Prediction of pH-sensing histidine residues in human cells
- 1University of Manchester
Abstract
Changes in pH play an important role in human physiology and cell behaviours, evidenced by studies of tissues and gene expression, and the biophysics of individual systems. Bridging between these scales to establish pH-sensing networks has only been partially explored. Here, amino acid conservation and structural context, and benchmarking with known pH-sensors, were used to predict histidine residues within the human proteome that could modulate pH-dependence. Proteins containing these histidines are enriched in many categories, most notably nucleic acid-binding and transcriptional regulation. DNA phosphate backbone interactions are proposed to play a major role in modulating some pH-sensors. Transcription factors with potential pH-sensors and the largest number of documented target genes are highlighted, including those involved in circadian and developmental processes. Certain CDK-cyclin pairs also feature, along with components of SWI/SNF and cohesin complexes. Focussing on histidines, including those that are solvent accessible in AlphaFold protomer models, this study generates benchmarked predictions for possible pH-sensors in the human proteome.
Related
- mGem: Innate immune sensing of HIV-1 transcription in myeloid cells—a tale of two transcription start sites
- Activation of cytosolic DNA sensing in NCM460 intestinal epithelial cells induces antiviral factors that restrict HIV infection in macrophages
- Molecular Checkpoints of Nucleic Acid Sensing in Tumor Cells: Linking Innate Immune Evasion to Precision Cancer Immunotherapy
- Antenna cells of ascidian larvae are gravity-sensing neurons
- Spatial Prediction of Opisthorchis viverrini Infection Risk Using Multi-Source Remote Sensing, Hexagonal Grid Optimization, and Ensemble Machine Learning: A Case Study From Northeastern Thailand.
BibTeX
@misc{sallah2026prediction,
title = {{Prediction of pH-sensing histidine residues in human cells}},
author = {S. Sallah and J. Warwicker},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.14.751505},
url = {https://www.biorxiv.org/content/10.64898/2026.09.14.751505v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Prediction of pH-sensing histidine residues in human cells
AU - S. Sallah
AU - J. Warwicker
PY - 2026
DA - 2026/09/14
PB - bioRxiv
DO - 10.64898/2026.09.14.751505
UR - https://www.biorxiv.org/content/10.64898/2026.09.14.751505v1
AB - Changes in pH play an important role in human physiology and cell behaviours, evidenced by studies of tissues and gene expression, and the biophysics of individual systems. Bridging between these scales to establish pH-sensing networks has only been partially explored. Here, amino acid conservation and structural context, and benchmarking with known pH-sensors, were used to predict histidine residues within the human proteome that could modulate pH-dependence. Proteins containing these histidines are enriched in many categories, most notably nucleic acid-binding and transcriptional regulation. DNA phosphate backbone interactions are proposed to play a major role in modulating some pH-sensors. Transcription factors with potential pH-sensors and the largest number of documented target genes are highlighted, including those involved in circadian and developmental processes. Certain CDK-cyclin pairs also feature, along with components of SWI/SNF and cohesin complexes. Focussing on histidines, including those that are solvent accessible in AlphaFold protomer models, this study generates benchmarked predictions for possible pH-sensors in the human proteome.
ER -