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Molecular genomic insights into melanoma associated proteins PRAME and BAP1

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Bhattacharya,  Tanishta
Max Planck Institute for Heart and Lung Research, Max Planck Society;

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Citation

Nawn, D., Hassan, S. S., Hromic-Jahjefendic, A., Bhattacharya, T., Basu, P., Redwan, E. M., et al. (2025). Molecular genomic insights into melanoma associated proteins PRAME and BAP1. JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS. doi:10.1080/07391102.2025.2475228.


Cite as: https://hdl.handle.net/21.11116/0000-0010-F250-2
Abstract
Melanoma, a globally prevalent skin cancer with over 325,000 new cases annually, necessitates a comprehensive under- standing of its molecular components. This study looks at the PRAME (cutaneous melanoma-associated antigen) and BAP1 (gene controlling gene-environment interactions) proteins. Both PRAME and BAP1 are associated with critical genomic alterations that significantly influence melanoma progression and patient outcomes. PRAME is overexpressed in various cancers, especially uveal melanoma (UM), where high levels correlate with poor prognosis and genomic instability linked to chromosome 8q12 alterations. Meanwhile, mutations in BAP1 contribute to increased genomic instability and a higher risk of metastasis in UM, highlighting its importance as a key prognostic marker in tumorigenesis. Established approaches along with features proposed in this work are used to investigate sequence conservation, polyglutamic acid presence, intrinsic disorder of proteins, polar-nonpolar residues arrangement PRAME and BAP1 conserved residues highlight their critical roles in protein function and interaction. Sequence invariance indicates the possibility of functional relevance and evolutionary conservation. PRAME has enhanced intrinsic disorder and flexibility, whereas BAP1 has changed disorder-promoting residue sequences. Polyglutamic acid strings are found in both proteins, emphasizing their modulatory involvement in protein interactions. The ratios and spatial arrangement of amino acids have a profound influence on interactions and gene dysregulation. This work contributes to a better knowledge of the two melanoma-associated proteins viz. PRAME and BAP1 by unraveling their structural and functional complexities.