PROSITE documentation PDOC51770HotDog acyl-CoA thioesterase (ACOT)-type domain profile
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 α+β fold structure, which adopts a five- to seven-stranded antiparallel β-sheet as the 'bun' wrapping around a central α-helix sausage [1].
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 (see <PDOC50848>) 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 [1].
The HotDog ACOT-type domain consists of a five-stranded β-sheet with topology β1/β3/β4/β5/β2 that wraps around a central five-turn α helix, α1, positioned between β1 and β2 (see <PDB:3D6L>) [2,3,4].
The profile we developed covers the entire HotDog ACOT-type domain.
Last update:August 2015 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Dillon S.C. Bateman A. |
| Title | The Hotdog fold: wrapping up a superfamily of thioesterases and dehydratases. | |
| Source | BMC Bioinformatics 5:109-109(2004). | |
| PubMed ID | 15307895 | |
| DOI | 10.1186/1471-2105-5-109 |
| 2 | Authors | Yokoyama T. Choi K.-J. Bosch A.M. Yeo H.-J. |
| Title | Structure and function of a Campylobacter jejuni thioesterase Cj0915, a hexameric hot dog fold enzyme. | |
| Source | Biochim. Biophys. Acta 1794:1073-1081(2009). | |
| PubMed ID | 19303060 | |
| DOI | 10.1016/j.bbapap.2009.03.002 |
| 3 | Authors | Forwood J.K. Thakur A.S. Guncar G. Marfori M. Mouradov D. Meng W. Robinson J. Huber T. Kellie S. Martin J.L. Hume D.A. Kobe B. |
| Title | Structural basis for recruitment of tandem hotdog domains in acyl-CoA thioesterase 7 and its role in inflammation. | |
| Source | Proc. Natl. Acad. Sci. U.S.A. 104:10382-10387(2007). | |
| PubMed ID | 17563367 | |
| DOI | 10.1073/pnas.0700974104 |
| 4 | Authors | Swarbrick C.M. Roman N. Cowieson N. Patterson E.I. Nanson J. Siponen M.I. Berglund H. Lehtio L. Forwood J.K. |
| Title | Structural basis for regulation of the human acetyl-CoA thioesterase 12 and interactions with the steroidogenic acute regulatory protein-related lipid transfer (START) domain. | |
| Source | J. Biol. Chem. 289:24263-24274(2014). | |
| PubMed ID | 25002576 | |
| DOI | 10.1074/jbc.M114.589408 |
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