NR-PTMkb is an open, comprehensive, manually curated platform for the study of post-translational modifications (PTMs) of nuclear receptors and their dynamic interactions with coregulators. The current version of NR-PTMkb includes 13 different types of PTMs and contains curated data on 2,976 PTM sites across human, mouse, and rat nuclear receptors. Additionally, 88 modifying enzymes responsible for these PTMs, along with their associated signaling implications and domain-specific interactions, have been systematically compiled.
NR-PTMkb offers four interactive modules: NR Roots, NR Tabs, NR Dock, and PTM Profiler designed for easy browsing, search, and retrieval of curated and predicted PTM data. NR Roots provides tree-based views (sequence and function-based) of human nuclear receptors and their PTMs, showing modification sites, flanking sequences, domains, modifiers, and signalling impact. NR Tabs serves as a central annotation hub with interactive 3D and sequence-based PTM visualization, along with variant data (ClinVar, dbSNP, AlphaMissense), GO terms, disease associations (DisGeNET), and tissue-specific expression. NR Dock includes energy-minimized structures of native and PTM-modified NRs (with/without agonists) and docking results with coregulators, validated in vitro. PTM Profiler compiles predicted PTMs across 48 NRs using a fine-tuned deep learning model (based on MIND-S) with experimental validation. Additional tools include Simple Search and an advanced Query Builder for hypothesis-driven exploration of PTM data.
NR-PTMkb integrates experimentally validated and predicted PTM data from curated databases such as dbPTM, qPTM, and UniProt, along with expert manual curation. Structural and functional annotations are derived from AlphaFold, HGNC, BioMart, STRING, Human Protein Atlas, DisGeNET, AlphaMissense, Reactome, ClinVar, and QuickGO, enabling comprehensive mapping of PTMs within biological and structural contexts of nuclear receptor.
NR-PTMkb is the first comprehensive database of curated and potential PTMs of NRs (emerging drug targets) and a systematically annotated NR-PTM-modifiers-signalling axis. The modules integrated in NR-PTMkb, utilises a combined evidence approach towards understanding the role of NRs and PTMs, including their potential biological effects and role in diseases like cancer, metabolic disorders, and inflammatory diseases. Field experts and researchers can systematically retrieve and organize pertinent information for precision therapeutic strategies in different disease conditions resulting from atypical PTMs in NRs.
Yes, All data associated with NR-PTMkb are publicly available at:
https://doi.org/10.6084/m9.figshare.31017709
and
https://datascience.imtech.res.in/anshu/nrptmkb/
Scripts used for analysis are available at
https://github.com/AB-DataScienceLab/NRPTMkb