A comprehensive analysis of small open reading frames (smORFs) in flies, mice and humans supports their classification into different functional groups, from inert DNA sequences to transcribed and translated smORFs that have various activities. The different smORF classes could represent steps in gene, peptide and protein evolution.

Analysis of the available human small ubiquitin-like modifier (SUMO) proteomics data provided evidence for the sumoylation of thousands of proteins and residues, and clustered the sumoylated proteins into functional networks. Sumoylation is a frequent modification, occurring mostly on nuclear proteins, with functions including transcription, mRNA processing and the DNA-damage response.

Binding of DNA and of RNA are no longer considered functionally distinct, partly owing to the discovery that DNA- and RNA-binding proteins (DRBPs) can bind long non-coding RNAs and DNA. The unique functional characteristics of DRBPs stem from their specific structural features and allow them to regulate various cellular processes.

The adhesive interaction of cells with the environment through integrins regulates multiple aspects of cellular physiology. The prominence of gene mutations in specific constituents of integrin-mediated adhesions, which are collectively known as the 'integrin adhesome', in diverse pathological states, is providing insight into the molecular mechanisms that underlie these diseases.

The p53 protein regulates the transcription of many target genes in response to a wide variety of stress signals. This Analysis article presents the most comprehensive list so far of human p53-regulated genes and their experimentally validated, functional binding sites that confer p53 regulation.

Although most proteins contain multiple domains, nearly all folding studies so far have been of single domains in isolation. Here we consider the importance of interdomain cooperativity in protein folding and propose evolutionary mechanisms that prevent misfolding in multidomain proteins.