PROSITE documentation PDOC50910
HEPN domain profile


The HEPN (higher eukaryotes and prokaryotes nucleotide-binding) domain is a region of 110 residues found in the C-terminus of sacsin, a chaperonin implicated in an early-onset neurodegenerative disease in human, and in many bacterial and archaebacterial proteins. There are three classes of proteins with HEPN domain:

  • Single-domain HEPN proteins found in many bacteria.
  • Two-domain proteins with N-terminal nucleotidyltransferase (NT) and C- terminal HEPN domains. This N-terminal NT domain belongs to a large family of NTs, which includes several classes of enzymes that are responsible for some types of bacterial resistance to aminoglycosides. These enzymes deactivate various antibiotics by transferring a nucleotidyl group to the drug.
  • A multidomain sacsin protein in genomes of fish and mammals. The HEPN domain is located at the C-terminus of the protein, directly after the DnaJ domain (see <PDOC00553>).

The crystal structure of the HEPN domain from the TM0613 protein of Thermotoga maritima indicates that it is structurally similar to the C-terminal all-α-helical domain of kanamycin nucleotidyltransferases (KNTases) (see <PDB:1O3U>). It is composed of five α helices, three of which form an up-and-down helical bundle, with a pair of short helices on the side. The distant structural similarity suggests that the HEPN domain might be involved in nucleotide binding [1].

The profile we developed covers the entire HEPN domain.

Last update:

June 2003 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

HEPN, PS50910; HEPN domain profile  (MATRIX)


1AuthorsGrynberg M. Erlandsen H. Godzik A.
TitleHEPN: a common domain in bacterial drug resistance and human neurodegenerative proteins.
SourceTrends Biochem. Sci. 28:224-226(2003).
PubMed ID12765831

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