putative urate transporter (UAT) function which was reported to catalyze the electrogenic efflux of urate from mammalian cells following degradation of the purine bases, adenine and guanine, to uric acid. A cDNA was isolated which encodes a protein of 322 amino acids. It is largely hydrophilic and is identical to a member of the family of galactose binding lectins, the galectins. The selective urate transport activity of the recombinant UAT was reconstituted in planar lipid bilayers. One report, based on bioinformatic studies, concluded that there are four TMSs (Leal-Pinto et al. 1999). Proline-derived quinoline formamide compounds are human urate transporter 1 inhibitors with potent uric acid-lowering activities (Li et al. 2024). Urate-lowering active peptides from hemp protein have been characterized (Liu et al. 2025).
Uric acid is the product of purine metabolism and its increased levels
result in hyperuricemia (Xu et al. 2017). A number of epidemiological reports link
hyperuricemia with multiple disorders, such as kidney diseases,
cardiovascular diseases and diabetes. Expression and functional changes of urate transporters are associated
with hyperuricemia. Uric acid transporters are divided into two
categories: urate reabsorption transporters, including urate anion
transporter 1 (URAT1), organic anion transporter 4 (OAT4) and glucose
transporter 9 (GLUT9), and urate excretion transporetrs, including OAT1,
OAT3, urate transporter (UAT), multidrug resistance protein 4
(MRP4/ABCC4), ABCG-2 and sodium-dependent phosphate transport protein (Xu et al. 2017). Long term high fructose diet induced metabolic syndrome with increased
blood pressure and proteinuria in rats. Metabolic syndrome was
associated with dual increase in renal glucose and uric acid
transporters, including SGLT1, SGLT2, GLUT2, GLUT9 and UAT (Ng et al. 2018).
The proposed transport reaction catalyzed by UAT is:
urate (in)  urate (out)
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| References: |
Leal-Pinto, E., B.E. Cohen, and R.G. Abramson. (1999). Functional analysis and molecular modeling of a cloned urate transporter/channel. J. Membr. Biol. 169: 13-27.
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Leal-Pinto, E., B.E. Cohen, M.S. Lipkowitz, and R.G. Abramson. (2002). Functional analysis and molecular model of the human urate transporter/channel, hUAT. Am. J. Physiol. Renal Physiol 283: F150-163.
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Leal-Pinto, E., W. Tao, J. Rappaport, M. Richardson, B.A. Knorr, and R.G. Abramson. (1997). Molecular cloning and functional reconstitution of a urate transporter/channel. J. Biol. Chem. 272: 617-625.
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Li, S., H. Liao, L. Luo, B. Meng, F. Zheng, L. Sheng, H. Zhao, Y. Huan, L. Lei, J. Zhai, K. Zhao, J. Tian, T. Wu, G. Li, J. Pang, and H. Huang. (2024). Proline-derived quinoline formamide compounds as human urate transporter 1 inhibitors with potent uric acid-lowering activities. Eur J Med Chem 269: 116327.
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Lipkowitz, M.S., E. Leal-Pinto, B.E. Cohen, and R.G. Abramson. (2002). Galectin 9 is the sugar-regulated urate transporter/channel UAT. Glycoconj J 19: 491-498.
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Liu, M.Q., H.F. Zhao, Z.Y. Zhao, Y.H. Zhang, and Y. Dong. (2025). Preparation, identification and potential mechanism of novel urate-lowering active peptide from hemp protein: From animal model to computer simulation. Food Res Int 214: 116643.
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Ng, H.Y., Y.T. Lee, W.H. Kuo, P.C. Huang, W.C. Lee, and C.T. Lee. (2018). Alterations of Renal Epithelial Glucose and Uric Acid Transporters in Fructose Induced Metabolic Syndrome. Kidney Blood Press Res 43: 1822-1831.
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Pang, Y., E. Maxwell, P. Sindrewicz-Goral, A. Shapanis, S. Li, M. Morgan, and L.G. Yu. (2022). Galectin-3 Is a Natural Binding Ligand of MCAM (CD146, MUC18) in Melanoma Cells and Their Interaction Promotes Melanoma Progression. Biomolecules 12:.
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Rappoport, J.Z., M.S. Lipkowitz, and R.G. Abramson. (2001). Localization and topology of a urate transporter/channel, a galectin, in epithelium-derived cells. Am. J. Physiol. Cell Physiol. 281: C1926-1939.
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Vollmer, W., M. von Rechenberg, and J.V. Höltje. (1999). Demonstration of molecular interactions between the murein polymerase PBP1B, the lytic transglycosylase MltA, and the scaffolding protein MipA of Escherichia coli. J. Biol. Chem. 274: 6726-6734.
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Wang, K., S. Fu, L. Dong, D. Zhang, M. Wang, X. Wu, E. Shen, L. Luo, C. Li, E.C. Nice, C. Huang, and B. Zou. (2023). Periplocin suppresses the growth of colorectal cancer cells by triggering LGALS3 (galectin 3)-mediated lysophagy. Autophagy 19: 3132-3150.
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Xu, L., Y. Shi, S. Zhuang, and N. Liu. (2017). Recent advances on uric acid transporters. Oncotarget 8: 100852-100862.
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| Examples: |
| TC# | Name | Organismal Type | Example |
| 9.B.9.1.1 | Galectin-9 or Lgals9, but also called the Urate transporter (UAT). Galectin 9 is reported to be the sugar-regulated urate transporter/channel UAT. It is of 354 aas with an uncertain number of TMSs. UAT is a multifunctional protein that can function as a urate channel/transporter, a regulator of thymocyte-epithelial cell interactions, a tumor antigen, an eosinophil chemotactic factor, and a mediator of apoptosis (Lipkowitz et al. 2002). The urate channel activity is regulated by sugars and adenosine (Lipkowitz et al. 2002). The presence and possible functions of at least 4 isoforms of UAT and a closely related gene hUAT2 were discussed (Lipkowitz et al. 2002). UAT is targeted to the plasma membranes of multiple epithelium-derived cell
lines and, in polarized cells, is targeted to both apical and
basolateral membranes. The amino and carboxy termini of UAT were both
detected on the cytoplasmic side of plasma membranes, whereas cell
surface biotinylation studies demonstrated that UAT is not merely a
cytosolic membrane-associated protein but contains at least one
extracellular domain. UAT is capable of forming both homo- and hetero-multimers (Rappoport et al. 2001). Recombinant UAT prepared from a cloned rat renal
cDNA library functions as a selective voltage-sensitive urate
transporter/channel when in lipid bilayers. UAT may be the mammalian electrogenic urate
transporter. Two compounds, oxonate (a
competitive uricase inhibitor) and pyrazinoate, that inhibit renal
electrogenic urate transport also block UAT activity. Of note, oxonate
selectively blocks from the cytoplasmic side of the channel while
pyrazinoate only blocks from the channel's extracellular face. Like
oxonate, anti-uricase (an electrogenic transport inhibitor) also
selectively blocks channel activity from the cytoplasmic side. Adenosine
blocks from the extracellular side exclusively while xanthine blocks
from both sides. These effects are consistent with newly identified
regions of homology to uricase and the adenosine A1/A3 receptor in UAT
and localize these homologous regions to the cytoplasmic and
extracellular faces of UAT, respectively. Additionally, computer
analyses identified four putative alpha-helical transmembrane domains,
two beta sheets, and blocks of homology to the E and B loops of
aquaporin-1 within UAT. The experimental observations substantiate the
proposal that UAT is the renal
electrogenic urate transporter with a proposed molecular structure (Leal-Pinto et al. 1999). The human urate transporter/channel, hUAT, has also been characterized (Leal-Pinto et al. 2002). Galectin-9C is 71% identical to this protein (Pang et al. 2022). | Mammals | UAT of Rattus norvegicus |
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| 9.B.9.1.10 | Uncharacterized protein of 561 aas and 2 TMSs. | | UP of Coryphaenoides rupestris (roundnose grenadier) |
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| 9.B.9.1.11 | Galectin4-like protein of 319 aas and one N-terminal TMS, and possibly two more, one centrally located and one near the C-terminus of the protein. | | Galectin4 of Syngnathus acus (greater pipefish) |
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| 9.B.9.1.13 | Galactoside-binding lectin of 205 aas and possibly two TMSs near the C-terminus of the protein. | | Lectin of Teladorsagia circumcincta |
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| 9.B.9.1.14 | Galectin-3 (LGALS-3 or MAC2) of 250 aas and 1 TMS (at residues 120 - 140). Periplocin suppresses the growth of colorectal cancer cells by triggering LGALS3 (galectin 3)-mediated lysophagy (Wang et al. 2023). | | Galectin-3 of Homo sapiens |
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| 9.B.9.1.15 | Uncharacterized protein of 344 aas and up to 5 TMSs. | | UP of Meloidogyne enterolobii |
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| 9.B.9.1.2 | Uncharacterized protein of 354 aas and an unknown number of TMSs. | | UP of Saprolegnia diclina |
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| 9.B.9.1.3 | 32 kDa beta-galactoside-binding lectin of 321 aas and 0 - 4 TMSs. | | Lectin of Zeugodacus cucurbitae (melon fly) |
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| 9.B.9.1.4 | Sushi, von Willebrand factor type A, EGF and pentraxin domain-containing protein 1-like of 386 aas and 2 (N- and C-terminal) TMSs and possibly others. | | Sushi of Gigantopelta aegis |
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| 9.B.9.1.5 | Galectin-8-like protein of 461 aa | | Galectin8 of Gigantopelta aegis |
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| 9.B.9.1.6 | Uncharacterized protein of 454 aas and 0 - 5 TMSs | | UP of Meloidogyne enterolobii |
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| 9.B.9.1.7 | DUF1963 domain-containing protein of 442 aas and 1 N-terminal TMS possibly plus more TMSs. | | DUF1963 protein of Microcystis |
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| 9.B.9.1.8 | Uncharacterized protein of 340 aas and 1 N-terminal TMS and possibly 1 C-terminal TMS | | UP of Glossina fuscipes |
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| 9.B.9.1.9 | Uncharacterized protein of 420 aas | | UP of Astyanax mexicanus (Mexican tetra) |
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| Examples: |
| TC# | Name | Organismal Type | Example |