Intrinsically disordered regions-based aquareceptors

In the emerging field of gasocrinology, it is important not only to identify all the gasoreceptors involved in gasocrine signaling, as well as those that exhibit duality or multimodality in sensing other molecules or factors.1,2 Earlier, I proposed that hemoglobin acts an oxygen gasoreceptor in a proto- or split-component signal transduction system (STS).3–5 Additionally, I proposed that hemoglobin is also one of the heme-based water-sensing aquareceptors.6 This rationale can be extended to other hemoproteins as well. For example, the Arabidopsis thaliana Delay of Germination-1 (DOG1) protein can be considered a potential gasoreceptor or aquareceptor.7 However, the sensing domain in receptors can vary.8 This raises the question: apart from heme domain-containing globin-based aquareceptors, are there other domain-based aquareceptors? Since some intrinsically disordered region (IDR) domain-containing proteins have water-sensing potential, I propose that IDR-domain containing proteins are potential water-sensing aquareceptors in split-, proto-, two-, one-, or multi-component STS. Therefore, the A. thaliana sterile alpha motif (SAM)-containing protein, SAM8 and FLOE1 and human Rel family transcription factor NFAT5 are also potential aquareceptor in split-component STS.9–11 However, further experiments are needed to determine if it is only an aquareceptor, a receptor for other ions, or an aquareceptor that exhibits duality or multimodality.12 Finally, it is worth also considering the role of potential IDR-like nucleic acids as potential water-sensing aquariboceptors.13–15 REFERENCES Anbalagan S. Gasocrine hypothesis - a potential supplement to cell theory. Acta Biochim Pol 2025; 72:15465. Anbalagan S. Sugar-sensing swodkoreceptors and swodkocrine signaling. Animal Model Exp Med 2025; 8:944–61. Anbalagan S. Hemoglobin as an oxygen gasoreceptor. Acta Biochim Pol 2025; 72:15546. Hardison R. Hemoglobins From Bacteria to Man: Evolution of Different Patterns of Gene Expression. Journal of Experimental Biology 1998; 201:1099–117. Storz JF. Hemoglobin: Insights into protein structure, function, and evolution Internet. Oxford, United Kingdom: Oxford University Press; 2018 cited 2025 Aug 6. Available from: https://doi.org/10.1093/oso/9780198810681.001.0001 Anbalagan S. Heme-based aquareceptors. Postepy Biochem 2024; 70:420–3. Nishimura N, Tsuchiya W, Moresco JJ, Hayashi Y, Satoh K, Kaiwa N, Irisa T, Kinoshita T, Schroeder JI, Yates JR, et al. Control of seed dormancy and germination by DOG1-AHG1 PP2C phosphatase complex via binding to heme. Nat Commun 2018; 9:2132. Roberts MS, Kruchten AE. Receptor Biology. Weinheim, Germany: John Wiley 2016. Wang Y, Zhu L, Yang Y, Li X, Zhang X, Fang X. Cellular water-potential sensing through biomolecular condensation. Nature 2026; :1–10. Dorone Y, Boeynaems S, Flores E, Jin B, Hateley S, Bossi F, Lazarus E, Pennington JG, Michiels E, De Decker M, et al. A prion-like protein regulator of seed germination undergoes hydration-dependent phase separation. Cell 2021; 184:4284-4298.e27. Khandwala CB, Sarkar P, Schmidt HB, Ma M, Pusapati GV, Lamoliatte F, Kinnebrew M, Patel BB, Tillo D, Lebensohn AM, et al. Direct ionic stress sensing and mitigation by the transcription factor NFAT5. Sci Adv 2025; 11:eadu3194. Moses D, Ginell GM, Holehouse AS, Sukenik S. Intrinsically disordered regions are poised to act as sensors of cellular chemistry. Trends Biochem Sci 2023; 48:1019–34. Anbalagan S. Gas-sensing riboceptors. RNA Biol 2024; 21:1–6. Anbalagan S. Temperature-sensing riboceptors. RNA Biol 2024; 21:1–6. Kavita K, Breaker RR. Discovering riboswitches: the past and the future. Trends Biochem Sci 2023; 48:119–41.