title: DBC1/CCAR2 and CCAR1 Are Largely Disordered Proteins that Have Evolved from One Common Ancestor.
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.
authors.affiliation: Department of Cell Biology, Microbiology, and Molecular Biology, College of Arts and Sciences, University of South Florida, 4202 East Fowler Avenue, ISA 2015, Tampa, FL 33620, USA.
authors.forename: Jessica
authors.identifier: 0000-0002-7268-9447
authors.initials: J
authors.lastname: Brunquell
authors.affiliation: Department of Cell Biology, Microbiology, and Molecular Biology, College of Arts and Sciences, University of South Florida, 4202 East Fowler Avenue, ISA 2015, Tampa, FL 33620, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Cell Biology, Microbiology, and Molecular Biology, College of Arts and Sciences, University of South Florida, 4202 East Fowler Avenue, ISA 2015, Tampa, FL 33620, USA.
authors.forename: Aqeela
authors.identifier: 0000-0002-0215-0868
authors.initials: A
authors.lastname: Erwin
authors.affiliation: Department of Cell Biology, Microbiology, and Molecular Biology, College of Arts and Sciences, University of South Florida, 4202 East Fowler Avenue, ISA 2015, Tampa, FL 33620, USA.
authors.forename: Sandy D
authors.initials: SD
authors.lastname: Westerheide
authors.affiliation: Department of Cell Biology, Microbiology, and Molecular Biology, College of Arts and Sciences, University of South Florida, 4202 East Fowler Avenue, ISA 2015, Tampa, FL 33620, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Xue
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics*; D019143:Evolution, Molecular; D006655:Histone Deacetylases / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008780:Methyltransferases / Q000737:chemistry / Q000235:genetics; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics; D056564:Sirtuin 1 / Q000737:chemistry / Q000235:genetics; D013329:Structure-Activity Relationship; D000099186:Histone Deacetylase 3
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D006655:Histone Deacetylases; D008780:Methyltransferases; D012097:Repressor Proteins; D056564:Sirtuin 1; D000099186:Histone Deacetylase 3; C477529:CCAR1 protein, human; C527450:CCAR2 protein, human; C407843:SUV39H1 protein, human; C447939:SIRT1 protein, human