Quantitative Deciphering of Mammalian Histamine Receptors through Mathematical Genomics
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Le résumé fourni par la source
Abstract Histamine receptors (HRH1–HRH4) are G-protein coupled receptors (GPCRs) that mediate essential physiological functions, including neurotransmission, gastric acid secretion, immune regulation, and presynaptic autoregulation. Despite their importance, systematic comparative analyses across mammalian histamine receptor sequences remain scarce. In this study, we performed a comprehensive evaluation of HRH1–HRH4 across multiple mammalian species, integrating sequence homology, invariant residue mapping, amino acid substitutions, compositional frequencies, Shannon entropy, polystring distributions, intrinsic disorder profiling, and phylogenetic clustering. HRH2 and HRH1 were highly conserved among primates, HRH3 showed strong cohesion within rodents, while HRH4 exhibited pronounced divergence consistent with immune-related specialization. Invariant residues localized to transmembrane helices and activation motifs (D107, W428/Y431, NPxxY), underscoring strict evolutionary constraints on ligand binding, receptor stability, and G-protein coupling. Substitutions were confined to non-essential lipid-facing and loop regions, predominantly conservative in nature, enabling diversification without disrupting the GPCR fold. Amino acid frequency and entropy analyses revealed hydrophobic dominance with subtype-specific enrichment of polar residues, while disorder profiling identified HRH1 as the most dynamic and HRH2 as the most structurally constrained. Polystring analysis highlighted conserved motifs (WWW, PP) alongside subtype- and species-specific repeats, reflecting evolutionary strategies balancing receptor stability with adaptive flexibility. Phylogenetic clustering confirmed subtype-specific cohesion, with HRH3 and HRH4 forming compact clades, HRH1 showing moderate dispersion, and HRH2 forming the most isolated cluster. Collectively, these findings demonstrate that mammalian histamine receptor evolution is governed by conserved biophysical cores and selective variability, offering insights into structural conservation, functional diversification, and translational relevance for drug design and model selection.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Quantitative Deciphering of Mammalian Histamine Receptors through Mathematical Genomics
- Date Crossref
- 12/01/2026
- Éditeur
- openRxiv
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Adamas University pays non établi dans la noticeUniversité ou école supérieure
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Central Council for Research in Homoeopathy pays non établi dans la noticeOrganisme public
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Jangipur College Department of Zoology pays non établi dans la noticeUniversité ou école supérieure
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Indian Statistical Institute Biological Science Division pays non établi dans la noticeUniversité ou école supérieure
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Peerless Hospital & B.K.Roy Research Centre pays non établi dans la noticeÉtablissement de santé
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University of South Florida pays non établi dans la noticeUniversité ou école supérieure
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Department of Mathematics pays non établi dans la noticeInstitution
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School Of Engineering & Technology Computer Science & Engineering pays non établi dans la noticeUniversité ou école supérieure
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DAC Regional Research Institute for Homoeopathy pays non établi dans la noticeStructure de recherche
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Peerless Hospital & B.K. Roy Research Center pays non établi dans la noticeStructure de recherche
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Morsani College of Medicine Department of Molecular Medicine pays non établi dans la noticeUniversité ou école supérieure
Adamas University, Central Council for Research in Homoeopathy et Department of Zoology — Jangipur College, avec 8 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.