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13  structures 1446  species 0  interactions 3240  sequences 24  architectures

Family: HEPN (PF05168)

Summary: HEPN domain

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This is the Wikipedia entry entitled "HEPN domain". More...

HEPN domain Edit Wikipedia article

HEPN domain
PDB 1ufb EBI.jpg
crystal structure of tt1696 from thermus thermophilus hb8
Symbol HEPN
Pfam PF05168
Pfam clan CL0291
InterPro IPR007842
SCOP 1o3u

In molecular biology, the HEPN domain (higher eukaryotes and prokaryotes nucleotide-binding domain) is a region of approximately 110 amino acids found in the C terminus of sacsin, a chaperonin implicated in an early-onset neurodegenerative disease in human, and in many bacterial and archaea proteins. There are three classes of proteins with HEPN domains:


  1. ^ Grynberg M, Erlandsen H, Godzik A (May 2003). "HEPN: a common domain in bacterial drug resistance and human neurodegenerative proteins". Trends Biochem. Sci. 28 (5): 224–6. doi:10.1016/S0968-0004(03)00060-4. PMID 12765831. 

This article incorporates text from the public domain Pfam and InterPro IPR007842

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Literature references

  1. Grynberg M, Erlandsen H, Godzik A; , Trends Biochem Sci 2003;28:224-226.: HEPN: a common domain in bacterial drug resistance and human neurodegenerative proteins. PUBMED:12765831 EPMC:12765831

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry 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 ( INTERPRO ).

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 ].

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan KNTase_C (CL0291), which has the following description:

This alpha helical domain is found associated with a variety of nucleotidyltransferase domains.

The clan contains the following 27 members:

AadA_C DUF294_C DUF4145 DUF5667 DUF86 GlnD_UR_UTase HEPN HEPN-like_int HEPN_AbiA_CTD HEPN_AbiU2 HEPN_AbiV HEPN_Apea HEPN_Cthe2314 HEPN_DZIP3 HEPN_LA2681 HEPN_MAE_28990 HEPN_RiboL-PSP HEPN_RnaseLS HEPN_SAV2148 HEPN_SAV_6107 HEPN_STY4199 HEPN_Swt1 KNTase_C NTase_sub_bind PaREP1 pEK499_p136 RnlA-toxin_DBD


We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

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Curation View help on the curation process

Seed source: COG2250
Previous IDs: DUF712;
Type: Family
Sequence Ontology: SO:0100021
Author: Bateman A
Number in seed: 78
Number in full: 3240
Average length of the domain: 117.70 aa
Average identity of full alignment: 16 %
Average coverage of the sequence by the domain: 15.35 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.7 21.7
Trusted cut-off 21.7 21.7
Noise cut-off 21.6 21.6
Model length: 117
Family (HMM) version: 16
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the HEPN domain has been found. There are 13 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
Q57607 View 3D Structure Click here
Q58022 View 3D Structure Click here
Q58700 View 3D Structure Click here