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4  structures 992  species 1  interaction 2053  sequences 37  architectures

Family: Diphthamide_syn (PF01866)

Summary: Putative diphthamide synthesis protein

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Putative diphthamide synthesis protein Provide feedback

Diphthamide_syn, diphthamide synthase, catalyses the last amidation step of diphthamide biosynthesis using ammonium and ATP. Q16439 is a candidate tumour suppressor gene [1]. DPH2 from yeast P32461 [2] which confers resistance to diphtheria toxin has been found to be involved in diphthamide synthesis. Diphtheria toxin inhibits eukaryotic protein synthesis by ADP-ribosylating diphthamide, a post-translationally modified histidine residue present in EF2. Diphthamide synthase is evolutionarily conserved in eukaryotes. Diphthamide is a post-translationally modified histidine residue found on archaeal and eukaryotic translation elongation factor 2 (eEF-2) [3].

Literature references

  1. Phillips NJ, Zeigler MR, Deaven LL; , Cancer Lett 1996;102:85-90.: A cDNA from the ovarian cancer critical region of deletion on chromosome 17p13.3. PUBMED:8603384 EPMC:8603384

  2. Mattheakis LC, Sor F, Collier RJ; , Gene 1993;132:149-154.: Diphthamide synthesis in Saccharomyces cerevisiae: structure of the DPH2 gene. PUBMED:8406038 EPMC:8406038

  3. Su X, Lin Z, Chen W, Jiang H, Zhang S, Lin H;, Proc Natl Acad Sci U S A. 2012;109:19983-19987.: Chemogenomic approach identified yeast YLR143W as diphthamide synthetase. PUBMED:23169644 EPMC:23169644


This tab holds annotation information from the InterPro database.

InterPro entry IPR016435

Archaeal and eukaryotic translation elongation factor 2 contain a unique posttranslationally modified histidine residue called diphthamide, the target of the diphtheria toxin. Diphtheria toxin inhibits eukaryotic protein synthesis by ADP-ribosylating diphthamide in EF2 [PUBMED:15485916].

Members of this family include DPH1 and DPH2, which are involved in the first step of diphthamide synthesis [PUBMED:15485916]. Archaeal DPHs are more similar to eukaryotic DPH1 than to DPH2 [PUBMED:20559380].

Domain organisation

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Alignments

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, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(245)
Full
(2053)
Representative proteomes UniProt
(3383)
NCBI
(4083)
Meta
(162)
RP15
(609)
RP35
(1228)
RP55
(1723)
RP75
(2170)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(245)
Full
(2053)
Representative proteomes UniProt
(3383)
NCBI
(4083)
Meta
(162)
RP15
(609)
RP35
(1228)
RP55
(1723)
RP75
(2170)
Alignment:
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Sequence:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(245)
Full
(2053)
Representative proteomes UniProt
(3383)
NCBI
(4083)
Meta
(162)
RP15
(609)
RP35
(1228)
RP55
(1723)
RP75
(2170)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download   Download  

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

HMM logo

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Trees

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

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Enright A
Previous IDs: none
Type: Family
Author: Enright A, Ouzounis C, Bateman A
Number in seed: 245
Number in full: 2053
Average length of the domain: 272.10 aa
Average identity of full alignment: 28 %
Average coverage of the sequence by the domain: 65.64 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 32.2 32.2
Trusted cut-off 32.4 32.9
Noise cut-off 32.1 32.1
Model length: 300
Family (HMM) version: 16
Download: download the raw HMM for this family

Species distribution

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

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Interactions

There is 1 interaction for this family. More...

Diphthamide_syn

Structures

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 Diphthamide_syn domain has been found. There are 4 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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