DBC1/CCAR2 and CCAR1 Are Largely Disordered Proteins that Have Evolved from One Common Ancestor

Biomed Res Int. 2014:2014:418458. doi: 10.1155/2014/418458. Epub 2014 Dec 11.

Abstract

Deleted in breast cancer 1 (DBC1, CCAR2, KIAA1967) is a large, predominantly nuclear, multidomain protein that modulates gene expression by inhibiting several epigenetic modifiers, including the deacetylases SIRT1 and HDAC3, and the methyltransferase SUV39H1. DBC1 shares many highly conserved protein domains with its paralog cell cycle and apoptosis regulator 1 (CCAR1, CARP-1). In this study, we examined the full-length sequential and structural properties of DBC1 and CCAR1 from multiple species and correlated these properties with evolution. Our data shows that the conserved domains shared between DBC1 and CCAR1 have similar domain structures, as well as similar patterns of predicted disorder in less-conserved intrinsically disordered regions. Our analysis indicates similarities between DBC1, CCAR1, and the nematode protein lateral signaling target 3 (LST-3), suggesting that DBC1 and CCAR1 may have evolved from LST-3. Our data also suggests that DBC1 emerged later in evolution than CCAR1. DBC1 contains regions that show less conservation across species as compared to the same regions in CCAR1, suggesting a continuously evolving scenario for DBC1. Overall, this study provides insight into the structure and evolution of DBC1 and CCAR1, which may impact future studies on the biological functions of these proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / genetics*
  • Animals
  • Apoptosis Regulatory Proteins / chemistry
  • Apoptosis Regulatory Proteins / genetics*
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics*
  • Evolution, Molecular*
  • Histone Deacetylases / chemistry
  • Histone Deacetylases / genetics
  • Humans
  • Methyltransferases / chemistry
  • Methyltransferases / genetics
  • Protein Structure, Tertiary
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics
  • Sirtuin 1 / chemistry
  • Sirtuin 1 / genetics
  • Structure-Activity Relationship

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • CCAR1 protein, human
  • CCAR2 protein, human
  • Cell Cycle Proteins
  • Repressor Proteins
  • SUV39H1 protein, human
  • Methyltransferases
  • SIRT1 protein, human
  • Sirtuin 1
  • Histone Deacetylases
  • histone deacetylase 3