The Hotdog fold: wrapping up a superfamily of thioesterases and dehydratases.
BACKGROUND
The Hotdog fold was initially identified in the structure of Escherichia coli FabA and subsequently in 4-hydroxybenzoyl-CoA thioesterase from Pseudomonas sp. strain CBS. Since that time structural determinations have shown a number of other apparently unrelated proteins also share the Hotdog fold.


RESULTS
Using sequence analysis we unify a large superfamily of HotDog domains. Membership includes numerous prokaryotic, archaeal and eukaryotic proteins involved in several related, but distinct, catalytic activities, from metabolic roles such as thioester hydrolysis in fatty acid metabolism, to degradation of phenylacetic acid and the environmental pollutant 4-chlorobenzoate. The superfamily also includes FapR, a non-catalytic bacterial homologue that is involved in transcriptional regulation of fatty acid biosynthesis. We have defined 17 subfamilies, with some characterisation. Operon analysis has revealed numerous HotDog domain-containing proteins to be fusion proteins, where two genes, once separate but adjacent open-reading frames, have been fused into one open-reading frame to give a protein with two functional domains. Finally we have generated a Hidden Markov Model library from our analysis, which can be used as a tool for predicting the occurrence of HotDog domains in any protein sequence.


CONCLUSIONS
The HotDog domain is both an ancient and ubiquitous motif, with members found in the three branches of life.
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK. scd@sanger.ac.uk
Shane C
SC
Dillon
Alex
A
Bateman
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D029681:Arabidopsis Proteins / Q000737:chemistry; D019843:Archaeal Proteins / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry; D005656:Fungal Proteins / Q000737:chemistry; D006801:Humans; D006836:Hydro-Lyases / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment / Q000379:methods; D013869:Thiolester Hydrolases / Q000737:chemistry*
D029681:Arabidopsis Proteins; D019843:Archaeal Proteins; D001426:Bacterial Proteins; D005656:Fungal Proteins; D010455:Peptides; D013869:Thiolester Hydrolases; D006836:Hydro-Lyases