Letunic et al. (2017) Nucleic Acids Res doi: 10.1093/nar/gkx922
Letunic et al. (2020) Nucleic Acids Res doi: 10.1093/nar/gkaa937

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HEPN Higher Eukarytoes and Prokaryotes Nucleotide-binding domain

SMART accession number:	SM00748
Description:	-
Interpro abstract (IPR007842):	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 archeabacterial 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 ( IPR001623 ). 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). 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 [ (PUBMED:12765831) ].
Family alignment:	View or CHROMA formatHMM/Web logoCLUSTALW formatMSF formatFASTA formatPIR format

There are 2378 HEPN domains in 2378 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Taxonomic distribution of proteins containing HEPN domain.

  This tree includes only several representative species. The complete taxonomic breakdown of all proteins with HEPN domain is also avaliable.

  Click on the protein counts, or double click on taxonomic names to display all proteins containing HEPN domain in the selected taxonomic class.

• Metabolism (metabolic pathways involving proteins which contain this domain)

• Click the image to view the interactive version of the map in iPath

  % proteins involved KEGG pathway ID Description 50.00 map00251 Glutamate metabolism 50.00 map00230 Purine metabolism This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with HEPN domain which could be assigned to a KEGG orthologous group, and not all proteins containing HEPN domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

• Structure (3D structures containing this domain)

• 3D Structures of HEPN domains in PDB

  PDB code	Main view	Title
  1o3u		Crystal structure of an hepn domain protein (tm0613) from thermotoga maritima at 1.75 A resolution
  1ufb		Crystal structure of TT1696 from Thermus thermophilus HB8
  1wol		Crystal Structure of ST0689, an archaeal HEPN homologue
  3o10		Crystal structure of the HEPN domain from human sacsin
  4nqf		Crystal structure of HEPN domain protein

• Links (links to other resources describing this domain)

• INTERPRO	IPR007842

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