title: DWNN, a novel ubiquitin-like domain, implicates RBBP6 in mRNA processing and ubiquitin-like pathways.
abstract: BACKGROUND
  RBBP6 is a 250 kDa splicing-associated protein that has been identified as an E3 ligase due to the presence of a RING finger domain. In humans and mice it interacts with both p53 and Rb, and plays a role in the induction of apoptosis and regulation of the cell cycle. RBBP6 has recently been shown to be highly up-regulated in oesophageal cancer, and to be a promising target for immunotherapy against the disease.
  
  
  RESULTS
  We show here using heteronuclear NMR that the N-terminal 81 amino acids of RBBP6 constitute a novel ubiquitin-like domain, which we have called the DWNN domain. The domain lacks conserved equivalents of K48 and K63, although the equivalents of K6 and K29 are highly, although not absolutely, conserved. The di-glycine motif that is characteristic of proteins involved in ubiquitination is found in the human and mouse form of the domain, although it is not present in all organisms. It forms part of a three-domain form of RBBP6 containing the DWNN domain, a zinc knuckle and a RING finger domain, which is found in all eukaryotic genomes so far examined, in the majority of cases at single copy number. The domain is also independently expressed in vertebrates as a single domain protein.
  
  
  CONCLUSIONS
  DWNN is a novel ubiquitin-like domain found only at the N-terminus of the RBBP6 family of splicing-associated proteins. The ubiquitin-like structure of the domain greatly increases the likelihood that RBBP6 functions through some form of ubiquitin-like modification. Furthermore, the fact that the DWNN domain is independently expressed in higher vertebrates leads us to propose that the domain may itself function as a novel ubiquitin-like modifier of other proteins.
authors.affiliation: Biotechnology Department, University of the Western Cape, Modderdam Road, Bellville 7535, South Africa. dpugh@uwc.ac.za
authors.forename: David J R
authors.initials: DJ
authors.lastname: Pugh
authors.forename: Eiso
authors.initials: E
authors.lastname: Ab
authors.forename: Andrew
authors.initials: A
authors.lastname: Faro
authors.forename: Portia T
authors.initials: PT
authors.lastname: Lutya
authors.forename: Eberhard
authors.initials: E
authors.lastname: Hoffmann
authors.forename: D Jasper G
authors.initials: DJ
authors.lastname: Rees
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry* / Q000502:physiology; D019295:Computational Biology; D004247:DNA / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000502:physiology; D004938:Esophageal Neoplasms / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015233:Models, Statistical; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D020033:Protein Isoforms; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D025801:Ubiquitin / Q000737:chemistry; D044767:Ubiquitin-Protein Ligases; D015854:Up-Regulation; D016335:Zinc Fingers
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D025801:Ubiquitin; D004247:DNA; C098584:RBBP6 protein, human; D044767:Ubiquitin-Protein Ligases