Potential split-component signal transducers of hemoglobin gasoreceptor activity

Receptors can trigger cellular signaling directly or via signal transducers.1 To the best of my knowledge, there is still no scientific consensus on the identity of oxygen receptors.2 I proposed hemoglobin as an gasoreceptor, aquareceptor and photoreceptor in proto- or split-component signaling transduction systems due to its catalytic activity- or its (“partner”) signal transducer-dependent signaling, respectively.3–5 A question arises on the identity of potential signal transducers of hemoglobin in the split-component signal transduction system. Based on the binding partners of human HBA1 and HBB listed in the protein-protein interaction database IID6, in addition to BAND3/SLC4A1, the following proteins are the potential signal transducers of hemoglobin in the split-component signal transduction system. Potential HBA1 signal transducers AGA GSTT1 GDPD1 NDUFAF5 PGPEP1 MAPK6 (ERK3) PNKP MACROD1 SLC2A14 (GLUT14) Potential HBB signal transducers AGA GSTT1 GDPD1 NDUFAF5 PGPEP1 MAPK6 PNKP DHRS2 MGAT4B PNPLA1 JOSD2 PSMC5 SLC2A14 Finally, it is worth noting that, as I mentioned previously3, HBA1 or HBB can also be potential signal transducers and the above listed proteins can be receptors for other molecules or factors. REFERENCE 1. Lim WA, Mayer BJ. Cell Signaling, 2nd edition: Principles and Mechanisms. CRC Press; 2024. 2. Ratcliffe PJ, Keeley TP. Making sense of oxygen sensing. EMBO J 2025; 3. Anbalagan S. Hemoglobin as an oxygen gasoreceptor. Acta Biochim Pol 2025; 72:15546. 4. Anbalagan S. [Heme-based aquareceptors]. Postepy Biochem 2024; 70:420–3. 5. Anbalagan S. Hemoglobin as an proto-photoreceptor. 2026 [cited 2026 Nov 7]; Available from: https://zenodo.org/records/23725829 6. Kotlyar M, Pastrello C, Abovsky M, Mizeranschi A, Keating A, Cameron L-C, Chandran V, Jurisica I. IID 2025: Physical protein interaction data with detection types, co-purified protein sets, molecular docking, and immune cell networks. Nucleic Acids Res 2026; 54:D593–600.