{
  "abstract": "Introduction: ITPR3 is an endoplasmic reticulum Ca2+ release channel that plays an important role in intracellular calcium signaling and has been implicated in cancer-associated cellular processes. Although several phosphorylation sites have been identified in ITPR3, the downstream regulatory networks associated with individual ITPR3 phosphosites remain poorly understood.\n\nMaterials and Methods: In this study, we integratively analysed the publicly available human phosphoproteomic studies to characterize the phosphorylation landscape of ITPR3. Qualitative profiling and quantitative differential datasets were curated to identify phosphosites, followed by co-regulation analysis, functional enrichment, protein-protein interaction network analysis, upstream kinase identification and analysis of cancer-associated phosphoproteomic data using cProSite.\n\nResults and Discussion: Analysis of qualitative profiling and quantitative differential phosphoproteomic datasets identified four predominant ITPR3 phosphosites (S1832, S934, S2670, and S916) based on their recurrent detection and perturbation across independent datasets. Functional enrichment analysis revealed associations with chromatin organization, transcriptional regulation, RNA processing, cytoskeletal organization, and cellular signaling, indicating distinct regulatory patterns across ITPR3 phosphosites. Mapping of co-regulated proteins to the KEGG calcium signaling pathway identified multiple components involved in receptor-mediated signaling, IP3 generation, intracellular Ca2+ release, store-operated calcium entry, and calcium-responsive signaling. Furthermore, analysis of cancer-derived phosphoproteomic datasets showed the recurrent detection of the four predominant phosphosites across diverse cancer cell lines. Analysis using cProSite revealed distinct tumor-specific phosphorylation patterns, including significant differential phosphorylation of S1832 residue in pancreatic ductal adenocarcinoma, S2670 in breast cancer, S934 in ovarian cancer and S916 in kidney cancer. These findings provide a comprehensive view of ITPR3 phosphorylation and highlight potential regulatory networks connecting specific ITPR3 phosphosites with calcium signaling and cancer-associated processes. Further experimental studies are needed to determine the functional role of these phosphosites and to establish their association with ITPR3-mediated calcium signaling and tumor biology.",
  "abstract_shown": true,
  "affiliations": [
    "Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to Be University), Mangalore, Karnataka, India",
    "School of Computer Science and Engineering, Vellore Institute of Technology, Chennai, Tamil Nadu, India"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Shanmitha B. Rai"
    },
    {
      "affs": [
        0
      ],
      "name": "Ayadathil Sujina"
    },
    {
      "affs": [
        0
      ],
      "name": "Sreeshma Ravindran Kammarambath"
    },
    {
      "affs": [
        0
      ],
      "name": "Althaf Mahin"
    },
    {
      "affs": [
        0
      ],
      "name": "Suhail Subair"
    },
    {
      "affs": [
        0
      ],
      "name": "Alimath Sambreena"
    },
    {
      "affs": [
        1
      ],
      "name": "S. Pavithra"
    },
    {
      "affs": [
        0
      ],
      "name": "Rajesh Raju"
    },
    {
      "affs": [
        0
      ],
      "name": "Akhina Palollathil"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ayjn9dq2wb4mr.bib",
  "cited_by": 0,
  "doi": "10.3389/fbinf.2026.1972498",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13731270/",
  "id": "ayjn9dq2wb4mr",
  "issns": [
    "2673-7647"
  ],
  "landing_url": "https://doi.org/10.3389/fbinf.2026.1972498",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "1607|Advanced Proteomics Techniques and Applications"
    ]
  ],
  "openalex": "W7223150055",
  "pdf_url": "https://www.frontiersin.org/journals/bioinformatics/articles/10.3389/fbinf.2026.1972498/pdf",
  "pmcid": "PMC13731270",
  "pmid": "42984818",
  "published": "2026-10-21",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/ayjn9dq2wb4mr.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:21:29Z",
      "native_id": "PMC13731270",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fbinf.2026.1972498"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1607|Advanced Proteomics Techniques and Applications",
      "subfield": "physical"
    }
  ],
  "title": "Decoding the phosphorylation landscape of ITPR3 across calcium signaling and regulatory networks in cancer",
  "title_text": "Decoding the phosphorylation landscape of ITPR3 across calcium signaling and regulatory networks in cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:21:29Z",
  "url": "https://research.draconitic.com/paper/ayjn9dq2wb4mr",
  "venue": "Frontiers in Bioinformatics",
  "versions": []
}