Hotdog acyl-CoA thioesterase (ACOT)-type domain (IPR033120)

Short name: HOTDOG_ACOT

Overlapping homologous superfamilies

Domain relationships


The HotDog domain is widespread in eukaryotes, bacteria, and archaea and is involved in a range of cellular processes, from thioester hydrolysis, to phenylacetic acid degradation and transcriptional regulation of fatty acid biosynthesis. The HotDog domain has a mixed alpha+beta fold structure, which adopts a five- to seven-stranded antiparallel beta-sheet as the 'bun' wrapping around a central alpha-helix sausage [PMID: 15307895].

The largest HotDog domain subfamily represents over a hundred acyl-CoA thioesterases (ACOTs) that are widespread throughout the prokaryotic kingdom, with members also found in eukaryotes. This group of enzymes catalyze the hydrolysis of acyl-CoA thioesters to free fatty acids and coenzyme A (CoA- SH). The subfamily includes thioesterases with activity towards medium and long chain acyl-CoAs (medium chain acyl-CoA hydrolase and cytosolic long-chain acyl-CoA hydrolase/brain acyl-CoA hydrolase (BACH) respectively) and also cytoplasmic acetyl-CoA hydrolase (CACH), which hydrolyzes acetyl-CoA to acetate and CoA-SH. Brown-fat-inducible thioesterase (BFIT), a cold-induced protein found in brown adipose tissue (BAT) is also included in this group. Both BFIT and CACH possess a StAR-related lipid-transfer (START) domain that is involved in lipid binding, consistent with the role of BFIT and CACH in lipid metabolism. Duplication of the HotDog domain and recruitment of the START domain seems to be a mammalian innovation [PMID: 15307895].

The HotDog ACOT-type domain consists of a five-stranded beta-sheet with topology beta1/beta3/beta4/beta5/beta2 that wraps around a central five-turn alpha helix, alpha1, positioned between beta1 and beta2 [PMID: 19303060, PMID: 17563367, PMID: 25002576].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE profiles