Structural protein analysis of driver gene mutations in conjunctival melanoma

Mak B. Djulbegovic, Vladimir N. Uversky, J. William Harbour, Anat Galor, Carol L. Karp

Research output: Contribution to journalArticlepeer-review

Abstract

In recent years, there has been tremendous enthusiasm with respect to detailing the genetic basis of many neoplasms, including conjunctival melanoma (CM). We aim to analyze five proteins associated with CM, namely BRAF, NRAS, c-KIT, NF1, and PTEN. We evaluated each protein for its intrinsically disordered protein regions (IDPRs) and its protein-protein interactions (PPI) with the Predictor of Natural Disordered Protein Regions (PONDR® ) and the Search Tool for the Retrieval of Interacting Genes (STRING® ). Our PONDR® analysis found high levels of IDPRs in all five proteins with mutations linked to CM. The highest levels of IDPRs were in BRAF (45.95%), followed by PTEN (31.76%), NF1 (22.19%), c-KIT (21.82%), and NRAS (14.81%). Our STRING analysis found that each of these five proteins had more predicted interactions then expected (p-value < 1.0 × 10−16 ). Our analysis demonstrates that the mutations linked to CM likely affected IDPRs and possibly altered their highly complex PPIs. Quantifying IDPRs in BRAF, NRAS, c-KIT, NF1, and PTEN and understanding these protein regions are important processes as IDPRs can be possible drug targets for novel targeted therapies for treating CM.

Original languageEnglish (US)
Article number1625
JournalGenes
Volume12
Issue number10
DOIs
StatePublished - Oct 2021

Keywords

  • Conjunctival melanoma
  • Genetics
  • Intrinsically disordered proteins
  • Mitogen-activated protein kinase (MAPK)
  • Neuroblastoma v-ras oncogene homolog (NRAS)
  • Neurofibromatosis type 1 (NF1)
  • Phosphate and tensin homolog (PTEN)
  • Phosphatidylinositol-3-Kinase and Protein Kinase B (PI3K-akt)
  • Proto-oncogene B-Raf (BRAF)
  • Receptor tyrosine kinase (c-KIT)
  • Structural analysis
  • Targeted therapies

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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