CREST - a large and diverse superfamily of putative transmembrane hydrolases

Jimin Pei, Douglas P. Millay, Eric N. Olson, Nick V. Grishin

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background: A number of membrane-spanning proteins possess enzymatic activity and catalyze important reactions involving proteins, lipids or other substrates located within or near lipid bilayers. Alkaline ceramidases are seven-transmembrane proteins that hydrolyze the amide bond in ceramide to form sphingosine. Recently, a group of putative transmembrane receptors called progestin and adipoQ receptors (PAQRs) were found to be distantly related to alkaline ceramidases, raising the possibility that they may also function as membrane enzymes.Results: Using sensitive similarity search methods, we identified statistically significant sequence similarities among several transmembrane protein families including alkaline ceramidases and PAQRs. They were unified into a large and diverse superfamily of putative membrane-bound hydrolases called CREST (alkaline ceramidase, PAQR receptor, Per1, SID-1 and TMEM8). The CREST superfamily embraces a plethora of cellular functions and biochemical activities, including putative lipid-modifying enzymes such as ceramidases and the Per1 family of putative phospholipases involved in lipid remodeling of GPI-anchored proteins, putative hormone receptors, bacterial hemolysins, the TMEM8 family of putative tumor suppressors, and the SID-1 family of putative double-stranded RNA transporters involved in RNA interference. Extensive similarity searches and clustering analysis also revealed several groups of proteins with unknown function in the CREST superfamily. Members of the CREST superfamily share seven predicted core transmembrane segments with several conserved sequence motifs.Conclusions: Universal conservation of a set of histidine and aspartate residues across all groups in the CREST superfamily, coupled with independent discoveries of hydrolase activities in alkaline ceramidases and the Per1 family as well as results from previous mutational studies of Per1, suggests that the majority of CREST members are metal-dependent hydrolases.Reviewers: This article was reviewed by Kira S. Markarova, Igor B. Zhulin and Rob Knight.

Original languageEnglish (US)
Article number37
JournalBiology Direct
Volume6
DOIs
StatePublished - Jun 6 2011

Fingerprint

Alkaline Ceramidase
Hydrolases
hydrolases
Receptor
progestational hormones
Proteins
Protein
Progesterone Receptors
receptors
protein
Lipids
lipid
transmembrane proteins
Sudden Infant Death
Similarity Search
Membrane
Progestins
membrane
Membranes
RNA

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology
  • Applied Mathematics
  • Modeling and Simulation
  • Ecology, Evolution, Behavior and Systematics

Cite this

CREST - a large and diverse superfamily of putative transmembrane hydrolases. / Pei, Jimin; Millay, Douglas P.; Olson, Eric N.; Grishin, Nick V.

In: Biology Direct, Vol. 6, 37, 06.06.2011.

Research output: Contribution to journalArticle

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