{PDOC50910}
{PS50910; HEPN}
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* HEPN domain profile *
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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-
alpha-helical domain   of  kanamycin  nucleotidyltransferases  (KNTases)  (see
<PDB:1O3U>). It  is composed of five alpha 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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: June 2003 / First entry.

[ 1] Grynberg M., Erlandsen H., Godzik A.
     "HEPN: a common domain in bacterial drug resistance and human
     neurodegenerative proteins."
     Trends Biochem. Sci. 28:224-226(2003).
     PubMed=12765831

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